53 Years Old is A Reasonable Cut-Off Value To Define Young And Old Patients In Clear Cell Renal Cell Carcinoma：A Study Based On TCGA And SEER Database

53 Years Old is A Reasonable Cut-Off Value To Define Young And Old Patients In Clear Cell Renal Cell Carcinoma：A Study Based On TCGA And SEER Database | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article 53 Years Old is A Reasonable Cut-Off Value To Define Young And Old Patients In Clear Cell Renal Cell Carcinoma：A Study Based On TCGA And SEER Database Fucai Tang, Zechao Lu, Chengwu He, Hanbin Zhang, Weijia Wu, Zhaohui He This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.12816/v2 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 May, 2021 Read the published version in BMC Cancer → Version 2 posted 7 You are reading this latest preprint version Show more versions Abstract Background: The objectives of this study were to screen out cut-off age value and age-related differentially expressed genes (DEGs) in clear cell renal cell carcinoma (CCRCC) from Surveillance Epidemiology and End Results (SEER) database and The Cancer Genome Atlas (TCGA) database. Methods: We selected 45,974 CCRCC patients from SEER and 530 RNA-seq data from TCGA database. The age cut-off value was defined using the X-tile program. Propensity score matching (PSM) was used to balance the differences between young and old groups. Hazard ratio (HR) was applied to evaluate prognostic risk of age in different subgroups. Age-related DEGs were identified via RNA-seq data. Survival analysis was used to assess the relationship between DEGs and prognosis. Results: In this study, we divided the patients into young (n=14276) and old (n=31698) subgroups according to cut-off value (age=53). Age >53 years was indicated as independent risk factor for overall survival (OS) and cancer specific survival (CSS) of CCRCC before and after PSM. The prognosis of old group was worse than that in young group. Eleven gene were differential expression between the younger and older groups in CCRCC. The expression levels of PLA2G2A and SIX2 were related to prognosis of the elderly. Conclusion: 53 years old was cut-off value in CCRCC. The prognosis of the elderly was worse than young people. It remind clinicians that more attention and better treatment should be given to CCRCC patients who are over 53 years old. PLA2G2A and SIX2 were age-related differential genes which might play an important role in the poor prognosis of elderly CCRCC patients. Cancer Biology Oncology Age age-related genes Clear cell renal cell carcinoma The Cancer Genome Atlas Surveillance Epidemiology and End Results Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Over the past two decades, the incidence of renal cell carcinoma (RCC) at every stages was increased and this situation resulted in a steady increase in mortality per unit of population [1]. It is estimated that 65340 Americans will be diagnosed with RCC, and 14970 Americans will die of this cancer in 2018. RCC comprises about 3.8% of all new cancer. And the median age of RCC patient is 64 ages old. Clear cell renal cell carcinoma (CCRCC) is the most common subtype of RCC, it accounts for about 80% of RCC [2]. Age has prognostic significance in many solid cancers, and one of renal cancer known risk factors is age [3,4]. RCC shows a more favorable prognosis in young patiens, which may be due to the lower state of diagnosis [5]. In addition, age can influence the structural and molecular properties of the tumor vasculature in CCRCC by comparing the vascular properties of patients who over the age of 65 and under 65 years old [6]. Furthermore, expression levels of Piwil 1 mRNA in patients who under 64 years old are higher than that in older people (> 64 years old). But there still is no optimal age cut off value to define elderly and young people in CCRCC. Therefore, we determined the optimal cut-off value for age analyzing the clinical data SEER database, and explored differentially expressed genes (DEGs) between older and younger people of CCRCC by analyzing RNA-seq data from TCGA in present study. Methods Study population from SEER SEER Stat software (version 8.3.5) was used to download CCRCC clinical data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. The downloaded data included: patient ID, the year and age at the time of diagnosis, sex, race, histological type, survival time, tumor size, marital status, Grade, SEER historic stage A, and cause of death. CCRCC patients were selected according to the following criteria: (1) site record International Classification of Diseases for Oncology, Third Revision (ICD-O-3) was C649; (2) histological type was 8310/3; (3) the year at time of diagnosis was 1988-2014. (4) CCRCC was primary tumor. The exclusion criteria were listed as following: (1) patients without race and gender information; (2) patients whose tumor size, survival time and other clinical information we need in this study were unknown. Variable declaration Race was defined as white, black and other. Marital was divided into Single/Other, and married. Tumor size was divided into less than 4 cm, 4 cm to 7 cm, and greater than 7 cm. Grade was grouped as I , II, III, IV. Laterality was divided into left and right. The SEER historic stage options included localized, regional and distant. And the chemotherapy, radiotherapy were divided into yes or no. Cut off age in CCRCC X-tile is a useful tool for biomarker assessment and outcome-based cut-point optimization (http://www.tissuearray.org/rimmlab/). The “x tile plot” can provide a single, global assessment of every possible way by dividing a population into low- and high-level marker expression [7]. The grouping strategy of the X-tile program includes trying to use each number between the retrieved count ranges as a critical value; then, using this number as a cut-off value to calculate the χ2 score and P value. We used X-tile plots to assessed all possible age cutoff value, and the survival at every age cutoff value was computed by the log rank test. Then the most appropriate cut-off value was selected which had the highest χ2 value. RNA-seq Analysis of CCRCC from TCGA The RNA sequencing and clinical information of CCRCC were download from TCGA database. We used these RNA-seq data for DEGs screening between younger and older group by Limma package (adjusted p value 53 years), including survival time and survival status. We selected the DEGs from the small to large false discovery rate (FDR). And the DEGs was for survival analysis. The differentially expression levels of DEGs in these old patients were obtained. The median of gene expression was used to classify low and high group. Log rank test was used to compare statistically significant differences between high and low expression groups. Statistical Analysis We divided the patients into young and old groups according to the X-tile's best cut-off value. Chi-square test was used to compare the differences in the distribution of variables between younger and older group. We calculated the overall survival (OS) and cancer specific survival (CSS). In the CSS calculation, the cause of death for other reasons was defined as censorship. Propensity score matching (PSM) used logistic regression included relevant variables of Sex, race, marital status, size, grade, SEER historic stage A, radiation and chemotherapy to balance the baseline differences between the younger and older groups. The OS and CSS Survival curves were generated using the Kaplane-Meier method. And univariate and multivariate analysis Cox regression models were applied to adjust prognostic variables. The cases were stratified according to the relevant variables. Hazard Ratio (HR) of the CSS was calculated according to the age. When the 2-sided P value was < 0.05, the differences were considered statistically significant. The SPSS 24.0 and R 3.4.3 were used to conduct statistical analysis and DEGs screening. Results 53 was the age cut-off value and Baseline Characteristics We obtained 45,974 CCRCC patients in totally. The median age of these patients was 60 years old (interquartile range: 51-69). At the same time, X tile result showed that 53 years old was defined as the best cut-off value for age (Figure 1). Then we divided the cohort into two groups: younger group (53 years or younger), older group (older than 53 years) according to the cut-off value. The detailed features of the patients between the two groups were presented in Table 1 ( Table 1). Survival Analysis In the young group, 5- and 10-year OS rates were 86.4% and 78.2% respectively. In the old group, 5- and 10-year OS rates were 72.8% and 54.5 respectively ( P <0.001; Figure 2 A). Univariate analysis results indicated that age, sex, race, marital status, size, grade, laterality, SEER historic stage A, radiation and chemotherapy,could predict patient suvival outcomes. Meanwhile, multivariate analysis showed that the age, sex, race, marital status, size, grade, laterality, SEER historic stage A, radiation and chemotherapy were independent prognostic factor for CCRCC OS(Table 2). In the young group, 5- and 10-year CSS rates were 89.4% and 81.7% respectively. In the old group, 5- and 10-year CSS rates were 84.3% and 72.8% respectively ( P <0.001; Figure 2 B).The results of univariate analysis showed that age, sex, marital status, size, grade, laterality, SEER historic stage A, radiation and chemotherapy were associated with patient's prognosis. Multivariate analysis showed that age, marital status, size, grade, SEER historic stage A, radiation and chemotherapy were independent prognostic factors for CCRCC CSS(Table 3). Survival Analysis after PSM The clinical characteristics of the patients between the younger and older groups had obvious differences. So PSM method was applied to balance the differences between the variables, and generated a new queue (All covariates were well balanced, P values > 0.05; Table 1). Univariate analysis results showed that HR for OS of the older patient were 2.056 (95% CI:1.948-2.170; P <0.001), HR for CSS were 1.496(95% CI, 1.399-1.600; P <0.001) when compared with the younger group. In the PSM queue, the younger people also had a higher survival rate than older people (Figure 2 C, D). Multivariate analysis results showed that compared with the younger group , HR for OS of the older patient were 2.128（95%CI:2.015-2.247; P <0.001）, HR for CSS were 1.573(95%CI:1.470-1.682; P <0.001). Other variable results were showed in Table 2, 3. Subgroup analysis We performed a subgroup analysis based on sex, race, marital status, size, grade, laterality, SEER historic stage A, radiation, and chemotherapy. In most subgroups, the older group had a worse prognosis than the younger group. However radiation, and chemotherapy and prognostic differences between young and old groups were not statistically significant ( P >0.05) (Figure 3). Differential expressed genes and prognosis related genes The RNA-seq data of 530 CCRCC samples were downloaded from TCGA database. According to the cut-off value of 53 years old, they were divided into 158 young group and 372 elderly group. We finally got 11 differential expressed genes(DEGs) between the younger and older groups in CCRCC (Table 4). Among them, SIX2, THBS4 and PLA2G2A were up regulated in elderly patients with CCRCC. NKX2-3, CD1A, SCUBE1, NEFH, MYL10, TBL1Y, DYTN and SLC4A10 were down regulated in elderly patients with CCRCC. Then, the DEGs were analyzed by survival. The results showed that high expression of SIX2 and PLA2G2A were associated with poor prognosis in the elderly (Figure 4). Discussion A total of 45,974 CCRCC patients were included in the SEER database, of which the 53-year-old cut-off value was used to divide the younger and older groups. Survival analysis results showed that younger age (under age 53) was an independent predictor of CCRCC. And we obtained some genes related to old patients with CCRCC by analyzing the RNA-seq data downloaded from TCGA. Some studies reported that the 40 years old was suitable to act as the dividing line between young and old CCRCC patients. Xavier Taccoen et al. found that young (under 40 years of age) age was an independent prognostic factor for CCRCC, with a better prognosis [8]. Atiqullah Aziz et al found that young patients with RCC (age 40 or under) have a significantly lower all cause and disease specific killed [9]. Ho Won Kang et al. also found that young age was associated with favorable pathological features, although it is not survival independent prognostic factors in surgically treated RCC patients. But the result of the Kaplan-Meier analysis showed that the CCS rate was significantly better in the young age group than the other groups (middle age: ≥ 4 and < 60 years; old age: ≥ 60 years) [10]. Analysis results between younger and older RCC patients (20-39 and 40-79) of Jeong Ho Kim et al found that younger RCC patients would have more favorable histological subtypes. And the 5-year CSS rates for young and older patients were 95.5% and 90.5% respectively. However, after PSM, the five-year CSS rate was 95.5% for the younger group and 94.7% for the older group, and the prognosis was not significantly different (log rank p = 0.184) [11]. In addition to the 40 years old, there were many age cut-off values, such as 45 and 55 years old. Yoshinobu Komai et al used the 45-year-old as a cut-off value for younger and older group. Compared with the older patients, the young patients with RCC had similar recurrence-free survival rates but better CSS rates [12]. Eun-Jung Jung et al believed that younger age was an independent predictor of prognosis through multivariate analysis. Whereas in their study, younger than 55 years of age was considered as young in CCRCC [13]. In this study, we used X-tile plots to assessed all possible age cut-off value, and finally selected the age 53 as the cut off value for dividing younger and older group. And younger groups had better OS and CSS compared to older groups. What’s more, in the subgroup analysis, the prognosis of old group was worse than that of young group in all subgroups of this study, especially in the Dmax <= 4cm subgroups (HR = 3.710(3.006-4.579), P < 0.001). It suggests that in future CCRCC clinical decision-making, patients older than 53 years old needed to pay more attention and better treatment options. Compared with younger people, older patients have a greater risk of worsening disease, lower survival rate, and worse treatment efficiency, which may be related to the physical fitness of the older patients and probably diseases that may existed in themselves. In recent years, with the development of cancer gene sequencing and targeted therapies, the research on gene expression of CCRCC had made some progress. In the CCRCC age-related studies, Xp11 translocation renal cell carcinoma was kind of RCC subtype, Malouf GG et al used the targeted therapy to treat patients, the objective responses was achieved and the patients got the better progression-free survival [14]. Mitchell TJ et al. analyzed the entire genome of CCRCC and found that 36% of patients experience 3p loss and 5q gain, which usually occured during childhood or adolescence. Meanwhile hotspots of point mutations in the 5' UTR of TERT, targeting a MYC-MAX-MAD1 repressor associated with telomere lengthening [15]. Malouf GG reported that ASPSCR1-TFE3 might be the most aggressive among the transcription factor E3 fusion genes in RCC patients [16]. In this study, we obtained 11 DEGs by comparing RNA-seq data from younger and older CCRCC patients. Then, the DEGs were used for survival analysis. As showed in the result (Figure 4), the expression of Secretory Phospholipase A2 Group IIA(PLA2G2A), and Sine oculis-related homeobox 2(SIX2) were related to the survival of the elderly. Secretory Phospholipase A2 Group IIA (PLA2G2A), one of the family members of PLA2, primarily targets extracellular phospholipids with implications in host antimicrobial defense, inflammatory response and tissue regeneration [17]. And PLA2G2A was found to be associated with different disease states including cancer. Our results indicate that PLA2G2A is highly expressed in the elderly and is closely related to poor prognosis in the elderly group. However, further studies are needed to illuminate the molecular and biological mechanism of PLA2G2A in CCRCC. Sine oculis-related homeobox 2 (SIX2) is composed of six homeobox genes (SIX1-SIX6), which serves as an important regulator of embryonic development. Wu Y et al [18] found that overexpression of Six 2 increased the proliferative capacity of cells and decreased apoptosis in clear cell renal cell carcinoma. At the same time, our research showed that SIX2 was age-related DEG. And high expression levels of SIX2 was related to poor prognosis of the elderly. These results suggest that PLA2G2A and SIX2 might have clinical monitoring value in CCRCC which deserved for further research. Our study had several potential limitations. The leading known risk factors for renal cancer were smoking, obesity and hypertension [19-24]. However, due to the lack of corresponding data in the SEER database, we were unable to study these factors. At the same time, retrospective analyses always carried the risk of various biases. We used the subgroup, PSM analysis and incorporate large amounts of patients in this study to minimize potential biases. Conclusions In conclusion, we proposed that 53-year-old was a reasonable cut-off value among CCRCC patients, and the elderly group had a worse prognosis than the younger group. These results remind clinicians that more attention and better treatment should be given to CCRCC patients older than 53 years old. At the same time, 11 gene were age-related differential genes. The high expression of PLA2G2A and SIX2 might be associated with poor prognosis in the elderly, but the specific mechanism remained to be further studied. Declarations Ethics approval and consent to participate The present study, the data download from Surveillance Epidemiology and End Results database and The Cancer Genome Atlas (TCGA) database, therefore, this article does not contain any studies with human participants or animals performed by any of the authors. Thus no ethical approval and patient consent are required. This article does not contain any studies with animals performed by any of the authors. Consent for publication Not applicable. Availability of data and materials The datasets analyzed during the current study download from Surveillance Epidemiology and End Results database (https://seer.cancer.gov/) and The Cancer Genome Atlas (TCGA) database. (https://cancergenome.nih.gov/). Competing interests All authors declare that they have no conflict of interest to state. Funding Not Applicable. Authors’ contributions ZH, FT and ZL conceived the study; ZH and FT conducted the work; CH, HZ and WW obtaining and analyzed the data; FT and ZL wrote the manuscript, and ZH reviewed the manuscript. All the authors listed have read and approved the manuscript. Acknowledgements Not Applicable. Abbreviations CCRCC: clear cell renal cell carcinoma; DEGs: Differentially expressed genes; SEER: Surveillance Epidemiology and End Results; TCGA: The Cancer Genome Atlas; OS：overall survival; CSS: cancer specific survival; PSM: Propensity score matching; HR: Hazard Ratio; FC: fold change; FDR: false discovery rate; CPM: counts per million. References 1 Ridge CA, Pua BB, Madoff DC. Epidemiology and staging of renal cell carcinoma. Semin Intervent Radiol. 2014; 31:3-8. 2 Liu K, Wang P, Zhu X, et al. Disparities of age-based cancer-specific survival improvement with various clinicopathologic characteristics for kidney cancer. 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Tables Table 1 ： The Clinical characteristic baseline of CCRC patients in SEER Characteristic Before PSM After PSM Younger ( 53 y ) N （ % ） P Younger ( 53 y ) N （ % ） P Sex <0.001 0.613 male 9134(63.98) 18958(59.81) 9124(63.96) 9165(64.24) female 5142(36.02) 12740(40.19) 5142(36.04) 5101(35.76) Race <0.001 0.322 Black 1020(7.14) 1939(6.12) 1014(7.11) 1063(7.45) White 12199(85.45) 27428(86.53) 12195(85.48) 12105(84.85) Other 1057(7.40) 2331(7.35) 1057(7.41) 1098(7.70) Marital <0.001 0.739 Single/Other 5124(35.89) 10484(33.07) 5116(35.86) 5143(36.05) married 9152(64.11) 21214(66.93) 9150(64.14) 9123(63.95) Size <0.001 0.571 Dmax<=4cm 7058(49.44) 12966(40.90) 7052(49.43) 6981(48.93) 4cm < Dmax7cm 3447(24.15) 8557(27) 3443(24.13) 3438(24.10) GRADE <0.001 0.566 Ⅰ 2204(15.44) 4226(13.33) 2199(15.41) 2243(15.72) Ⅱ 7893(55.29) 16362(51.62) 7890(55.31) 7873(55.19) Ⅲ 3376(23.65) 8978(28.32) 3375(23.66) 3309(23.20) Ⅳ 803(5.62) 2132(6.73) 802(5.62) 841(5.90) Laterality 0.228 0.840 Left 6949(48.68) 15622(49.28) 6946(48.69) 6963(48.81) Right 7327(51.32) 16076(50.72) 7320(51.31) 7303(51.19) SEER historic stage A <0.001 0.754 Localized 11405(79.89) 21988(69.37) 11395(79.88) 11345(79.52) Regional 1865(13.06) 6576(20.75) 1865(13.07) 1892(13.26) Distant 1006(7.05) 3134(9.89) 1006(7.05) 1029(7.21) Radiation 0.035 0.202 NO 13967(97.84) 30909(97.51) 13960(97.86) 13928(97.63) YES 309(2.16) 789(2.49) 306(2.14) 338(2.37) chemotherapy <0.001 0.274 NO 13664(95.71) 29986(94.60) 13655(95.72) 13617(95.45) YES 612(4.29) 1712(5.40) 611(4.28) 649(4.55) Table 2 ： cox regression analysis of overall survival Characteristic Univariate cox regression before PSM Multivariate cox regression before PSM Multivariate cox regression after PSM 95%CI P 95%CI P 95%CI P Age young ( ≤ 53 y ) Reference Reference Reference old ( >53 y ) 2.338 (2.228-2.453) <0.001 2.132(2.031-2.238) <0.001 2.128 （ 2.015-2.247 ） <0.001 Sex male Reference Reference Reference female 0.829(0.789-0.862) <0.001 0.909 （ 0.873-0.947 ） <0.001 0.910 （ 0.859-0.964 ） 0.001 Race Black Reference Reference Reference White 0.895(0.831-0.964) 0.003 0.836 （ 0.776-0.901 ） <0.001 0.795 （ 0.722-0.876 ） <0.001 Other 0.798(0.721-0.884) 0<0.001 0.716 （ 0.647-0.794 ） <0.001 0.682 （ 0.593-0.783 ） <0.001 Marital Single/Other Reference Reference Reference married 0.780(0.751-0.811) <0.001 0.729 （ 0.701-0.758 ） <0.001 0.711 （ 0.674-0.750 ） <0.001 Size Dmax<=4cm Reference Reference Reference 4cm< Dmax<=7cm 1.967(1.868-2.070) <0.001 1.403 （ 1.330-1.480 ） <0.001 1.382 （ 1.284-1.488 ） 7cm 4.084(3.895-4.283) <0.001 1.849 （ 1.748-1.956 ） <0.001 1.965 （ 1.823-2.118 ） <0.001 GRADE Ⅰ Reference Reference Reference Ⅱ 1.151 （ 1.081-1.225 ） <0.001 0.966 （ 0.907-1.029 ） 0.283 0.988 （ 0.907-1.075 ） 0.773 Ⅲ 2.225 （ 2.086-2.373 ） <0.001 1.213 （ 1.133-1.298 ） <0.001 1.287 （ 1.172-1.412 ） <0.001 Ⅳ 5.296 （ 4.911-5.712 ） <0.001 1.823 （ 1.681-1.978 ） <0.001 1.856 （ 1.661-2.075 ） <0.001 Laterality <0.001 Left Reference Reference Reference Right 0.936 （ 0.902-0.971 ） <0.001 0.953 （ 0.918-0.989 ） 0.012 0.947 （ 0.899-0.997 ） 0.038 SEER historic stage A Localized Reference Reference Reference Regional 2.705 （ 2.585-2.831 ） <0.001 1.830(1.740-1.925) <0.001 1.860 （ 1.727-2.003 ） <0.001 Distant 11.243 （ 10.734-11.776 ） <0.001 5.996(5.631-6.383) <0.001 6.694 （ 6.115-7.329 ） <0.001 Radiation NO Reference Reference Reference YES 6.150 （ 5.725-6.607 ） <0.001 1.340(1.239-1.450) <0.001 1.319 （ 1.187-1.465 ） <0.001 chemotherapy NO Reference Reference Reference YES 5.959 （ 5.637-6.299 ） <0.001 1.196(1.120-1.278) <0.001 1.254 （ 1.144-1.375 ） <0.001 Table 3 ： cox regression analysis of cancer-specific survival Characteristic Univariate cox regression before PSM Multivariate cox regression before PSM Multivariate cox regression after PSM 95%CL P 95%CL P 95%CL P age young ( ≤ 53 y ) Reference Reference Reference old (>53 y) 1.834(1.731-1.942) <0.001 1.549(1.462-1.642) <0.001 1.573(1.470-1.682) <0.001 Sex male Reference Reference Reference female 0.781(0.743-0.821) <0.001 1.008(0.957-1.061) 0.769 1.023(0.950-1.102) 0.549 Race Black Reference Reference Reference White 0.969(0.879-1.068) 0.525 Other 0.924(0.811-1.052) 0.233 Marital Single/Other Reference Reference Reference married 0.911(0.866-0.957) <0.001 0.843(0.801-.887) <0.001 0.824(0.769-0.884) <0.001 SIZE Dmax<=4cm Reference Reference Reference 4cm< Dmax<=7cm 3.886(3.566-4.233) <0.001 2.324(2.127-2.540) <0.001 2.433(2.153-2.750) 7cm 11.792(10.896-12.762) <0.001 3.710(3.393-4.055) <0.001 4.299(3.814-4.845) <0.001 GRADE Ⅰ Reference Reference Reference Ⅱ 1.420(1.287-1.567) <0.001 1.028(0.931-1.135) 0.583 1.051(0.918-1.203) 0.472 Ⅲ 4.020(3.649-4.428) <0.001 1.514(1.369-1.675) <0.001 1.615(1.405-1.855) <0.001 Ⅳ 10.814(9.738-12.009) <0.001 2.229(1.995-2.490) <0.001 2.264(1.944-2.636) <0.001 Laterality Left Reference Reference Reference Right 0.931(0.887-0.976) 0.003 0.954(0.910-1.001) 0.054 0.940(0.880-1.005) 0.07 SEER historic stage A Localized Reference Reference Reference Regional 4.934(4.637-5.249) <0.001 2.615(2.443-2.798) <0.001 2.641(2.402-2.903) <0.001 Distant 25.576(24.104-27. 138) <0.001 9.900(9.172-10.685) <0.001 10.134(9.108-11.276) <0.001 Radiation NO Reference Reference Reference YES 9.242(8.574-9.962) <0.001 1.446(1.334-1.568) <0.001 1.458(1.309-1.625) <0.001 chemotherapy NO Reference Reference Reference YES 8.887(8.369-9.438) <0.001 1.179(1.100-1.263) <0.001 1.268(1.152-1.396) <0.001 Table 4 ： The 11 age-related differentially expressed genes gene conMean treatMean logFC pValue FDR NKX2-3 0.248444555 0.090005562 -1.464837864 0.000165397 0.037107612 PLA2G2A 0.538674035 1.300683714 1.271785754 0.00040971 0.045159714 CD1A 0.499103859 0.182836665 -1.448784648 2.71E-05 0.018220037 SCUBE1 0.90569885 0.448615793 -1.013551014 2.35E-05 0.018220037 NEFH 0.536764531 0.234581834 -1.194198049 2.75E-06 0.006374551 DYTN 0.029518103 0.006416315 -2.201783071 4.53E-05 0.019711439 SIX2 0.240527498 0.499819682 1.055205878 0.000307207 0.043814576 TBL1Y 0.119504132 0.055953453 -1.094761418 1.76E-05 0.017134562 MYL10 0.058554689 0.024582676 -1.252142696 0.000530706 0.047321306 SLC4A10 0.111875634 0.049159421 -1.186356037 3.25E-05 0.018220037 THBS4 1.421111755 3.163220721 1.154374215 3.38E-05 0.018220037 Supplementary Files TableS1.docx Cite Share Download PDF Status: Published Journal Publication published 29 May, 2021 Read the published version in BMC Cancer → Version 2 posted Editorial decision: Major revision 05 Apr, 2021 Review # 1 received at journal 27 Dec, 2020 Reviewer # 1 agreed at journal 17 Dec, 2020 Reviewers invited by journal 16 Oct, 2020 Editor assigned by journal 12 Oct, 2020 Submission checks completed at journal 11 Oct, 2020 Editor invited by journal 11 Oct, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3555","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":3365271,"identity":"c62c9653-c64d-42c7-86a6-e4dbaf490e32","order_by":0,"name":"Fucai Tang","email":"","orcid":"","institution":"Guangdong Provincial Work Injury Rehabilitation Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fucai","middleName":"","lastName":"Tang","suffix":""},{"id":3365272,"identity":"57d17be6-3ab2-4d8c-a78b-6b79e90d4950","order_by":1,"name":"Zechao Lu","email":"","orcid":"","institution":"First Clinical College of Guangzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zechao","middleName":"","lastName":"Lu","suffix":""},{"id":3365273,"identity":"b7d101fc-257c-45bf-b0f7-15bf87b758f5","order_by":2,"name":"Chengwu He","email":"","orcid":"","institution":"Department of Urology, The Eighth Affiliated Hospital, Sun Yat-sen University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chengwu","middleName":"","lastName":"He","suffix":""},{"id":3365274,"identity":"37b60dcd-039f-46de-8786-7fd35dcc2177","order_by":3,"name":"Hanbin Zhang","email":"","orcid":"","institution":"The Second Clinical College of Guangzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hanbin","middleName":"","lastName":"Zhang","suffix":""},{"id":3365275,"identity":"5438ed39-cc33-42f3-ad73-ad1e5905dcd4","order_by":4,"name":"Weijia Wu","email":"","orcid":"","institution":"Department of Urology, The Eighth Affiliated Hospital, Sun Yat-sen University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Weijia","middleName":"","lastName":"Wu","suffix":""},{"id":3365276,"identity":"5a78d247-7cff-4d1e-960b-9af677562272","order_by":5,"name":"Zhaohui He","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAu0lEQVRIiWNgGAWjYJACZgaGA3Js7O0HSNNizMdzJoE0LYnzJBwMiFMu73/8mnTBnzvpbRIMCQw/KrYR1mJ44EyZ9AyeZ7lt0o0HGHvO3CZCS2NPmjSPxOHcNpkDCcyMbcRoaeYBajE4nM4mkWBAnBZ5NvZj0jwJhxOI12LAw8NszXPgsGEbMJAPEuUX+f7jD2/z/DksL9/efvDBjwpibDnAYyIB4xwgrB5kSwP74w9EqRwFo2AUjIKRCwCctTxgf1qeeAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-2289-9603","institution":"The Eighth Affiliated Hospital, Sun Yat-sen University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Zhaohui","middleName":"","lastName":"He","suffix":""}],"badges":[],"createdAt":"2019-08-07 14:04:23","currentVersionCode":2,"declarations":"","doi":"10.21203/rs.2.12816/v2","doiUrl":"https://doi.org/10.21203/rs.2.12816/v2","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12885-021-08376-5","type":"published","date":"2021-05-29T20:46:26+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":3067597,"identity":"4c33fea9-9749-4b11-9c84-c79721e215c6","added_by":"auto","created_at":"2020-10-19 19:41:35","extension":"tif","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":244218,"visible":true,"origin":"","legend":"X-Tile analysis of survival data from the Surveillance, Epidemiology, and End Results (SEER) registry. X-Tile analysis was performed using patient data from the SEER registry. The plot showed the χ2 log-rank values produced when dividing the cohort with two cut-points, producing low and high subsets. The X-axis represented all potential tangent points from low to high that defined a low subset, while the Y-axis represented the high to low tangent points that defined a high subset. The arrows indicated the direction in which the size of the low subset (X-axis) and the high subset (Y-axis) increased. (A) X-Tile plot of the patient age divided at the mean age, the optimal cut-point highlighted by the black circle in middle of the color bar. (B) Histogram of the entire cohort, optimal cut-off values of age at diagnosis were identified as 53 years based on cancer-specific survival (CSS). (C) Kaplan-Meier survival curve developed based on these cutoff values.","description":"","filename":"Fig1.tif","url":"https://assets-eu.researchsquare.com/files/rs-3555/v2/53a526d9dfc94bd49a109581.tif"},{"id":3067599,"identity":"f18c6132-a19e-40ee-ac6a-a1ae2d6aeb5f","added_by":"auto","created_at":"2020-10-19 19:41:36","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":379869,"visible":true,"origin":"","legend":"The overall survival (OS) and cancer-specific survival (CSS) curve of younger and older patients. (A) Kaplan-Meier survival curve of OS using unadjusted data in the Surveillance, Epidemiology, and End Results (SEER) data set. The 5- and 1-Year OS rates were 86.4% and 78.2%, respectively, and 72.8% and 54.5%, respectively (P \u003c0.001). (B) Kaplan-Meier survival curve of CSS Using unadjusted data in the SEER data set. The 5- and 10-Year OS rates were 89.4% and 81.7%, respectively, and 84.3% and 72.8%, respectively (P \u003c0.001). (C) Kaplan-Meier survival curve of OS using propensity score matching adjusted data set. The hazard ratios of OS using univariate analysis in the matched cohort were 2.056(95% CI,1.948-2.170; P \u003c0.001). (D) Kaplan-Meier survival curve of CSS using propensity score matching adjusted data set. The hazard ratios of OS using univariate analysis in the matched cohort were 1.496(95% CI,1.399-1.600; P \u003c0.001). The P values were calculated using the cox model. ","description":"","filename":"fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3555/v2/9e73571bee471dcb73238b65.jpg"},{"id":3067600,"identity":"6964c96a-05d9-4d45-a026-a0a3b3abff3b","added_by":"auto","created_at":"2020-10-19 19:41:36","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":418370,"visible":true,"origin":"","legend":"Subgroup analysis according to variable and the probability of CCRCC cancer-specific survival analysis according to age (Young group vs. Older group) in the SEER data set. The subgroup analyses were performed according to sex, race, marital status, size, grade, laterality, SEER historic stage A, radiation, and chemotherapy.","description":"","filename":"fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3555/v2/1164cc308cabc0d5e19122a2.jpg"},{"id":3067601,"identity":"c720fdf1-8459-4443-b18f-140428e2d821","added_by":"auto","created_at":"2020-10-19 19:41:36","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":162155,"visible":true,"origin":"","legend":"Survival analysis of DEGs. A: Kaplan-Meier analysis were developed based on expression level of PLA2G2A (p = 0.002); B: Kaplan-Meier analysis were developed based on expression level of SIX2 (p = 0.008).","description":"","filename":"fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3555/v2/eef0d029b85102e13de5a1d4.jpg"},{"id":13604476,"identity":"7f08a1f9-93a2-43ab-b05a-19889ea86975","added_by":"auto","created_at":"2021-09-17 06:00:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":817005,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3555/v2/4f8170cf-11c4-4c0b-a058-7b3b849b35b9.pdf"},{"id":3067598,"identity":"fad7aed6-41e1-4a3b-afdd-0d079d6864b5","added_by":"auto","created_at":"2020-10-19 19:41:36","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":32395,"visible":true,"origin":"","legend":"","description":"","filename":"TableS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-3555/v2/3b28ee015418a8b88834d2f7.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003e53 Years Old is A Reasonable Cut-Off Value To Define Young And Old Patients In Clear Cell Renal Cell Carcinoma：A Study Based On TCGA And SEER Database\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eOver the past two decades, the incidence of renal cell carcinoma (RCC) at every stages was increased and this situation resulted in a steady increase in mortality per unit of population [1]. It is estimated that 65340 Americans will be diagnosed with RCC, and 14970 Americans will die of this cancer in 2018. RCC comprises about 3.8% of all new cancer. And the median age of RCC patient is 64 ages old. Clear cell renal cell carcinoma (CCRCC) is the most common subtype of RCC, it accounts for about 80% of RCC [2]. Age has prognostic significance in many solid cancers, and one of renal cancer known risk factors is age [3,4]. RCC shows a more favorable prognosis in young patiens, which may be due to the lower state of diagnosis [5]. In addition, age can influence the structural and molecular properties of the tumor vasculature in CCRCC by comparing the vascular properties of patients who over the age of 65 and under 65 years old [6]. Furthermore, expression levels of Piwil 1 mRNA in patients who under 64 years old are higher than that in older people (\u0026gt; 64 years old). But there still is no optimal age cut off value to define elderly and young people in CCRCC. Therefore, we determined the optimal cut-off value for age analyzing the clinical data SEER database, and explored differentially expressed genes (DEGs) between older and younger people of CCRCC by analyzing RNA-seq data from TCGA in present study.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy population from SEER\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSEER Stat software (version 8.3.5) was used to download CCRCC clinical data from the National Cancer Institute\u0026rsquo;s Surveillance, Epidemiology, and End Results (SEER) database. The downloaded data included: patient ID, the year and age at the time of diagnosis, sex, race, histological type, survival time, tumor size, marital status, Grade, SEER historic stage A, and cause of death.\u003c/p\u003e\n\u003cp\u003eCCRCC patients were selected according to the following criteria: (1) site record International Classification of Diseases for Oncology, Third Revision (ICD-O-3) was C649; (2) histological type was 8310/3; (3) the year at time of diagnosis was 1988-2014. (4) CCRCC was primary tumor. The exclusion criteria were listed as following: (1) patients without race and gender information; (2) patients whose tumor size, survival time and other clinical information we need in this study were unknown.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVariable declaration \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRace was defined as white, black and other. Marital was divided into Single/Other, and married. Tumor size was divided into less than 4 cm, 4 cm to 7 cm, and greater than 7 cm. Grade was grouped as I , II, III, IV. Laterality was divided into left and right. The SEER historic stage options included localized, regional and distant. And the chemotherapy, radiotherapy were divided into yes or no.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCut off age in CCRCC\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eX-tile is a useful tool for biomarker assessment and outcome-based cut-point optimization (http://www.tissuearray.org/rimmlab/). The \u0026ldquo;x tile plot\u0026rdquo; can provide a single, global assessment of every possible way by dividing a population into low- and high-level marker expression [7]. The grouping strategy of the X-tile program includes trying to use each number between the retrieved count ranges as a critical value; then, using this number as a cut-off value to calculate the \u0026chi;2 score and P value. We used X-tile plots to assessed all possible age cutoff value, and the survival at every age cutoff value was computed by the log rank test. Then the most appropriate cut-off value was selected which had the highest \u0026chi;2 value.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRNA-seq Analysis of CCRCC from TCGA\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe RNA sequencing and clinical information of CCRCC were download from TCGA database. We used these RNA-seq data for DEGs screening between younger and older group by Limma package (adjusted p value \u0026lt;0.05 and\u0026nbsp;| log2\u0026nbsp;fold change (FC) | \u0026ge;1). Then, we extracted clinical data from older adults (\u0026gt;53 years), including survival time and survival status. We selected the DEGs from the small to large false discovery rate (FDR). And the DEGs was for survival analysis. The differentially expression levels of DEGs in these old patients were obtained. The median of gene expression was used to classify low and high group. Log rank test was used to compare statistically significant differences between high and low expression groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe divided the patients into young and old groups according to the X-tile's best cut-off value. Chi-square test was used to compare the differences in the distribution of variables between younger and older group. We calculated the overall survival (OS) and cancer specific survival (CSS). In the CSS calculation, the cause of death for other reasons was defined as censorship. Propensity score matching (PSM) used logistic regression included relevant variables of Sex, race, marital status, size, grade, SEER historic stage A, radiation and chemotherapy to balance the baseline differences between the younger and older groups. The OS and CSS Survival curves were generated using the Kaplane-Meier method. And univariate and multivariate analysis Cox regression models were applied to adjust prognostic variables. The cases were stratified according to the relevant variables. Hazard Ratio (HR) of the CSS was calculated according to the age. When the 2-sided \u003cem\u003eP\u003c/em\u003e value was \u0026lt; 0.05, the differences were considered statistically significant. The SPSS 24.0 and R 3.4.3 were used to conduct statistical analysis and DEGs screening.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e53 was the age cut-off value and Baseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe obtained 45,974 CCRCC patients in totally. The median age of these patients was 60 years old (interquartile range: 51-69). At the same time, X tile result showed that 53 years old was defined as the best cut-off value for age (Figure 1). Then we divided the cohort into two groups: younger group (53 years or younger), older group (older than 53 years) according to the cut-off value. The detailed features of the patients between the two groups were presented in Table 1 \u003cstrong\u003e(\u003c/strong\u003eTable 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurvival Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the young group, 5- and 10-year OS rates were 86.4% and 78.2% respectively. In the old group, 5- and 10-year OS rates were 72.8% and 54.5 respectively (\u003cem\u003eP\u003c/em\u003e \u0026lt;0.001; Figure 2 A). Univariate analysis results indicated that age, sex, race, marital status, size, grade, laterality, SEER historic stage A, radiation and chemotherapy,could predict patient suvival outcomes. Meanwhile, multivariate analysis showed that the age, sex, race, marital status, size, grade, laterality, SEER historic stage A, radiation and chemotherapy were independent prognostic factor for CCRCC OS(Table 2).\u003c/p\u003e\n\u003cp\u003eIn the young group, 5- and 10-year CSS rates were 89.4% and 81.7% respectively. In the old group, 5- and 10-year CSS rates were 84.3% and 72.8% respectively (\u003cem\u003eP\u003c/em\u003e \u0026lt;0.001; Figure 2 B).The results of univariate analysis showed that age, sex, marital status, size, grade, laterality, SEER historic stage A, radiation and chemotherapy were associated with patient's prognosis. Multivariate analysis showed that age, marital status, size, grade, SEER historic stage A, radiation and chemotherapy were independent prognostic factors for CCRCC CSS(Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurvival Analysis after PSM\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe clinical characteristics of the patients between the younger and older groups had obvious differences. So PSM method was applied to balance the differences between the variables, and generated a new queue (All covariates were well balanced, \u003cem\u003eP\u003c/em\u003e values \u0026gt; 0.05; Table 1). Univariate analysis results showed that HR for OS of the older patient were 2.056 (95% CI:1.948-2.170; \u003cem\u003eP\u003c/em\u003e \u0026lt;0.001), HR for CSS were 1.496(95% CI, 1.399-1.600; \u003cem\u003eP\u003c/em\u003e \u0026lt;0.001) when compared with the younger group. In the PSM queue, the younger people also had a higher survival rate than older people (Figure 2 C, D). Multivariate analysis results showed that compared with the younger group , HR for OS of the older patient were 2.128（95%CI:2.015-2.247; \u003cem\u003eP \u003c/em\u003e\u0026lt;0.001）, HR for CSS were 1.573(95%CI:1.470-1.682; \u003cem\u003eP \u003c/em\u003e\u0026lt;0.001). Other variable results were showed in Table 2, 3.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubgroup analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe performed a subgroup analysis based on sex, race, marital status, size, grade, laterality, SEER historic stage A, radiation, and chemotherapy. In most subgroups, the older group had a worse prognosis than the younger group. However radiation, and chemotherapy and prognostic differences between young and old groups were not statistically significant (\u003cem\u003eP \u003c/em\u003e\u0026gt;0.05) (Figure 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDifferential expressed genes\u003c/strong\u003e\u003cstrong\u003e and prognosis related genes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe RNA-seq data of 530 CCRCC samples were downloaded from TCGA database. According to the cut-off value of 53 years old, they were divided into 158 young group and 372 elderly group. We finally got 11 differential expressed genes(DEGs) between the younger and older groups in CCRCC (Table 4). Among them, SIX2, THBS4 and PLA2G2A were up regulated in elderly patients with CCRCC. NKX2-3, CD1A, SCUBE1, NEFH, MYL10, TBL1Y, DYTN and SLC4A10 were down regulated in elderly patients with CCRCC. Then, the DEGs were analyzed by survival. The results showed that high expression of SIX2 and PLA2G2A were associated with poor prognosis in the elderly (Figure 4).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eA total of 45,974 CCRCC patients were included in the SEER database, of which the 53-year-old cut-off value was used to divide the younger and older groups. Survival analysis results showed that younger age (under age 53) was an independent predictor of CCRCC. And we obtained some genes related to old patients with CCRCC by analyzing the RNA-seq data downloaded from TCGA.\u003c/p\u003e\n\u003cp\u003eSome studies reported that the 40 years old was suitable to act as the dividing line between young and old CCRCC patients. Xavier Taccoen et al. found that young (under 40 years of age) age was an independent prognostic factor for CCRCC, with a better prognosis [8]. Atiqullah Aziz et al found that young patients with RCC (age 40 or under) have a significantly lower all cause and disease specific killed [9]. Ho Won Kang et al. also found that young age was associated with favorable pathological features, although it is not survival independent prognostic factors in surgically treated RCC patients. But the result of the Kaplan-Meier analysis showed that the CCS rate was significantly better in the young age group than the other groups (middle age: \u0026ge; 4 and \u0026lt; 60 years; old age: \u0026ge; 60 years) [10]. Analysis results between younger and older RCC patients (20-39 and 40-79) of Jeong Ho Kim et al found that younger RCC patients would have more favorable histological subtypes. And the 5-year CSS rates for young and older patients were 95.5% and 90.5% respectively. However, after PSM, the five-year CSS rate was 95.5% for the younger group and 94.7% for the older group, and the prognosis was not significantly different (log rank \u003cem\u003ep \u003c/em\u003e= 0.184) [11]. In addition to the 40 years old, there were many age cut-off values, such as 45 and 55 years old. Yoshinobu Komai et al used the 45-year-old as a cut-off value for younger and older group. Compared with the older patients, the young patients with RCC had similar recurrence-free survival rates but better CSS rates [12]. Eun-Jung Jung et al believed that younger age was an independent predictor of prognosis through multivariate analysis. Whereas in their study, younger than 55 years of age was considered as young in CCRCC [13]. In this study, we used X-tile plots to assessed all possible age cut-off value, and finally selected the age 53 as the cut off value for dividing younger and older group. And younger groups had better OS and CSS compared to older groups. What\u0026rsquo;s more, in the subgroup analysis, the prognosis of old group was worse than that of young group in all subgroups of this study, especially in the Dmax \u0026lt;= 4cm subgroups (HR = 3.710(3.006-4.579), \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.001). It suggests that in future CCRCC clinical decision-making, patients older than 53 years old needed to pay more attention and better treatment options. Compared with younger people, older patients have a greater risk of worsening disease, lower survival rate, and worse treatment efficiency, which may be related to the physical fitness of the older patients and probably diseases that may existed in themselves.\u003c/p\u003e\n\u003cp\u003eIn recent years, with the development of cancer gene sequencing and targeted therapies, the research on gene expression of CCRCC had made some progress. In the CCRCC age-related studies, Xp11 translocation renal cell carcinoma was kind of RCC subtype, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Malouf%20GG%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=20154303\"\u003eMalouf GG\u003c/a\u003e et al used the targeted therapy to treat patients, the objective responses was achieved and the patients got the better progression-free survival [14]. Mitchell TJ et al. analyzed the entire genome of CCRCC and found that 36% of patients experience 3p loss and 5q gain, which usually occured during childhood or adolescence. Meanwhile hotspots of point mutations in the 5' UTR of TERT, targeting a MYC-MAX-MAD1 repressor associated with telomere lengthening [15]. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Malouf%20GG%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=21074195\"\u003eMalouf GG\u003c/a\u003e reported that ASPSCR1-TFE3 might be the most aggressive among the transcription factor E3 fusion\u0026nbsp;genes in RCC patients [16].\u003c/p\u003e\n\u003cp\u003eIn this study, we obtained 11 DEGs by comparing RNA-seq data from younger and older CCRCC patients. Then, the DEGs were used for survival analysis. As showed in the result (Figure 4), the expression of Secretory Phospholipase A2 Group IIA(PLA2G2A), and Sine oculis-related homeobox 2(SIX2) were related to the survival of the elderly. Secretory Phospholipase A2 Group IIA (PLA2G2A),\u0026nbsp;one of the family members of PLA2, primarily targets extracellular phospholipids with implications in host antimicrobial defense, inflammatory response and tissue regeneration\u0026nbsp;[17]. And PLA2G2A\u0026nbsp;was found to be associated with different disease states including cancer. Our results indicate that PLA2G2A is highly expressed in the elderly and is closely related to poor prognosis in the elderly group. However, further studies are needed to illuminate the molecular and biological mechanism of PLA2G2A in CCRCC. Sine oculis-related homeobox 2 (SIX2) is composed of six homeobox genes (SIX1-SIX6), which\u0026nbsp;serves as an important regulator of embryonic development.\u0026nbsp;Wu Y et al\u0026nbsp;[18] found that overexpression of Six 2 increased\u0026nbsp;the proliferative capacity of cells\u0026nbsp;and decreased apoptosis in clear cell renal cell carcinoma. At the same time, our research showed that SIX2 was age-related DEG. And high expression levels of SIX2 was related to poor prognosis of the elderly. These results suggest that PLA2G2A and SIX2 might have clinical monitoring value in CCRCC which deserved for further research.\u003c/p\u003e\n\u003cp\u003eOur study had several potential limitations. The leading known risk factors for renal cancer were smoking, obesity and hypertension [19-24]. However, due to the lack of corresponding data in the SEER database, we were unable to study these factors. At the same time, retrospective analyses always carried the risk of various biases. We used the subgroup, PSM analysis and incorporate large amounts of patients in this study to minimize potential biases.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, we proposed that 53-year-old was a reasonable cut-off value among CCRCC patients, and the elderly group had a worse prognosis than the younger group. \u0026nbsp;These results remind clinicians that more attention and better treatment should be given to CCRCC patients older than 53 years old. At the same time, 11 gene were age-related differential genes. The high expression of PLA2G2A and SIX2 might be associated with poor prognosis in the elderly, but the specific mechanism remained to be further studied.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present study, the data download from Surveillance Epidemiology and End Results database and The Cancer Genome Atlas (TCGA) database, therefore, this article does not contain any studies with human participants or animals performed by any of the authors. Thus no ethical approval and patient consent are required. This article does not contain any studies with animals performed by any of the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed during the current study download from Surveillance Epidemiology and End Results database (https://seer.cancer.gov/) and The Cancer Genome Atlas (TCGA) database. (https://cancergenome.nih.gov/).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that they have no conflict of interest to state.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZH, FT and ZL conceived the study; ZH and FT conducted the work; CH, HZ and WW obtaining and analyzed the data; FT and ZL wrote the manuscript, and ZH reviewed the manuscript. All the authors listed have read and approved the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCCRCC: clear cell renal cell carcinoma; DEGs: Differentially expressed genes; SEER: Surveillance Epidemiology and End Results; TCGA: The Cancer Genome Atlas; OS：overall survival; CSS: cancer specific survival; PSM: Propensity score matching; HR: Hazard Ratio; FC: fold change; FDR: false discovery rate; CPM: counts per million.\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1 Ridge CA, Pua BB, Madoff DC. Epidemiology and staging of renal cell carcinoma.\u0026nbsp;\u003cem\u003eSemin Intervent Radiol. \u003c/em\u003e2014; 31:3-8.\u003c/p\u003e\n\u003cp\u003e2 Liu K, Wang P, Zhu X, et al. Disparities of age-based cancer-specific survival improvement with various clinicopathologic characteristics for kidney cancer.\u0026nbsp;\u003cem\u003eCancer Manag Res. \u003c/em\u003e2018; 10:2259-2268.\u003c/p\u003e\n\u003cp\u003e3 Takada S, Namiki M, Takahara S, et al. Serum HGF levels in acute renal rejection after living related renal transplantation.\u0026nbsp;\u003cem\u003eTranspl Int.\u003c/em\u003e 1996; 9:151-4.\u003c/p\u003e\n\u003cp\u003e4 Meehan B, Appu S, St Croix B, et al. Age-related properties of the tumour vasculature in renal cell carcinoma.\u0026nbsp;\u003cem\u003eBJU Int.\u003c/em\u003e 2011; 107:416-24.\u003c/p\u003e\n\u003cp\u003e5 Al-Janabi O, Wach S, Nolte E, et al. Piwi-like 1 and 4 gene transcript levels are associated with clinicopathological parameters in renal cell carcinomas.\u0026nbsp;\u003cem\u003eBiochim Biophys Acta. \u003c/em\u003e2014; 1842:686-90.\u003c/p\u003e\n\u003cp\u003e6 Yusim I, Mermershtain W, Neulander E, et al. Influence of age on the prognosis of patients with renal cell carcinoma (RCC).\u0026nbsp;\u003cem\u003eOnkologie.\u003c/em\u003e 2002; 25:548-50.\u003c/p\u003e\n\u003cp\u003e7 Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization.\u0026nbsp;\u003cem\u003eClin Cancer Res\u003c/em\u003e 2004; 10:7252-9.\u003c/p\u003e\n\u003cp\u003e8 Taccoen X, Valeri A, Descotes JL, et al. Renal cell carcinoma in adults 40 years old or less: young age is an independent prognostic factor for cancer-specific survival.\u0026nbsp;\u003cem\u003eEur Urol\u003c/em\u003e. 2007; 51:980-7.\u003c/p\u003e\n\u003cp\u003e9 Aziz A, May M, Zigeuner R, et al. Do young patients with renal cell carcinoma feature a distinct outcome after surgery? A comparative analysis of patient age based on the multinational CORONA database.\u0026nbsp;\u003cem\u003eJ Urol.\u003c/em\u003e 2014; 191:310-5.\u003c/p\u003e\n\u003cp\u003e10 Kang HW, Seo SP, Kim WT, et al. Impact of Young Age at Diagnosis on Survival in Patients with Surgically Treated Renal Cell Carcinoma: a Multicenter Study.\u0026nbsp;\u003cem\u003eJ Korean Med Sci. \u003c/em\u003e2016; 31:1976-1982.\u003c/p\u003e\n\u003cp\u003e11 Kim JH, Park YH, Kim YJ, et al. Is there a difference in clinicopathological outcomes of renal tumor between young and old patients? A multicenter matched-pair analysis.\u0026nbsp;\u003cem\u003eScand J Urol.\u003c/em\u003e 2016; 50:387-91.\u003c/p\u003e\n\u003cp\u003e12 Komai Y, Fujii Y, Iimura Y, et al. Young age as favorable prognostic factor for cancer-specific survival in localized renal cell carcinoma.\u0026nbsp;\u003cem\u003eUrology.\u003c/em\u003e 2011; 77:842-7.\u003c/p\u003e\n\u003cp\u003e13 Jung EJ, Lee HJ, Kwak C, et al. 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Smoking negatively impacts renal cell carcinoma overall and cancer-specific survival.\u0026nbsp;Cancer. 2012; 118:1795-802.\u003c/p\u003e\n\u003cp\u003e21 Golabek T, Bukowczan J, Szopinski T, et al. Obesity and renal cancer incidence and mortality--a systematic review of prospective cohort studies.\u0026nbsp;Ann Agric Environ Med. 2016; 23.37-43.\u003c/p\u003e\n\u003cp\u003e22 Park J, Morley TS, Kim M, et al. Obesity and cancer--mechanisms underlying tumour progression and recurrence.\u0026nbsp;Nat Rev Endocrinol. 2014; 10: 455-465\u003c/p\u003e\n\u003cp\u003e23 Chow WH, Dong LM, Devesa SS. Epidemiology and risk factors for kidney cancer.\u0026nbsp;Nat Rev Urol 2010; 7.245-57.\u003c/p\u003e\n\u003cp\u003e24 Colt JS, Schwartz K, Graubard BI, et al. Hypertension and risk of renal cell carcinoma among white and black Americans.\u0026nbsp;Epidemiology. 2011; 22.797-804.\u003c/p\u003e"},{"header":"Tables","content":"\u003cp style='margin-top:0in;margin-right:22.0pt;margin-bottom:8.0pt;margin-left:0in;text-align:center;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif; color: rgb(0, 0, 0);'\u003eTable 1\u003c/span\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 15px; line-height: 107%; font-family: SimSun;\"\u003e：\u003c/span\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;The Clinical characteristic baseline of CCRC patients in SEER\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 4.2e+2pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 82.6pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 23.1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eCharacteristic\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 170.75pt;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;padding: 0in 5.4pt;height: 23.1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:center;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eBefore PSM\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 171.3pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 23.1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:center;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAfter PSM\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 66.9pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 38.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eYounger\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e(\u003c/span\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;=53 y\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN\u003c/span\u003e\u003cspan style=\"font-family:SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e%\u003c/span\u003e\u003cspan style=\"font-family:SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62.8pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 38.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eOlder\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e(\u003c/span\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026gt;53 y\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN\u003c/span\u003e\u003cspan style=\"font-family:SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e%\u003c/span\u003e\u003cspan style=\"font-family:SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41.05pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 38.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:10.5pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eP\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 38.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eYounger\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e(\u003c/span\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;=53 y\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eN\u003c/span\u003e\u003cspan style=\"font-family:SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e%\u003c/span\u003e\u003cspan style=\"font-family:SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.15pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 38.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eOlder\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e(\u003c/span\u003e\u003cspan style='font-size: 15px; 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line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:68.8pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:3.0pt;margin-bottom:8.0pt;margin-left:3.0pt;text-align:left;line-height:16.0pt;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:12px;font-family:\"Times New Roman\",serif;'\u003e306(2.14)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:3.0pt;margin-bottom:8.0pt;margin-left:3.0pt;text-align:left;line-height:16.0pt;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:12px;font-family:\"Times New Roman\",serif;'\u003e338(2.37)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 32.35pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82.6pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003echemotherapy\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66.9pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:12px;line-height:107%;font-family:\"Times New Roman\",serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.15pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 32.35pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:12px;line-height:107%;font-family:\"Times New Roman\",serif;'\u003e0.274\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82.6pt;border: none;padding: 0in 5.4pt;height: 21.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eNO\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66.9pt;border: none;padding: 0in 5.4pt;height: 21.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:12px;line-height:107%;font-family:\"Times New Roman\",serif;'\u003e13664(95.71)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62.8pt;border: none;padding: 0in 5.4pt;height: 21.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:12px;line-height:107%;font-family:\"Times New Roman\",serif;'\u003e29986(94.60)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41.05pt;border: none;padding: 0in 5.4pt;height: 21.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:68.8pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:21.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:3.0pt;margin-bottom:8.0pt;margin-left:3.0pt;text-align:left;line-height:16.0pt;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:12px;font-family:\"Times New Roman\",serif;'\u003e13655(95.72)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:21.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:3.0pt;margin-bottom:8.0pt;margin-left:3.0pt;text-align:left;line-height:16.0pt;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:12px;font-family:\"Times New Roman\",serif;'\u003e13617(95.45)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 32.35pt;border: none;padding: 0in 5.4pt;height: 21.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eYES\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:12px;line-height:107%;font-family:\"Times New Roman\",serif;'\u003e612(4.29)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:12px;line-height:107%;font-family:\"Times New Roman\",serif;'\u003e1712(5.40)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:68.8pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:3.0pt;margin-bottom:8.0pt;margin-left:3.0pt;text-align:left;line-height:16.0pt;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:12px;font-family:\"Times New Roman\",serif;'\u003e611(4.28)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.15pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:3.0pt;margin-bottom:8.0pt;margin-left:3.0pt;text-align:left;line-height:16.0pt;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:12px;font-family:\"Times New Roman\",serif;'\u003e649(4.55)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 32.35pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:center;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eTable 2\u003c/span\u003e\u003cspan style=\"font-size: 15px; line-height: 107%; font-family: SimSun;\"\u003e：\u003c/span\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003ecox regression\u0026nbsp;analysis of overall survival\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 5.2e+2pt;margin-left:-53.65pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:76.35pt;border:none;border-top:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:62.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eCharacteristic\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:147.65pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:62.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eUnivariate cox regression before PSM\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:150.25pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:62.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eMultivariate cox regression before PSM\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:149.35pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:62.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eMultivariate cox regression after PSM\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.95pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;border-top:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.95pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.95pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.95pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.95pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; 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line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eRace\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:17.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:17.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:17.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:17.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:17.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:17.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eBlack\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eWhite\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.895(0.831-0.964)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.003\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.836\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.776-0.901\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.795\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.722-0.876\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eOther\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.798(0.721-0.884)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.716\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.647-0.794\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.682\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.593-0.783\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 76.35pt;border: none;padding: 0in 5.4pt;height: 15.45pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eMarital\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; 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font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e4cm\u0026lt; Dmax\u0026lt;=7cm\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.967(1.868-2.070)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.403\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.330-1.480\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.382\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.284-1.488\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eDmax\u0026gt;7cm\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e4.084(3.895-4.283)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.849\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.748-1.956\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.965\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.823-2.118\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 76.35pt;border: none;padding: 0in 5.4pt;height: 17.25pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eGRADE\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:17.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:17.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:17.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:17.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:17.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:17.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eⅠ\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eⅡ\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.151\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.081-1.225\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.966\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.907-1.029\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.283\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.988\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.907-1.075\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.773\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eⅢ\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e2.225\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e2.086-2.373\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.213\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.133-1.298\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.287\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.172-1.412\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eⅣ\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e5.296\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e4.911-5.712\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.823\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.681-1.978\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.856\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.661-2.075\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:16.65pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eLaterality\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:16.65pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:16.65pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:16.65pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:16.65pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:16.65pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:16.65pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:29.7pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eLeft\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:29.7pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:29.7pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:29.7pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:29.7pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:29.7pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:29.7pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eRight\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.936\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.902-0.971\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.953\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.918-0.989\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.012\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.947\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.899-0.997\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e0.038\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eSEER historic stage A\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eLocalized\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eRegional\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e2.705\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e2.585-2.831\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.830(1.740-1.925)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.860\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.727-2.003\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eDistant\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e11.243\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e10.734-11.776\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e5.996(5.631-6.383)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e6.694\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e6.115-7.329\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:46.35pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 76.35pt;border: none;padding: 0in 5.4pt;height: 15.45pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eRadiation\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 76.35pt;border: none;padding: 0in 5.4pt;height: 15.45pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eNO\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:96.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; 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font-family: \"Times New Roman\", serif;'\u003e5.959\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e5.637-6.299\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:51.1pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:46.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.15pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:46.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.196(1.120-1.278)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.1pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:46.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.65pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:46.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.254\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e（\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.144-1.375\u003c/span\u003e\u003cspan style=\"line-height: 107%; font-family: SimSun;\"\u003e）\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.7pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:46.85pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eTable 3\u003c/span\u003e\u003cspan style=\"font-size: 15px; line-height: 107%; font-family: SimSun;\"\u003e：\u003c/span\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003ecox regression\u0026nbsp;analysis of cancer-specific survival\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 5.1e+2pt;margin-left:-43.35pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.35pt;border:none;border-top:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:70.2pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eCharacteristic\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:140.7pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:70.2pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eUnivariate cox regression before PSM\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:146.75pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:70.2pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eMultivariate cox regression before PSM\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:152.7pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:70.2pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eMultivariate cox regression after PSM\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.35pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.6pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e95%CL\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.1pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eP\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:100.35pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e95%CL\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:46.4pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eP\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.5pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e95%CL\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.2pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eP\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:11.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eage\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.6pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:11.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:11.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:100.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:11.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:46.4pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:11.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:11.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:11.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 15px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:19.2pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eyoung\u003c/span\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;'\u003e(\u003c/span\u003e\u003cspan style=\"line-height:107%;font-family: SimSun;\"\u003e\u0026le;\u003c/span\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e53 y\u003c/span\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;'\u003e)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.6pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:19.2pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:19.2pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:100.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:19.2pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:46.4pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:19.2pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:19.2pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:19.2pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; 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font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:9.7pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eReference\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:44.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:9.7pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69.35pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 5.55pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003eYES\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.6pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:5.55pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e8.887(8.369-9.438)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.1pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:5.55pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:100.35pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:5.55pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e1.179(1.100-1.263)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:46.4pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:5.55pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; font-family: \"Times New Roman\", serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:108.5pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:5.55pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='line-height: 107%; 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line-height: 107%; font-family: \"Times New Roman\", serif;'\u003egene\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:69.2pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:.6pt .6pt 0in .6pt;height:16.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;vertical-align:middle;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 16px; line-height: 107%; font-family: \"Times New Roman\", serif;'\u003econMean\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:69.2pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:.6pt .6pt 0in .6pt;height:16.45pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:\"Calibri\",sans-serif;vertical-align:middle;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 16px; 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color: rgb(0, 0, 0);'\u003e\u0026nbsp;\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Age, age-related genes, Clear cell renal cell carcinoma, The Cancer Genome Atlas, Surveillance Epidemiology and End Results ","lastPublishedDoi":"10.21203/rs.2.12816/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.12816/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eThe objectives of this study were to screen out cut-off age value and age-related differentially expressed genes (DEGs) in clear cell renal cell carcinoma (CCRCC) from Surveillance Epidemiology and End Results (SEER) database and The Cancer Genome Atlas (TCGA) database. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe selected 45,974 CCRCC patients from SEER and 530 RNA-seq data from TCGA database. The age cut-off value was defined using the X-tile program. Propensity score matching (PSM) was used to balance the differences between young and old groups. Hazard ratio (HR) was applied to evaluate prognostic risk of age in different subgroups. Age-related DEGs were identified via RNA-seq data. Survival analysis was used to assess the relationship between DEGs and prognosis.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eIn this study, we divided the patients into young (n=14276) and old (n=31698) subgroups according to cut-off value (age=53). Age \u0026gt;53 years was indicated as independent risk factor for overall survival (OS) and cancer specific survival (CSS) of CCRCC before and after PSM. The prognosis of old group was worse than that in young group. Eleven gene were differential expression between the younger and older groups in CCRCC. The expression levels of PLA2G2A and SIX2 \u0026nbsp;were related to prognosis of the elderly. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003e53 years old was cut-off value in CCRCC. The prognosis of the elderly was worse than young people. It\u0026nbsp;remind clinicians that more attention and better treatment should be given to CCRCC\u0026nbsp;patients who are over 53 years old. PLA2G2A and SIX2 were age-related differential genes which might play an important role in the poor prognosis of elderly CCRCC patients.\u003c/p\u003e","manuscriptTitle":"53 Years Old is A Reasonable Cut-Off Value To Define Young And Old Patients In Clear Cell Renal Cell Carcinoma：A Study Based On TCGA And SEER Database","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2020-10-19 19:41:34","doi":"10.21203/rs.2.12816/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2021-04-06T00:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-12-28T00:00:00+00:00","index":1,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\n\"PEER REVIEWER ASSESSMENTS:\n\nOBJECTIVE - Full research articles: is there a clear objective that addresses one or several testable research questions? (Brief or other article types: is there a clear objective?)\nYes - there is a clear objective\n\nDESIGN - Is the current approach (including controls and analysis protocols) appropriate for the objective?\nYes - the approach is appropriate\n\nEXECUTION - Are the experiments and analyses performed with sufficient technical rigor to allow confidence in the results?\nYes - experiments and analyses were performed appropriately\n\nSTATISTICS - Is the use of statistics in the manuscript appropriate?\nYes - appropriate statistical analyses have been used in the study\n\nINTERPRETATION - Is the current interpretation/discussion of the results reasonable and not overstated?\nYes - the author's interpretation is reasonable\n\nOVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently for you to now recommend the work as a technically sound contribution? If not, can further revisions be made to make the work technically sound?\nProbably - with minor revisions\n\nPEER REVIEWER COMMENTS:\n\nGENERAL COMMENTS: I was not a previous reviewer, so I read the paper for the first time. The authors were partially responsive to the previous reviews. I share some of the previous reviewers' concerns that the authors did not fully address. The age cut point of 53 is not necessarily a meaningful cut point in the USA (related to Reviewer 1 concern). Universal health insurance (Medicare) in the United States starts at the age of 65. Hence, many may see grouping those 53-64 with those 65+ as problematic because health insurance access issues between those two age groups can drive further clinical outcome differences. Having more than two cut points would have strengthened the paper. Also, Figure 3 is still very difficult to understand (Reviewer 2 concern). After some time, I was able to figure out these may be the hazard ratio estimates for older versus younger cases within each of the subgroups. Figure 1 was also still difficult to understand (Related to Reviewer 1 and 2 concerns).\nADDITIONAL REQUESTS/SUGGESTIONS:\nMinor comments\n1) The authors could note the limitation of examining two age groups. Dichotomizing a sample from the United States based on two age points is not necessarily clinically meaningful. Universal Medicare health insurance coverage begins at age 65. Hence, the clinical experiences of those under 65 and those 65 and over are not necessarily comparable because of health care access concerns.\n2) Figure 1 is still too confusing (as a previous reviewer noted). The authors state \"The plot showed the χ2 log-rank values…\" There does not seem to be a color guide to map to actual values for Figure 1 a. The plot is largely the same color red. Perhaps a wider range of colors could be used with a color legend mapping colors to numbers to guide the reader. The term \"tangent point\" is used but does not seem clearly defined in the paper or figure. Figure 1b is also confusing. It does not seem to represent chi-squared statistics, but the density of the age distribution in the sample. If Figure 1B is the distribution of the chi-squared statistics, then 53 does not seem to be the optimal value.\n3) The authors could further clarify the interpretation of Figure 3, as it is still difficult to understand.\n4) The column titles in Table 4 could be better defined. I think the conMean and treatMean refer to the mean in a young group versus a mean in an older group.\"* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons after the final decision on the manuscript has been made. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **This reviewer has been recruited by a partner organization, Research Square. Reviewers with declared or apparent competing interests are not utilized for these reviews. This reviewer has agreed to publication of their comments online under a Creative Commons Attribution License attributed to Research Square and was paid a small honorarium for completing the review within a specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer recommendation.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2020-12-18T00:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-10-16T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-10-12T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-10-11T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-10-11T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2019-08-14 01:59:16","doi":"10.21203/rs.2.12816/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-08-25T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-08-16T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after discretionary revisions\nForm responses:\n---\n\nComments to Author:\n---\nThrough this document I send my statistical review of: \"53 years old is a reasonable cut-off value to define young and old patients in clear cell renal cell carcinoma: A study based on TCGA and SEER database\"\n\nThe study is very interesting and it shows that the researchers did a magnificent and hard job. However, there are aspects that make it difficult to appreciate the results in a practical way. Therefore, the following points are suggested.\nThese are the following:\n\n1. It is suggested to order the presentation of the results in the tables, and put the result on a line next to the 95% CI and the p-value.\n2. Explain what was the criterion for choosing the 10 genes that most expressed? and why not the 5 or 7 genes most expressed?\n3. What would be the clinical and practical application of the study results?\n\n4. Regarding the X tile plot, it is necessary to include a mark at the cut-off point, where the red pixel is brighter and a more exhaustive explanation of the meaning found in this diagram, in order that the reader can understand it.\n\n5. Figure 3 shows the HRs in the subgroup of patients with CCRCC in SEER. It is confusing that the HR with the smallest tumor size and with a lower degree have the highest HR, since the fault in the Kaplan Meir is death. This would mean that those with a smaller grade and the smaller tumor size are at higher risk of dying. Please explain and correct I it I necessary.\n\nIn the attachment I send the comments on the paper.\nThank you.\n\nMagdalena Castro C. RN MSc\nEpidemiology\nResearch Unit. Academic Department\nClínica Las Condes\nSantiago-Chile\n\n\n\n\n\n\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **No**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2020-07-13T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-12-04T12:00:00+00:00","index":1,"fulltext":"Recommendation: Reject\nForm responses:\n---\n\nComments to Author:\n---\nThe authors attempted to find the optimal cut-off age value and examined age-related DEGs in clear cell RCC using SEER database and TCGA RNA-seq data. Age \u003e53 years was independently associated with overall survival and cancer specific survival. The expression levels of KCNE5, CLDN6 and CACNG6 were related to prognosis of the elderly.\nThe paper is potentially significant, but there are too many significant limitations in the data. A propensity-score matched analysis was performed, but such methodology cannot account for unobserved numerous confounding factors. More importantly, the cut-off age value, which is the primary endpoint, is not of clinical importance.\n\n* Clinical implications of these results should be more discussed and provided clearly.\n* Please provide the results as N (%) in table 1.\n* Please provide detailed information on X-tile methods.\n* Was there difference in prognosis-related genes between young and eldery patients?\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Not suitable for publication unless extensively edited**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: **\nI agree to the open peer review policy of the journal**\n"},{"type":"reviewerAgreed","content":"","date":"2019-11-24T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2019-09-26T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-09-05T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-08-07T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-08-07T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2019-07-30T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"788981a6-94b9-46af-a600-9a3a30d00844","owner":[],"postedDate":"October 19th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":824033,"name":"Cancer Biology"},{"id":824034,"name":"Oncology"}],"tags":[],"updatedAt":"2021-08-06T02:33:27+00:00","versionOfRecord":{"articleIdentity":"rs-3555","link":"https://doi.org/10.1186/s12885-021-08376-5","journal":{"identity":"bmc-cancer","isVorOnly":false,"title":"BMC Cancer"},"publishedOn":"2021-05-29 20:46:26","publishedOnDateReadable":"May 29th, 2021"},"versionCreatedAt":"2020-10-19 19:41:34","video":"","vorDoi":"10.1186/s12885-021-08376-5","vorDoiUrl":"https://doi.org/10.1186/s12885-021-08376-5","workflowStages":[]},"version":"v2","identity":"rs-3555","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-3555","version":["v2"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}