Predictive value of macrophage inflammatory protein 3β in the risk of death in sepsis patients

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Methods 177 sepsis patients visited the emergency medicine department of Beijing Chaoyang Hospital between October 2020 and April 2021. Within an hour of admission, serum levels of WBC (white blood cell), PLT (platelet), TBIL (total bilirubin), PCT (procalcitonin), CRP (C-reactive protein), and MIP-3β were measured, and patients were assessed with organ failure scores—SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute physiology and chronic health evaluation) scores. Logistic regression was used to predict independent risk factors for 28-day mortality, and Receiver Operating Characteristic (ROC)curves were used to assess predictive value. Results MIP-3β, SOFA, and APACHE II scores were statistically different ( P < 0.05) between the survival and death groups. The logistic regression analysis revealed that the MIP-3β, SOFA, and APACHE II scores were independent risk factors for 28-day mortality ( P < 0.05) in sepsis patients. The area under the ROC curve (AUC) for the MIP-3β area was 0.635 (sensitivity 0.573, specificity 0.679, critical value 93.43), which was slightly lower than that of the SOFA score 0.839 (sensitivity 0.573, specificity 0.962, critical value 7.5, Z = 3.446, P = 0.0006) and APACHE II score 0.773 (sensitivity 0.556, specificity 0.925, critical value 21.5, Z = 2.304, P = 0.0212); however, the combined prediction using MIP-3β and SOFA scores (AUC area 0.86, sensitivity 0.637, specificity 0.981, Z = 4.552, P < 0.0001) had higher AUC area, sensitivity, and specificity than MIP-3β alone. Conclusions MIP-3β, SOFA, and APACHE II scores were independent risk factors for 28-day mortality in sepsis patients. The predictive value of MIP-3β combined with SOFA score was higher than that of MIP-3β alone, which is crucial for reducing mortality in sepsis patients. Sepsis Macrophage inflammatory protein 3β Figures Figure 1 Introduction Sepsis is a complex disorder characterized by acute organ dysfunction and a high risk of death; it results from a dysregulated host response to an infection [ 1 ]. Sepsis is highly prevalent and remains one of the leading causes of death in patients worldwide [ 2 , 3 ]. Early identification and diagnosis of sepsis is crucial for reducing mortality. Sepsis is closely related to the inflammatory response [ 4 – 8 ]. The sequential organ failure (SOFA) score [ 1 , 3 , 9 ] and the severity of illness APACHE II score in critically ill patients [ 10 ] are strongly associated with mortality in patients with sepsis or critical illness; however, estimating patient mortality is challenging due to the complexity. Moreover, the sensitivity of these two scores could be improved. Exploring additional biomarkers to predict mortality in sepsis patients is essential. Macrophage inflammatory protein 3β, also known as CC-chemokine ligand 19 (CCL19), is a cytokine associated with leukocyte migration through its interaction with C-chem factor receptor 7 (CCR7) [ 11 – 13 ]. The MIP-3β-CCR7 pathway is associated with the initiation and progression of inflammation in chronic inflammatory diseases [ 14 – 28 ]. Therefore, also as an inflammation-related disease, is sepsis associated with the MIP-3β-CCR7 pathway? No studies have demonstrated the relationship between sepsis patients and MIP-3β. We examined MIP-3β in the serum of sepsis patients and explored its value for the prognosis. In the present study, MIP-3β, SOFA, and APACHE II scores were all independent risk factors for 28-day mortality in sepsis patients. The predictive value of MIP-3β combined with SOFA score was higher, which is crucial for reducing mortality of sepsis patients. Materials and methods Study design and participants The study was conducted at Beijing Chaoyang Hospital, Capital Medical University. The study included 177 sepsis patients admitted to the Department of Emergency Medicine between October 2020 and April 2021. The study was approved by the Ethics Committee of Beijing Chaoyang Hospital (2021-S-636). Written informed consent was obtained from the patients or their families, and data confidentiality was strictly maintained. Inclusion criteria were as follows: (1) patients signed an informed consent form; (2) age > 18 years; (3) sepsis patients (definite infection, SOFA score ≥ 2 according to Sepsis-3 criteria). Exclusion criteria were as follows: (1) age < 18 years; (2) malignancy, chronic kidney disease maintenance dialysis, connective tissue disease, long-term immunosuppression, and hematologic disorders; (3) refusal of the patient or his family to participate in the study or transfer to another hospital. Baseline patient demographics General patient data, including gender, age, type of disease (cardiovascular, respiratory, and other systemic diseases), all clinical events and outcomes, and 28-day mortality, were collected and recorded upon admission. Serum markers Blood samples were collected within an hour of the patient's admission to the emergency department. The PCT levels were measured using a point-of-care testing analyzer (POCT, automatic fluorescence immunoassay analyzer, Vazyme Biotech Co., Ltd., China). Circulating levels of MIP-3β in the plasma samples were measured using the Human XL Cytokine Luminex Performance Assay 46-plex Fixed Panel (LKTM014B, R&D) according to the manufacturer's instructions. Blood samples with severe hemolysis, lipid clouding, and high bilirubin concentrations were excluded. Other laboratory-related indices, including blood counts and routine biochemical indices, were measured in the clinical laboratory of Beijing Chaoyang Hospital. Clinical scoring The SOFA and APACHE II scores were calculated based on the clinical data of admitted patients. Statistical analysis Data was processed using the Statistical Package for Social Sciences (SPSS) 26.0 (IBM SPSS Inc., Armonk, NY, USA) software. None of the data tested conformed to a normal distribution. The data were statistically analyzed using the Mann-Whitney test, which was statistically described by the median, 25%, and 75% of the positional values. Categorical variables were statistically analyzed using the chi-square test. Logistic regression analysis was used to predict independent risk factors for patients who died within 28 days, and ROC curves were calculated for subjects to determine their sensitivity, specificity, and AUC. Threshold values were determined using the Youden method. AUC comparisons were performed using the Z test. The final multiple regression model included all potential variables significantly associated with the results. Differences were statistically significant at P 0.05) in gender, age, and underlying diseases (diabetes, hypertension, and coronary artery disease) between the two groups. The primary diagnosis was respiratory disease in 59 (33.3%) patients, cardiovascular disease in 43 (24.3%) patients, and urologic and other systemic diseases in 75 (42.4%) patients. In terms of scores, the SOFA scores (5 (3,6) vs. 8 (6,10)) and APACHE II scores (15 (11.5,18.5) vs. 22 (17,27.75)) were higher in the death group than those in the survival group, and the differences were statistically significant ( P < 0.001) (Table 1 ). These findings are consistent with those of previous studies. Among the serological indicators tested, only MIP-3β (64.40 (41.13,130.68) vs. 104.10 (61.69,155.20)) was significantly different between the two groups ( P < 0.01), and there were no statistically significant differences in other indicators (Table 1 ). Table 1 Comparison of patient baseline data Survivor group(n = 53) Nonsurvivor group (n = 124) P Gender (male/female) 32/21 70/54 0.628 Age (years) 71 (62.5,83) 75.5 (65,83) 0.419 Underlying disease Hypertension (yes/no) 25/28 57/67 0.883 Diabetes (yes/no) 18/35 38/86 0.664 Coronary heart disease (yes/no) 16/37 31/93 0.474 Main diagnosis Respiratory system 14 45 Cardiovascular system diseases 12 31 Other 27 48 SOFA 5 (3,6) 8 (6,10) 0.001 APACHE II 15 (11.5,18.5) 22 (17,27.75) 0.001 WBC (*10^9/L) 8.6 (7.15,12.05) 9.2 (7.3,11.88) 0.868 PLT (*10^9/L) 218 (145,302.5) 179 (137,253.75) 0.127 TBIL (µmol/L) 14.9 (11.3,20.75) 14.6 (9.45,24.15) 0.738 PCT (ng/mL) 0.05 (0.05,1.12) 0.05 (0.05,0.58) 0.986 CRP (mg/L) 12 (8,71.5) 18.6 (8,84) 0.524 MIP-3β (pg/mL) 64.40 (41.13,130.68) 104.10 (61.69,155.20) 0.004 APACHE II: acute physiology and chronic health evaluation II; SOFA: sequential organ failure assessment score; WBC: white blood cell; PLT: platelet; TBIL: total bilirubin; PCT: procalcitonin; CRP: C-reactive protein; MIP-3β: macrophage inflammatory protein 3β; The differences were statistically significant when P < 0.05. MIP-3β, SOFA, and APACHE II scores were all independent risk factors for 28-day mortality in sepsis patients Incorporating the positive indicators from the aforementioned univariate analysis into the multivariate regression analysis revealed that MIP-3β (1.008 (1.002,1.014), SOFA score (1.116 (1.042,1.196), P = 0.001), and APACHE II score (1.520 (1.263,1.830), P = 0.002) were independent risk factors for 28-day mortality in sepsis patients (Table 2 ). Table 2 Multivariate regression analysis of MIP-3β, SOFA, APACHE II scores and 28-day prognosis in critically ill patients β SE Wald P OR (95%CI) MIP-3β 0.008 0.003 6.725 0.01 1.008 (1.002,1.014) SOFA 0.419 0.095 19.61 0.001 1.116 (1.042,1.196) APACHE II 0.110 0.035 9.737 0.002 1.520 (1.263,1.830) APACHE II: acute physiology and chronic health evaluation II; SOFA: sequential organ failure assessment score; MIP-3β: macrophage inflammatory protein 3β; SE: standard error. The differences were statistically significant when P < 0.05. MIP-3β combined with SOFA score predicted 28-day mortality in sepsis patients In the diagnostic analysis of the three indicators screened using the logistic regression, ROC curve analysis demonstrated that the magnitude of the MIP-3β, SOFA score, and APACHE II score predicted a 28-day prognosis in sepsis patients (Table 3 and Fig. 1 ). The AUC of the ROC curve for MIP-3β was 0.635 (sensitivity 57.3%, specificity 67.9%, and critical value 93.43), slightly lower than that of the SOFA score (AUC 0.839, sensitivity 57.3%, specificity 96.2%, and critical value 7.5) and the APACHE II score (AUC 0.773, sensitivity 55.6%, specificity 92.5%, and critical value 21.5). The diagnostic value of MIP-3β was statistically different compared with that of the other two indices (SOFA score, Z = 3.446, P = 0.0006; APACHE II score, Z = 2.304, P = 0.0212). Moreover, the combined assessment of MIP-3β and SOFA score (AUC 0.860, sensitivity 63.7%, specificity 98.1%; Z = 4.552, P = 0.0001) had a better diagnostic value and higher sensitivity (63.7%) and specificity (98.1%) than MIP-3β alone (Table 3 ). Table 3 Predictive value of MIP-3β, SOFA, APACHE II scores, and 28-day prognosis in critically ill patients AUC 95%CI P Cut-off Sensitivity (%) Specificity (%) MIP-3β 0.635 (0.545–0.725) 0.004 93.43 0.573 0.679 SOFA 0.839 (0.778–0.901) 0.001 7.500 0.573 0.962 APACHE II 0.773 (0.698–0.847) 0.001 21.50 0.556 0.925 MIP-3β + SOFA 0.860 (0.802,0.917) 0.001 0.637 0.981 MIP-3β + APACHE II 0.791 (0.719,0.863) 0.001 0.613 0.868 APACHE II: acute physiology and chronic health evaluation II; SOFA: sequential organ failure assessment score; MIP-3β: macrophage inflammatory protein 3β; AUC: area under ROC curve; Cut-off: the cut-off value was determined using the Youden method. AUC comparisons were performed using the Z test. The differences were statistically significant when P < 0.05. Discussion In emergency medicine, sepsis is a common, life-threatening organ dysfunction caused by a dysregulated host response to infection [ 1 ]. When exposed to pathogens, pattern recognition receptors on cells of the innate immune system recognize molecular patterns associated with microbial pathogens and activate immune pathways, which mediate the development of inflammatory responses and micro thrombosis, involving inflammation-related mediators, such as tumor necrosis factor α, interleukin 1, interleukin 2, interleukin 6, and interleukin 8. Studies have suggested that a systemic inflammatory response against infection and an immunosuppressive process characterized by allergy, lymphopenia, and secondary infection may coexist in sepsis patients [ 4 , 5 , 29 ]. The ensuing tissue hypoxia, mitochondrial dysfunction, and apoptosis are essential mediators of sepsis-induced organ dysfunction [ 6 – 8 ]. The morbidity and mortality of sepsis are high and impose a significant global economic burden [ 2 , 3 , 30 ]. Therefore, exploring biological indicators that influence the prognosis of sepsis patients is essential to reduce its mortality. In our study, serologic levels and disease severity scores were evaluated in 177 sepsis patients upon hospital admission, which helped in the timely risk grading, diagnosis, and treatment of patients. MIP-3β, also known as CCL19, is a cytokine that mediates the migration of immune cells and is expressed in various cells [ 11 ]. Unlike other chemokines, MIP-3β is a constitutively expressed chemokine that binds to and functions with CC-chemokine receptor 7 (CCR7) [ 13 ]. The MIP-3β-CCR7 pathway is implicated in the development, regulation, and peripheral and central tolerance of the body's immune system establishment of the immune system [ 11 ]. The MIP-3β-CCR7 pathway is associated with the initiation and progression of inflammation in various chronic inflammatory diseases, such as multiple sclerosis [ 14 – 18 ], rheumatoid arthritis [ 19 – 22 ], and psoriasis [ 23 – 27 ]. The MIP-3β-CCR7 pathway promotes T cell proliferation and antigen uptake by dendritic cells [ 31 , 32 ], thereby exerting its anti-inflammatory effects. Overexpression of MIP-3β activates immune system-targeted gene immunotherapy, exerting powerful anti-colon tumor effects [ 33 ]. Xiang Gao et al. found that overexpression of MIP-3β inhibited M2 macrophage polarization by inducing dendritic cell maturation, thereby suppressing cancer growth [ 34 ]. The current study suggests that MIP-3β was closely associated with the development of chronic diseases, such as inflammation or tumors, but its mechanism of action is poorly understood. Sepsis is a syndrome closely related to the inflammatory response, and the MIP-3β-CCR7 pathway is also involved in developing chronic inflammation. The MIP-3β-CCR7 pathway is also involved in the development of the inflammatory process in sepsis; therefore, is there a correlation between MIP-3β expression and the prognosis of sepsis? Recent studies by our team have found that MIP-3α is strongly associated with mortality in sepsis patients [ 35 ], but no studies have demonstrated a relationship between sepsis and the MIP-3β-CCR7 pathway. Therefore, we hypothesized that the increased expression of MIP-3β in sepsis patients correlates with their poor prognosis. Our study found that the MIP-3β levels in the serum of sepsis patients were significantly lower in the survival group (64.40 (41.13,130.68)) than in the death group (104.10 (61.69,155.20)) ( P < 0.01). The logistic regression analysis revealed that MIP-3β predicted 28-day mortality in sepsis patients with a sensitivity of 57.3% and specificity of 67.9%, which had a high diagnostic value. This finding suggests that MIP-3β—an inflammation-related indicator—plays a pro-inflammatory role in the development of sepsis and is associated with its poor prognosis, which is consistent with our hypothesis. The APACHE II score, a disease severity score for critically ill patients, is strongly associated with mortality in critically ill patients [ 10 ]. Our study also found that the APACHE II score in the survival group (15 (11.5,18.5)) was significantly lower than in the 28-day mortality group (22 (17,27.75)) ( P < 0.001). Similarly, the APACHE II score predicted 28-day mortality in sepsis patients with a sensitivity of 55.6% and a specificity of 92.5%, consistent with those of previous studies [ 10 ]. The SOFA score was used to assess the degree of organ dysfunction in sepsis patients [ 1 ]. The higher the SOFA score, the more severe the patient's condition. We found that SOFA score was significantly lower in the survival group (5 (3,6)) than in the 28-day mortality group (8 (6,10)) ( P < 0.001) and that SOFA score was an independent risk factor for 28-day mortality in sepsis patients with a sensitivity of 57.3% and a specificity of 96.2%, which is consistent with those of previous studies (1, 5). Notably, the combined assessment of MIP-3β and SOFA score (AUC 0.860, sensitivity 63.7%, specificity 98.1%; Z = 4.552, P = 0.0001) had a better diagnostic value than MIP-3β alone, with higher sensitivity (63.7%) and specificity (98.1%). We concluded that MIP-3β was an independent risk factor for 28-day mortality in sepsis patients and that MIP-3β combined with SOFA score could better assess the prognosis of sepsis patients. Our results have some clinical value. Our study has some limitations. First, it is a single-center study with patients limited to one region and small sample size, so a large-scale, multicenter study is required to validate the results. Second, we did not further explore the expression of the CCR7-MIP-3β pathway and its mechanism of action in sepsis patients, and we did not dynamically observe the relationship between changes in MIP-3β and patient prognosis, which requires further study. Finally, the initial serological index only reflects the inflammatory status and disease severity when the disease first occurs, and it helps clinicians to assess the patient's condition but cannot fully represent the patient's final prognosis. Conclusion In conclusion, MIP-3β, SOFA, and APACHE II scores could be used as independent risk factors affecting the prognosis of sepsis patients. MIP-3β combined with SOFA score has a higher diagnostic value than the aforementioned indices alone, and early and rapid assessment is crucial for treatment and assessment of prognosis. Declarations Ethics approval and consent to participate The study was approved by the Ethics Committee of Beijing Chao-Yang Hospital of Capital Medical University, and it was conducted in accordance with the Declaration of Helsinki. Written informed consent was provided by all participants. Clinical Trial Not applicable. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Availability of data and material Data openly available in a public repository. Competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Funding This research was funded by the Shijing Shan District Medical Key Support Specialty Building Foundation. Authors' contributions Dr. BW and Dr. YGL were responsible for the initial initiation of the study and data review, YG was responsible for the statistics and analysis of the data, and the writing and revision of the article, and XBP, YZ, and XQZ were responsible for the data collection. Acknowledgements Funding from the Shijing Shan District medical key support specialty construction foundation is gratefully acknowledged. References Singer M, Deutschman C S, Seymour C W, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard G R, Chiche J D, Coopersmith C M, Hotchkiss R S, Levy M M, Marshall J C, Martin G S, Opal S M, Rubenfeld G D, van der Poll T, Vincent J L, Angus D C. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama . 2016;315(8):801-10. 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Supplementary Files cutoff.xlsx file.spv Cite Share Download PDF Status: Published Journal Publication published 29 Jan, 2026 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 03 Oct, 2025 Reviews received at journal 31 May, 2025 Reviewers agreed at journal 31 May, 2025 Reviews received at journal 28 May, 2025 Reviewers agreed at journal 23 May, 2025 Reviewers invited by journal 15 May, 2025 Editor invited by journal 23 Apr, 2025 Editor assigned by journal 23 Apr, 2025 Submission checks completed at journal 23 Apr, 2025 First submitted to journal 17 Apr, 2025 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6471946","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":457342595,"identity":"9fd645ac-7997-4a6a-94ed-5c2684d32e39","order_by":0,"name":"Yu Gu","email":"","orcid":"","institution":"Beijing Chao-Yang Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Gu","suffix":""},{"id":457342596,"identity":"4065f33e-ebb6-4f2f-a5ac-62ef637dc52c","order_by":1,"name":"Xue-Bin Pei","email":"","orcid":"","institution":"Beijing Chao-Yang Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xue-Bin","middleName":"","lastName":"Pei","suffix":""},{"id":457342597,"identity":"c1536d77-b7a5-4e4f-b805-e01e83d33110","order_by":2,"name":"Xiang-Qun Zhang","email":"","orcid":"","institution":"Beijing Chao-Yang Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiang-Qun","middleName":"","lastName":"Zhang","suffix":""},{"id":457342598,"identity":"b5c057c0-ee20-488f-84ac-859eb54e48a7","order_by":3,"name":"Ye Zhang","email":"","orcid":"","institution":"Beijing Chao-Yang Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ye","middleName":"","lastName":"Zhang","suffix":""},{"id":457342599,"identity":"a1aaadc0-8058-4dba-a299-6b165f701cbd","order_by":4,"name":"Bing Wei","email":"","orcid":"","institution":"Beijing Chao-Yang Hospital","correspondingAuthor":false,"prefix":"","firstName":"Bing","middleName":"","lastName":"Wei","suffix":""},{"id":457342600,"identity":"3ee2ef76-f36e-4013-899d-1a32790871b2","order_by":5,"name":"Yu-Geng Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYBADGTYG5gMHPlSQoIWHjYEt8eCMM6RoASLjw7wtRCg1uJF+8XHBLwYePomcDwd4Gxjk+cUOENKSU2w8sw/oMIncDQckdzAYzpydQFBLmjRvD1SL4RmGBIPbhLWk/4ZoyXlwILGNKC3px5h5foC1MBw4SIwWyTNvmKWBvuZh43lmcLDhjARhv/AdT3/4mecPg5x8e/Ljz38qbOT5pQloUTjAY8DA2PYfxpfArxwE5BvYHzAw/CGscBSMglEwCkYwAACNiEUxLAzjywAAAABJRU5ErkJggg==","orcid":"","institution":"Beijing Chao-Yang Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yu-Geng","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2025-04-17 12:53:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6471946/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6471946/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-026-12723-x","type":"published","date":"2026-01-29T15:58:22+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":83148511,"identity":"3ffbc244-66a6-4ff1-b9a0-12a52d80504c","added_by":"auto","created_at":"2025-05-20 13:24:09","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":85091,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve of MIP-3β, SOFA, and APACHE II score predicting 28-day prognosis in critically ill patients.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6471946/v1/00e9d559bf3e75fea2cc42a1.png"},{"id":101691896,"identity":"6fafa575-2dfe-4dbd-a8b4-f1cd37915969","added_by":"auto","created_at":"2026-02-02 16:16:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":610668,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6471946/v1/a117247e-49fc-40c6-809a-12f7156d583d.pdf"},{"id":83148514,"identity":"96a7bfad-1460-4725-94a8-a022120707da","added_by":"auto","created_at":"2025-05-20 13:24:09","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":32786,"visible":true,"origin":"","legend":"","description":"","filename":"cutoff.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6471946/v1/3ca35b84dc0375d1aa3dc721.xlsx"},{"id":83148522,"identity":"e1b79ef4-4b5c-4c0a-9630-436bb5651bcd","added_by":"auto","created_at":"2025-05-20 13:24:09","extension":"spv","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":939198,"visible":true,"origin":"","legend":"","description":"","filename":"file.spv","url":"https://assets-eu.researchsquare.com/files/rs-6471946/v1/c4f4561e0d5b9f22db274b9d.spv"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictive value of macrophage inflammatory protein 3β in the risk of death in sepsis patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSepsis is a complex disorder characterized by acute organ dysfunction and a high risk of death; it results from a dysregulated host response to an infection [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Sepsis is highly prevalent and remains one of the leading causes of death in patients worldwide [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Early identification and diagnosis of sepsis is crucial for reducing mortality. Sepsis is closely related to the inflammatory response [\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The sequential organ failure (SOFA) score [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and the severity of illness APACHE II score in critically ill patients [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] are strongly associated with mortality in patients with sepsis or critical illness; however, estimating patient mortality is challenging due to the complexity. Moreover, the sensitivity of these two scores could be improved. Exploring additional biomarkers to predict mortality in sepsis patients is essential.\u003c/p\u003e \u003cp\u003eMacrophage inflammatory protein 3β, also known as CC-chemokine ligand 19 (CCL19), is a cytokine associated with leukocyte migration through its interaction with C-chem factor receptor 7 (CCR7) [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The MIP-3β-CCR7 pathway is associated with the initiation and progression of inflammation in chronic inflammatory diseases [\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Therefore, also as an inflammation-related disease, is sepsis associated with the MIP-3β-CCR7 pathway? No studies have demonstrated the relationship between sepsis patients and MIP-3β. We examined MIP-3β in the serum of sepsis patients and explored its value for the prognosis.\u003c/p\u003e \u003cp\u003eIn the present study, MIP-3β, SOFA, and APACHE II scores were all independent risk factors for 28-day mortality in sepsis patients. The predictive value of MIP-3β combined with SOFA score was higher, which is crucial for reducing mortality of sepsis patients.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eStudy design and participants\u003c/p\u003e \u003cp\u003eThe study was conducted at Beijing Chaoyang Hospital, Capital Medical University. The study included 177 sepsis patients admitted to the Department of Emergency Medicine between October 2020 and April 2021. The study was approved by the Ethics Committee of Beijing Chaoyang Hospital (2021-S-636). Written informed consent was obtained from the patients or their families, and data confidentiality was strictly maintained. Inclusion criteria were as follows: (1) patients signed an informed consent form; (2) age\u0026thinsp;\u0026gt;\u0026thinsp;18 years; (3) sepsis patients (definite infection, SOFA score\u0026thinsp;\u0026ge;\u0026thinsp;2 according to Sepsis-3 criteria). Exclusion criteria were as follows: (1) age\u0026thinsp;\u0026lt;\u0026thinsp;18 years; (2) malignancy, chronic kidney disease maintenance dialysis, connective tissue disease, long-term immunosuppression, and hematologic disorders; (3) refusal of the patient or his family to participate in the study or transfer to another hospital.\u003c/p\u003e \u003cp\u003eBaseline patient demographics\u003c/p\u003e \u003cp\u003eGeneral patient data, including gender, age, type of disease (cardiovascular, respiratory, and other systemic diseases), all clinical events and outcomes, and 28-day mortality, were collected and recorded upon admission.\u003c/p\u003e \u003cp\u003eSerum markers\u003c/p\u003e \u003cp\u003eBlood samples were collected within an hour of the patient's admission to the emergency department. The PCT levels were measured using a point-of-care testing analyzer (POCT, automatic fluorescence immunoassay analyzer, Vazyme Biotech Co., Ltd., China). Circulating levels of MIP-3β in the plasma samples were measured using the Human XL Cytokine Luminex Performance Assay 46-plex Fixed Panel (LKTM014B, R\u0026amp;D) according to the manufacturer's instructions. Blood samples with severe hemolysis, lipid clouding, and high bilirubin concentrations were excluded. Other laboratory-related indices, including blood counts and routine biochemical indices, were measured in the clinical laboratory of Beijing Chaoyang Hospital.\u003c/p\u003e \u003cp\u003eClinical scoring\u003c/p\u003e \u003cp\u003eThe SOFA and APACHE II scores were calculated based on the clinical data of admitted patients.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData was processed using the Statistical Package for Social Sciences (SPSS) 26.0 (IBM SPSS Inc., Armonk, NY, USA) software. None of the data tested conformed to a normal distribution. The data were statistically analyzed using the Mann-Whitney test, which was statistically described by the median, 25%, and 75% of the positional values. Categorical variables were statistically analyzed using the chi-square test. Logistic regression analysis was used to predict independent risk factors for patients who died within 28 days, and ROC curves were calculated for subjects to determine their sensitivity, specificity, and AUC. Threshold values were determined using the Youden method. AUC comparisons were performed using the \u003cem\u003eZ\u003c/em\u003e test. The final multiple regression model included all potential variables significantly associated with the results. Differences were statistically significant at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eComparison of patients' baseline data\u003c/p\u003e \u003cp\u003eThe baseline data of 177 patients are displayed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. According to Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, there were no significant differences (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) in gender, age, and underlying diseases (diabetes, hypertension, and coronary artery disease) between the two groups. The primary diagnosis was respiratory disease in 59 (33.3%) patients, cardiovascular disease in 43 (24.3%) patients, and urologic and other systemic diseases in 75 (42.4%) patients. In terms of scores, the SOFA scores (5 (3,6) vs. 8 (6,10)) and APACHE II scores (15 (11.5,18.5) vs. 22 (17,27.75)) were higher in the death group than those in the survival group, and the differences were statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). These findings are consistent with those of previous studies. Among the serological indicators tested, only MIP-3β (64.40 (41.13,130.68) vs. 104.10 (61.69,155.20)) was significantly different between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01), and there were no statistically significant differences in other indicators (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\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\u003eComparison of patient baseline data\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=\"left\" 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\u003eSurvivor group(n\u0026thinsp;=\u0026thinsp;53)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNonsurvivor group (n\u0026thinsp;=\u0026thinsp;124)\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\u003eGender (male/female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32/21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70/54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.628\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71 (62.5,83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.5 (65,83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.419\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnderlying disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension (yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25/28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57/67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.883\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes (yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18/35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38/86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.664\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoronary heart disease (yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16/37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31/93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.474\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMain diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory system\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45\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\u003eCardiovascular system diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31\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\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48\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\u003eSOFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (3,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (6,10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPACHE II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (11.5,18.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (17,27.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (*10^9/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.6 (7.15,12.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.2 (7.3,11.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.868\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLT (*10^9/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e218 (145,302.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e179 (137,253.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.127\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTBIL (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.9 (11.3,20.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.6 (9.45,24.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.738\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCT (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.05 (0.05,1.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.05 (0.05,0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.986\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (8,71.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.6 (8,84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.524\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMIP-3β (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64.40 (41.13,130.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104.10 (61.69,155.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAPACHE II: acute physiology and chronic health evaluation II; SOFA: sequential organ failure assessment score; WBC: white blood cell; PLT: platelet; TBIL: total bilirubin; PCT: procalcitonin; CRP: C-reactive protein; MIP-3β: macrophage inflammatory protein 3β; The differences were statistically significant when \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMIP-3β, SOFA, and APACHE II scores were all independent risk factors for 28-day mortality in sepsis patients\u003c/p\u003e \u003cp\u003eIncorporating the positive indicators from the aforementioned univariate analysis into the multivariate regression analysis revealed that MIP-3β (1.008 (1.002,1.014), SOFA score (1.116 (1.042,1.196), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), and APACHE II score (1.520 (1.263,1.830), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) were independent risk factors for 28-day mortality in sepsis patients (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\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\u003eMultivariate regression analysis of MIP-3β, SOFA, APACHE II scores and 28-day prognosis in critically ill patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWald\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMIP-3β\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.725\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.008 (1.002,1.014)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.419\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.095\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e19.61\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\u003e1.116 (1.042,1.196)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPACHE II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9.737\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.520 (1.263,1.830)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAPACHE II: acute physiology and chronic health evaluation II; SOFA: sequential organ failure assessment score; MIP-3β: macrophage inflammatory protein 3β; SE: standard error. The differences were statistically significant when \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMIP-3β combined with SOFA score predicted 28-day mortality in sepsis patients\u003c/p\u003e \u003cp\u003eIn the diagnostic analysis of the three indicators screened using the logistic regression, ROC curve analysis demonstrated that the magnitude of the MIP-3β, SOFA score, and APACHE II score predicted a 28-day prognosis in sepsis patients (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The AUC of the ROC curve for MIP-3β was 0.635 (sensitivity 57.3%, specificity 67.9%, and critical value 93.43), slightly lower than that of the SOFA score (AUC 0.839, sensitivity 57.3%, specificity 96.2%, and critical value 7.5) and the APACHE II score (AUC 0.773, sensitivity 55.6%, specificity 92.5%, and critical value 21.5). The diagnostic value of MIP-3β was statistically different compared with that of the other two indices (SOFA score, \u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3.446, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0006; APACHE II score, \u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.304, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0212). Moreover, the combined assessment of MIP-3β and SOFA score (AUC 0.860, sensitivity 63.7%, specificity 98.1%; \u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;4.552, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0001) had a better diagnostic value and higher sensitivity (63.7%) and specificity (98.1%) than MIP-3β alone (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePredictive value of MIP-3β, SOFA, APACHE II scores, and 28-day prognosis in critically ill patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAUC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95%CI\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 \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCut-off\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSensitivity (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSpecificity (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMIP-3β\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.635\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e(0.545\u0026ndash;0.725)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e93.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.573\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.679\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.839\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e(0.778\u0026ndash;0.901)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.573\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.962\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPACHE II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.773\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e(0.698\u0026ndash;0.847)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e21.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.556\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.925\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMIP-3β\u0026thinsp;+\u0026thinsp;SOFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.860\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e(0.802,0.917)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.637\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.981\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMIP-3β\u0026thinsp;+\u0026thinsp;APACHE II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.791\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e(0.719,0.863)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.613\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.868\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAPACHE II: acute physiology and chronic health evaluation II; SOFA: sequential organ failure assessment score; MIP-3β: macrophage inflammatory protein 3β; AUC: area under ROC curve; Cut-off: the cut-off value was determined using the Youden method. AUC comparisons were performed using the \u003cem\u003eZ\u003c/em\u003e test. The differences were statistically significant when \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn emergency medicine, sepsis is a common, life-threatening organ dysfunction caused by a dysregulated host response to infection [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. When exposed to pathogens, pattern recognition receptors on cells of the innate immune system recognize molecular patterns associated with microbial pathogens and activate immune pathways, which mediate the development of inflammatory responses and micro thrombosis, involving inflammation-related mediators, such as tumor necrosis factor α, interleukin 1, interleukin 2, interleukin 6, and interleukin 8. Studies have suggested that a systemic inflammatory response against infection and an immunosuppressive process characterized by allergy, lymphopenia, and secondary infection may coexist in sepsis patients [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The ensuing tissue hypoxia, mitochondrial dysfunction, and apoptosis are essential mediators of sepsis-induced organ dysfunction [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The morbidity and mortality of sepsis are high and impose a significant global economic burden [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Therefore, exploring biological indicators that influence the prognosis of sepsis patients is essential to reduce its mortality. In our study, serologic levels and disease severity scores were evaluated in 177 sepsis patients upon hospital admission, which helped in the timely risk grading, diagnosis, and treatment of patients.\u003c/p\u003e \u003cp\u003eMIP-3β, also known as CCL19, is a cytokine that mediates the migration of immune cells and is expressed in various cells [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Unlike other chemokines, MIP-3β is a constitutively expressed chemokine that binds to and functions with CC-chemokine receptor 7 (CCR7) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The MIP-3β-CCR7 pathway is implicated in the development, regulation, and peripheral and central tolerance of the body's immune system establishment of the immune system [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The MIP-3β-CCR7 pathway is associated with the initiation and progression of inflammation in various chronic inflammatory diseases, such as multiple sclerosis [\u003cspan additionalcitationids=\"CR15 CR16 CR17\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], rheumatoid arthritis [\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], and psoriasis [\u003cspan additionalcitationids=\"CR24 CR25 CR26\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The MIP-3β-CCR7 pathway promotes T cell proliferation and antigen uptake by dendritic cells [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], thereby exerting its anti-inflammatory effects. Overexpression of MIP-3β activates immune system-targeted gene immunotherapy, exerting powerful anti-colon tumor effects [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Xiang Gao et al. found that overexpression of MIP-3β inhibited M2 macrophage polarization by inducing dendritic cell maturation, thereby suppressing cancer growth [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. The current study suggests that MIP-3β was closely associated with the development of chronic diseases, such as inflammation or tumors, but its mechanism of action is poorly understood. Sepsis is a syndrome closely related to the inflammatory response, and the MIP-3β-CCR7 pathway is also involved in developing chronic inflammation. The MIP-3β-CCR7 pathway is also involved in the development of the inflammatory process in sepsis; therefore, is there a correlation between MIP-3β expression and the prognosis of sepsis? Recent studies by our team have found that MIP-3α is strongly associated with mortality in sepsis patients [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], but no studies have demonstrated a relationship between sepsis and the MIP-3β-CCR7 pathway. Therefore, we hypothesized that the increased expression of MIP-3β in sepsis patients correlates with their poor prognosis.\u003c/p\u003e \u003cp\u003eOur study found that the MIP-3β levels in the serum of sepsis patients were significantly lower in the survival group (64.40 (41.13,130.68)) than in the death group (104.10 (61.69,155.20)) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). The logistic regression analysis revealed that MIP-3β predicted 28-day mortality in sepsis patients with a sensitivity of 57.3% and specificity of 67.9%, which had a high diagnostic value. This finding suggests that MIP-3β\u0026mdash;an inflammation-related indicator\u0026mdash;plays a pro-inflammatory role in the development of sepsis and is associated with its poor prognosis, which is consistent with our hypothesis.\u003c/p\u003e \u003cp\u003eThe APACHE II score, a disease severity score for critically ill patients, is strongly associated with mortality in critically ill patients [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Our study also found that the APACHE II score in the survival group (15 (11.5,18.5)) was significantly lower than in the 28-day mortality group (22 (17,27.75)) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Similarly, the APACHE II score predicted 28-day mortality in sepsis patients with a sensitivity of 55.6% and a specificity of 92.5%, consistent with those of previous studies [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe SOFA score was used to assess the degree of organ dysfunction in sepsis patients [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The higher the SOFA score, the more severe the patient's condition. We found that SOFA score was significantly lower in the survival group (5 (3,6)) than in the 28-day mortality group (8 (6,10)) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and that SOFA score was an independent risk factor for 28-day mortality in sepsis patients with a sensitivity of 57.3% and a specificity of 96.2%, which is consistent with those of previous studies (1, 5). Notably, the combined assessment of MIP-3β and SOFA score (AUC 0.860, sensitivity 63.7%, specificity 98.1%; \u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;4.552, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0001) had a better diagnostic value than MIP-3β alone, with higher sensitivity (63.7%) and specificity (98.1%). We concluded that MIP-3β was an independent risk factor for 28-day mortality in sepsis patients and that MIP-3β combined with SOFA score could better assess the prognosis of sepsis patients. Our results have some clinical value.\u003c/p\u003e \u003cp\u003eOur study has some limitations. First, it is a single-center study with patients limited to one region and small sample size, so a large-scale, multicenter study is required to validate the results. Second, we did not further explore the expression of the CCR7-MIP-3β pathway and its mechanism of action in sepsis patients, and we did not dynamically observe the relationship between changes in MIP-3β and patient prognosis, which requires further study. Finally, the initial serological index only reflects the inflammatory status and disease severity when the disease first occurs, and it helps clinicians to assess the patient's condition but cannot fully represent the patient's final prognosis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, MIP-3β, SOFA, and APACHE II scores could be used as independent risk factors affecting the prognosis of sepsis patients. MIP-3β combined with SOFA score has a higher diagnostic value than the aforementioned indices alone, and early and rapid assessment is crucial for treatment and assessment of prognosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of Beijing Chao-Yang Hospital of Capital Medical University, and it was conducted in accordance with the Declaration of Helsinki. Written informed consent was provided by all participants.\u003c/p\u003e\n\u003cp\u003eClinical Trial\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAvailability of data and material\u003c/p\u003e\n\u003cp\u003eData openly available in a public repository.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis research was funded by the Shijing Shan District Medical Key Support Specialty Building Foundation.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions\u003c/p\u003e\n\u003cp\u003eDr. BW and Dr. YGL were responsible for the initial initiation of the study and data review, YG was responsible for the statistics and analysis of the data, and the writing and revision of the article, and XBP, YZ, and XQZ were responsible for the data collection.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eFunding from the Shijing Shan District medical key support specialty construction foundation is gratefully acknowledged.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSinger M, Deutschman C S, Seymour C W, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard G R, Chiche J D, Coopersmith C M, Hotchkiss R S, Levy M M, Marshall J C, Martin G S, Opal S M, Rubenfeld G D, van der Poll T, Vincent J L, Angus D C. 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Dendritic Cells and CCR7 Expression: An Important Factor for Autoimmune Diseases, Chronic Inflammation, and Cancer. \u003cem\u003eInt J Mol Sci\u003c/em\u003e. 2021;22(15)\u003c/li\u003e\n\u003cli\u003eBelikan P, B\u0026uuml;hler U, Wolf C, Pramanik G K, Gollan R, Zipp F, Siffrin V. CCR7 on CD4(+) T Cells Plays a Crucial Role in the Induction of Experimental Autoimmune Encephalomyelitis. \u003cem\u003eJ Immunol\u003c/em\u003e. 2018;200(8):2554-2562.\u003c/li\u003e\n\u003cli\u003eBezemer R, Bartels S A, Bakker J, Ince C. Clinical review: Clinical imaging of the sublingual microcirculation in the critically ill--where do we stand? \u003cem\u003eCrit Care\u003c/em\u003e. 2012;16(3):224.\u003c/li\u003e\n\u003cli\u003eTiru B, DiNino E K, Orenstein A, Mailloux P T, Pesaturo A, Gupta A, McGee W T. The Economic and Humanistic Burden of Severe Sepsis. \u003cem\u003ePharmacoeconomics\u003c/em\u003e. 2015;33(9):925-37.\u003c/li\u003e\n\u003cli\u003eYan Y, Chen R, Wang X, Hu K, Huang L, Lu M, Hu Q. CCL19 and CCR7 Expression, Signaling Pathways, and Adjuvant Functions in Viral Infection and Prevention. \u003cem\u003eFront Cell Dev Biol\u003c/em\u003e. 2019;7:212.\u003c/li\u003e\n\u003cli\u003eYamashita N, Tashimo H, Matsuo Y, Ishida H, Yoshiura K, Sato K, Yamashita N, Kakiuchi T, Ohta K. Role of CCL21 and CCL19 in allergic inflammation in the ovalbumin-specific murine asthmatic model. \u003cem\u003eJ Allergy Clin Immunol\u003c/em\u003e. 2006;117(5):1040-6.\u003c/li\u003e\n\u003cli\u003eLiu X, Wang B, Li Y, Hu Y, Li X, Yu T, Ju Y, Sun T, Gao X, Wei Y. Powerful Anticolon Tumor Effect of Targeted Gene Immunotherapy Using Folate-Modified Nanoparticle Delivery of CCL19 To Activate the Immune System. \u003cem\u003eACS Cent Sci\u003c/em\u003e. 2019;5(2):277-289.\u003c/li\u003e\n\u003cli\u003eHe Y, Wang M, Li X, Yu T, Gao X. Targeted MIP-3\u0026beta; plasmid nanoparticles induce dendritic cell maturation and inhibit M2 macrophage polarisation to suppress cancer growth. \u003cem\u003eBiomaterials\u003c/em\u003e. 2020;249:120046.\u003c/li\u003e\n\u003cli\u003eLiu M, Duan Y J, Zhang Y, Yang J, Wei B, Wang J. Prognostic Value of Macrophage Inflammatory Protein-3alpha (MIP3-Alpha) and Severity Scores in Elderly Patients with Sepsis. \u003cem\u003eJ Inflamm Res\u003c/em\u003e. 2024;17:1503-1509.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Sepsis, Macrophage inflammatory protein 3β","lastPublishedDoi":"10.21203/rs.3.rs-6471946/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6471946/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThis study aims to explore the predictive value of macrophage inflammatory protein 3β (MIP-3β) for mortality risk in sepsis patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e177 sepsis patients visited the emergency medicine department of Beijing Chaoyang Hospital between October 2020 and April 2021. Within an hour of admission, serum levels of WBC (white blood cell), PLT (platelet), TBIL (total bilirubin), PCT (procalcitonin), CRP (C-reactive protein), and MIP-3β were measured, and patients were assessed with organ failure scores\u0026mdash;SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute physiology and chronic health evaluation) scores. Logistic regression was used to predict independent risk factors for 28-day mortality, and Receiver Operating Characteristic (ROC)curves were used to assess predictive value.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eMIP-3β, SOFA, and APACHE II scores were statistically different (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) between the survival and death groups. The logistic regression analysis revealed that the MIP-3β, SOFA, and APACHE II scores were independent risk factors for 28-day mortality (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in sepsis patients. The area under the ROC curve (AUC) for the MIP-3β area was 0.635 (sensitivity 0.573, specificity 0.679, critical value 93.43), which was slightly lower than that of the SOFA score 0.839 (sensitivity 0.573, specificity 0.962, critical value 7.5, \u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3.446, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0006) and APACHE II score 0.773 (sensitivity 0.556, specificity 0.925, critical value 21.5, \u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.304, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0212); however, the combined prediction using MIP-3β and SOFA scores (AUC area 0.86, sensitivity 0.637, specificity 0.981, \u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;4.552, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) had higher AUC area, sensitivity, and specificity than MIP-3β alone.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eMIP-3β, SOFA, and APACHE II scores were independent risk factors for 28-day mortality in sepsis patients. The predictive value of MIP-3β combined with SOFA score was higher than that of MIP-3β alone, which is crucial for reducing mortality in sepsis patients.\u003c/p\u003e","manuscriptTitle":"Predictive value of macrophage inflammatory protein 3β in the risk of death in sepsis patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-20 13:23:47","doi":"10.21203/rs.3.rs-6471946/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-03T16:26:40+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-31T14:06:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"208771972333860979130828566519107956521","date":"2025-05-31T13:06:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-28T07:05:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"128061244097710814428776750730798117705","date":"2025-05-23T07:15:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-15T17:46:03+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-23T21:01:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-23T08:36:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-23T08:35:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-04-17T12:48:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b830a307-d9d1-4107-b5b2-5a7d52d1a99d","owner":[],"postedDate":"May 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-02T16:13:40+00:00","versionOfRecord":{"articleIdentity":"rs-6471946","link":"https://doi.org/10.1186/s12879-026-12723-x","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2026-01-29 15:58:22","publishedOnDateReadable":"January 29th, 2026"},"versionCreatedAt":"2025-05-20 13:23:47","video":"","vorDoi":"10.1186/s12879-026-12723-x","vorDoiUrl":"https://doi.org/10.1186/s12879-026-12723-x","workflowStages":[]},"version":"v1","identity":"rs-6471946","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6471946","identity":"rs-6471946","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}