{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T07:14:49Z","timestamp":1783235689000,"version":"3.54.6"},"reference-count":37,"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>Aim<\/jats:title>\n                    <jats:p>To explore the causal effects of protein C and protein S on ischemic stroke (IS) risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Employing a two-sample bidirectional Mendelian randomization (MR) framework, we investigated the causal association between protein C, protein S and anti-thrombin with ischemic stroke and further performed the mediating analysis based on several risk factors for IS. Then, systematic review and meta-analysis of relevant literature was conducted to validate the association between protein C and ischemic stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genetic data from a genome-wide association study involving 440,328 individuals, including 34,217 IS patients and 406,111 controls, revealed odds ratios for IS per standard deviation (SD) increases of 0.918 (95% CI: 0.884-0.954; P=1.027e-05) for protein C, 0.997 (95% CI: 0.986-1.035; P=1.027e-05) for protein S, and 0.990 (95% CI: 0.895-1.094; P=8.383e-01) for anti-thrombin (three anticoagulation factor). Mediation analysis indicated that body mass index (BMI) partially mediated this effect, with a mediated proportion of 5.88% (95% CI, 2.236% to 7.232%). In the meta-analysis of 2107 IS patients and 12209 healthy controls, we found that patients with decreased protein C had a significantly higher risk of IS compared with controls (risk ratio: 5.47; 95% CI 3.33, 9.00).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest a potential relationship between protein C and ischemic stroke and BMI mediates this causal relationship, which might offer prevention strategies targeting protein C and ischemic stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10760296261465494","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:43:13Z","timestamp":1782992593000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Protein C, but Not Protein S or Antithrombin With Ischemic Stroke: Bidirectional Two-Sample Mendelian Randomization and Meta-Analysis"],"prefix":"10.1177","volume":"32","author":[{"given":"Liang","family":"Shu","sequence":"first","affiliation":[{"name":"Shanghai Ninth People\u2019s Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"He","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Yu","sequence":"additional","affiliation":[{"name":"Shanghai Pudong Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Tongren Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liguo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Shibei Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-4923","authenticated-orcid":false,"given":"Ping","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shanghai Pudong New area People's Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000659"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/17474930221123175"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.3109\/02699052.2012.666437"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03577.x"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc0956"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.12.038"},{"key":"e_1_3_7_8_2","first-page":"225","article-title":"Prevalence of activated protein C resistance among women with recurrent miscarriage","volume":"40","author":"Abraitis V","year":"2004","unstructured":"Abraitis V, Simoli\u016bniene R, Mongirdiene A, Makari S. 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