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已发表论文
内皮损伤诱导的血栓调节蛋白脱落作为预测脓毒症不良预后的生物标志物
Authors Meng X , Chen X, Liu J, Yuan X, Guo D
Received 23 April 2025
Accepted for publication 30 August 2025
Published 20 September 2025 Volume 2025:18 Pages 13055—13072
DOI https://doi.org/10.2147/JIR.S535854
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Anh Ngo
Xinmeichen Meng,1 Xuemei Chen,1 Jiwen Liu,2 Xiaoyan Yuan,2 Dongfeng Guo1,2
1Postgraduate Training Base at Shanghai Gongli Hospital, Ningxia Medical University, Shanghai, 200135, People’s Republic of China; 2Department of Emergency, Shanghai Pudong New Area Gongli Hospital, Shanghai, 200135, People’s Republic of China
Correspondence: Dongfeng Guo, Department of Emergency, Shanghai Pudong New Area Gongli Hospital, Shanghai, 200135, People’s Republic of China, Email guodf334@163.com Xiaoyan Yuan, Department of Emergency, Shanghai Pudong New Area Gongli Hospital, Shanghai, 200135, People’s Republic of China, Email yxy_828@126.com
Purpose: Sepsis-associated endothelial injury drives thrombomodulin (TM) shedding and severe coagulopathy. We hypothesized that plasma TM levels predict sepsis severity and prognosis. This study investigated the prognostic association of plasma TM as a sepsis biomarker and validated it in a murine model.
Patients and Methods: In a prospective cohort (Gongli Hospital, Shanghai; July 2024–January 2025), 68 sepsis patients (45 survivors, 23 nonsurvivors) and 50 controls underwent plasma TM, CD64 index, procalcitonin (PCT), C-reactive protein (CRP), Sequential Organ Failure Assessment (SOFA) score, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score assessments. Survival analysis, multivariable regression, and receiver operating characteristic (ROC) curve modeling were performed. Mechanistic validation utilized Cecal Ligation and Puncture (CLP) mice with plasma/aortic TM quantification.
Results: Elevated plasma TM and CD64 index correlated with poor prognosis (p< 0.05). The combined TM/CD64 Index ROC model achieved superior predictive performance (AUC=0.9671, p< 0.05) compared with TM alone (AUC=0.9333) or CD64 alone (AUC=0.8628). The multiple linear regression model indicated a positive correlation between TM levels in sepsis patients and SOFA and APACHE II scores. In vivo, experiments indicate plasma TM increased while aortic endothelial TM expression decreased.
Conclusion: This study demonstrates that the combined plasma TM and CD64 index assessment enhances early prediction of adverse sepsis outcomes, with strong correlations to clinical severity scores. The paradoxical TM dynamics (plasma elevation vs endothelial depletion) suggest endothelial injury as a key mechanism. Future research should focus on multicenter validation, and mechanistic studies are warranted to optimize clinical translation.
Keywords: sepsis, thrombomodulin, TM, CD64 index, biomarker
1Postgraduate Training Base at Shanghai Gongli Hospital, Ningxia Medical University, Shanghai, 200135, People’s Republic of China; 2Department of Emergency, Shanghai Pudong New Area Gongli Hospital, Shanghai, 200135, People’s Republic of China
Correspondence: Dongfeng Guo, Department of Emergency, Shanghai Pudong New Area Gongli Hospital, Shanghai, 200135, People’s Republic of China, Email guodf334@163.com Xiaoyan Yuan, Department of Emergency, Shanghai Pudong New Area Gongli Hospital, Shanghai, 200135, People’s Republic of China, Email yxy_828@126.com
Purpose: Sepsis-associated endothelial injury drives thrombomodulin (TM) shedding and severe coagulopathy. We hypothesized that plasma TM levels predict sepsis severity and prognosis. This study investigated the prognostic association of plasma TM as a sepsis biomarker and validated it in a murine model.
Patients and Methods: In a prospective cohort (Gongli Hospital, Shanghai; July 2024–January 2025), 68 sepsis patients (45 survivors, 23 nonsurvivors) and 50 controls underwent plasma TM, CD64 index, procalcitonin (PCT), C-reactive protein (CRP), Sequential Organ Failure Assessment (SOFA) score, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score assessments. Survival analysis, multivariable regression, and receiver operating characteristic (ROC) curve modeling were performed. Mechanistic validation utilized Cecal Ligation and Puncture (CLP) mice with plasma/aortic TM quantification.
Results: Elevated plasma TM and CD64 index correlated with poor prognosis (p< 0.05). The combined TM/CD64 Index ROC model achieved superior predictive performance (AUC=0.9671, p< 0.05) compared with TM alone (AUC=0.9333) or CD64 alone (AUC=0.8628). The multiple linear regression model indicated a positive correlation between TM levels in sepsis patients and SOFA and APACHE II scores. In vivo, experiments indicate plasma TM increased while aortic endothelial TM expression decreased.
Conclusion: This study demonstrates that the combined plasma TM and CD64 index assessment enhances early prediction of adverse sepsis outcomes, with strong correlations to clinical severity scores. The paradoxical TM dynamics (plasma elevation vs endothelial depletion) suggest endothelial injury as a key mechanism. Future research should focus on multicenter validation, and mechanistic studies are warranted to optimize clinical translation.
Keywords: sepsis, thrombomodulin, TM, CD64 index, biomarker