{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:37:10Z","timestamp":1792463830935,"version":"4.5.0"},"reference-count":256,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T00:00:00Z","timestamp":1740268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2504500"],"award-info":[{"award-number":["2022YFC2504500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172142"],"award-info":[{"award-number":["82172142"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The mortality rate of sepsis is approximately 22.5%, accounting for 19.7% of the total global mortality. Since Lewis Thomas proposed in 1972 that \u201cit is our response that makes the disease (sepsis)\u201d rather than the invading microorganisms, numerous drugs have been developed to suppress the \u201coverwhelming\u201d inflammatory response, but none of them has achieved the desired effect. Continued failure has led investigators to question whether deaths in septic patients are indeed caused by uncontrolled inflammation. Here, we review the history of clinical trials based on evolving concepts of sepsis pathogenesis over the past half century, summarize the factors that led to the failure of these historical drugs and the prerequisites for the success of future drugs, and propose the basic principles of preclinical research to ensure successful clinical translation. The strategy of targeting inflammatory factors are like attempting to eliminate invaders by suppressing the host's armed forces, which is logically untenable. Sepsis may not be that complex; rather, sepsis may be the result of a failure to fight microbes when the force of an invading pathogen overwhelms our defenses. Thus, strengthening the body's defense forces instead of suppressing them may be the correct strategy to overcome sepsis.<\/jats:p>","DOI":"10.1002\/mco2.70109","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T01:15:32Z","timestamp":1741742132000},"source":"Crossref","is-referenced-by-count":22,"title":["Sepsis: the evolution of molecular pathogenesis concepts and clinical management"],"prefix":"10.1002","volume":"6","author":[{"given":"Zhongxue","family":"Feng","sequence":"first","affiliation":[{"name":"Institute of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelian","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Kang","sequence":"additional","affiliation":[{"name":"Institute of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit of Gynecology and Obstetrics West China Second University Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-024-01377-0"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1415274"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-024-07586-2"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1431791"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25147770"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-024-05032-9"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000004224"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-023-04385-x"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197209142871109"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ccm.0001003868.37051.52"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201810128"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70136-6"},{"issue":"16","key":"e_1_2_12_15_1","first-page":"1699","volume":"355","author":"Russell JA","year":"2006","journal-title":"Management of sepsis"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccc.2008.12.003"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.101.6.1644"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000050454.01978.3B"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1586\/eri.12.50"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200319523"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-120-9-199405010-00009"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199707000-00001"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199703273361311"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1067\/msy.2000.104118"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-199903000-00001"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-200116020-00001"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-197808000-00014"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3552"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-024-04875-6"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-024-05069-w"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116453"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431x20198595"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1101\/SQB.1989.054.01.003"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1208623"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20236049"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2008.06.004"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra021333"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161209788453248"},{"issue":"6","key":"e_1_2_12_40_1","first-page":"4","article-title":"The effectiveness of hydrocortisone in the management of severe infections","volume":"183","author":"Bennett IL","year":"1963","journal-title":"Jama"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2013.09.015"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00025.2008"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199308000-00026"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199107253250411"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2011.558190"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181b07b78"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.2194"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199605000-00003"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.362.6411.142"},{"issue":"19","key":"e_1_2_12_50_1","first-page":"278","article-title":"TNF\u2010alpha blockers in inflammatory bowel diseases: practical consensus recommendations and a user's guide","volume":"139","author":"Pache I","year":"2009","journal-title":"Swiss Med Wkly"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209322"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12070-022-03203-0"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.4.4.637"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2018.09.003"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30012-3"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.5582\/irdr.2018.01050"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115806"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2015.03.015"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57158"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-019-4618-7"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2023.117352"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S384351"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2005615117"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00676-0"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.11330"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2295"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-021-06416-z"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203834"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199707000-00010"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100817"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2014.08.031"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X20959575"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1250483"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2024.115318"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-021-00303-x"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.07.014"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-313738"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13862"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21975"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-013-2099-8"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-014-0320-2"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01003"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00588-9"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-021-06506-y"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200103083441001"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050935"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.08020.x"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60411-5"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000000325"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD004388.pub5"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-197609000-00011"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198709103171101"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k3284"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-017-4683-6"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa071366"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1705835"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1705716"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002955"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2005.02834.x"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(80)92334-X"},{"key":"e_1_2_12_101_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-017-1764-4"},{"key":"e_1_2_12_102_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000215452.84291.C6"},{"key":"e_1_2_12_103_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000005337"},{"key":"e_1_2_12_104_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-036616"},{"key":"e_1_2_12_105_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-020-05507-4"},{"key":"e_1_2_12_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.107205"},{"key":"e_1_2_12_107_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00101-5"},{"key":"e_1_2_12_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.101898"},{"key":"e_1_2_12_109_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0357-7"},{"key":"e_1_2_12_110_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V67.2.257.257"},{"key":"e_1_2_12_111_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.5.1427.1427"},{"key":"e_1_2_12_112_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.7.2509.2509"},{"key":"e_1_2_12_113_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004310050884"},{"key":"e_1_2_12_114_1","doi-asserted-by":"publisher","DOI":"10.3109\/08880018.2011.644880"},{"key":"e_1_2_12_115_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.103.4.796"},{"key":"e_1_2_12_116_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.107.1.36"},{"key":"e_1_2_12_117_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60071-4"},{"key":"e_1_2_12_118_1","doi-asserted-by":"publisher","DOI":"10.1136\/fetalneonatal-2011-301470"},{"key":"e_1_2_12_119_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200903-0363OC"},{"key":"e_1_2_12_120_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.102.1.6"},{"key":"e_1_2_12_121_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.107.1.30"},{"issue":"2","key":"e_1_2_12_122_1","first-page":"64","article-title":"The effect of granulocyte colony stimulating factor administration on preterm infant with neutropenia and clinical sepsis: a randomized clinical trial","volume":"3","author":"Borjianyazdi L","year":"2013","journal-title":"Iran J Ped Hematol Oncol"},{"key":"e_1_2_12_123_1","doi-asserted-by":"publisher","DOI":"10.1093\/tropej\/fmr012"},{"key":"e_1_2_12_124_1","doi-asserted-by":"publisher","DOI":"10.4103\/2249-4847.105993"},{"key":"e_1_2_12_125_1","doi-asserted-by":"publisher","DOI":"10.1086\/519261"},{"key":"e_1_2_12_126_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2009005"},{"key":"e_1_2_12_127_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2020.5503"},{"key":"e_1_2_12_128_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2012.06716.x"},{"key":"e_1_2_12_129_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa630"},{"key":"e_1_2_12_130_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28083539"},{"key":"e_1_2_12_131_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-024-08985-y"},{"key":"e_1_2_12_132_1","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2016-0125"},{"key":"e_1_2_12_133_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.9.2951"},{"key":"e_1_2_12_134_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000001819"},{"key":"e_1_2_12_135_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2022.07.009"},{"issue":"5","key":"e_1_2_12_136_1","first-page":"698","article-title":"Thymosin alpha1. SciClone Pharmaceuticals","volume":"3","author":"Billich A","year":"2002","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_2_12_137_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.vh.2016.04.003"},{"key":"e_1_2_12_138_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2018.06.041"},{"key":"e_1_2_12_139_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc11932"},{"key":"e_1_2_12_140_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106873"},{"key":"e_1_2_12_141_1","doi-asserted-by":"publisher","DOI":"10.5005\/jp-journals-10071-24298"},{"key":"e_1_2_12_142_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26492"},{"key":"e_1_2_12_143_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.107143"},{"key":"e_1_2_12_144_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2021.04.043"},{"key":"e_1_2_12_145_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.664776"},{"key":"e_1_2_12_146_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.568789"},{"key":"e_1_2_12_147_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.107143"},{"key":"e_1_2_12_148_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.673693"},{"key":"e_1_2_12_149_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109584"},{"key":"e_1_2_12_150_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-023-01354-2"},{"key":"e_1_2_12_151_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2024-082583","article-title":"The efficacy and safety of thymosin \u03b11 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial","author":"Wu J","year":"2025","journal-title":"BMJ"},{"key":"e_1_2_12_152_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.15.1.749"},{"key":"e_1_2_12_153_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adl2016"},{"key":"e_1_2_12_154_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2022.10.007"},{"key":"e_1_2_12_155_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201204-0645OC"},{"key":"e_1_2_12_156_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-14-166"},{"key":"e_1_2_12_157_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-019-4526-x"},{"key":"e_1_2_12_158_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0479-x"},{"key":"e_1_2_12_159_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023019721"},{"key":"e_1_2_12_160_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2022.103120"},{"key":"e_1_2_12_161_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.98960"},{"key":"e_1_2_12_162_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-023-01109-w"},{"key":"e_1_2_12_163_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab256"},{"key":"e_1_2_12_164_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.16485"},{"key":"e_1_2_12_165_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809422106"},{"key":"e_1_2_12_166_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000001443"},{"key":"e_1_2_12_167_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-019-05704-z"},{"key":"e_1_2_12_168_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108192"},{"key":"e_1_2_12_169_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21174-8"},{"key":"e_1_2_12_170_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.018580"},{"key":"e_1_2_12_171_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.3.387"},{"key":"e_1_2_12_172_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2309995"},{"key":"e_1_2_12_173_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201704-0814OC"},{"key":"e_1_2_12_174_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-016-4358-8"},{"key":"e_1_2_12_175_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-1568"},{"key":"e_1_2_12_176_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.10.013"},{"key":"e_1_2_12_177_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2021.101127"},{"key":"e_1_2_12_178_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.15.1760"},{"key":"e_1_2_12_179_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3780115"},{"key":"e_1_2_12_180_1","doi-asserted-by":"publisher","DOI":"10.1161\/hq0701.092143"},{"key":"e_1_2_12_181_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02684000"},{"key":"e_1_2_12_182_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000034048.38910.91"},{"key":"e_1_2_12_183_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000163840.63685.0c"},{"key":"e_1_2_12_184_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201006-0955OC"},{"key":"e_1_2_12_185_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201209-1718OC"},{"key":"e_1_2_12_186_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1403285"},{"key":"e_1_2_12_187_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-009-1429-0"},{"key":"e_1_2_12_188_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.280031"},{"key":"e_1_2_12_189_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc11895"},{"key":"e_1_2_12_190_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1401520"},{"key":"e_1_2_12_191_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijccm.IJCCM_474_16"},{"key":"e_1_2_12_192_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000011578"},{"key":"e_1_2_12_193_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e318225742c"},{"key":"e_1_2_12_194_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2014-006251"},{"issue":"2","key":"e_1_2_12_195_1","first-page":"159","article-title":"Influence of simvastatin treatment on Toll\u2010like receptor 4 in monocytes of peripheral blood in patients with sepsis and severe sepsis]","volume":"28","author":"Shao H","year":"2016","journal-title":"Zhonghua wei zhong bing ji jiu yi xue"},{"key":"e_1_2_12_196_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2018.11.003"},{"key":"e_1_2_12_197_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.211"},{"key":"e_1_2_12_198_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-01034-9"},{"key":"e_1_2_12_199_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.05.004"},{"key":"e_1_2_12_200_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-024-10741-3"},{"key":"e_1_2_12_201_1","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szae003"},{"key":"e_1_2_12_202_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1905"},{"key":"e_1_2_12_203_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.111575"},{"key":"e_1_2_12_204_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2010.06.019"},{"key":"e_1_2_12_205_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9222379"},{"key":"e_1_2_12_206_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200208000-00008"},{"key":"e_1_2_12_207_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e318236edb8"},{"key":"e_1_2_12_208_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCE.0000000000000577"},{"key":"e_1_2_12_209_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(22)00297-1"},{"key":"e_1_2_12_210_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-028664"},{"key":"e_1_2_12_211_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2022.156006"},{"key":"e_1_2_12_212_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.10.012"},{"key":"e_1_2_12_213_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(07)70226-8"},{"key":"e_1_2_12_214_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2026131"},{"key":"e_1_2_12_215_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.910516"},{"key":"e_1_2_12_216_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00108"},{"key":"e_1_2_12_217_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2019.10.008"},{"key":"e_1_2_12_218_1","doi-asserted-by":"publisher","DOI":"10.1057\/s41599-019-0251-8"},{"key":"e_1_2_12_219_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2019.02.008"},{"key":"e_1_2_12_220_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201609-1848OC"},{"key":"e_1_2_12_221_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065777"},{"key":"e_1_2_12_222_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.12179"},{"key":"e_1_2_12_223_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38156-7"},{"key":"e_1_2_12_224_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2022.2145069"},{"key":"e_1_2_12_225_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107476"},{"key":"e_1_2_12_226_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1853"},{"key":"e_1_2_12_227_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(01)00093-7"},{"key":"e_1_2_12_228_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606774"},{"key":"e_1_2_12_229_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1503093"},{"key":"e_1_2_12_230_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1507643"},{"key":"e_1_2_12_231_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1602252"},{"key":"e_1_2_12_232_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1510665"},{"key":"e_1_2_12_233_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504627"},{"key":"e_1_2_12_234_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32517-X"},{"key":"e_1_2_12_235_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.12.033"},{"key":"e_1_2_12_236_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.165985.113"},{"key":"e_1_2_12_237_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-020-00212-5"},{"key":"e_1_2_12_238_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc12711"},{"key":"e_1_2_12_239_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2023.109249"},{"key":"e_1_2_12_240_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa191"},{"key":"e_1_2_12_241_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.214"},{"key":"e_1_2_12_242_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-009-1440-5"},{"key":"e_1_2_12_243_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V124.21.2773.2773"},{"key":"e_1_2_12_244_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00046308"},{"key":"e_1_2_12_245_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.04.005"},{"key":"e_1_2_12_246_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3000678"},{"key":"e_1_2_12_247_1","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2024.2415945"},{"key":"e_1_2_12_248_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adl6162"},{"key":"e_1_2_12_249_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16020149"},{"key":"e_1_2_12_250_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.04.005"},{"key":"e_1_2_12_251_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40635-018-0189-y"},{"key":"e_1_2_12_252_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-021-03862-5"},{"key":"e_1_2_12_253_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-020-02993-5"},{"key":"e_1_2_12_254_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40779-022-00422-y"},{"key":"e_1_2_12_255_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00816-9"},{"key":"e_1_2_12_256_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.o1354"},{"key":"e_1_2_12_257_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01713976"}],"container-title":["MedComm"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.70109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T01:07:19Z","timestamp":1743037639000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mco2.70109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,23]]},"references-count":256,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/mco2.70109"],"URL":"https:\/\/doi.org\/10.1002\/mco2.70109","archive":["Portico"],"relation":{},"ISSN":["2688-2663","2688-2663"],"issn-type":[{"value":"2688-2663","type":"print"},{"value":"2688-2663","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,23]]},"article-number":"e70109"}}