Revisiting contemporary laboratory characteristics of patients with syphilis: insights from a multicenter study

Revisiting contemporary laboratory characteristics of patients with syphilis: insights from a multicenter study | 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 Article Revisiting contemporary laboratory characteristics of patients with syphilis: insights from a multicenter study Hang-Ping Yao, Rui Chen, Han-Xin Mao, Jia-Le Zhang, Lin-Wei Zhu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4600372/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Despite the persistent susceptibility of Treponema pallidum to penicillin, the global incidence of syphilis remains high. Syphilis is a complex disease with physical consequences extending beyond manifestations. In this multicenter case–control study, we analyzed data from 536 patients with syphilis who underwent complete blood cell analysis, biochemical examination, and coagulation function tests at the First Affiliated Hospital Zhejiang University School of Medicine and People’s Hospital of Hangzhou Medical College in China. Moreover, we included 84 bone marrow-derived stem cell donors in the control group. Our findings indicated that patients with syphilis exhibited macrocytic anemia, coagulation abnormalities, multiple organ dysfunction, reduced anabolism and glucose metabolism, and electrolyte imbalance. Notably, HIV infection was noted to exacerbate coagulation disorders and liver injury in patients with syphilis. Furthermore, patients with neurosyphilis demonstrated decreases in the levels of hemostasis and anabolism. The aforementioned laboratory-based pathogenic features represent a contemporary understanding of syphilis progression. As such, when administering anti- T. pallidum treatment to patients with syphilis, particularly those exhibiting penicillin allergy and latent syphilis, medical professionals should address the associated physical damage. Biological sciences/Microbiology/Clinical microbiology Biological sciences/Microbiology/Pathogens Syphilis Laboratory-based pathogenic feature Systemic damage Anti-Treponema pallidum treatment Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Syphilis, a complex disease, is characterized as a sexually transmitted disease caused by Treponema pallidum . The natural progression of syphilis involves a persistent infectious process, which may ultimately advance to late stages characterized by prominent clinical manifestations several decades after initial infection[ 1 ]. In total, 15–40% of untreated patients may develop tertiary syphilis, with manifestations including destructive cardiac lesions, neurological disorders, severe cutaneous or visceral lesions, and evident skeletal involvement [ 2 , 3 ]. However, with the extensive use of penicillin and the related treatment effects, the incidence of severe physical damage due to syphilis has decreased in developed countries [ 4 , 5 ]. The contemporary pathological manifestations of syphilis encompass painless ulcers during the primary stage, systemic rashes during the secondary stage, and paralytic dementia during the neurosyphilis stage [ 6 , 7 ]. Other pathological manifestations include ocular syphilis characterized by uveitis, and ear syphilis by auditory impairment [ 8 ]. The physical consequences of syphilis extend beyond these manifestations [ 9 ]. In a study, among 175 early cases of syphilis, 17 demonstrated liver injury, and 14 exhibited histopathological abnormalities in the liver; moreover, T. pallidum was detected in the livers of 7 cases, indicating its potential to induce hepatitis [ 10 ]. T. pallidum may also lead to syphilitic arthritis [ 11 ], renal impairment [ 12 ], vasculitis, bile duct injury [ 13 ], and pathological changes, including syphilitic proctitis, gastritis, and hepatitis [ 14 ]. Numerous case reports and epidemiological studies have reported that HIV infection–induced immunosuppression significantly hampers the ability to clear T. pallidum [ 15 ]. Simultaneously, HIV-infected monocytes can infiltrate the central nervous system by traversing the blood–brain barrier, thereby inducing direct damage to various components, including the brain, the spinal cord, and peripheral nerves. Consequently, this process facilitates enhanced transmigration of T. pallidum across the blood–brain barrier and expedites neurosyphilis progression [ 16 , 17 ]. Although T. pallidum remains susceptible to penicillin, its utilization poses challenges related to emerging resistance to second-line drugs (e.g., macrolides) among previously responsive patients with syphilis, particularly those who are pregnant [ 18 ]. Penicillin G benzathine shortages have been documented in various European countries, including France, Albania, Austria, Bulgaria, and the Czech Republic [ 19 ], as well as in the United States [ 20 ]. Global production and supply challenges related to penicillin have resulted in an increase in the occurrence of treatment failure and congenital syphilis [ 21 ]. Notably, latent syphilis is elusive in nature, leading to numerous uncertainties regarding the potential long-term damage caused by T. pallidum [ 22 ]. Only a few studies have comprehensively elucidated the contemporary pathological characteristics of syphilis, encompassing alterations in hemorheology, multiple organ dysfunction, histopathological inflammation, and systemic metabolic dysregulation. This has hindered the selection of therapeutic interventions for managing pathological damage caused by T. pallidum infection. In this study, we retrospectively analyzed organ function biomarkers variations, systematic metabolite changes, blood cell count fluctuations, and coagulation time deviations among patients diagnosed as having syphilis on the basis of clinical laboratory diagnosis perspectives. Our main objective was to reveal contemporary laboratory pathogenic characteristics associated with syphilis and provide guidance for managing multiorgan system damage caused by T. pallidum . Methods Study design and participants In this multicenter case–control study, we collected data from patients diagnosed as having syphilis at two tertiary hospitals in Hangzhou, China, from December 2020 to December 2023. All syphilis diagnoses were established according to the guidelines of the U.S. Centers for Disease Control and Prevention guidelines [ 8 ], through a combination of personal history taking (including clinical characteristics, sexual history, or both) and positive results on syphilis serological tests (including T. pallidum particle agglutination [TPPA] and rapid plasma reagin test [RPR]). All the included patients received a main diagnosis of T. pallidum infection at one of the study hospitals; however, we excluded patients who had a coinfection with other pathogens, except HIV. During the study period, 582,086 individuals received serological testing for syphilis; of them, 3,528 were diagnosed as having syphilis. However, only 536 syphilis patients with complete blood cell analysis, biochemical examination, and coagulation function testing data were analyzed in this study. Our control group included bone marrow-derived stem cell donors. As such, our final study population included 620 individuals, including 406 patients with syphilis and 84 control individuals from the First Affiliated Hospital of Zhejiang University School of Medicine, and 130 patients with syphilis from Zhejiang Provincial People’s Hospital. This study was approved by the Ethics Committees of the First Affiliated Hospital of Zhejiang University School of Medicine with a waiver of informed consent because of the retrospective nature of the study. Our study was in compliance with China’s legislation and the Declaration of Helsinki guidelines. Clinical information All clinical specimens were collected conventionally in each hospital and sent to the respective clinical laboratories for examination. Moreover, medical history, physical examination, and laboratory investigation were collected from each participant. Clinical laboratory examination Blood cell analysis was performed on an automatic blood cell analyzer (BC6800; Mindray Biomedical Electronics, Shenzhen, China). Moreover, blood biochemical examination was conducted on an automatic biochemical analyzer (AU5800; Beckman Coulter, California, USA), and blood coagulation function testing was performed on an automatic blood coagulation analyzer (CN6000; Sysmex International Reagents, Tokyo, Japan). Syphilis serological testing was performed using kits for RPR (InTec, Xiamen, China) and TPPA (Fujirebio, Tokyo, Japan), according to the manufacturer’s instructions [ 23 ]. The First Affiliated Hospital of Zhejiang University School of Medicine and Zhejiang Provincial People's Hospital had passed consistency evaluation in the interlaboratory examination by Chinese National Center for Clinical Laboratories. Statistical analysis Continuous variables are presented as means ± standard deviations (SDs) or medians (interquartile ranges [IQRs]), whereas categorical variables are expressed as frequencies (percentages). We used the Student t and Mann–Whitney U tests to assess continuous variables with normal and skewed distributions, respectively. All statistical analyses were performed using SPSS for Windows (version 19.0; SPSS, Chicago, IL, USA). Statistical significance was defined using a two-sided P value of < 0.05. Results Participant characteristics Table 1 summarizes the clinical characteristics of all participants. In this study, the control individuals and patients with syphilis exhibited no significant differences in terms of age ( P = 0.119) or sex ( P = 0.096). Table 1 Clinical characteristics of all participants. Control individuals Patients with syphilis P Age 38.00 (31.25–46.75) 42.00 (28.00–58.00) 0.119 Sex 84 536 0.096 Female 57 (67.86%) 312 (58.21%) Male 27 (32.14%) 224 (41.79%) IQR, interquartile range; P , control vs. syphilis groups. Data are expressed as medians (IQRs) or frequencies (percentages) as appropriate. The Wilcoxon and chi-square tests were used to compare age and sex ratios in different groups, respectively. Uniform presentation of simple macrocytic anemia patients with syphilis Erythrocyte count, hematocrit level, and hemoglobin concentration were lower in the syphilis group than in the control group (4.585 × 10 12 /L [4.19 × 10 12 /L to 5.04 × 10 12 /L] vs. 5.1 × 10 12 /L [4.75 × 10 12 /L to 5.32 × 10 12 /L], 41.65% [37.70–45.38%] vs. 45.95% [43.03–47.50%], and 140 [125–153] vs. 154 [143–159], respectively; all P < 0.001; Fig. 1 A–C). Similarly, the mean corpuscular volume and hemoglobin content were higher in the syphilis group than in the control group (91.10 [88.30–94.50] vs. 89.90 [87.85–92.00] fL [ P = 0.017] and 30.4 [29.4–31.8] vs. 30.1 [29.23–30.8] pg [ P = 0.011], respectively; Fig. 1 E and F). However, erythrocyte distribution widths did not differ significantly between the syphilis group and the control group (12.6 [12.2–13.2] and 12.6 [12.1–13.1] fL, respectively; P = 0.250; Fig. 1 D); a similar result was noted for mean corpuscular hemoglobin concentration (334 [326–341] and 333 [327–339] g/L, respectively; P = 0.6934; Fig. 1 G). Coagulation process inhibition in patients with syphilis Compared with the control group, the syphilis group demonstrated lower platelet count and platelet pressure ([226.4 ± 59.17] × 10 9 /L vs. [246.5 ± 55.48] × 10 9 /L [ P = 0.004] and 0.23% [0.19–0.26%] vs. 0.25% [0.22–0.28%] [ P = 0.001], respectively; Fig. 2 A and B) but higher platelet distribution width (12.80 [10.90–14.80] vs. 11.5 [10.4–12.78] fL, P < 0.001; Fig. 2 C). However, the mean platelet volume did not differ significantly between the syphilis and control groups (10.20 [9.50–11.00] vs. 10.15 [9.50–10.98] fL, P = 0.8279; Fig. 2 D). Moreover, compared with the control group, the syphilis group demonstrated lower mean (range) fibrinogen level (2.49 [2.15–2.99] vs. 2.65 [2.43–3.02] g/L, P = 0.003; Fig. 2 E) but longer thrombin time, longer prothrombin time, and higher international standardized ratio (17.91 ± 1.20 vs. 17.19 ± 0.75 s, 12.25 ± 0.95 vs. 11.33 ± 0.66 s, and 1.05 [1.01–1.10] vs. 0.98 [0.94–1.03], respectively; P < 0.001; Fig. 2 F–H). Notably, partial thromboplastin activation time was shorter in the syphilis group than in the control group (28.07 ± 2.58 vs. 29.52 ± 2.32 s, P < 0.001; Fig. 2 I). Organ function may exhibit impaired functionality in patients with syphilis Compared with the control group, the syphilis group demonstrated higher alanine aminotransferase and glutamyl transpeptidase concentrations (28 [22–38] vs. 18 [ 12 – 23 ] and 27 [22–40] vs. 20 [ 13 – 29 ] U/L, respectively; both P < 0.001; Fig. 3 A and B) but lower glomerular filtration rate [100.30 [89.61–115.70] vs. 105.10 [97.10–117.10] mL/[min·1.73 m 2 ]; P = 0.005; Fig. 3 C). Moreover, the syphilis group exhibited higher aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase concentrations (23 [ 19 – 27 ] vs. 18 [ 16 – 22 ] U/L [ P < 0.001], 187 [163–216] vs. 170 [152–189] U/L [ P < 0.001], and79 [64–95] vs. 71 [60–86] U/L [ P = 0.006], respectively; Fig. 3 D–F). Diminished synthesis metabolism in patients with syphilis Total bilirubin, direct bilirubin, and indirect bilirubin concentrations were lower in the syphilis group than in the control group (9.50 [7.10–12.50] vs. 11.05[8.53–13.20] µmol/L [ P = 0.016], 3.50 [2.60–4.70] vs. 4.15 [3.40–5.10] µmol/L [ P < 0.001], and 5.50 [3.90–8.00] vs. 6.70 [5.1–8.1] µmol/L [ P = 0.011], respectively; Fig. 4 A–C). Notably, the syphilis group demonstrated a significant decrease in total protein and albumin concentrations (70.54 ± 6.24 vs. 73.15 ± 3.81 g/L and 43.50 [41.00–46.30] vs. 47.75 [46.15–49.40] g/L, respectively; both P < 0.001; Fig. 4 D and E) but higher globulin concentrations (26.80 [24.00–29.60] vs. 25.20 [23.70–27.45] g/L, P < 0.001; Fig. 4 F). Furthermore, cholinesterase, glycylprolyl dipeptidase, and α-L-fucosidase concentrations were lower in the syphilis group than in the control group (8370 ± 2073 vs. 9252 ± 1717 U/L [ P < 0.001], 76 [63–93] vs. 81 [70–95] U/L [ P = 0.020] and 20.30 [16.93–24.60] vs. 23.05 [18.83–26.20] U/L [ P = 0.003], respectively; Fig. 4 G–I). Similarly, creatinine and phosphocreatine kinase concentrations were lower in the syphilis group (73 [60–84] vs. 81 [72–90] µmol/L and 68.50 [51.00–97.50] vs. 100.00 [75.25–141.30] µmol/L, respectively; both P < 0.001; Fig. 4 J and K). Glucose, lipid, amino acid, and purine metabolic disorders in patients with syphilis Compared with the control group, the syphilis group demonstrated lower fasting blood glucose and total cholesterol levels (5.02 [4.60–5.58] vs. 5.17 [4.97–5.42] mmol/L [ P = 0.047] and 4.25 [3.70–4.99] vs. 4.56 [3.94–5.13] mmol/L [ P = 0.029], respectively; Fig. 5 A and C) but higher triglyceride levels (1.33 [1.01–1.73] vs. 1.19 [0.93–1.59] mmol/L, P = 0.013; Fig. 5 B). Total bile acid concentrations did not differ significantly between the syphilis and control groups (3.60 [2.55–5.70] and 3.60 [2.80–4.88] µmol/L, respectively; P = 0.730; Fig. 5 G). Compared with the control group, the syphilis group exhibited lower very-low-density and low-density lipoprotein levels (0.55 [0.34–0.78] vs. 0.73 [0.52–0.93] g/L [ P < 0.001] and 2.52 ± 0.71 vs. 2.70 ± 0.76 g/L [ P = 0.041], respectively; Fig. 5 D and E) but higher high-density lipoprotein levels (1.21 [0.99–1.45] vs. 1.13 [0.91–1.34] g/L, P = 0.030; Fig. 5 F). Finally, the syphilis group demonstrated higher blood urea but lower uric acid concentrations (4.94 [3.99–6.16] vs. 4.72 [4.00–5.20] mmol/L [ P = 0.028] and 319 [253–392] vs. 364 [307–438] µmol/L [ P < 0.001], respectively; Fig. 5 H and I). Electrolyte imbalance in patients with syphilis Compared with the control group, the syphilis group demonstrated significantly lower natrium, kalium, chlorine, and calcium ion concentrations (141 [140–143] vs. 143 [142–144] mmol/L, 4.07 ± 0.35 vs. 4.24 ± 0.27 mmol/L, 105 [103–106] vs. 106 [104–107] mmol/L, 2.29 ± 0.11 vs. 2.36 ± 0.090 mmol/L, respectively; all P < 0.001; Fig. 6 A–D) but higher phosphorus ion concentration (1.16 [1.03–1.30] vs. 1.09 [0.98–1.21] mmol/L, P = 0.004; Fig. 5 E). Laboratory pathological characteristics of HIV-positive patients with syphilis and HIV-negative patients with neurosyphilis As shown in Table 2 , we conducted a comprehensive analysis of the laboratory pathological characteristics in 20 HIV-positive patients with syphilis and 42 HIV-negative patients with neurosyphilis. Compared with the HIV-negative syphilis/non-neurosyphilis group, the HIV-positive syphilis group demonstrated higher erythrocyte count, hematocrit level, and hemoglobin concentration (5.02 × 10 12 /L [4.46 × 10 12 /L to 5.20 × 10 12 /L] vs. 4.55 × 10 12 /L [4.17 × 10 12 /L to 5.02 × 10 12 /L] [ P = 0.034], 45.10% [43.10–46.60%] vs. 41.70% [37.60–45.23%] [ P = 0.005], and 153 [146–156] vs. 139 [124–152] g/L [ P = 0.003]) but lower platelet count, platelet hematocrit level, and fibrinogen level ([188.10 ± 43.75] × 10 9 /L vs. 226.80 ± 59.99 × 10 9 /L [ P = 0.015], 0.18% [0.17–0.24%] vs. 0.23% [0.19–0.27%] [ P = 0.029], and 2.42 [2.17–2.90] vs. 2.63 [2.17–3.09] g/L [ P = 0.037], respectively). Moreover, the HIV-positive syphilis group demonstrated a significantly longer thrombin time, longer prothrombin time, higher international normalized ratio, and longer activated partial thromboplastin time (18.85 [18.18–19.40] vs. 17.00 [16.30–17.90] s [ P < 0.001], 12.89 ± 0.67 vs. 12.22 ± 0.93 s [ P = 0.026], 1.12 [1.04–1.14] vs. 1.04 [1.01–1.10] [ P = 0.035], and 31.47 ± 2.67 vs. 28.01 ± 2.59 s [ P < 0.001], respectively). Furthermore, compared with the HIV-negative syphilis/non-neurosyphilis group, the HIV-positive syphilis group exhibited elevated alanine aminotransferase and alkaline phosphatase concentrations (28 [24–44] vs. 23 [ 20 – 27 ] U/L [ P = 0.008] and 94 [75–100] vs. 78 [63–95] U/L [ P = 0.017], respectively) but decreased lactate dehydrogenase concentration (156 [145–180] vs. 187 [164–216] U/L, P = 0.034). Total bilirubin, direct bilirubin, creatinine, and phosphocreatine kinase concentrations were higher in HIV-positive syphilis group (12.05 [9.40–14.40] vs. 9.50 [7.25–12.50] µmol/L [ P = 0.039], 4.70 [2.95–5.50] vs. 3.50 [2.60–4.50] µmol/L [ P = 0.021], 84 [79–91] vs. 72 [60–83] µmol/L [ P < 0.001], and 80 [62–104] vs. 67 [51–92] µmol/L [ P = 0.015], respectively). Moreover, the HIV-positive syphilis group exhibited higher total protein, albumin, globulin, and cholinesterase concentrations (76.38 ± 5.66 vs. 70.54 ± 6.10 g/L [ P = 0.004], 45.50 [42.40–49.83] vs. 43.70 [41.20–46.40] g/L [ P = 0.045], 28.80 [24.93–36.18] vs. 26.90 [24.10–29.60] g/L [ P = 0.031], and 9256 ± 1791 vs. 8376 ± 2092 U/L [ P = 0.030], respectively) but lower total cholesterol and low-density lipoprotein concentrations (3.45 [2.84–4.16] vs. 4.31 [3.81–5.06] mmol/L [ P = 0.003] and 2.17 ± 0.61 vs. 2.55 ± 0.70 g/L [ P = 0.031], respectively). In contrast, the HIV-positive syphilis group demonstrated higher total bile acid, urea, and uric acid concentrations (4.60 [2.90–8.00] vs. 3.50 [2.50–5.60] µmol/L [ P = 0.032], 5.90 [4.34–6.77] vs. 4.92 [3.69–6.10] mmol/L [ P = 0.026], and 367 [342–409] vs. 314 [253–392] µmol/L [ P = 0.010], respectively). Furthermore, the HIV-positive syphilis group exhibited higher calcium concentrations and lower phosphorus levels (2.35 ± 0.09 vs. 2.29 ± 0.11 mmol/L [ P = 0.032] and 1.09 ± 0.17 vs. 1.17 ± 0.20 mmol/L [ P = 0.027], respectively). Table 2 Laboratory characteristics in HIV-positive syphilis, HIV-negative neurosyphilis, and HIV-negative syphilis/non-neurosyphilis groups. Characteristic Mean ± SD/Median (IQR) P P a P b P c HIV-positive syphilis HIV-negative neurosyphilis HIV-negative syphilis/non-neurosyphilis Erythrocyte count (×10 12 /L) 5.02 (4.46–5.20) 4.63 (4.17–4.89) 4.55 (4.17–5.02) 0.038 0.044 0.034 > 0.999 Hematocrit (%) 45.10 (43.10–46.60) 41.10 (38.60-45.05) 41.70 (37.60-45.23) 0.007 0.039 0.005 > 0.999 Hemoglobin concentration (pg) 153 (146–156) 138 (126–151) 139 (124–152) 0.004 0.036 0.003 > 0.999 Erythrocyte distribution width (fL) 12.40 (12.20–13.10) 12.75 (12.30-13.38) 12.60 (12.10–13.20) 0.408 Mean corpuscular volume (fL) 91.00 (87.60–95.40) 92.20 (88.98–95.25) 90.95 (88.30–94.40) 0.427 Mean hemoglobin concentration(pg) 30.20 (29.20–32.00) 30.65 (30.00-32.10) 30.40 (29.30–31.70) 0.160 Mean corpuscular hemoglobin concentration (g/L) 336 (325–343) 335 (327–342) 334 (326–341) 0.841 Platelet count (x10 9 /L) 188.10 ± 43.75 227.30 ± 60.05 226.80 ± 59.99 0.021 0.044 0.015 0.998 Plateletcrit (%) 0.18 (0.17–0.24) 0.23 (0.20–0.26) 0.23 (0.19–0.27) 0.031 0.045 0.029 > 0.999 Platelet distribution width (fL) 12.40 (10.80–15.60) 12.20 (10.60-14.35) 13.00 (11.10–15.90) 0.178 Mean platelet volume (fL) 10.10 (9.70–10.90) 10.40 (9.70–11.10) 10.20 (9.50–11.00) 0.680 Fibrinogen concentration (g/L) 2.42 (2.17–2.90) 2.49 (2.09–2.93) 2.63 (2.17–3.09) 0.025 0.742 0.037 0.031 Thrombin time (s) 18.85 (18.18–19.40) 18.50 (17.50–19.10) 17.00 (16.30–17.90) < 0.001 0.579 < 0.001 0.999 0.035 0.041 Activated partial thromboplastin time (s) 31.47 ± 2.67 27.63 ± 2.41 28.01 ± 2.59 < 0.001 < 0.001 0.999 Glutamine transpeptidase concentration (U/L) 25 (22–38) 34 (27–55) 27 (21–40) 0.010 0.024 > 0.999 0.007 Glomerular filtration rate (mL/[min·1.73 m 2 ]) 106.90 (93.00-116.60) 100.00 (92.44–115.50) 100.20 (89.05–115.30) 0.782 Aspartate aminotransferase concentration (U/L) 21 (17–29) 22 (19–27) 23 (20–27) 0.538 Lactate dehydrogenase concentration (U/L) 156 (145–180) 197 (181–218) 187 (164–216) 0.009 0.006 0.034 0.323 Alkaline phosphatase concentration (U/L) 94 (75–100) 84 (67–102) 78 (63–95) 0.027 0.582 0.017 0.043 Total bilirubin concentration (µmol/L) 12.05 (9.40–14.40) 8.60 (6.15–12.30) 9.50 (7.25–12.50) 0.021 0.017 0.039 0.647 Direct bilirubin concentration (µmol/L) 4.70 (2.95–5.50) 3.40 (2.70–4.30) 3.50 (2.60–4.50) 0.032 0.027 0.021 > 0.999 Indirect bilirubin concentration (µmol/L) 5.80 (4.70–8.20) 5.30 (3.55–7.95) 5.50 (3.95-8.00) 0.629 Total protein concentration (g/L) 76.38 ± 5.66 67.71 ± 5.95 70.54 ± 6.10 < 0.001 < 0.001 0.004 0.024 Albumin concentration (g/L) 45.50 (42.40-49.83) 42.15 (39.33–43.75) 43.70 (41.20–46.40) 0.001 0.002 0.045 0.018 Globulin concentration (g/L) 28.80 (24.93–36.18) 25.40 (23.00-28.30) 26.90 (24.10–29.60) 0.022 0.027 0.031 0.010 Cholinesterase concentration (U/L) 9256 ± 1791 7926 ± 1927 8376 ± 2092 0.037 0.016 0.030 0.034 Glycylproline dipeptide aminopeptidase concentration (U/L) 60 (51–74) 66 (56–86) 77 (65–94) 0.007 0.951 0.012 0.027 α-L-Fucosidase concentration (U/L) 21 (20–22) 21 (17–24) 20 (17–25) 0.846 Creatinine concentration (µmol/L) 84 (79–91) 76 (59–82) 72 (60–83) 0.005 0.005 0.999 Creatine kinase concentration (U/L) 80 (62–104) 69 (45–97) 67 (51–92) 0.026 0.037 0.015 > 0.999 Glucose concentration (mmol/L) 4.97 (4.62–5.99) 5.11 (4.69–5.57) 5.02 (4.57–5.58) 0.705 Triglyceride concentration (mmol/L) 1.19 (0.94–1.63) 1.28 (1.01–1.625) 1.34 (1.01–1.79) 0.600 Total cholesterol concentration (mmol/L) 3.45 (2.84–4.16) 4.00 (3.44–4.59) 4.31 (3.81–5.06) 0.003 0.045 0.003 0.028 Total bile acid concentration (µmol/L) 4.60 (2.90-8.00) 4.70 (2.90–7.80) 3.50 (2.50–5.60) 0.015 > 0.999 0.032 0.024 Very-low-density lipoprotein concentration (g/L) 0.60 (0.47–0.78) 0.62 (0.46–0.83) 0.52 (0.31–0.76) 0.653 Low-density lipoprotein concentration (g/L) 2.17 ± 0.61 2.29 ± 0.69 2.55 ± 0.70 0.004 0.608 0.031 0.041 High-density lipoprotein concentration (g/L) 0.92 (0.86–1.08) 1.20 (0.99–1.46) 1.23 (1-1.45) 0.021 0.043 0.017 > 0.999 Urea concentration (mmol/L) 5.90 (4.34–6.77) 4.96 (3.57–5.83) 4.92 (3.69–6.10) 0.038 0.030 0.026 > 0.999 Uric acid concentration (µmol/L) 367 (342–409) 314 (245–393) 314 (253–392) 0.013 0.034 0.010 > 0.999 Sodium concentration (mmol/L) 141 (140–141) 142 (142–143) 141 (140–143) 0.250 Phosphate concentration (mmol/L) 4.04 ± 0.32 3.98 ± 0.41 4.08 ± 0.35 0.186 Chlorine concentration (mmol/L) 103 (103–105) 105 (103–106) 103 (103–105) 0.262 Calcium concentration (mmol/L) 2.35 ± 0.09 2.26 ± 0.10 2.29 ± 0.11 0.012 0.011 0.032 0.898 Phosphorus concentration (mmol/L) 1.09 ± 0.17 1.18 ± 0.21 1.17 ± 0.20 0.034 0.032 0.027 > 0.999 P , HIV-positive syphilis vs. HIV-negative neurosyphilis vs. HIV-negative syphilis/non-neurosyphilis groups; P a , HIV-positive syphilis vs. HIV-negative neurosyphilis groups; P b , HIV-positive syphilis vs. HIV-negative syphilis/non-neurosyphilis groups; P c , HIV-negative neurosyphilis vs. HIV-negative syphilis/non-neurosyphilis groups. Data expressed as means ± SDs or medians (IQRs), as appropriate. The Wilcoxon test or one-way analysis of variance was employed to compare different groups. Compared with the HIV-negative syphilis/non-neurosyphilis group, the HIV-negative neurosyphilis group exhibited lower fibrinogen concentration (2.49 [2.09–2.93] vs. 2.63 [2.17–3.09] g/L, P = 0.031) but a longer thrombin time, longer prothrombin time, and higher international normalized ratio (18.50 [17.50–19.10] vs. 17.00 [16.30–17.90] s [ P < 0.001], 12.60 ± 0.95 vs. 12.22 ± 0.93 s [ P = 0.039], and 1.10 [1.03–1.15] vs. 1.04 [1.01–1.10] [ P = 0.041], respectively). Moreover, the HIV-negative neurosyphilis group demonstrated higher glutamyltransferase and alkaline phosphatase levels (34 [27–55] vs. 27 [21–40] U/L [ P = 0.007] and 84 [67–102] vs. 78 [63–95] U/L [ P = 0.043], respectively). Notably, the HIV-negative neurosyphilis group demonstrated lower total protein, albumin, globulin, cholinesterase, total cholesterol, and low-density lipoprotein concentrations (67.71 ± 5.95 vs. 70.54 ± 6.10 g/L [ P = 0.024], 42.15 [39.33–43.75] vs. 43.70 [41.20–46.40] g/L [ P = 0.018], 25.40 [23.00––28.30] vs. 26.90 [24.10–29.60] g/L [ P = 0.010], 7926 ± 1927 vs. 8376 ± 2092 U/L [ P = 0.034], 4.00 [3.44–4.59] vs. 4.31 [3.81–5.06] mmol/L [ P = 0.028], and 2.29 ± 0.69 vs. 2.55 ± 0.70 g/L [ P = 0.041], respectively) but higher total bile acid concentration (4.70 [2.90–7.80] vs. 3.50 [2.50–5.60] µmol/L, P = 0.024). Discussion Despite T. pallidum persistently demonstrating susceptibility to penicillin, the global incidence of syphilis remains considerably high [ 24 ]. In particular, syphilis incidence [ 25 , 26 ] has increased because of the escalating prevalence of latent syphilis, the emergence of multidrug resistance among macrolides, the presence of inadequate control measures in underdeveloped regions, and the global shortage of penicillin G benzathine. As such, a comprehensive elucidation of contemporary pathological manifestations associated with syphilis is highly warranted. The current results can considerably aid in assessing the magnitude of systemic damage caused by T. pallidum infection in humans. In our study, patients with syphilis exhibited a more homogeneous simple macrocytic anemia, suggesting that T. pallidum impedes or competitively hinders the assimilation of vitamin B12 and folic acid in the host. Anemia then leads to inadequate oxygen supply to the body, indicating that T. pallidum may obtain energy through glycolysis and reduce aerobic glucose oxidation pathway utilization. In the patients with syphilis, the hemorheological analysis results revealed heterogeneous platelet reduction, accompanied by a decrease in fibrinogen levels and prolonged coagulation time, suggesting impaired coagulation function. Although some coagulation enzymes demonstrated shortened activation time, overall inhibition of the coagulation state was noted. A low-coagulation environment may facilitate the spread of T. pallidum to other organs and activate endogenous coagulation pathways during the process of blood dissemination. Moreover, in the limited analysis of organ function biomarkers, patients with syphilis demonstrated increases in the levels of biomarkers associated with hepatobiliary function impairment, renal dysfunction, cardiac damage, and skeletal injury risk at varying degrees—consistent with previous results [ 27 – 29 ]. The potential T. pallidum -induced damage to the blood system and parenchymal organs may be partially mitigated by the robust compensatory mechanisms of the body, resulting in relatively nonsignificant clinical manifestations. Moreover, we investigated the impact of syphilis on the requisite homeostasis of multiorgan systems and noted that the patients with syphilis experienced reductions in bilirubin levels, indicating anemia, accompanied by a decrease in the content of total protein, particularly albumin. In contrast, increased globulin production may be a defense mechanism against T. pallidum invasion. Furthermore, we noted a decrease in the levels of liver synthesis products and muscle metabolites in the patients with syphilis, suggesting the presence of low metabolism. Notably, in individuals with latent syphilis, prolonged hypometabolism can result in considerable physical damage due to the condition’s insidious nature [ 30 ]. Therefore, syphilis treatment should focus on rebalancing metabolic dysfunctions in the affected patients. In further analysis of the systemic metabolic status, patients with syphilis demonstrated a decrease in blood glucose levels, indicating impaired glucose utilization. A decrease in uric acid and creatinine levels and an increase in urea levels were also observed. Considering the strong compensatory ability of the kidneys, the aforementioned metabolite changes are most likely attributable to alterations in the rates of upstream metabolic pathway utilization. Thus, patients with syphilis may demonstrate a reduction in glucose and purine metabolism but an elevation in amino acid metabolism. Our patients with syphilis demonstrated dysregulated lipid metabolism, as indicated by high triglyceride and low cholesterol levels; changes in lipoprotein levels further confirmed the presence of this disruption. In our patients with syphilis, T. pallidum affected the metabolic status, suggesting that rather than glucose metabolism, amino acid and lipid metabolism may be crucial energy supply pathways for T. pallidum —corroborating the results of a previous study [ 31 ]. Reestablishing and maintaining electrolyte homeostasis is a fundamental prerequisite for the human body to sustain vital physiological processes. In the current study, our patients with syphilis exhibited hyponatremia, hypokalemia, hypochloremia, hypocalcemia, and hyperphosphatemia. Patients with primary syphilis develop evident genital ulcers; nevertheless, the ulcers can be painless. This paradox may be attributable to neuronal hyperpolarization [ 32 ], with electrolyte imbalance potentially playing a major role in the process. Calcium ions are crucial factors involved in the body’s coagulation cascade; in patients with syphilis, reduced levels of calcium might synergistically contribute to platelet and fibrinogen depletion, leading to a hypocoagulability state. HIV–neurosyphilis coinfection is a major concern in patients with syphilis. In particular, individuals diagnosed as having syphilis may be highly susceptible to HIV infection and demonstrate expedited neurosyphilis progression [ 15 , 16 ]. However, neurosyphilis often lacks distinctive clinical manifestations, which leads to treatment delays. In this study, we analyzed the laboratory pathological characteristics of HIV-positive patients with syphilis and HIV-negative patients with neurosyphilis. Our findings revealed that coagulation disorders were further suppressed in both the patient subgroups, potentially facilitating rapid dissemination of HIV and T. pallidum within the host and promoting disease progression. These individuals also demonstrated exacerbated liver injury, possibly resulting in decreased coagulation factor synthesis and worsened coagulation disorders within the host. Furthermore, we observed a reduction in the metabolism and synthesis of neurotransmitters, such as cholinesterase, in HIV-negative patients with neurosyphilis. This indicated that T. pallidum may inhibit neurotransmitter inactivation within the central nervous system, leading to neuronal activity disturbances and subsequent manifestation of nonspecific characteristics. However, further research elucidating the pathogenic mechanisms underlying these aforementioned characteristics is warranted. This study has several limitations. First, we used a cross-sectional design and did not perform classification analysis on patients with syphilis; as such, we did not collect a sufficient amount of laboratory pathological characteristics data from patients with different syphilis subtypes. Future studies should include patients with different forms of syphilis to enable comprehensive tracking and analysis of their pathogenic features. Second, because we included relatively few HIV-positive patients with syphilis and HIV-negative patients with neurosyphilis in this study, our statistical analysis may demonstrate low robustness. Finally, although T. pallidum -induced organ damage has been observed in animal models [ 9 ], we did not include data related to direct histopathological staining of T. pallidum -damaged tissue and organ sections. Conclusions In summary, our findings indicated that patients with syphilis exhibit macrocytic anemia, coagulation abnormalities, multiple organ dysfunction, decreased anabolism and glucose metabolism, and electrolyte imbalance. Notably, HIV infection exacerbates coagulation disorders and liver injury in these patients. Furthermore, patients with neurosyphilis demonstrate decreased hemostasis and anabolism. These laboratory-based pathogenic features can facilitate a contemporary understanding of syphilis progression. Consequently, during the administration of anti- T. pallidum treatments to patients with syphilis, particularly those with penicillin allergy or latent syphilis, the related physical damage should be considered. Declarations Ethics approval This study was approved by the Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine [IIT20240463A], and was in compliance with national legislation and the Declaration of Helsinki guidelines. Consent for publication Not applicable. Data availability All relevant data supporting the findings of this study are contained within the manuscript. Competing interests The authors declare no conflicts of interest. Funding This work was supported in part from the Fundamental Research Funds for the Central Universities [grant number 2022ZFJH003]; the Zhejiang Plan for the Special Support for Top-notch Talents [grant number 2022R52029]; and State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Project [grant numbers zz202407]. Authors' contributions Hang-Ping Yao contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Rui Chen, Han-Xin Mao, Jia-Le Zhang, Lin-Wei Zhu and Kai Wu. The first draft of the manuscript was written by Rui Chen and Han-Xin Mao, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgments The authors would like to thank the fellows at the First Affiliated Hospital, Zhejiang University School of Medicine and People's Hospital of Hangzhou Medical College and 620 participants for their support. References Hook EW 3rd, Marra CM. 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Treponema pallidum-induced prostaglandin E2 secretion in skin fibroblasts leads to neuronal hyperpolarization: A cause of painless ulcers. J Eur Acad Dermatol Venereol. 2024 Feb 20. doi: 10.1111/jdv.19902 . Online ahead of print. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jia-Le","middleName":"","lastName":"Zhang","suffix":""},{"id":323799425,"identity":"9b859024-12ca-4f2c-b4f4-f1ba268bbbde","order_by":4,"name":"Lin-Wei Zhu","email":"","orcid":"","institution":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Lin-Wei","middleName":"","lastName":"Zhu","suffix":""},{"id":323799426,"identity":"b2a9fe17-2179-43d9-9d04-1edc081cccdb","order_by":5,"name":"Kai Wu","email":"","orcid":"","institution":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kai","middleName":"","lastName":"Wu","suffix":""}],"badges":[],"createdAt":"2024-06-18 13:37:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4600372/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4600372/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60604924,"identity":"241feb9f-badd-4e34-845f-c738738d0664","added_by":"auto","created_at":"2024-07-18 16:39:56","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":353396,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Fig.11.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4600372/v1/018ff8f3d2d333974d8e9dae.jpg"},{"id":60604930,"identity":"80059fa2-2a4f-40f7-9392-ba9829b9cf98","added_by":"auto","created_at":"2024-07-18 16:39:57","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":384576,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Fig.12.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4600372/v1/6472377bac816f6e9e4856f1.jpg"},{"id":60605450,"identity":"88964fdf-05e7-413a-b0b9-6ba958bf994e","added_by":"auto","created_at":"2024-07-18 16:47:56","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":383260,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Fig.13.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4600372/v1/da2e9b084f4ed00e07c13b4b.jpg"},{"id":60604926,"identity":"54c64abd-9333-4149-b127-448ba1964bba","added_by":"auto","created_at":"2024-07-18 16:39:56","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":675649,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Fig.14.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4600372/v1/8031b5c19dc9869e29bc6c97.jpg"},{"id":60604928,"identity":"af9092f5-7a6d-4bca-a340-c3e0767358a3","added_by":"auto","created_at":"2024-07-18 16:39:56","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":441774,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Fig.16.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4600372/v1/d912c55cbc66a4c14f117df9.jpg"},{"id":60604925,"identity":"4ffa4ea7-99b6-421c-877c-fc1d7ed379aa","added_by":"auto","created_at":"2024-07-18 16:39:56","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":299445,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Fig.17.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4600372/v1/e70241571d0de7d85242bdbc.jpg"},{"id":66904710,"identity":"419b8f9d-90a4-49cf-83da-5bc5eb56c6e9","added_by":"auto","created_at":"2024-10-17 17:39:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3874564,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4600372/v1/07a8174e-5180-4f11-b4ef-7a82e7a41257.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Revisiting contemporary laboratory characteristics of patients with syphilis: insights from a multicenter study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSyphilis, a complex disease, is characterized as a sexually transmitted disease caused by \u003cem\u003eTreponema pallidum\u003c/em\u003e. The natural progression of syphilis involves a persistent infectious process, which may ultimately advance to late stages characterized by prominent clinical manifestations several decades after initial infection[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In total, 15\u0026ndash;40% of untreated patients may develop tertiary syphilis, with manifestations including destructive cardiac lesions, neurological disorders, severe cutaneous or visceral lesions, and evident skeletal involvement [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, with the extensive use of penicillin and the related treatment effects, the incidence of severe physical damage due to syphilis has decreased in developed countries [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The contemporary pathological manifestations of syphilis encompass painless ulcers during the primary stage, systemic rashes during the secondary stage, and paralytic dementia during the neurosyphilis stage [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Other pathological manifestations include ocular syphilis characterized by uveitis, and ear syphilis by auditory impairment [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe physical consequences of syphilis extend beyond these manifestations [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In a study, among 175 early cases of syphilis, 17 demonstrated liver injury, and 14 exhibited histopathological abnormalities in the liver; moreover, \u003cem\u003eT. pallidum\u003c/em\u003e was detected in the livers of 7 cases, indicating its potential to induce hepatitis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. \u003cem\u003eT. pallidum\u003c/em\u003e may also lead to syphilitic arthritis [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], renal impairment [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], vasculitis, bile duct injury [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and pathological changes, including syphilitic proctitis, gastritis, and hepatitis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Numerous case reports and epidemiological studies have reported that HIV infection\u0026ndash;induced immunosuppression significantly hampers the ability to clear \u003cem\u003eT. pallidum\u003c/em\u003e [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Simultaneously, HIV-infected monocytes can infiltrate the central nervous system by traversing the blood\u0026ndash;brain barrier, thereby inducing direct damage to various components, including the brain, the spinal cord, and peripheral nerves. Consequently, this process facilitates enhanced transmigration of \u003cem\u003eT. pallidum\u003c/em\u003e across the blood\u0026ndash;brain barrier and expedites neurosyphilis progression [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Although \u003cem\u003eT. pallidum\u003c/em\u003e remains susceptible to penicillin, its utilization poses challenges related to emerging resistance to second-line drugs (e.g., macrolides) among previously responsive patients with syphilis, particularly those who are pregnant [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Penicillin G benzathine shortages have been documented in various European countries, including France, Albania, Austria, Bulgaria, and the Czech Republic [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], as well as in the United States [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Global production and supply challenges related to penicillin have resulted in an increase in the occurrence of treatment failure and congenital syphilis [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Notably, latent syphilis is elusive in nature, leading to numerous uncertainties regarding the potential long-term damage caused by \u003cem\u003eT. pallidum\u003c/em\u003e [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOnly a few studies have comprehensively elucidated the contemporary pathological characteristics of syphilis, encompassing alterations in hemorheology, multiple organ dysfunction, histopathological inflammation, and systemic metabolic dysregulation. This has hindered the selection of therapeutic interventions for managing pathological damage caused by \u003cem\u003eT. pallidum\u003c/em\u003e infection. In this study, we retrospectively analyzed organ function biomarkers variations, systematic metabolite changes, blood cell count fluctuations, and coagulation time deviations among patients diagnosed as having syphilis on the basis of clinical laboratory diagnosis perspectives. Our main objective was to reveal contemporary laboratory pathogenic characteristics associated with syphilis and provide guidance for managing multiorgan system damage caused by \u003cem\u003eT. pallidum\u003c/em\u003e.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eIn this multicenter case\u0026ndash;control study, we collected data from patients diagnosed as having syphilis at two tertiary hospitals in Hangzhou, China, from December 2020 to December 2023. All syphilis diagnoses were established according to the guidelines of the U.S. Centers for Disease Control and Prevention guidelines [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], through a combination of personal history taking (including clinical characteristics, sexual history, or both) and positive results on syphilis serological tests (including \u003cem\u003eT. pallidum\u003c/em\u003e particle agglutination [TPPA] and rapid plasma reagin test [RPR]). All the included patients received a main diagnosis of \u003cem\u003eT. pallidum\u003c/em\u003e infection at one of the study hospitals; however, we excluded patients who had a coinfection with other pathogens, except HIV.\u003c/p\u003e \u003cp\u003eDuring the study period, 582,086 individuals received serological testing for syphilis; of them, 3,528 were diagnosed as having syphilis. However, only 536 syphilis patients with complete blood cell analysis, biochemical examination, and coagulation function testing data were analyzed in this study. Our control group included bone marrow-derived stem cell donors. As such, our final study population included 620 individuals, including 406 patients with syphilis and 84 control individuals from the First Affiliated Hospital of Zhejiang University School of Medicine, and 130 patients with syphilis from Zhejiang Provincial People\u0026rsquo;s Hospital.\u003c/p\u003e \u003cp\u003e This study was approved by the Ethics Committees of the First Affiliated Hospital of Zhejiang University School of Medicine with a waiver of informed consent because of the retrospective nature of the study. Our study was in compliance with China\u0026rsquo;s legislation and the Declaration of Helsinki guidelines.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eClinical information\u003c/h2\u003e \u003cp\u003eAll clinical specimens were collected conventionally in each hospital and sent to the respective clinical laboratories for examination. Moreover, medical history, physical examination, and laboratory investigation were collected from each participant.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eClinical laboratory examination\u003c/h2\u003e \u003cp\u003eBlood cell analysis was performed on an automatic blood cell analyzer (BC6800; Mindray Biomedical Electronics, Shenzhen, China). Moreover, blood biochemical examination was conducted on an automatic biochemical analyzer (AU5800; Beckman Coulter, California, USA), and blood coagulation function testing was performed on an automatic blood coagulation analyzer (CN6000; Sysmex International Reagents, Tokyo, Japan). Syphilis serological testing was performed using kits for RPR (InTec, Xiamen, China) and TPPA (Fujirebio, Tokyo, Japan), according to the manufacturer\u0026rsquo;s instructions [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The First Affiliated Hospital of Zhejiang University School of Medicine and Zhejiang Provincial People's Hospital had passed consistency evaluation in the interlaboratory examination by Chinese National Center for Clinical Laboratories.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables are presented as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations (SDs) or medians (interquartile ranges [IQRs]), whereas categorical variables are expressed as frequencies (percentages). We used the Student \u003cem\u003et\u003c/em\u003e and Mann\u0026ndash;Whitney \u003cem\u003eU\u003c/em\u003e tests to assess continuous variables with normal and skewed distributions, respectively. All statistical analyses were performed using SPSS for Windows (version 19.0; SPSS, Chicago, IL, USA). Statistical significance was defined using a two-sided \u003cem\u003eP\u003c/em\u003e value of \u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eParticipant characteristics\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the clinical characteristics of all participants. In this study, the control individuals and patients with syphilis exhibited no significant differences in terms of age (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.119) or sex (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.096).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of all participants.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl individuals\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients with syphilis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.00 (31.25\u0026ndash;46.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.00 (28.00\u0026ndash;58.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.119\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e536\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.096\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (67.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e312 (58.21%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (32.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e224 (41.79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eIQR, interquartile range; \u003cem\u003eP\u003c/em\u003e, control vs. syphilis groups.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are expressed as medians (IQRs) or frequencies (percentages) as appropriate. The Wilcoxon and chi-square tests were used to compare age and sex ratios in different groups, respectively.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eUniform presentation of simple macrocytic anemia patients with syphilis\u003c/h2\u003e \u003cp\u003eErythrocyte count, hematocrit level, and hemoglobin concentration were lower in the syphilis group than in the control group (4.585 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L [4.19 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L to 5.04 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L] vs. 5.1 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L [4.75 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L to 5.32 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L], 41.65% [37.70\u0026ndash;45.38%] vs. 45.95% [43.03\u0026ndash;47.50%], and 140 [125\u0026ndash;153] vs. 154 [143\u0026ndash;159], respectively; all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA\u0026ndash;C). Similarly, the mean corpuscular volume and hemoglobin content were higher in the syphilis group than in the control group (91.10 [88.30\u0026ndash;94.50] vs. 89.90 [87.85\u0026ndash;92.00] fL [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017] and 30.4 [29.4\u0026ndash;31.8] vs. 30.1 [29.23\u0026ndash;30.8] pg [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011], respectively; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE and F). However, erythrocyte distribution widths did not differ significantly between the syphilis group and the control group (12.6 [12.2\u0026ndash;13.2] and 12.6 [12.1\u0026ndash;13.1] fL, respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.250; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD); a similar result was noted for mean corpuscular hemoglobin concentration (334 [326\u0026ndash;341] and 333 [327\u0026ndash;339] g/L, respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.6934; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eG).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eCoagulation process inhibition in patients with syphilis\u003c/h2\u003e \u003cp\u003eCompared with the control group, the syphilis group demonstrated lower platelet count and platelet pressure ([226.4\u0026thinsp;\u0026plusmn;\u0026thinsp;59.17] \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L vs. [246.5\u0026thinsp;\u0026plusmn;\u0026thinsp;55.48] \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004] and 0.23% [0.19\u0026ndash;0.26%] vs. 0.25% [0.22\u0026ndash;0.28%] [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001], respectively; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA and B) but higher platelet distribution width (12.80 [10.90\u0026ndash;14.80] vs. 11.5 [10.4\u0026ndash;12.78] fL, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). However, the mean platelet volume did not differ significantly between the syphilis and control groups (10.20 [9.50\u0026ndash;11.00] vs. 10.15 [9.50\u0026ndash;10.98] fL, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.8279; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD). Moreover, compared with the control group, the syphilis group demonstrated lower mean (range) fibrinogen level (2.49 [2.15\u0026ndash;2.99] vs. 2.65 [2.43\u0026ndash;3.02] g/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE) but longer thrombin time, longer prothrombin time, and higher international standardized ratio (17.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.20 vs. 17.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75 s, 12.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.95 vs. 11.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66 s, and 1.05 [1.01\u0026ndash;1.10] vs. 0.98 [0.94\u0026ndash;1.03], respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eF\u0026ndash;H). Notably, partial thromboplastin activation time was shorter in the syphilis group than in the control group (28.07\u0026thinsp;\u0026plusmn;\u0026thinsp;2.58 vs. 29.52\u0026thinsp;\u0026plusmn;\u0026thinsp;2.32 s, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eI).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eOrgan function may exhibit impaired functionality in patients with syphilis\u003c/h2\u003e \u003cp\u003eCompared with the control group, the syphilis group demonstrated higher alanine aminotransferase and glutamyl transpeptidase concentrations (28 [22\u0026ndash;38] vs. 18 [\u003cspan additionalcitationids=\"CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and 27 [22\u0026ndash;40] vs. 20 [\u003cspan additionalcitationids=\"CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] U/L, respectively; both \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA and B) but lower glomerular filtration rate [100.30 [89.61\u0026ndash;115.70] vs. 105.10 [97.10\u0026ndash;117.10] mL/[min\u0026middot;1.73 m\u003csup\u003e2\u003c/sup\u003e]; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). Moreover, the syphilis group exhibited higher aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase concentrations (23 [\u003cspan additionalcitationids=\"CR20 CR21 CR22 CR23 CR24 CR25 CR26\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] vs. 18 [\u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20 CR21\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] U/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001], 187 [163\u0026ndash;216] vs. 170 [152\u0026ndash;189] U/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001], and79 [64\u0026ndash;95] vs. 71 [60\u0026ndash;86] U/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006], respectively; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD\u0026ndash;F).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eDiminished synthesis metabolism in patients with syphilis\u003c/h2\u003e \u003cp\u003eTotal bilirubin, direct bilirubin, and indirect bilirubin concentrations were lower in the syphilis group than in the control group (9.50 [7.10\u0026ndash;12.50] vs. 11.05[8.53\u0026ndash;13.20] \u0026micro;mol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016], 3.50 [2.60\u0026ndash;4.70] vs. 4.15 [3.40\u0026ndash;5.10] \u0026micro;mol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001], and 5.50 [3.90\u0026ndash;8.00] vs. 6.70 [5.1\u0026ndash;8.1] \u0026micro;mol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011], respectively; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA\u0026ndash;C). Notably, the syphilis group demonstrated a significant decrease in total protein and albumin concentrations (70.54\u0026thinsp;\u0026plusmn;\u0026thinsp;6.24 vs. 73.15\u0026thinsp;\u0026plusmn;\u0026thinsp;3.81 g/L and 43.50 [41.00\u0026ndash;46.30] vs. 47.75 [46.15\u0026ndash;49.40] g/L, respectively; both \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD and E) but higher globulin concentrations (26.80 [24.00\u0026ndash;29.60] vs. 25.20 [23.70\u0026ndash;27.45] g/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eF). Furthermore, cholinesterase, glycylprolyl dipeptidase, and α-L-fucosidase concentrations were lower in the syphilis group than in the control group (8370\u0026thinsp;\u0026plusmn;\u0026thinsp;2073 vs. 9252\u0026thinsp;\u0026plusmn;\u0026thinsp;1717 U/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001], 76 [63\u0026ndash;93] vs. 81 [70\u0026ndash;95] U/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020] and 20.30 [16.93\u0026ndash;24.60] vs. 23.05 [18.83\u0026ndash;26.20] U/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003], respectively; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eG\u0026ndash;I). Similarly, creatinine and phosphocreatine kinase concentrations were lower in the syphilis group (73 [60\u0026ndash;84] vs. 81 [72\u0026ndash;90] \u0026micro;mol/L and 68.50 [51.00\u0026ndash;97.50] vs. 100.00 [75.25\u0026ndash;141.30] \u0026micro;mol/L, respectively; both \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eJ and K).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eGlucose, lipid, amino acid, and purine metabolic disorders in patients with syphilis\u003c/h2\u003e \u003cp\u003eCompared with the control group, the syphilis group demonstrated lower fasting blood glucose and total cholesterol levels (5.02 [4.60\u0026ndash;5.58] vs. 5.17 [4.97\u0026ndash;5.42] mmol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047] and 4.25 [3.70\u0026ndash;4.99] vs. 4.56 [3.94\u0026ndash;5.13] mmol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.029], respectively; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA and C) but higher triglyceride levels (1.33 [1.01\u0026ndash;1.73] vs. 1.19 [0.93\u0026ndash;1.59] mmol/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB). Total bile acid concentrations did not differ significantly between the syphilis and control groups (3.60 [2.55\u0026ndash;5.70] and 3.60 [2.80\u0026ndash;4.88] \u0026micro;mol/L, respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.730; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eG). Compared with the control group, the syphilis group exhibited lower very-low-density and low-density lipoprotein levels (0.55 [0.34\u0026ndash;0.78] vs. 0.73 [0.52\u0026ndash;0.93] g/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001] and 2.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71 vs. 2.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76 g/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.041], respectively; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eD and E) but higher high-density lipoprotein levels (1.21 [0.99\u0026ndash;1.45] vs. 1.13 [0.91\u0026ndash;1.34] g/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eF). Finally, the syphilis group demonstrated higher blood urea but lower uric acid concentrations (4.94 [3.99\u0026ndash;6.16] vs. 4.72 [4.00\u0026ndash;5.20] mmol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028] and 319 [253\u0026ndash;392] vs. 364 [307\u0026ndash;438] \u0026micro;mol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001], respectively; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eH and I).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eElectrolyte imbalance in patients with syphilis\u003c/h2\u003e \u003cp\u003eCompared with the control group, the syphilis group demonstrated significantly lower natrium, kalium, chlorine, and calcium ion concentrations (141 [140\u0026ndash;143] vs. 143 [142\u0026ndash;144] mmol/L, 4.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35 vs. 4.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27 mmol/L, 105 [103\u0026ndash;106] vs. 106 [104\u0026ndash;107] mmol/L, 2.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11 vs. 2.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.090 mmol/L, respectively; all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eA\u0026ndash;D) but higher phosphorus ion concentration (1.16 [1.03\u0026ndash;1.30] vs. 1.09 [0.98\u0026ndash;1.21] mmol/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eE).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eLaboratory pathological characteristics of HIV-positive patients with syphilis and HIV-negative patients with neurosyphilis\u003c/h2\u003e \u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, we conducted a comprehensive analysis of the laboratory pathological characteristics in 20 HIV-positive patients with syphilis and 42 HIV-negative patients with neurosyphilis. Compared with the HIV-negative syphilis/non-neurosyphilis group, the HIV-positive syphilis group demonstrated higher erythrocyte count, hematocrit level, and hemoglobin concentration (5.02 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L [4.46 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L to 5.20 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L] vs. 4.55 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L [4.17 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L to 5.02 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L] [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.034], 45.10% [43.10\u0026ndash;46.60%] vs. 41.70% [37.60\u0026ndash;45.23%] [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005], and 153 [146\u0026ndash;156] vs. 139 [124\u0026ndash;152] g/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003]) but lower platelet count, platelet hematocrit level, and fibrinogen level ([188.10\u0026thinsp;\u0026plusmn;\u0026thinsp;43.75] \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L vs. 226.80\u0026thinsp;\u0026plusmn;\u0026thinsp;59.99 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015], 0.18% [0.17\u0026ndash;0.24%] vs. 0.23% [0.19\u0026ndash;0.27%] [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.029], and 2.42 [2.17\u0026ndash;2.90] vs. 2.63 [2.17\u0026ndash;3.09] g/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.037], respectively). Moreover, the HIV-positive syphilis group demonstrated a significantly longer thrombin time, longer prothrombin time, higher international normalized ratio, and longer activated partial thromboplastin time (18.85 [18.18\u0026ndash;19.40] vs. 17.00 [16.30\u0026ndash;17.90] s [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001], 12.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67 vs. 12.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93 s [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.026], 1.12 [1.04\u0026ndash;1.14] vs. 1.04 [1.01\u0026ndash;1.10] [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035], and 31.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.67 vs. 28.01\u0026thinsp;\u0026plusmn;\u0026thinsp;2.59 s [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001], respectively). Furthermore, compared with the HIV-negative syphilis/non-neurosyphilis group, the HIV-positive syphilis group exhibited elevated alanine aminotransferase and alkaline phosphatase concentrations (28 [24\u0026ndash;44] vs. 23 [\u003cspan additionalcitationids=\"CR21 CR22 CR23 CR24 CR25 CR26\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] U/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008] and 94 [75\u0026ndash;100] vs. 78 [63\u0026ndash;95] U/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017], respectively) but decreased lactate dehydrogenase concentration (156 [145\u0026ndash;180] vs. 187 [164\u0026ndash;216] U/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.034). Total bilirubin, direct bilirubin, creatinine, and phosphocreatine kinase concentrations were higher in HIV-positive syphilis group (12.05 [9.40\u0026ndash;14.40] vs. 9.50 [7.25\u0026ndash;12.50] \u0026micro;mol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.039], 4.70 [2.95\u0026ndash;5.50] vs. 3.50 [2.60\u0026ndash;4.50] \u0026micro;mol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021], 84 [79\u0026ndash;91] vs. 72 [60\u0026ndash;83] \u0026micro;mol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001], and 80 [62\u0026ndash;104] vs. 67 [51\u0026ndash;92] \u0026micro;mol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015], respectively). Moreover, the HIV-positive syphilis group exhibited higher total protein, albumin, globulin, and cholinesterase concentrations (76.38\u0026thinsp;\u0026plusmn;\u0026thinsp;5.66 vs. 70.54\u0026thinsp;\u0026plusmn;\u0026thinsp;6.10 g/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004], 45.50 [42.40\u0026ndash;49.83] vs. 43.70 [41.20\u0026ndash;46.40] g/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.045], 28.80 [24.93\u0026ndash;36.18] vs. 26.90 [24.10\u0026ndash;29.60] g/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031], and 9256\u0026thinsp;\u0026plusmn;\u0026thinsp;1791 vs. 8376\u0026thinsp;\u0026plusmn;\u0026thinsp;2092 U/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030], respectively) but lower total cholesterol and low-density lipoprotein concentrations (3.45 [2.84\u0026ndash;4.16] vs. 4.31 [3.81\u0026ndash;5.06] mmol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003] and 2.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61 vs. 2.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70 g/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031], respectively). In contrast, the HIV-positive syphilis group demonstrated higher total bile acid, urea, and uric acid concentrations (4.60 [2.90\u0026ndash;8.00] vs. 3.50 [2.50\u0026ndash;5.60] \u0026micro;mol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032], 5.90 [4.34\u0026ndash;6.77] vs. 4.92 [3.69\u0026ndash;6.10] mmol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.026], and 367 [342\u0026ndash;409] vs. 314 [253\u0026ndash;392] \u0026micro;mol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.010], respectively). Furthermore, the HIV-positive syphilis group exhibited higher calcium concentrations and lower phosphorus levels (2.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09 vs. 2.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11 mmol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032] and 1.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17 vs. 1.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20 mmol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.027], respectively).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory characteristics in HIV-positive syphilis, HIV-negative neurosyphilis, and HIV-negative syphilis/non-neurosyphilis groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD/Median (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u003cem\u003eb\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHIV-positive syphilis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHIV-negative neurosyphilis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHIV-negative syphilis/non-neurosyphilis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eErythrocyte count (\u0026times;10\u003c/b\u003e\u003csup\u003e\u003cb\u003e12\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.02 (4.46\u0026ndash;5.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.63 (4.17\u0026ndash;4.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.55 (4.17\u0026ndash;5.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHematocrit (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.10 (43.10\u0026ndash;46.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.10 (38.60-45.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41.70 (37.60-45.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHemoglobin concentration (pg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e153 (146\u0026ndash;156)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e138 (126\u0026ndash;151)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e139 (124\u0026ndash;152)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eErythrocyte distribution width (fL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.40 (12.20\u0026ndash;13.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.75 (12.30-13.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.60 (12.10\u0026ndash;13.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.408\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMean corpuscular volume (fL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91.00 (87.60\u0026ndash;95.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92.20 (88.98\u0026ndash;95.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90.95 (88.30\u0026ndash;94.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.427\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMean hemoglobin concentration(pg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.20 (29.20\u0026ndash;32.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.65 (30.00-32.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.40 (29.30\u0026ndash;31.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMean corpuscular hemoglobin concentration (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e336 (325\u0026ndash;343)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e335 (327\u0026ndash;342)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e334 (326\u0026ndash;341)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.841\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePlatelet count (x10\u003c/b\u003e\u003csup\u003e\u003cb\u003e9\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e188.10\u0026thinsp;\u0026plusmn;\u0026thinsp;43.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e227.30\u0026thinsp;\u0026plusmn;\u0026thinsp;60.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e226.80\u0026thinsp;\u0026plusmn;\u0026thinsp;59.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePlateletcrit (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.18 (0.17\u0026ndash;0.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.23 (0.20\u0026ndash;0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.23 (0.19\u0026ndash;0.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePlatelet distribution width (fL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.40 (10.80\u0026ndash;15.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.20 (10.60-14.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.00 (11.10\u0026ndash;15.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMean platelet volume (fL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.10 (9.70\u0026ndash;10.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.40 (9.70\u0026ndash;11.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.20 (9.50\u0026ndash;11.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.680\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFibrinogen concentration (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.42 (2.17\u0026ndash;2.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.49 (2.09\u0026ndash;2.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.63 (2.17\u0026ndash;3.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.742\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThrombin time (s)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.85 (18.18\u0026ndash;19.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.50 (17.50\u0026ndash;19.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.00 (16.30\u0026ndash;17.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.579\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProthrombin time (s)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.319\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInternational normalized ratio\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.12 (1.04\u0026ndash;1.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.10 (1.03\u0026ndash;1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.04 (1.01\u0026ndash;1.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eActivated partial thromboplastin time (s)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.63\u0026thinsp;\u0026plusmn;\u0026thinsp;2.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.01\u0026thinsp;\u0026plusmn;\u0026thinsp;2.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.725\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlanine aminotransferase concentration (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (24\u0026ndash;44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (19\u0026ndash;27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (20\u0026ndash;27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlutamine transpeptidase concentration (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (22\u0026ndash;38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (27\u0026ndash;55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (21\u0026ndash;40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlomerular filtration rate (mL/[min\u0026middot;1.73 m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e])\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e106.90 (93.00-116.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100.00 (92.44\u0026ndash;115.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100.20 (89.05\u0026ndash;115.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.782\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAspartate aminotransferase concentration (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (17\u0026ndash;29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (19\u0026ndash;27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (20\u0026ndash;27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.538\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLactate dehydrogenase concentration (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e156 (145\u0026ndash;180)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e197 (181\u0026ndash;218)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e187 (164\u0026ndash;216)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.323\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlkaline phosphatase concentration (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94 (75\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84 (67\u0026ndash;102)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78 (63\u0026ndash;95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.582\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.043\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal bilirubin concentration (\u0026micro;mol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.05 (9.40\u0026ndash;14.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.60 (6.15\u0026ndash;12.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.50 (7.25\u0026ndash;12.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.647\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDirect bilirubin concentration (\u0026micro;mol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.70 (2.95\u0026ndash;5.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.40 (2.70\u0026ndash;4.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.50 (2.60\u0026ndash;4.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIndirect bilirubin concentration (\u0026micro;mol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.80 (4.70\u0026ndash;8.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.30 (3.55\u0026ndash;7.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.50 (3.95-8.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.629\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal protein concentration (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76.38\u0026thinsp;\u0026plusmn;\u0026thinsp;5.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.71\u0026thinsp;\u0026plusmn;\u0026thinsp;5.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e70.54\u0026thinsp;\u0026plusmn;\u0026thinsp;6.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlbumin concentration (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.50 (42.40-49.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.15 (39.33\u0026ndash;43.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43.70 (41.20\u0026ndash;46.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlobulin concentration (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.80 (24.93\u0026ndash;36.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.40 (23.00-28.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.90 (24.10\u0026ndash;29.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCholinesterase concentration (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9256\u0026thinsp;\u0026plusmn;\u0026thinsp;1791\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7926\u0026thinsp;\u0026plusmn;\u0026thinsp;1927\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8376\u0026thinsp;\u0026plusmn;\u0026thinsp;2092\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlycylproline dipeptide aminopeptidase concentration (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (51\u0026ndash;74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (56\u0026ndash;86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e77 (65\u0026ndash;94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.951\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eα-L-Fucosidase concentration (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (20\u0026ndash;22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (17\u0026ndash;24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (17\u0026ndash;25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.846\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCreatinine concentration (\u0026micro;mol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84 (79\u0026ndash;91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76 (59\u0026ndash;82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72 (60\u0026ndash;83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCreatine kinase concentration (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80 (62\u0026ndash;104)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69 (45\u0026ndash;97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67 (51\u0026ndash;92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlucose concentration (mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.97 (4.62\u0026ndash;5.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.11 (4.69\u0026ndash;5.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.02 (4.57\u0026ndash;5.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.705\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTriglyceride concentration (mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.19 (0.94\u0026ndash;1.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.28 (1.01\u0026ndash;1.625)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.34 (1.01\u0026ndash;1.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.600\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal cholesterol concentration (mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.45 (2.84\u0026ndash;4.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.00 (3.44\u0026ndash;4.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.31 (3.81\u0026ndash;5.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal bile acid concentration (\u0026micro;mol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.60 (2.90-8.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.70 (2.90\u0026ndash;7.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.50 (2.50\u0026ndash;5.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVery-low-density lipoprotein concentration (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.60 (0.47\u0026ndash;0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.62 (0.46\u0026ndash;0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.52 (0.31\u0026ndash;0.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.653\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLow-density lipoprotein concentration (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.608\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHigh-density lipoprotein concentration (g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.92 (0.86\u0026ndash;1.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.20 (0.99\u0026ndash;1.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.23 (1-1.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.043\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUrea concentration (mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.90 (4.34\u0026ndash;6.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.96 (3.57\u0026ndash;5.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.92 (3.69\u0026ndash;6.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUric acid concentration (\u0026micro;mol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e367 (342\u0026ndash;409)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e314 (245\u0026ndash;393)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e314 (253\u0026ndash;392)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSodium concentration (mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e141 (140\u0026ndash;141)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e142 (142\u0026ndash;143)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e141 (140\u0026ndash;143)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePhosphate concentration (mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.186\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChlorine concentration (mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e103 (103\u0026ndash;105)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105 (103\u0026ndash;106)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e103 (103\u0026ndash;105)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCalcium concentration (mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.898\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePhosphorus concentration (mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003eP\u003c/em\u003e, HIV-positive syphilis vs. HIV-negative neurosyphilis vs. HIV-negative syphilis/non-neurosyphilis groups; \u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sup\u003e, HIV-positive syphilis vs. HIV-negative neurosyphilis groups; \u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u003cem\u003eb\u003c/em\u003e\u003c/sup\u003e, HIV-positive syphilis vs. HIV-negative syphilis/non-neurosyphilis groups; \u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003e, HIV-negative neurosyphilis vs. HIV-negative syphilis/non-neurosyphilis groups.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eData expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;SDs or medians (IQRs), as appropriate.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eThe Wilcoxon test or one-way analysis of variance was employed to compare different groups.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCompared with the HIV-negative syphilis/non-neurosyphilis group, the HIV-negative neurosyphilis group exhibited lower fibrinogen concentration (2.49 [2.09\u0026ndash;2.93] vs. 2.63 [2.17\u0026ndash;3.09] g/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031) but a longer thrombin time, longer prothrombin time, and higher international normalized ratio (18.50 [17.50\u0026ndash;19.10] vs. 17.00 [16.30\u0026ndash;17.90] s [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001], 12.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.95 vs. 12.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93 s [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.039], and 1.10 [1.03\u0026ndash;1.15] vs. 1.04 [1.01\u0026ndash;1.10] [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.041], respectively). Moreover, the HIV-negative neurosyphilis group demonstrated higher glutamyltransferase and alkaline phosphatase levels (34 [27\u0026ndash;55] vs. 27 [21\u0026ndash;40] U/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007] and 84 [67\u0026ndash;102] vs. 78 [63\u0026ndash;95] U/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.043], respectively). Notably, the HIV-negative neurosyphilis group demonstrated lower total protein, albumin, globulin, cholinesterase, total cholesterol, and low-density lipoprotein concentrations (67.71\u0026thinsp;\u0026plusmn;\u0026thinsp;5.95 vs. 70.54\u0026thinsp;\u0026plusmn;\u0026thinsp;6.10 g/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024], 42.15 [39.33\u0026ndash;43.75] vs. 43.70 [41.20\u0026ndash;46.40] g/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018], 25.40 [23.00\u0026ndash;\u0026ndash;28.30] vs. 26.90 [24.10\u0026ndash;29.60] g/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.010], 7926\u0026thinsp;\u0026plusmn;\u0026thinsp;1927 vs. 8376\u0026thinsp;\u0026plusmn;\u0026thinsp;2092 U/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.034], 4.00 [3.44\u0026ndash;4.59] vs. 4.31 [3.81\u0026ndash;5.06] mmol/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028], and 2.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69 vs. 2.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70 g/L [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.041], respectively) but higher total bile acid concentration (4.70 [2.90\u0026ndash;7.80] vs. 3.50 [2.50\u0026ndash;5.60] \u0026micro;mol/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eDespite \u003cem\u003eT. pallidum\u003c/em\u003e persistently demonstrating susceptibility to penicillin, the global incidence of syphilis remains considerably high [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In particular, syphilis incidence [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] has increased because of the escalating prevalence of latent syphilis, the emergence of multidrug resistance among macrolides, the presence of inadequate control measures in underdeveloped regions, and the global shortage of penicillin G benzathine. As such, a comprehensive elucidation of contemporary pathological manifestations associated with syphilis is highly warranted. The current results can considerably aid in assessing the magnitude of systemic damage caused by \u003cem\u003eT. pallidum\u003c/em\u003e infection in humans.\u003c/p\u003e \u003cp\u003eIn our study, patients with syphilis exhibited a more homogeneous simple macrocytic anemia, suggesting that \u003cem\u003eT. pallidum\u003c/em\u003e impedes or competitively hinders the assimilation of vitamin B12 and folic acid in the host. Anemia then leads to inadequate oxygen supply to the body, indicating that \u003cem\u003eT. pallidum\u003c/em\u003e may obtain energy through glycolysis and reduce aerobic glucose oxidation pathway utilization. In the patients with syphilis, the hemorheological analysis results revealed heterogeneous platelet reduction, accompanied by a decrease in fibrinogen levels and prolonged coagulation time, suggesting impaired coagulation function. Although some coagulation enzymes demonstrated shortened activation time, overall inhibition of the coagulation state was noted. A low-coagulation environment may facilitate the spread of \u003cem\u003eT. pallidum\u003c/em\u003e to other organs and activate endogenous coagulation pathways during the process of blood dissemination. Moreover, in the limited analysis of organ function biomarkers, patients with syphilis demonstrated increases in the levels of biomarkers associated with hepatobiliary function impairment, renal dysfunction, cardiac damage, and skeletal injury risk at varying degrees\u0026mdash;consistent with previous results [\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The potential \u003cem\u003eT. pallidum\u003c/em\u003e-induced damage to the blood system and parenchymal organs may be partially mitigated by the robust compensatory mechanisms of the body, resulting in relatively nonsignificant clinical manifestations. Moreover, we investigated the impact of syphilis on the requisite homeostasis of multiorgan systems and noted that the patients with syphilis experienced reductions in bilirubin levels, indicating anemia, accompanied by a decrease in the content of total protein, particularly albumin. In contrast, increased globulin production may be a defense mechanism against \u003cem\u003eT. pallidum\u003c/em\u003e invasion. Furthermore, we noted a decrease in the levels of liver synthesis products and muscle metabolites in the patients with syphilis, suggesting the presence of low metabolism. Notably, in individuals with latent syphilis, prolonged hypometabolism can result in considerable physical damage due to the condition\u0026rsquo;s insidious nature [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Therefore, syphilis treatment should focus on rebalancing metabolic dysfunctions in the affected patients.\u003c/p\u003e \u003cp\u003eIn further analysis of the systemic metabolic status, patients with syphilis demonstrated a decrease in blood glucose levels, indicating impaired glucose utilization. A decrease in uric acid and creatinine levels and an increase in urea levels were also observed. Considering the strong compensatory ability of the kidneys, the aforementioned metabolite changes are most likely attributable to alterations in the rates of upstream metabolic pathway utilization. Thus, patients with syphilis may demonstrate a reduction in glucose and purine metabolism but an elevation in amino acid metabolism. Our patients with syphilis demonstrated dysregulated lipid metabolism, as indicated by high triglyceride and low cholesterol levels; changes in lipoprotein levels further confirmed the presence of this disruption. In our patients with syphilis, \u003cem\u003eT. pallidum\u003c/em\u003e affected the metabolic status, suggesting that rather than glucose metabolism, amino acid and lipid metabolism may be crucial energy supply pathways for \u003cem\u003eT. pallidum\u003c/em\u003e\u0026mdash;corroborating the results of a previous study [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Reestablishing and maintaining electrolyte homeostasis is a fundamental prerequisite for the human body to sustain vital physiological processes. In the current study, our patients with syphilis exhibited hyponatremia, hypokalemia, hypochloremia, hypocalcemia, and hyperphosphatemia. Patients with primary syphilis develop evident genital ulcers; nevertheless, the ulcers can be painless. This paradox may be attributable to neuronal hyperpolarization [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], with electrolyte imbalance potentially playing a major role in the process. Calcium ions are crucial factors involved in the body\u0026rsquo;s coagulation cascade; in patients with syphilis, reduced levels of calcium might synergistically contribute to platelet and fibrinogen depletion, leading to a hypocoagulability state.\u003c/p\u003e \u003cp\u003eHIV\u0026ndash;neurosyphilis coinfection is a major concern in patients with syphilis. In particular, individuals diagnosed as having syphilis may be highly susceptible to HIV infection and demonstrate expedited neurosyphilis progression [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, neurosyphilis often lacks distinctive clinical manifestations, which leads to treatment delays. In this study, we analyzed the laboratory pathological characteristics of HIV-positive patients with syphilis and HIV-negative patients with neurosyphilis. Our findings revealed that coagulation disorders were further suppressed in both the patient subgroups, potentially facilitating rapid dissemination of HIV and \u003cem\u003eT. pallidum\u003c/em\u003e within the host and promoting disease progression. These individuals also demonstrated exacerbated liver injury, possibly resulting in decreased coagulation factor synthesis and worsened coagulation disorders within the host. Furthermore, we observed a reduction in the metabolism and synthesis of neurotransmitters, such as cholinesterase, in HIV-negative patients with neurosyphilis. This indicated that \u003cem\u003eT. pallidum\u003c/em\u003e may inhibit neurotransmitter inactivation within the central nervous system, leading to neuronal activity disturbances and subsequent manifestation of nonspecific characteristics. However, further research elucidating the pathogenic mechanisms underlying these aforementioned characteristics is warranted.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, we used a cross-sectional design and did not perform classification analysis on patients with syphilis; as such, we did not collect a sufficient amount of laboratory pathological characteristics data from patients with different syphilis subtypes. Future studies should include patients with different forms of syphilis to enable comprehensive tracking and analysis of their pathogenic features. Second, because we included relatively few HIV-positive patients with syphilis and HIV-negative patients with neurosyphilis in this study, our statistical analysis may demonstrate low robustness. Finally, although \u003cem\u003eT. pallidum\u003c/em\u003e-induced organ damage has been observed in animal models [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], we did not include data related to direct histopathological staining of \u003cem\u003eT. pallidum\u003c/em\u003e-damaged tissue and organ sections.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn summary, our findings indicated that patients with syphilis exhibit macrocytic anemia, coagulation abnormalities, multiple organ dysfunction, decreased anabolism and glucose metabolism, and electrolyte imbalance. Notably, HIV infection exacerbates coagulation disorders and liver injury in these patients. Furthermore, patients with neurosyphilis demonstrate decreased hemostasis and anabolism. These laboratory-based pathogenic features can facilitate a contemporary understanding of syphilis progression. Consequently, during the administration of anti-\u003cem\u003eT. pallidum\u003c/em\u003e treatments to patients with syphilis, particularly those with penicillin allergy or latent syphilis, the related physical damage should be considered.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine [IIT20240463A], and was\u0026nbsp;in compliance with national legislation and the Declaration of Helsinki guidelines.\u0026nbsp;\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\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll relevant data supporting the findings of this study are contained within the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported in part from\u0026nbsp;the\u0026nbsp;Fundamental Research Funds for the Central Universities [grant number 2022ZFJH003];\u0026nbsp;the Zhejiang Plan for the Special Support for Top-notch Talents [grant number 2022R52029]; and\u0026nbsp;State Key Laboratory for Diagnosis and Treatment of Infectious Diseases\u0026nbsp;Project\u0026nbsp;[grant\u0026nbsp;numbers\u0026nbsp;zz202407].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHang-Ping Yao contributed to the study conception and design. Material\u0026nbsp;preparation, data collection, and analysis were performed by\u0026nbsp;Rui Chen, Han-Xin Mao, Jia-Le Zhang, Lin-Wei Zhu and Kai Wu. The first draft of the manuscript was written by Rui Chen and Han-Xin Mao, and all authors\u0026nbsp;commented on previous versions of the manuscript.\u0026nbsp;All authors read and approved the final\u0026nbsp;manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the fellows at the First Affiliated Hospital, Zhejiang University School of Medicine and People\u0026apos;s Hospital of Hangzhou Medical College and 620 participants for their support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHook EW 3rd, Marra CM. Acquired syphilis in adults. 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Treatment of bacterial sexually transmitted infections in Europe: gonorrhoea, Mycoplasma genitalium, and syphilis. Lancet Reg Health Eur. 2023; 34:100737.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNelson R. Syphilis rates soar in the USA amid penicillin shortage. Lancet. 2023; 402(10401):515.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNurse-Findlay S, Taylor MM, Savage M, et al. Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis: An evaluation from multi-country surveys and stakeholder interviews. PLoS Med. 2017;14(12):e1002473.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeeling RW, Mabey D, Chen XS, Garcia PJ. Syphilis. Lancet. 2023;402(10398):336\u0026ndash;346.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen R, Lin LR, Xiao Y, Ke WJ, Yang TC. 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J Eur Acad Dermatol Venereol. 2021;35(3): 574\u0026ndash;588.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu LL, Lin Y, Zhuang JC, et al. Analysis of serum metabolite profiles in syphilis patients by untargeted metabolomics. J Eur Acad Dermatol Venereol. 2019;33(7):1378\u0026ndash;1385.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHe Y, Yi DY, Pan L, et al. Treponema pallidum-induced prostaglandin E2 secretion in skin fibroblasts leads to neuronal hyperpolarization: A cause of painless ulcers. J Eur Acad Dermatol Venereol. 2024 Feb 20. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/jdv.19902\u003c/span\u003e\u003cspan address=\"10.1111/jdv.19902\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Online ahead of print.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Syphilis, Laboratory-based pathogenic feature, Systemic damage, Anti-Treponema pallidum treatment","lastPublishedDoi":"10.21203/rs.3.rs-4600372/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4600372/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDespite the persistent susceptibility of \u003cem\u003eTreponema pallidum\u003c/em\u003e to penicillin, the global incidence of syphilis remains high. Syphilis is a complex disease with physical consequences extending beyond manifestations. In this multicenter case\u0026ndash;control study, we analyzed data from 536 patients with syphilis who underwent complete blood cell analysis, biochemical examination, and coagulation function tests at the First Affiliated Hospital Zhejiang University School of Medicine and People\u0026rsquo;s Hospital of Hangzhou Medical College in China. Moreover, we included 84 bone marrow-derived stem cell donors in the control group. Our findings indicated that patients with syphilis exhibited macrocytic anemia, coagulation abnormalities, multiple organ dysfunction, reduced anabolism and glucose metabolism, and electrolyte imbalance. Notably, HIV infection was noted to exacerbate coagulation disorders and liver injury in patients with syphilis. Furthermore, patients with neurosyphilis demonstrated decreases in the levels of hemostasis and anabolism. The aforementioned laboratory-based pathogenic features represent a contemporary understanding of syphilis progression. As such, when administering anti-\u003cem\u003eT. pallidum\u003c/em\u003e treatment to patients with syphilis, particularly those exhibiting penicillin allergy and latent syphilis, medical professionals should address the associated physical damage.\u003c/p\u003e","manuscriptTitle":"Revisiting contemporary laboratory characteristics of patients with syphilis: insights from a multicenter study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-18 16:39:51","doi":"10.21203/rs.3.rs-4600372/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e689e9b1-2296-4ba8-a43a-aab239d465f0","owner":[],"postedDate":"July 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":34241434,"name":"Biological sciences/Microbiology/Clinical microbiology"},{"id":34241435,"name":"Biological sciences/Microbiology/Pathogens"}],"tags":[],"updatedAt":"2024-10-31T06:08:11+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-18 16:39:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4600372","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4600372","identity":"rs-4600372","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}