{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:38:18Z","timestamp":1790444298565,"version":"4.1.0"},"reference-count":70,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,3,24]]},"abstract":"\n BACKGROUND:<\/jats:title>\n \n Acute myocardial infarction (AMI) caused by thrombosis is a major cause of mortality. A polymorphism in\n Aldh2<\/jats:italic>\n gene (rs671) is found in approximately 30% to 50% of East Asians, and it is a risk factor for AMI. This mutation impairs aldehyde dehydrogenase 2 (ALDH2) function, but the effect of ALDH2 on platelet activation and thrombosis is unknown.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n \n Platelets were isolated from platelet-specific\n Aldh2<\/jats:italic>\n knockout (\n Aldh2<\/jats:italic>\n -\/-<\/jats:sup>\n ) and ALDH2\n E506K<\/jats:sup>\n knock-in mice (which corresponds to human\n Aldh2<\/jats:italic>\n rs671 gene mutation), as well as from healthy human donors with the\n Aldh2<\/jats:italic>\n rs671. Arterial thrombosis was measured in a FeCl\n 3<\/jats:sub>\n -induced thrombosis mouse model. The efficacy of Alda-1, an ALDH2 activator, in mitigating thrombogenesis was measured in ALDH2\n E506K<\/jats:sup>\n mice. Using a murine model of myocardial infarction (MI) model, we analyzed the effects of platelet\n Aldh2<\/jats:italic>\n on micro-thrombosis and infarct expansion post-MI. In addition, we enrolled 118 patients of different\n Aldh2<\/jats:italic>\n rs671 genotypes (GG, GA, and AA) diagnosed with ST elevation myocardial infarction (STEMI) to analyze the association between rs671 genotype and platelet activation and thrombosis.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n Platelets from\n Aldh<\/jats:italic>\n 2\n -\/-<\/jats:sup>\n and ALDH2\n E506K<\/jats:sup>\n mice showed enhanced agonist induced aggregation, ATP release, integrin \u03b1IIb\u03b23 activation, P-selectin release, spreading, and clot retraction. Human platelets with the\n Aldh2<\/jats:italic>\n rs671 variant also exhibited increased activation. Mutation of\n Aldh2<\/jats:italic>\n or platelet-specific knockout of\n Aldh2<\/jats:italic>\n exacerbated thrombus formation in a mouse model of thrombosis. The ALDH2 activator, Alda-1, reduced thrombosis in ALDH2\n E506K<\/jats:sup>\n mice. We explored pathways mediating the effect of\n Aldh2<\/jats:italic>\n on platelet activation. We found that platelets lacking\n Aldh2<\/jats:italic>\n produced more reactive oxygen species (ROS) and less nitric oxide (NO) than wild-type platelets. Furthermore, platelets lacking\n Aldh2<\/jats:italic>\n are also more susceptible to activation by aldehydes. Additionally, platelets from mice lacking\n Aldh2<\/jats:italic>\n had increased elevated mitophagy and hyperactivity. ACAD10 mediated some of the effects of ALDH2 on mitophagy. Mice lacking\n Aldh2<\/jats:italic>\n had increased micro-thrombosis and myocardial infarct expansion. Finally, elevated platelet activation and thrombus markers were also observed in plasma from patients with STEMI patients who had the rs671 variant.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n \n The\n Aldh2<\/jats:italic>\n rs671 variant, which impairs ALDH2 function, increases platelet activation and thrombus formation in vivo through aldehyde accumulation and ROS buildup. Abnormal ACAD10 homeostasis might also contribute to this hyperactivity via enhancing platelet mitophagy. Our findings suggest the potential of ALDH2 as a novel antiplatelet target. Future studies are needed to explore the effects of more aggressive antiplatelet therapy for patients at risk of MI who carry the\n Aldh2<\/jats:italic>\n rs671 mutation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/circulationaha.125.074318","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T10:01:17Z","timestamp":1770372077000},"page":"902-921","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["The Aldehyde Dehydrogenase 2 rs671 Variant Enhances Platelet Activation and Arterial Thrombosis"],"prefix":"10.1161","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3321-4003","authenticated-orcid":true,"given":"Song","family":"Sun","sequence":"first","affiliation":[{"name":"Departments of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Department of Clinical Laboratory (S.S., Y.Z.), Qilu Hospital of Shandong University, Jinan, Shandong, China."},{"name":"Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China\u2019s Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., Y.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China\u2019s Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1839-4699","authenticated-orcid":true,"given":"Hongwei","family":"Yue","sequence":"additional","affiliation":[{"name":"Departments of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China\u2019s Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6392-7768","authenticated-orcid":true,"given":"Cuiqin","family":"Fan","sequence":"additional","affiliation":[{"name":"Departments of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China\u2019s Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0440-1798","authenticated-orcid":true,"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory (S.S., Y.Z.), Qilu Hospital of Shandong University, Jinan, Shandong, China."},{"name":"Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., Y.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyun","family":"Guo","sequence":"additional","affiliation":[{"name":"Departments of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China\u2019s Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingming","family":"Li","sequence":"additional","affiliation":[{"name":"Departments of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China\u2019s Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7933-4800","authenticated-orcid":true,"given":"Sumei","family":"Cui","sequence":"additional","affiliation":[{"name":"Departments of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China\u2019s Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5135-9839","authenticated-orcid":true,"given":"Kehui","family":"Yang","sequence":"additional","affiliation":[{"name":"Departments of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China\u2019s Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8874-5354","authenticated-orcid":true,"given":"Xiangkai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Departments of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China\u2019s Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3672-6543","authenticated-orcid":true,"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology (C.Z.), Qilu Hospital of Shandong University, Jinan, Shandong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Pan","sequence":"additional","affiliation":[{"name":"Departments of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China\u2019s Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. Zhao, C.P., F.X., Y.C.)."},{"name":"NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Qilu Hospital of Shandong University, Jinan, Shandong, China (S.S., X. Zhang, H.Y., C.F., Y.G., X.L., S.C., K.Y., X. 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