{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T15:04:33Z","timestamp":1789916673322,"version":"4.0.1"},"reference-count":40,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clin Appl Thromb Hemost"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Early detection of sepsis-induced coagulopathy (SIC) is of great clinical significance, as its closely correlates with disease progression in patients with sepsis. In the present study, we focused on mining the major coagulation factors that participate in the development and progression of SIC, and exploring the potential regulatory networks of these core factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Meta-analysis was performed to explore the association between SIC and mortality. eQTLs significantly associate with sepsis-related 28-day mortality and pQTLs were analyzed, to mine the significant sites or genes. Mendelian randomization (MR) was then applied to evaluate the role of coagulation factors in SIC and to explore their genetic regulation via DNA sequence analysis. Moreover, QGRS Mapper combined with ThT fluorescence assays were used to detect G-quadruplexes (G4s) structures within coagulation factor genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sepsis patients with SIC exhibited higher sequential organ failure assessment (SOFA) scores and increased 28-day mortality compared to those without SIC. MR and clinical analyses demonstrated that PAI-1 serves as a major contributor to higher sepsis incidence and 28-day mortality. Notably, the PAI-1 rs1799762 genetic polymorphism alters this biological effect. Mechanistically, G4-forming capacity negatively correlates with PAI-1 expression. In particular, the 5G\/5G genotype was associated with a higher G4-forming propensity in the PAI-1 gene, which in turn weakened gene transcription and lowered PAI-1 expression relative to other genotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>G4s formation in the PAI-1 gene modulates circulating PAI-1 levels and may serve as a novel prognostic marker and therapeutic target for sepsis severity assessment, particularly in patients with SIC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10760296261491812","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T09:06:44Z","timestamp":1789722404000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["G-Quadruplexes Formation in the PAI-1 Gene Modulates Sepsis-Induced Coagulopathy and Mortality Risk"],"prefix":"10.1177","volume":"32","author":[{"given":"Fang","family":"Sun","sequence":"first","affiliation":[{"name":"Nanjing First Hospital"},{"name":"Nanjing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nanjing First Hospital"},{"name":"Nanjing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenlin","family":"Nie","sequence":"additional","affiliation":[{"name":"Nanjing First Hospital"},{"name":"Nanjing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangshun","family":"He","sequence":"additional","affiliation":[{"name":"Nanjing First Hospital"},{"name":"Nanjing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Tang","sequence":"additional","affiliation":[{"name":"Nanjing First Hospital"},{"name":"Nanjing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2155-7839","authenticated-orcid":false,"given":"Tianyi","family":"Gao","sequence":"additional","affiliation":[{"name":"Nanjing First Hospital"},{"name":"Nanjing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"issue":"1","key":"e_1_3_7_2_2","article-title":"Relationship between coagulopathy score and survival in critically ill patients with liver cirrhosis and sepsis: a retrospective study","volume":"25","author":"Tao W","year":"2025","unstructured":"Tao W, Decai W, Ruizi S, et al. Relationship between coagulopathy score and survival in critically ill patients with liver cirrhosis and sepsis: a retrospective study. BMC Infect Dis. 2025;25(1).","journal-title":"BMC Infect Dis"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.10.029"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000004155"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-022-01093-7"},{"issue":"5","key":"e_1_3_7_6_2","article-title":"Analysis of the diagnostic value of coagulation markers and coagulation function indices on the occurrence of DIC in sepsis and its prognosis","volume":"52","author":"Xiaowei F","year":"2024","unstructured":"Xiaowei F, Wei F, Luyang X, Yichao Q. Analysis of the diagnostic value of coagulation markers and coagulation function indices on the occurrence of DIC in sepsis and its prognosis. Allergol Immunopathol (Madr). 2024;52(5).","journal-title":"Allergol Immunopathol (Madr)"},{"issue":"1","key":"e_1_3_7_7_2","article-title":"Association analysis of sepsis progression to sepsis-induced coagulopathy: a study based on the MIMIC-IV database","volume":"25","author":"Jian-Yue Y","year":"2025","unstructured":"Jian-Yue Y, Li-Li L, Su-Zhen F. Association analysis of sepsis progression to sepsis-induced coagulopathy: a study based on the MIMIC-IV database. BMC Infect Dis. 2025;25(1).","journal-title":"BMC Infect Dis"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S504184"},{"issue":"16","key":"e_1_3_7_9_2","article-title":"PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity","volume":"136","author":"Shaowei J","year":"2023","unstructured":"Shaowei J, Yang W, Liang C, et al. PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity. Chin Med J (Engl). 2023;136(16).","journal-title":"Chin Med J (Engl)"},{"issue":"4","key":"e_1_3_7_10_2","article-title":"G-Quadruplex Unwinding Molecular Mechanisms by Helicases and Their Applications","volume":"27","author":"Jiawen S","year":"2026","unstructured":"Jiawen S, Yangzhi W, Yihua H, Zhongzhou C. G-Quadruplex Unwinding Molecular Mechanisms by Helicases and Their Applications. Int J Mol Sci. 2026;27(4).","journal-title":"Int J Mol Sci"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"issue":"1","key":"e_1_3_7_12_2","article-title":"Sepsis-induced coagulopathy (SIC) in the management of sepsis","volume":"14","author":"Toshiaki I","year":"2024","unstructured":"Toshiaki I, Julie H, Jerrold HL. Sepsis-induced coagulopathy (SIC) in the management of sepsis. Ann Intensive Care. 2024;14(1).","journal-title":"Ann Intensive Care"},{"issue":"11","key":"e_1_3_7_13_2","article-title":"Drug targets for haemorrhoidal disease: proteome-wide Mendelian randomisation and colocalisation analyses","volume":"73","author":"Shifang L","year":"2024","unstructured":"Shifang L, Meijiao G. Drug targets for haemorrhoidal disease: proteome-wide Mendelian randomisation and colocalisation analyses. Gut. 2024;73(11).","journal-title":"Gut"},{"issue":"0","key":"e_1_3_7_14_2","article-title":"Genetic insights into the effect of trace elements on cardiovascular diseases: multi-omics Mendelian randomization combined with linkage disequilibrium score regression analysis","volume":"15","author":"Bohang C","year":"2024","unstructured":"Bohang C, Chuqiao W, Wenjie L. Genetic insights into the effect of trace elements on cardiovascular diseases: multi-omics Mendelian randomization combined with linkage disequilibrium score regression analysis. Front Immunol. 2024;15(0).","journal-title":"Front Immunol"},{"issue":"6","key":"e_1_3_7_15_2","article-title":"Comparison of a new criteria for sepsis-induced coagulopathy and International Society on Thrombosis and Haemostasis disseminated intravascular coagulation score in critically ill patients with sepsis 3.0: a retrospective study","volume":"29","author":"Renyu D","year":"2018","unstructured":"Renyu D, Zhong W, Yuan L, Baoyan L, Zhidan Z, Xiaochun M. Comparison of a new criteria for sepsis-induced coagulopathy and International Society on Thrombosis and Haemostasis disseminated intravascular coagulation score in critically ill patients with sepsis 3.0: a retrospective study. Blood Coagul Fibrinolysis. 2018;29(6).","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"4","key":"e_1_3_7_16_2","article-title":"Evaluation of Sepsis-Induced Coagulopathy in Critically Ill Pediatric Patients with Septic Shock","volume":"121","author":"Won Kyoung J","year":"2020","unstructured":"Won Kyoung J, Seong Jong P. Evaluation of Sepsis-Induced Coagulopathy in Critically Ill Pediatric Patients with Septic Shock. Thromb Haemost. 2020;121(4).","journal-title":"Thromb Haemost"},{"issue":"0","key":"e_1_3_7_17_2","article-title":"Low-molecular-weight heparin therapy reduces 28-day mortality in patients with sepsis-3 by improving inflammation and coagulopathy","volume":"10","author":"Ze Z","year":"2023","unstructured":"Ze Z, Taotao Y, Danfeng R, et al. Low-molecular-weight heparin therapy reduces 28-day mortality in patients with sepsis-3 by improving inflammation and coagulopathy. Front Med (Lausanne). 2023;10(0).","journal-title":"Front Med (Lausanne)"},{"issue":"1","key":"e_1_3_7_18_2","article-title":"Persistent high sepsis-induced coagulopathy and sequential organ failure assessment scores can predict the 28-day mortality of patients with sepsis: A prospective study","volume":"24","author":"Junyu L","year":"2024","unstructured":"Junyu L, Huizhen L, Na W, et al. Persistent high sepsis-induced coagulopathy and sequential organ failure assessment scores can predict the 28-day mortality of patients with sepsis: A prospective study. BMC Infect Dis. 2024;24(1).","journal-title":"BMC Infect Dis"},{"issue":"0","key":"e_1_3_7_19_2","article-title":"Prognostic Accuracy of the Different Scoring Systems for Assessing Coagulopathy in Sepsis: A Retrospective Study","volume":"29","author":"Yuwei C","year":"2023","unstructured":"Yuwei C, Weiwei C, Fuhua B, et al. Prognostic Accuracy of the Different Scoring Systems for Assessing Coagulopathy in Sepsis: A Retrospective Study. Clin Appl Thromb Hemost. 2023;29(0).","journal-title":"Clin Appl Thromb Hemost"},{"issue":"3","key":"e_1_3_7_20_2","article-title":"Validation of Two Revised, Simplified Criteria for Assessing Sepsis-Associated Disseminated Intravascular Coagulation in ICU Patients with Sepsis-3: A Retrospective Study","volume":"54","author":"Bin W","year":"2022","unstructured":"Bin W, Bo Z, Ying S, Jiaoyuan L, Xu Y, Ning T. Validation of Two Revised, Simplified Criteria for Assessing Sepsis-Associated Disseminated Intravascular Coagulation in ICU Patients with Sepsis-3: A Retrospective Study. Lab Med. 2022;54(3).","journal-title":"Lab Med"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.22514\/sv.2024.069"},{"key":"e_1_3_7_22_2","unstructured":"Mengyao Y Pengfei H Yuhan L et al. SAA1 as a Potential Early Diagnostic Biomarker for Sepsis Through Integrated Proteomics and Metabolomics. Immunology;2025(0)."},{"issue":"0","key":"e_1_3_7_23_2","article-title":"Clinical Study on the Assessment of Infection-Induced Disseminated Intravascular Coagulation (DIC) and Its Prognosis in Neonates by Tissue-Type Plasminogen Activator-Plasminogen Activator Inhibitor-1 Complex","author":"Xu W","year":"2025","unstructured":"Xu W, Jinlin W, Ge Z, Chuyang L, Lei Y. Clinical Study on the Assessment of Infection-Induced Disseminated Intravascular Coagulation (DIC) and Its Prognosis in Neonates by Tissue-Type Plasminogen Activator-Plasminogen Activator Inhibitor-1 Complex. Int J Lab Hematol. 2025(0).","journal-title":"Int J Lab Hematol"},{"issue":"0","key":"e_1_3_7_24_2","article-title":"Functional stability of plasminogen activator inhibitor-1","volume":"2014","author":"Songul YY","year":"2014","unstructured":"Songul YY, Pinar K, Ebru TO, Mehmet A. Functional stability of plasminogen activator inhibitor-1. ScientificWorldJournal. 2014;2014(0).","journal-title":"ScientificWorldJournal"},{"issue":"23","key":"e_1_3_7_25_2","article-title":"Precise detection of G-quadruplexs in living systems: principles, applications, and perspectives","volume":"16","author":"Huanhuan L","year":"2025","unstructured":"Huanhuan L, Zelong J, Shuxin G, Shi K, Chunyang L, Zhou N. Precise detection of G-quadruplexs in living systems: principles, applications, and perspectives. Chem Sci. 2025;16(23).","journal-title":"Chem Sci"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12020601"},{"issue":"0","key":"e_1_3_7_27_2","article-title":"Novel nomogram for the prediction of sepsis-induced coagulopathy in the PICU: A multicentre retrospective study","volume":"243","author":"Yan G","year":"2024","unstructured":"Yan G, Yanan F, Enyu G, et al. Novel nomogram for the prediction of sepsis-induced coagulopathy in the PICU: A multicentre retrospective study. Thromb Res. 2024;243(0).","journal-title":"Thromb Res"},{"key":"e_1_3_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2021.10.007"},{"issue":"8","key":"e_1_3_7_29_2","article-title":"Increased Level of Thrombomodulin is Associated with Endothelial Injury in Patients with Sepsis-Induced Disseminated Intravascular Coagulation","volume":"67","author":"Tao J","year":"2021","unstructured":"Tao J, Guo X, Li D, Li Y. Increased Level of Thrombomodulin is Associated with Endothelial Injury in Patients with Sepsis-Induced Disseminated Intravascular Coagulation. Clinical laboratory. 2021;67(8).","journal-title":"Clinical laboratory"},{"issue":"5","key":"e_1_3_7_30_2","article-title":"Persistent and Late-Onset Disseminated Intravascular Coagulation Are Closely Related to Poor Prognosis in Patients with Sepsis","volume":"124","author":"Tadashi M","year":"2023","unstructured":"Tadashi M, Kazuma Y, Toshiaki I, Koichiro H, Junichi S. Persistent and Late-Onset Disseminated Intravascular Coagulation Are Closely Related to Poor Prognosis in Patients with Sepsis. Thromb Haemost. 2023;124(5).","journal-title":"Thromb Haemost"},{"issue":"0","key":"e_1_3_7_31_2","article-title":"Potential Biomarkers for Early Diagnosis, Evaluation, and Prognosis of Sepsis-Induced Coagulopathy","volume":"29","author":"Yuting L","year":"2023","unstructured":"Yuting L, Hongxiang L, Youquan W, Jianxing G, Dong Z. Potential Biomarkers for Early Diagnosis, Evaluation, and Prognosis of Sepsis-Induced Coagulopathy. Clin Appl Thromb Hemost. 2023;29(0).","journal-title":"Clin Appl Thromb Hemost"},{"issue":"3","key":"e_1_3_7_32_2","article-title":"Past, Present, and Future Perspectives of Plasminogen Activator Inhibitor 1 (PAI-1)","volume":"49","author":"Gael BM","year":"2022","unstructured":"Gael BM, Nicola JM. Past, Present, and Future Perspectives of Plasminogen Activator Inhibitor 1 (PAI-1). Semin Thromb Hemost. 2022;49(3).","journal-title":"Semin Thromb Hemost"},{"issue":"5","key":"e_1_3_7_33_2","article-title":"A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: To Target or Not to Target?","volume":"22","author":"Machteld S","year":"2021","unstructured":"Machteld S, Paul JD. A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: To Target or Not to Target? Int J Mol Sci. 2021;22(5).","journal-title":"Int J Mol Sci"},{"key":"e_1_3_7_34_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm-22-5221"},{"issue":"0","key":"e_1_3_7_35_2","article-title":"PAI-1 and t-PA\/PAI-1 complex potential markers of fibrinolytic bleeding after cardiac surgery employing cardiopulmonary bypass","volume":"12","author":"Agnese O","year":"2012","unstructured":"Agnese O, Eva S, Inta J, Angelika K, Lars JB, Indulis V. PAI-1 and t-PA\/PAI-1 complex potential markers of fibrinolytic bleeding after cardiac surgery employing cardiopulmonary bypass. BMC Anesthesiol. 2012;12(0).","journal-title":"BMC Anesthesiol"},{"key":"e_1_3_7_36_2","doi-asserted-by":"publisher","DOI":"10.21037\/apm-21-2222"},{"key":"e_1_3_7_37_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9364037"},{"key":"e_1_3_7_38_2","first-page":"107602962211029","article-title":"Clinical Efficacy of Soluble Thrombomodulin, Tissue Plasminogen Activator Inhibitor complex, Thrombin-Antithrombin complex,\u03b12-Plasmininhibitor-Plasmin complex in Pediatric Sepsis","volume":"28","author":"Li J","year":"2022","unstructured":"Li J, Zhou J, Ren H, et al. Clinical Efficacy of Soluble Thrombomodulin, Tissue Plasminogen Activator Inhibitor complex, Thrombin-Antithrombin complex,\u03b12-Plasmininhibitor-Plasmin complex in Pediatric Sepsis. Clinical and applied thrombosis\/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis\/Hemostasis. 2022;28:10760296221102929.","journal-title":"Clinical and applied thrombosis\/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis\/Hemostasis"},{"issue":"0","key":"e_1_3_7_39_2","article-title":"Low ionic strength enhances the fluorescence of Thioflavin T bound to parallel G-quadruplexes","volume":"349","author":"Tao L","year":"2025","unstructured":"Tao L, Zhihao L, Bangshun H, et al. Low ionic strength enhances the fluorescence of Thioflavin T bound to parallel G-quadruplexes. Spectrochim Acta A Mol Biomol Spectrosc. 2025;349(0).","journal-title":"Spectrochim Acta A Mol Biomol Spectrosc"},{"issue":"17","key":"e_1_3_7_40_2","article-title":"CRISPR-Cas9 targeting of G-Quadruplex DNA in ADH1 promoter highlights its role in transcriptome and metabolome regulation","volume":"53","author":"Ikenna O","year":"2025","unstructured":"Ikenna O, Pallabi S, Nasim S. CRISPR-Cas9 targeting of G-Quadruplex DNA in ADH1 promoter highlights its role in transcriptome and metabolome regulation. Nucleic Acids Res. 2025;53(17).","journal-title":"Nucleic Acids Res"},{"issue":"0","key":"e_1_3_7_41_2","article-title":"Discovery of Y502-2304, a potent c-Myc G-quadruplex stabilizer for the treatment of multiple myeloma","volume":"301","author":"Jian G","year":"2025","unstructured":"Jian G, Xinxin Q, Mengting L, Pingting J, Guanghui C, Jiacheng Y. Discovery of Y502-2304, a potent c-Myc G-quadruplex stabilizer for the treatment of multiple myeloma. Eur J Med Chem. 2025;301(0).","journal-title":"Eur J Med Chem"}],"container-title":["Clinical and Applied Thrombosis\/Hemostasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10760296261491812","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/10760296261491812","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10760296261491812","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:48:00Z","timestamp":1789915680000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/10760296261491812"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":40,"alternative-id":["10.1177\/10760296261491812"],"URL":"https:\/\/doi.org\/10.1177\/10760296261491812","relation":{},"ISSN":["1076-0296","1938-2723"],"issn-type":[{"value":"1076-0296","type":"print"},{"value":"1938-2723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"article-number":"10760296261491812"}}