首页 期刊 论文 学科刊群 资讯 加盟 关于
EN
image
Article(id=1320440981187576818, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1320440935603880850, articleNumber=null, orderNo=null, doi=10.16016/j.2097-0927.202512135, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1766505600000, receivedDateStr=2025-12-24, revisedDate=1769356800000, revisedDateStr=2026-01-26, acceptedDate=null, acceptedDateStr=null, onlineDate=1792747262522, onlineDateStr=2026-10-23, pubDate=1773504000000, pubDateStr=2026-03-15, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1792747262522, onlineIssueDateStr=2026-10-23, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1792747262522, creator=13701087609, updateTime=1792747262522, updator=13701087609, issue=Issue{id=1320440935603880850, tenantId=1146029695717560320, journalId=1319373162502258839, year='2026', volume='48', issue='5', pageStart='523', pageEnd='662', issueExtLink='null', onlineDate='null', pubDate='1773504000000', pubDateStr='2026-03-15', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1792747251654, creator='13701087609', updateTime=1792749737175, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1320451360810713528, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1320440935603880850, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1320451360810713529, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1320440935603880850, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=543, endPage=550, ext={EN=ArticleExt(id=1320440983678993396, articleId=1320440981187576818, tenantId=1146029695717560320, journalId=1319373162502258839, language=EN, title=Carnitine and kynurenine drive CD8+T cell senescence: a bidirectional Mendelian randomization study elucidates novel mechanisms of uremia-associated immune dysregulation, columnId=1320434418116837551, journalTitle=Journal of Army Medical University, columnName=Basic Medicine, runingTitle=null, highlight=null, articleAbstract=
Objective

To systematically investigate the bidirectional causal relationship between 10 uremia-related toxins and metabolites and CD8+ T cell senescence phenotypes using Mendelian randomization (MR).

Methods

A bidirectional MR analysis was performed using genome-wide association studies (GWAS) data to extract single nucleotide polymorphisms closely associated with 10 uremia-related toxins and metabolites and CD8+ T cell senescence phenotypes as instrumental variables. The primary analytical method was inverse variance weighting (IVW), supplemented by MR-Egger, weighted median, simple mode, and weighted mode. The robustness and potential pleiotropy of the results were verified by sensitivity analyses including Cochran’s Q test, MR-Egger intercept test, MR-PRESSO and leave-one-out analysis.

Results

MR analysis showed that carnitine level was positively associated with the proportion of terminally differentiated CD8+ T cells (IVW: β=1.71, 95%CI: 0.59 to 2.83, P=0.003), the proportion of CD45RA+CD28⁻CD8+T cells (IVW: β=2.23, 95%CI: 0.65 to 3.80, P=0.006), and the proportion of CD28⁻CD8+T cells (IVW: β=1.13, 95%CI: 0.11 to 2.15, P=0.030). Kynurenine level also showed a significant positive association with the proportion of terminally differentiated CD8+T cells (IVW: β=1.69, 95%CI: 0.57 to 2.82, P=0.000 3), while IL-6 level presented a positive correlation with the proportion of CD28⁻CD8+T cells (IVW: β=0.28, 95%CI: 0.03 to 0.53, P=0.026) and the proportion of CD45RA+CD28⁻CD8+T cells (IVW: β=0.41, 95%CI: 0.02 to 0.79, P=0.04). N2,N2-dimethylguanosine level was positively correlated with CD45RA+CD28⁻CD8+T cell absolute count (IVW: β=2.53, 95%CI: 0.51 to 4.55, P=0.014). Reverse MR analysis revealed an increase in the absolute count of CD45RA+CD28⁻CD8+T cells was causally associated with a reduction in carnitine levels (IVW: β=-0.000 03, 95%CI: -0.000 062 to 0.000 004, P=0.024). All sensitivity analyses supported the robustness of the main findings.

Conclusion

There are bidirectional causal associations between uremia-related toxins and metabolites and CD8+T cell senescence, providing novel causal insights and potential intervention targets for immune dysfunction in uremic patients.

, authors=Yuewen SUN, Qigang LAN, Jinghong ZHAO, authorsList=Yuewen SUN, Qigang LAN, Jinghong ZHAO, authorCompany=null, correspAuthors=Jinghong ZHAO, authorNote=null, correspAuthorsNote=null, copyrightStatement=© 2026 Journal of Army Medical University, copyrightOwner=Editorial Office of Journal of Army Medical University, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1320440992524780542, articleId=1320440981187576818, tenantId=1146029695717560320, journalId=1319373162502258839, language=CN, title=肉碱与犬尿氨酸驱动CD8+T细胞衰老：一项双向孟德尔随机化研究阐释尿毒症免疫紊乱新机制, columnId=1320434418343329969, journalTitle=陆军军医大学学报, columnName=论著·基础医学, runingTitle=null, highlight=null, articleAbstract=
目的

通过应用孟德尔随机化（Mendelian randomization， MR）方法，系统探究10种尿毒症相关毒素及代谢物与CD8+T细胞衰老表型之间的双向因果关系。

方法

采用双向MR方法，基于全基因组关联研究（genome-wide association studies， GWAS）数据库汇总数据，提取与10种尿毒症相关毒素及代谢物以及4种CD8+T细胞衰老表型显著相关的单核苷酸多态性位点作为工具变量。逆方差加权法（inverse variance weighting， IVW）作为主要分析方法，同时采用MR-Egger、加权中位数法、简单众数法及加权众数法进行补充分析。通过Cochran’s Q检验、MR-Egger截距检验、MR-PRESSO及留一法等敏感性分析验证结果的稳健性与潜在多效性。

结果

MR分析显示，肉碱水平与终末分化CD8+T细胞比例（IVW：β=1.71，95%CI：0.59~2.83，P=0.003）、CD45RA+CD28-CD8+T细胞比例（IVW：β=2.23，95%CI：0.65~3.80，P=0.006）、CD28-CD8+T细胞比例（IVW：β=1.13，95%CI：0.11~2.15，P=0.030）正相关。犬尿氨酸水平与终末分化CD8+T细胞比例正相关（IVW：β=1.69，95%CI：0.57~2.82，P=0.000 3），而白介素-6水平与CD28-CD8+T细胞比例（IVW：β=0.28，95%CI：0.03~0.53，P=0.026）和CD45RA+CD28-CD8+T细胞比例（IVW：β=0.41，95%CI：0.02~0.79，P=0.04）正相关。N2，N2-二甲基鸟苷水平与CD45RA+CD28-CD8+T细胞绝对计数（IVW：β=2.53，95%CI：0.51~4.55，P=0.014）正相关。反向MR分析显示，CD45RA+CD28-CD8+T细胞绝对计数增加可降低肉碱水平（IVW：β=-0.00 003，95%CI：-0.000 062~-0.000 004，P=0.024）。所有敏感性分析均支持主要结果的稳健性。

结论

部分尿毒症相关毒素及代谢物与CD8+T细胞衰老之间存在双向因果关联，为尿毒症患者免疫功能紊乱的机制提供了新的因果证据与潜在干预靶点。

, authors=孙跃文, 蓝琦港, 赵景宏, authorsList=孙跃文, 蓝琦港, 赵景宏, authorCompany=null, correspAuthors=赵景宏, authorNote=null, correspAuthorsNote=
赵景宏，E-mail：
ZHAO Jinghong， E-mail：
, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=/jb3L4dqYUtbQvlQixWdgQ==, magXml=y+ayEU11aLCY9pL1ybLE8Q==, pdfUrl=null, pdf=6Z3eZUqNmq558a7R9Db16g==, pdfFileSize=938302, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=uKqAF+U9/xVureeg2HyMJg==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=WZ0NGBU74Kx0VEmh2ekO9Q==, mapNumber=null, fund=null)}, authors=[Author(id=1320440995859251202, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1320440996308041732, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, authorId=1320440995859251202, language=EN, stringName=Yuewen SUN, firstName=Yuewen, middleName=null, lastName=SUN, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Disease， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University（Third Military Medical University）， Chongqing， China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1320440996748443653, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, authorId=1320440995859251202, language=CN, stringName=孙跃文, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1320440995460793343, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, xref=1, ext=[AuthorCompanyExt(id=1320440995481764864, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, companyId=1320440995460793343, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Disease， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University（Third Military Medical University）， Chongqing， China), AuthorCompanyExt(id=1320440995494346752, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, companyId=1320440995460793343, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆)])]), Author(id=1320440997096570887, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1320440997255954441, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, authorId=1320440997096570887, language=EN, stringName=Qigang LAN, firstName=Qigang, middleName=null, lastName=LAN, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Disease， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University（Third Military Medical University）， Chongqing， China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1320440997591498762, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, authorId=1320440997096570887, language=CN, stringName=蓝琦港, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1320440995460793343, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, xref=1, ext=[AuthorCompanyExt(id=1320440995481764864, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, companyId=1320440995460793343, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Disease， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University（Third Military Medical University）， Chongqing， China), AuthorCompanyExt(id=1320440995494346752, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, companyId=1320440995460793343, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆)])]), Author(id=1320440998015123468, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=zhaojh@tmmu.edu.cn, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1320440998799458318, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, authorId=1320440998015123468, language=EN, stringName=Jinghong ZHAO, firstName=Jinghong, middleName=null, lastName=ZHAO, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Disease， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University（Third Military Medical University）， Chongqing， China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1320441000489762831, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, authorId=1320440998015123468, language=CN, stringName=赵景宏, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1320440995460793343, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, xref=1, ext=[AuthorCompanyExt(id=1320440995481764864, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, companyId=1320440995460793343, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Disease， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University（Third Military Medical University）， Chongqing， China), AuthorCompanyExt(id=1320440995494346752, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, companyId=1320440995460793343, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆)])])], keywords=[Keyword(id=1320441001362178064, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=EN, orderNo=1, keyword=uremia-related toxins and metabolites), Keyword(id=1320441001773219857, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=EN, orderNo=2, keyword=CD8+ T cell senescence), Keyword(id=1320441002641440786, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=EN, orderNo=3, keyword=Mendelian randomization analysis), Keyword(id=1320441003828428819, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=CN, orderNo=1, keyword=尿毒症相关毒素及代谢物), Keyword(id=1320441005128663060, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=CN, orderNo=2, keyword=CD8+T细胞衰老), Keyword(id=1320441005908803605, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=CN, orderNo=3, keyword=孟德尔随机化研究)], refs=[Reference(id=1320441019393490979, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1016/S0140-6736（18）31694-5, pmid=null, pmcid=null, year=2018, volume=392, issue=10159, pageStart=2052, pageEnd=2090, url=null, language=null, rfNumber=1, rfOrder=0, authorNames=FOREMAN K J, MARQUEZ N, DOLGERT A, journalName=Lancet, refType=null, unstructuredReference=FOREMAN K J， MARQUEZ N， DOLGERT A， et al. Forecasting life expectancy， years of life lost， and all-cause and cause-specific mortality for 250 causes of death： reference and alternative scenarios for 2016-40 for 195 countries and territories［J］. Lancet， 2018， 392（10159）： 2052-2090., articleTitle=Forecasting life expectancy， years of life lost， and all-cause and cause-specific mortality for 250 causes of death： reference and alternative scenarios for 2016-40 for 195 countries and territories, refAbstract=null), Reference(id=1320441020186214436, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1016/j.kisu.2021.11.003, pmid=null, pmcid=null, year=2022, volume=12, issue=1, pageStart=7, pageEnd=11, url=null, language=null, rfNumber=2, rfOrder=1, authorNames=KOVESDY C P, journalName=Kidney Int Suppl, refType=null, unstructuredReference=KOVESDY C P. Epidemiology of chronic kidney disease： an update 2022［J］. Kidney Int Suppl， 2022， 12（1）： 7-11., articleTitle=Epidemiology of chronic kidney disease： an update 2022, refAbstract=null), Reference(id=1320441020773416997, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1093/ndt/gfy276, pmid=null, pmcid=null, year=2020, volume=35, issue=4, pageStart=624, pageEnd=632, url=null, language=null, rfNumber=3, rfOrder=2, authorNames=CRÉPIN T, LEGENDRE M, CARRON C, journalName=Nephrol Dial Transplant, refType=null, unstructuredReference=CRÉPIN T， LEGENDRE M， CARRON C， et al. Uraemia-induced immune senescence and clinical outcomes in chronic kidney disease patients［J］. Nephrol Dial Transplant， 2020， 35（4）： 624-632., articleTitle=Uraemia-induced immune senescence and clinical outcomes in chronic kidney disease patients, refAbstract=null), Reference(id=1320441021075406886, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1007/s00011-024-01897-2, pmid=null, pmcid=null, year=2024, volume=73, issue=8, pageStart=1299, pageEnd=1309, url=null, language=null, rfNumber=4, rfOrder=3, authorNames=WU W S, SONG A H, XIE K W, journalName=Inflamm Res, refType=null, unstructuredReference=WU W S， SONG A H， XIE K W， et al. Characteristics of T cell premature senescence in maintenance hemodialysis patients［J］. Inflamm Res， 2024， 73（8）： 1299-1309., articleTitle=Characteristics of T cell premature senescence in maintenance hemodialysis patients, refAbstract=null), Reference(id=1320441022748934184, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1038/s41590-021-00927-z, pmid=null, pmcid=null, year=2021, volume=22, issue=6, pageStart=687, pageEnd=698, url=null, language=null, rfNumber=5, rfOrder=4, authorNames=MITTELBRUNN M, KROEMER G, journalName=Nat Immunol, refType=null, unstructuredReference=MITTELBRUNN M， KROEMER G. Hallmarks of T cell aging［J］. Nat Immunol， 2021， 22（6）： 687-698., articleTitle=Hallmarks of T cell aging, refAbstract=null), Reference(id=1320441023130615849, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1038/s41581-025-01006-4, pmid=null, pmcid=null, year=2026, volume=22, issue=1, pageStart=50, pageEnd=68, url=null, language=null, rfNumber=6, rfOrder=5, authorNames=GLORIEUX G, BURTEY S, EVENEPOEL P, journalName=Nat Rev Nephrol, refType=null, unstructuredReference=GLORIEUX G， BURTEY S， EVENEPOEL P， et al. A guide to uraemic toxicity［J］. Nat Rev Nephrol， 2026， 22（1）： 50-68., articleTitle=A guide to uraemic toxicity, refAbstract=null), Reference(id=1320441023940116522, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.3389/fimmu.2023.1154699, pmid=null, pmcid=null, year=2023, volume=14, issue=null, pageStart=1154699, pageEnd=null, url=null, language=null, rfNumber=7, rfOrder=6, authorNames=GUO L, LI X T, GOULD T, journalName=Front Immunol, refType=null, unstructuredReference=GUO L， LI X T， GOULD T， et al. T cell aging and Alzheimer’s disease［J］. Front Immunol， 2023， 14： 1154699., articleTitle=T cell aging and Alzheimer’s disease, refAbstract=null), Reference(id=1320441024804143147, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1038/s41591-019-0675-0, pmid=null, pmcid=null, year=2019, volume=25, issue=12, pageStart=1822, pageEnd=1832, url=null, language=null, rfNumber=8, rfOrder=7, authorNames=FURMAN D, CAMPISI J, VERDIN E, journalName=Nat Med, refType=null, unstructuredReference=FURMAN D， CAMPISI J， VERDIN E， et al. Chronic inflammation in the etiology of disease across the life span［J］. Nat Med， 2019， 25（12）： 1822-1832., articleTitle=Chronic inflammation in the etiology of disease across the life span, refAbstract=null), Reference(id=1320441026112765996, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1681/ASN.2013101062, pmid=null, pmcid=null, year=2014, volume=25, issue=9, pageStart=1897, pageEnd=1907, url=null, language=null, rfNumber=9, rfOrder=8, authorNames=VANHOLDER R, SCHEPERS E, PLETINCK A, journalName=J Am Soc Nephrol, refType=null, unstructuredReference=VANHOLDER R， SCHEPERS E， PLETINCK A， et al. The uremic toxicity of indoxyl sulfate and p-cresyl sulfate： a systematic review［J］. J Am Soc Nephrol， 2014， 25（9）： 1897-1907., articleTitle=The uremic toxicity of indoxyl sulfate and p-cresyl sulfate： a systematic review, refAbstract=null), Reference(id=1320441027312336942, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1093/eurheartj/ehad736, pmid=null, pmcid=null, year=2023, volume=44, issue=47, pageStart=4913, pageEnd=4924, url=null, language=null, rfNumber=10, rfOrder=9, authorNames=LARSSON S C, BUTTERWORTH A S, BURGESS S, journalName=Eur Heart J, refType=null, unstructuredReference=LARSSON S C， BUTTERWORTH A S， BURGESS S. Mendelian randomization for cardiovascular diseases： principles and applications［J］. Eur Heart J， 2023， 44（47）： 4913-4924., articleTitle=Mendelian randomization for cardiovascular diseases： principles and applications, refAbstract=null), Reference(id=1320441027756933167, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1001/jama.2021.18236, pmid=null, pmcid=null, year=2021, volume=326, issue=16, pageStart=1614, pageEnd=1621, url=null, language=null, rfNumber=11, rfOrder=10, authorNames=SKRIVANKOVA V W, RICHMOND R C, WOOLF B A R, journalName=JAMA, refType=null, unstructuredReference=SKRIVANKOVA V W， RICHMOND R C， WOOLF B A R， et al. Strengthening the reporting of observational studies in epidemiology using Mendelian randomization： the STROBE-MR statement［J］. JAMA， 2021， 326（16）： 1614-1621., articleTitle=Strengthening the reporting of observational studies in epidemiology using Mendelian randomization： the STROBE-MR statement, refAbstract=null), Reference(id=1320441028579016753, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1093/ije/dyv080, pmid=null, pmcid=null, year=2015, volume=44, issue=2, pageStart=512, pageEnd=525, url=null, language=null, rfNumber=12, rfOrder=11, authorNames=BOWDEN J, DAVEY SMITH G, BURGESS S, journalName=Int J Epidemiol, refType=null, unstructuredReference=BOWDEN J， DAVEY SMITH G， BURGESS S. Mendelian randomization with invalid instruments： effect estimation and bias detection through Egger regression［J］. Int J Epidemiol， 2015， 44（2）： 512-525., articleTitle=Mendelian randomization with invalid instruments： effect estimation and bias detection through Egger regression, refAbstract=null), Reference(id=1320441029820530738, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.16016/j.2097-0927.202505006, pmid=null, pmcid=null, year=2025, volume=47, issue=19, pageStart=2437, pageEnd=2445, url=null, language=null, rfNumber=13, rfOrder=12, authorNames=LI X M, REN H, ZHANG Z, journalName=J Army Med Univ, refType=null, unstructuredReference=LI X M， REN H， ZHANG Z， et al. Subjective sleep problems is associated with epigenetic age acceleration： a Mendelian randomization study［J］. J Army Med Univ， 2025， 47（19）： 2437-2445., articleTitle=Subjective sleep problems is associated with epigenetic age acceleration： a Mendelian randomization study, refAbstract=null), Reference(id=1320441030294487091, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1016/j.kint.2016.07.013, pmid=null, pmcid=null, year=2016, volume=90, issue=4, pageStart=897, pageEnd=904, url=null, language=null, rfNumber=14, rfOrder=13, authorNames=CHEIKH HASSAN H I, TANG M L, DJURDJEV O, journalName=Kidney Int, refType=null, unstructuredReference=CHEIKH HASSAN H I， TANG M L， DJURDJEV O， et al. Infection in advanced chronic kidney disease leads to increased risk of cardiovascular events， end-stage kidney disease and mortality［J］. Kidney Int， 2016， 90（4）： 897-904., articleTitle=Infection in advanced chronic kidney disease leads to increased risk of cardiovascular events， end-stage kidney disease and mortality, refAbstract=null), Reference(id=1320441031997374516, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1126/sciadv.aea8105, pmid=null, pmcid=null, year=2025, volume=11, issue=51, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=15, rfOrder=14, authorNames=WITNEY M J, CROFT N P, WONG Y C, journalName=Sci Adv, refType=null, unstructuredReference=WITNEY M J， CROFT N P， WONG Y C， et al. Apoxvirus model reveals general correlates of antigen presentation and immunogenicity for viral CD8+ T cell epitopes［J］. Sci Adv， 2025， 11（51）： eaea8105., articleTitle=Apoxvirus model reveals general correlates of antigen presentation and immunogenicity for viral CD8+ T cell epitopes, refAbstract=null), Reference(id=1320441032353890357, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1007/978-1-0716-1507-2_15, pmid=null, pmcid=null, year=2021, volume=2325, issue=null, pageStart=215, pageEnd=227, url=null, language=null, rfNumber=16, rfOrder=15, authorNames=ROCCHETTI M T, COSOLA C, RANIERI E, journalName=Methods Mol Biol, refType=null, unstructuredReference=ROCCHETTI M T， COSOLA C， RANIERI E， et al. Protein-bound uremic toxins and immunity［J］. Methods Mol Biol， 2021， 2325： 215-227., articleTitle=Protein-bound uremic toxins and immunity, refAbstract=null), Reference(id=1320441032806875190, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1007/978-3-662-08390-1_8, pmid=null, pmcid=null, year=1987, volume=82, issue=Suppl 1, pageStart=63, pageEnd=73, url=null, language=null, rfNumber=17, rfOrder=16, authorNames=SCHOLTE H R, LUYT-HOUWEN I E, VAANDRAGER-VERDUIN M H, journalName=Basic Res Cardiol, refType=null, unstructuredReference=SCHOLTE H R， LUYT-HOUWEN I E， VAANDRAGER-VERDUIN M H. The role of the carnitine system in myocardial fatty acid oxidation： carnitine deficiency， failing mitochondria and cardiomyopathy［J］. Basic Res Cardiol， 1987， 82（Suppl 1）： 63-73., articleTitle=The role of the carnitine system in myocardial fatty acid oxidation： carnitine deficiency， failing mitochondria and cardiomyopathy, refAbstract=null), Reference(id=1320441033658318903, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.3390/nu17061010, pmid=null, pmcid=null, year=2025, volume=17, issue=6, pageStart=1010, pageEnd=null, url=null, language=null, rfNumber=18, rfOrder=17, authorNames=DONISI I, BALESTRIERI A, DEL VECCHIO V, journalName=Nutrients, refType=null, unstructuredReference=DONISI I， BALESTRIERI A， DEL VECCHIO V， et al. L-carnitine and acetyl-l-carnitine induce metabolism alteration and mitophagy-related cell death in colorectal cancer cells［J］. Nutrients， 2025， 17（6）： 1010., articleTitle=L-carnitine and acetyl-l-carnitine induce metabolism alteration and mitophagy-related cell death in colorectal cancer cells, refAbstract=null), Reference(id=1320441034497179704, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1016/j.immuni.2011.12.007, pmid=null, pmcid=null, year=2012, volume=36, issue=1, pageStart=68, pageEnd=78, url=null, language=null, rfNumber=19, rfOrder=18, authorNames=VAN DER WINDT G J W, EVERTS B, CHANG C H, journalName=Immunity, refType=null, unstructuredReference=VAN DER WINDT G J W， EVERTS B， CHANG C H， et al. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development［J］. Immunity， 2012， 36（1）： 68-78., articleTitle=Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development, refAbstract=null), Reference(id=1320441036174901305, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1172/JCI158447, pmid=null, pmcid=null, year=2022, volume=132, issue=13, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=20, rfOrder=19, authorNames=MIWA S, KASHYAP S, CHINI E, journalName=J Clin Invest, refType=null, unstructuredReference=MIWA S， KASHYAP S， CHINI E， et al. Mitochondrial dysfunction in cell senescence and aging［J］. J Clin Invest， 2022， 132（13）： e158447., articleTitle=Mitochondrial dysfunction in cell senescence and aging, refAbstract=null), Reference(id=1320441036569165882, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1038/s41380-019-0414-4, pmid=null, pmcid=null, year=2020, volume=25, issue=1, pageStart=131, pageEnd=147, url=null, language=null, rfNumber=21, rfOrder=20, authorNames=SAVITZ J, journalName=Mol Psychiatry, refType=null, unstructuredReference=SAVITZ J. The kynurenine pathway： a finger in every pie［J］. Mol Psychiatry， 2020， 25（1）： 131-147., articleTitle=The kynurenine pathway： a finger in every pie, refAbstract=null), Reference(id=1320441037370277947, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1111/acel.13920, pmid=null, pmcid=null, year=2024, volume=23, issue=1, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=22, rfOrder=21, authorNames=CHINI C C S, CORDEIRO H S, LE KIM T, journalName=Aging Cell, refType=null, unstructuredReference=CHINI C C S， CORDEIRO H S， LE KIM T， et al. NAD metabolism： Role in senescence regulation and aging［J］. Aging Cell， 2024， 23（1）： e13920., articleTitle=NAD metabolism： Role in senescence regulation and aging, refAbstract=null), Reference(id=1320441037475135548, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=null, pmid=null, pmcid=null, year=1990, volume=null, issue=2, pageStart=32, pageEnd=34, url=null, language=null, rfNumber=23, rfOrder=22, authorNames=VIL’NER G A, LITOV M B, PASSOV L B, journalName=Med Tekh, refType=null, unstructuredReference=VIL’NER G A， LITOV M B， PASSOV L B， et al. The complex adjustment system for the microprocessor units［J］. Med Tekh， 1990（2）： 32-34., articleTitle=The complex adjustment system for the microprocessor units, refAbstract=null), Reference(id=1320441038196555837, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1111/acel.14258, pmid=null, pmcid=null, year=2024, volume=23, issue=10, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=24, rfOrder=23, authorNames=HERBSTEIN F, SAPOCHNIK M, ATTORRESI A, journalName=Aging Cell, refType=null, unstructuredReference=HERBSTEIN F， SAPOCHNIK M， ATTORRESI A， et al. The SASP factor IL-6 sustains cell-autonomous senescent cells via a cGAS-STING-NFκB intracrine senescent noncanonical pathway［J］. Aging Cell， 2024， 23（10）： e14258., articleTitle=The SASP factor IL-6 sustains cell-autonomous senescent cells via a cGAS-STING-NFκB intracrine senescent noncanonical pathway, refAbstract=null), Reference(id=1320441038649540670, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1093/nar/gkaf579, pmid=null, pmcid=null, year=2025, volume=53, issue=13, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=25, rfOrder=24, authorNames=MATSUDA T, YAMAGAMI R, IHARA A, journalName=Nucleic Acids Res, refType=null, unstructuredReference=MATSUDA T， YAMAGAMI R， IHARA A， et al. A transfer RNA methyltransferase with an unusual domain composition catalyzes 2'-O-methylation at position 6 in tRNA［J］. Nucleic Acids Res， 2025， 53（13）： gkaf579., articleTitle=A transfer RNA methyltransferase with an unusual domain composition catalyzes 2'-O-methylation at position 6 in tRNA, refAbstract=null), Reference(id=1320441039085748288, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1111/jre.13042, pmid=null, pmcid=null, year=2022, volume=57, issue=5, pageStart=1024, pageEnd=1033, url=null, language=null, rfNumber=26, rfOrder=25, authorNames=FU Y H, DU M Y, CAO Z G, journalName=J Periodontal Res, refType=null, unstructuredReference=FU Y H， DU M Y， CAO Z G， et al. PGC-1α attenuates TNF-α-induced inflammatory responses in OCCM-30 cells［J］. J Periodontal Res， 2022， 57（5）： 1024-1033., articleTitle=PGC-1α attenuates TNF-α-induced inflammatory responses in OCCM-30 cells, refAbstract=null), Reference(id=1320441040750886977, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.1016/j.metabol.2006.10.007, pmid=null, pmcid=null, year=2007, volume=56, issue=2, pageStart=267, pageEnd=279, url=null, language=null, rfNumber=27, rfOrder=26, authorNames=KIM M S, SWEENEY T R, SHIGENAGA J K, journalName=Metabolism, refType=null, unstructuredReference=KIM M S， SWEENEY T R， SHIGENAGA J K， et al. Tumor necrosis factor and interleukin 1 decrease RXRalpha， PPARalpha， PPARgamma， LXRalpha， and the coactivators SRC-1， PGC-1alpha， and PGC-1beta in liver cells［J］. Metabolism， 2007， 56（2）： 267-279., articleTitle=Tumor necrosis factor and interleukin 1 decrease RXRalpha， PPARalpha， PPARgamma， LXRalpha， and the coactivators SRC-1， PGC-1alpha， and PGC-1beta in liver cells, refAbstract=null), Reference(id=1320441041161928770, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.16016/j.2097-0927.202505029, pmid=null, pmcid=null, year=2025, volume=47, issue=16, pageStart=1962, pageEnd=1969, url=null, language=null, rfNumber=28, rfOrder=27, authorNames=王业, 钟威, 商微, journalName=陆军军医大学学报, refType=null, unstructuredReference=王业，钟威，商微，等.子宫内膜异位症亚型与不孕症的因果关系：双向孟德尔随机化研究［J］.陆军军医大学学报，2025，47（16）：1962-1969., articleTitle=子宫内膜异位症亚型与不孕症的因果关系：双向孟德尔随机化研究, refAbstract=null), Reference(id=1320441041623302212, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, doi=10.16016/j.2097-0927.202505029, pmid=null, pmcid=null, year=2025, volume=47, issue=16, pageStart=1962, pageEnd=1969, url=null, language=null, rfNumber=28, rfOrder=28, authorNames=WANG Y, ZHONG W, SHANG W, journalName=J Army Med Univ, refType=null, unstructuredReference=WANG Y， ZHONG W， SHANG W， et al. Causal effects between different sub-phenotypes of endometriosis and female infertility： a bidirectional Mendelian randomization study［J］. J Army Med Univ， 2025， 47（16）： 1962-1969., articleTitle=Causal effects between different sub-phenotypes of endometriosis and female infertility： a bidirectional Mendelian randomization study, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1320440995460793343, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, xref=1, ext=[AuthorCompanyExt(id=1320440995481764864, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, companyId=1320440995460793343, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Disease， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University（Third Military Medical University）， Chongqing， China), AuthorCompanyExt(id=1320440995494346752, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, companyId=1320440995460793343, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆)])], figs=[ArticleFig(id=1320441007821406230, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=EN, label=Figure 1, caption=Workflow of this study, figureFileSmall=72V89DGfG5SbSpdjgjMfdA==, figureFileBig=uKqAF+U9/xVureeg2HyMJg==, tableContent=null), ArticleFig(id=1320441009335549975, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=CN, label=图1, caption=研究流程图, figureFileSmall=72V89DGfG5SbSpdjgjMfdA==, figureFileBig=uKqAF+U9/xVureeg2HyMJg==, tableContent=null), ArticleFig(id=1320441011428507672, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=EN, label=Figure 2, caption=Effects of different toxins and metabolites on CD8+T cell senescence, figureFileSmall=gOOROPiEr0jaCBAXzsgysg==, figureFileBig=mHyonfX/93MQI4aQsMtg6w==, tableContent=null), ArticleFig(id=1320441011797606425, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=CN, label=图2, caption=不同毒素及代谢物对CD8+T细胞衰老的影响

A： Causal relationships between different metabolites or toxins with the proportion of terminally differentiated CD8+T cells； B： Causal relationships between different metabolites or toxins with CD45RA+CD28-CD8+T cells absolute counts； C： Causal relationships between different metabolites or toxins with the proportion of CD28-CD8+T cells； D： Causal relationships between different metabolites or toxins with the proportion of CD45RA+CD28-CD8+T cells. IL-6： Interleukin-6； FA： Fatty acids. IVW： Inverse variance weighted； MR： Mendelian randomization； IL-6： Interleukin-6； FA： Fatty acid

, figureFileSmall=gOOROPiEr0jaCBAXzsgysg==, figureFileBig=mHyonfX/93MQI4aQsMtg6w==, tableContent=null), ArticleFig(id=1320441012204453914, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=EN, label=Figure 3, caption=Effects of CD8+T Cell Senescence on Different toxins and metabolites, figureFileSmall=k4XiaxPPjcrtemD9u1GqhA==, figureFileBig=PMCaiADVyxJEoAAg2eSPQg==, tableContent=null), ArticleFig(id=1320441013928312859, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=CN, label=图3, caption=CD8+T细胞衰老对不同毒素及代谢物的影响

IVW： Inverse variance weighted； MR： Mendelian randomization； IL-6： Interleukin-6； FA： Fatty acid

, figureFileSmall=k4XiaxPPjcrtemD9u1GqhA==, figureFileBig=PMCaiADVyxJEoAAg2eSPQg==, tableContent=null), ArticleFig(id=1320441014716842012, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=EN, label=Figure 4, caption=Scatter plot and leave-one-out sensitivity analysis of the MR study for the effect of CD45RA+CD28-CD8+T cells absolute counts on plasma carnitine level, figureFileSmall=CtwQhNoPqVH/VLVlpPRg7A==, figureFileBig=XS/NDDJfyf42z++vvOF4kw==, tableContent=null), ArticleFig(id=1320441015215964189, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=CN, label=图4, caption=CD45RA+CD28-CD8+T细胞绝对计数对肉碱水平MR的散点图和留一法分析

A： Scatter plot of the MR analysis for the effect of the CD45RA+CD28-CD8+T cells absolute counts on carnitine level； B： Leave-one-out sensitivity analysis of the MR analysis for the effect of the CD45RA+CD28-CD8+T cells absolute counts on carnitine level. MR： Mendelian randomization； SNP： Single nucleotide polymorphism

, figureFileSmall=CtwQhNoPqVH/VLVlpPRg7A==, figureFileBig=XS/NDDJfyf42z++vvOF4kw==, tableContent=null), ArticleFig(id=1320441015966744606, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=EN, label=Table 1, caption=

Information on GWAS datasets utilized in the MR study

, figureFileSmall=null, figureFileBig=null, tableContent=
PhenotypeGWAS IDnSNPSample size
Carnitinemet-a-3792 545 5637 797
Kynureninemet-a-3752 545 6667 816
Interleukin-6prot-a-153810 534 7353 301
N2，N2-dimethylguanosinemet-a-6792 543 6965 228
Total fatty acidsmet-c-93611 412 09213 505
Ureamet-c-93911 807 29818 814
Osteocalcinprot-a-24610 534 7353 301
Phenylacetylglutaminemet-a-6772 545 6537 812
Uridinemet-a-3162 545 6767 800
Endothelin-2prot-a-89210 534 7353 301
Terminally Differentiated CD8+T cell%CD8+T cellsebi-a-GCST9000155815 141 5883 427
CD45RA+CD28-CD8+T cell%CD8+T cellsebi-a-GCST9000169915 138 0163 425
CD28-CD8+T cell%CD8+ T cellsebi-a-GCST9000168615 147 6193 440
CD45RA+CD28-CD8+T cells absolute countsebi-a-GCST9000169815 135 5973 408
), ArticleFig(id=1320441016432312351, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=CN, label=表1, caption=

MR研究GWAS数据的信息

, figureFileSmall=null, figureFileBig=null, tableContent=
PhenotypeGWAS IDnSNPSample size
Carnitinemet-a-3792 545 5637 797
Kynureninemet-a-3752 545 6667 816
Interleukin-6prot-a-153810 534 7353 301
N2，N2-dimethylguanosinemet-a-6792 543 6965 228
Total fatty acidsmet-c-93611 412 09213 505
Ureamet-c-93911 807 29818 814
Osteocalcinprot-a-24610 534 7353 301
Phenylacetylglutaminemet-a-6772 545 6537 812
Uridinemet-a-3162 545 6767 800
Endothelin-2prot-a-89210 534 7353 301
Terminally Differentiated CD8+T cell%CD8+T cellsebi-a-GCST9000155815 141 5883 427
CD45RA+CD28-CD8+T cell%CD8+T cellsebi-a-GCST9000169915 138 0163 425
CD28-CD8+T cell%CD8+ T cellsebi-a-GCST9000168615 147 6193 440
CD45RA+CD28-CD8+T cells absolute countsebi-a-GCST9000169815 135 5973 408
), ArticleFig(id=1320441016918851616, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=EN, label=Table 2, caption=

Summary of instrumental variables intensity of each exposure factor

, figureFileSmall=null, figureFileBig=null, tableContent=
ExposurenSNPMean FMinimum F
Carnitine6734.5323.90
Kynurenine1139.0423.76
Interleukin-6326.2625.21
N2，N2-dimethylguanosine1626.5723.95
Total fatty acids1645.7625.01
Urea225.1624.27
Osteocalcin735.7024.29
Phenylacetylglutamine527.0324.19
Uridine832.2423.96
Endothelin-2659.6524.12
The proportion of terminally differentiated CD8+T cells578.9226.38
The proportion of CD45RA+CD28-CD8+T cells335.1025.35
The proportion of CD28-CD8+T cells828.7024.62
CD45RA+CD28-CD8+T cells absolute counts6031.1024.14
), ArticleFig(id=1320441018558824482, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, language=CN, label=表2, caption=

各暴露工具变量强度汇总

, figureFileSmall=null, figureFileBig=null, tableContent=
ExposurenSNPMean FMinimum F
Carnitine6734.5323.90
Kynurenine1139.0423.76
Interleukin-6326.2625.21
N2，N2-dimethylguanosine1626.5723.95
Total fatty acids1645.7625.01
Urea225.1624.27
Osteocalcin735.7024.29
Phenylacetylglutamine527.0324.19
Uridine832.2423.96
Endothelin-2659.6524.12
The proportion of terminally differentiated CD8+T cells578.9226.38
The proportion of CD45RA+CD28-CD8+T cells335.1025.35
The proportion of CD28-CD8+T cells828.7024.62
CD45RA+CD28-CD8+T cells absolute counts6031.1024.14
)], attaches=null, journal=Journal(id=1319372634082869396, delFlag=0, nameCn=陆军军医大学学报, nameEn=Journal of Army Medical University, nameHistory1=null, nameHistory2=null, issn=2097-0927, eissn=null, cn=50-1223/R, coden=null, periodic=3, language=CN, oaType=null, ccby=null, superviseOffice=null, ownerOffice=null, pubOffice=null, editorOffice=null, officeType=null, aims=null, clcCode=null, officeProv=null, officeCity=null, officeAddr=null, officeZip=null, officeEmail=null, officePhone=null, editDirector=null, officeDirector=null, officeDirectorPhone=null, officeStaffNum=null, officeEmpNum=null, coverPicUrl=zdiTazv9TbsMJqLaCJ/k7A==, journalPrice=null, startedYear=null, abbrevIsoEn=Journal of Army Medical University, journalRemark=null, publicationField=null, createdTime=1792492548725, updatedTime=1792745216517, createdBy=18614031015, updatedBy=13701087609, firstLetterCn=L, firstLetterEn=L, subjectCode=Medical and Pharmaceutical Sciences, subjectName=null, subjectCodeEn=Medical and Pharmaceutical Sciences, subjectNameEn=null, picCn=zdiTazv9TbsMJqLaCJ/k7A==, picEn=931BgeD2k9AIsc7QjHoQKg==, jcr=null, cjcr=null, exts=[JournalExt(id=1320432400862135101, language=CN, name=陆军军医大学学报, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1792745216813, updatedTime=1792745216813, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=https://ljjydx.portal.founderss.cn, submissionEditorUrl=https://journal.ids.fzyun.cn, submissionReviewUrl=https://ljjydx.portal.founderss.cn, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""}), JournalExt(id=1320432400933438270, language=EN, name=Journal of Army Medical University, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1792745216830, updatedTime=1792745216830, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=https://ljjydx.portal.founderss.cn, submissionEditorUrl=https://journal.ids.fzyun.cn, submissionReviewUrl=https://ljjydx.portal.founderss.cn, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""})], databaseList=null, tenantJournalId=1319373162502258839, websiteList=[Website(id=1319376331821925278, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1319373162502258839, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN, language=CN, createTime=1792493430333, createBy=18614031015, updateTime=1792493552921, updateBy=18614031015, name=陆军军医大学学报-中文, tplId=1146099689490845704, title=陆军军医大学学报, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1319376971570729589, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=articleTextType, value=kx, createTime=1792493582861, updateTime=1792493582861, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971549758066, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=banner, value=null, createTime=1792493582856, updateTime=1792493582856, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971591701112, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=grayFlag, value=0, createTime=1792493582866, updateTime=1792493582866, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971541369457, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=logo, value=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/file/pic?fileId=Mmvh7crXM7dcUwf9n9+ehg==, createTime=1792493582854, updateTime=1792493582854, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971608478330, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=minRunFlag, value=0, createTime=1792493582870, updateTime=1792493582870, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971562340980, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/file/pic, createTime=1792493582859, updateTime=1792493582859, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971600089721, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=silenceFlag, value=0, createTime=1792493582868, updateTime=1792493582868, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971558146675, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_cn_619/, createTime=1792493582858, updateTime=1792493582858, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971574923894, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=themeColor, value=null, createTime=1792493582862, updateTime=1792493582862, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971583312503, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=themeStyle, value=null, createTime=1792493582864, updateTime=1792493582864, creator=18614031015, updator=18614031015)]), Website(id=1319376331905811365, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1319373162502258839, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN, language=EN, createTime=1792493430353, createBy=18614031015, updateTime=1792493548158, updateBy=18614031015, name=陆军军医大学学报-英文, tplId=1146101810881728533, title=Journal of Army Medical University, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1319376935873008230, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=articleTextType, value=kx, createTime=1792493574350, updateTime=1792493574350, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935843648099, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=banner, value=null, createTime=1792493574343, updateTime=1792493574343, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935902368361, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=grayFlag, value=0, createTime=1792493574357, updateTime=1792493574357, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935835259490, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=logo, value=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN/file/pic?fileId=Mmvh7crXM7dcUwf9n9+ehg==, createTime=1792493574341, updateTime=1792493574341, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935914951275, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=minRunFlag, value=0, createTime=1792493574360, updateTime=1792493574360, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935864619621, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN/file/pic, createTime=1792493574348, updateTime=1792493574348, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935906562666, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=silenceFlag, value=0, createTime=1792493574358, updateTime=1792493574358, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935856231012, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_en_623/, createTime=1792493574346, updateTime=1792493574346, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935881396839, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=themeColor, value=null, createTime=1792493574352, updateTime=1792493574352, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935889785448, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=themeStyle, value=null, createTime=1792493574354, updateTime=1792493574354, creator=18614031015, updator=18614031015)])], journalTitle=陆军军医大学学报, weixinUrl=null, journalUrl=https://aammt.tmmu.edu.cn/, iacademicId=null, status=1, seqNo=null, journalTitleEn=Journal of Army Medical University, journalPhotoCn=zdiTazv9TbsMJqLaCJ/k7A==, journalPhotoEn=931BgeD2k9AIsc7QjHoQKg==, journalFirstLetter=L, journalRecommend=null, journalNew=null, journalCollection=null, jcrJf=null, cjcrJf=null, jcrJfStr=null, cjcrJfStr=null, submissionFirstDecision=null, sciSubjectClassification=null, casSubjectClassification=null, citeScore=null, totalCitationFrequency=null, icpCode=null, psCode=null, advertisingLicenseCode=null, copyrightInformation=null, country=null, option=, provinceCode=null, provinceName=null, collectFlag=false, interPubPlatform=, interPubPlatformUrl=null), detailUrlCn=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/10.16016/j.2097-0927.202512135, detailUrlEn=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN/10.16016/j.2097-0927.202512135, pdfUrlCn=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/PDF/10.16016/j.2097-0927.202512135, pdfUrlEn=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN/PDF/10.16016/j.2097-0927.202512135, aliStartDate=0, aliEndDate=0, collectionFlag=false, citedCount=null, citedUrl=null, previewStatus=0, delFlag=0, hasFullText=1, orderTime=1773504000000, fullTextJson=null, articleText=null, reference=null)
收藏切换
肉碱与犬尿氨酸驱动CD8+T细胞衰老：一项双向孟德尔随机化研究阐释尿毒症免疫紊乱新机制
收藏切换
PDF下载
孙跃文 , 蓝琦港 , 赵景宏
陆军军医大学学报 | 论著·基础医学 2026,48(5): 543-550
收起
收藏切换
陆军军医大学学报 |论著·基础医学 2026 , 48 (5) : 543 -550
肉碱与犬尿氨酸驱动CD8+T细胞衰老：一项双向孟德尔随机化研究阐释尿毒症免疫紊乱新机制
全屏
[Author(id=1320440995859251202, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1320440996308041732, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, authorId=1320440995859251202, language=EN, stringName=Yuewen SUN, firstName=Yuewen, middleName=null, lastName=SUN, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Disease， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University（Third Military Medical University）， Chongqing， China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1320440996748443653, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, authorId=1320440995859251202, language=CN, stringName=孙跃文, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1320440995460793343, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, xref=1, ext=[AuthorCompanyExt(id=1320440995481764864, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, companyId=1320440995460793343, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Disease， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University（Third Military Medical University）， Chongqing， China), AuthorCompanyExt(id=1320440995494346752, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, companyId=1320440995460793343, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆)])]), Author(id=1320440997096570887, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1320440997255954441, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, authorId=1320440997096570887, language=EN, stringName=Qigang LAN, firstName=Qigang, middleName=null, lastName=LAN, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Disease， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University（Third Military Medical University）， Chongqing， China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1320440997591498762, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, authorId=1320440997096570887, language=CN, stringName=蓝琦港, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1320440995460793343, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, xref=1, ext=[AuthorCompanyExt(id=1320440995481764864, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, companyId=1320440995460793343, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Disease， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University（Third Military Medical University）， Chongqing， China), AuthorCompanyExt(id=1320440995494346752, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, companyId=1320440995460793343, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆)])]), Author(id=1320440998015123468, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=zhaojh@tmmu.edu.cn, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1320440998799458318, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, authorId=1320440998015123468, language=EN, stringName=Jinghong ZHAO, firstName=Jinghong, middleName=null, lastName=ZHAO, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Disease， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University（Third Military Medical University）， Chongqing， China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1320441000489762831, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, authorId=1320440998015123468, language=CN, stringName=赵景宏, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1320440995460793343, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, xref=1, ext=[AuthorCompanyExt(id=1320440995481764864, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, companyId=1320440995460793343, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Disease， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University（Third Military Medical University）， Chongqing， China), AuthorCompanyExt(id=1320440995494346752, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320440981187576818, companyId=1320440995460793343, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆)])])]
孙跃文, 蓝琦港, 赵景宏
作者信息
  • 1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆
通讯作者:
赵景宏，E-mail：
ZHAO Jinghong， E-mail：
Carnitine and kynurenine drive CD8+T cell senescence: a bidirectional Mendelian randomization study elucidates novel mechanisms of uremia-associated immune dysregulation
Yuewen SUN, Qigang LAN, Jinghong ZHAO
Affiliations
  • 1Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Disease， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University（Third Military Medical University）， Chongqing， China
出版时间: 2026-03-15 doi: 10.16016/j.2097-0927.202512135
文章导航
收藏切换
摘要
收起
目的

通过应用孟德尔随机化（Mendelian randomization， MR）方法，系统探究10种尿毒症相关毒素及代谢物与CD8+T细胞衰老表型之间的双向因果关系。

方法

采用双向MR方法，基于全基因组关联研究（genome-wide association studies， GWAS）数据库汇总数据，提取与10种尿毒症相关毒素及代谢物以及4种CD8+T细胞衰老表型显著相关的单核苷酸多态性位点作为工具变量。逆方差加权法（inverse variance weighting， IVW）作为主要分析方法，同时采用MR-Egger、加权中位数法、简单众数法及加权众数法进行补充分析。通过Cochran’s Q检验、MR-Egger截距检验、MR-PRESSO及留一法等敏感性分析验证结果的稳健性与潜在多效性。

结果

MR分析显示，肉碱水平与终末分化CD8+T细胞比例（IVW：β=1.71，95%CI：0.59~2.83，P=0.003）、CD45RA+CD28-CD8+T细胞比例（IVW：β=2.23，95%CI：0.65~3.80，P=0.006）、CD28-CD8+T细胞比例（IVW：β=1.13，95%CI：0.11~2.15，P=0.030）正相关。犬尿氨酸水平与终末分化CD8+T细胞比例正相关（IVW：β=1.69，95%CI：0.57~2.82，P=0.000 3），而白介素-6水平与CD28-CD8+T细胞比例（IVW：β=0.28，95%CI：0.03~0.53，P=0.026）和CD45RA+CD28-CD8+T细胞比例（IVW：β=0.41，95%CI：0.02~0.79，P=0.04）正相关。N2，N2-二甲基鸟苷水平与CD45RA+CD28-CD8+T细胞绝对计数（IVW：β=2.53，95%CI：0.51~4.55，P=0.014）正相关。反向MR分析显示，CD45RA+CD28-CD8+T细胞绝对计数增加可降低肉碱水平（IVW：β=-0.00 003，95%CI：-0.000 062~-0.000 004，P=0.024）。所有敏感性分析均支持主要结果的稳健性。

结论

部分尿毒症相关毒素及代谢物与CD8+T细胞衰老之间存在双向因果关联，为尿毒症患者免疫功能紊乱的机制提供了新的因果证据与潜在干预靶点。

尿毒症相关毒素及代谢物  /  CD8+T细胞衰老  /  孟德尔随机化研究
Objective

To systematically investigate the bidirectional causal relationship between 10 uremia-related toxins and metabolites and CD8+ T cell senescence phenotypes using Mendelian randomization (MR).

Methods

A bidirectional MR analysis was performed using genome-wide association studies (GWAS) data to extract single nucleotide polymorphisms closely associated with 10 uremia-related toxins and metabolites and CD8+ T cell senescence phenotypes as instrumental variables. The primary analytical method was inverse variance weighting (IVW), supplemented by MR-Egger, weighted median, simple mode, and weighted mode. The robustness and potential pleiotropy of the results were verified by sensitivity analyses including Cochran’s Q test, MR-Egger intercept test, MR-PRESSO and leave-one-out analysis.

Results

MR analysis showed that carnitine level was positively associated with the proportion of terminally differentiated CD8+ T cells (IVW: β=1.71, 95%CI: 0.59 to 2.83, P=0.003), the proportion of CD45RA+CD28⁻CD8+T cells (IVW: β=2.23, 95%CI: 0.65 to 3.80, P=0.006), and the proportion of CD28⁻CD8+T cells (IVW: β=1.13, 95%CI: 0.11 to 2.15, P=0.030). Kynurenine level also showed a significant positive association with the proportion of terminally differentiated CD8+T cells (IVW: β=1.69, 95%CI: 0.57 to 2.82, P=0.000 3), while IL-6 level presented a positive correlation with the proportion of CD28⁻CD8+T cells (IVW: β=0.28, 95%CI: 0.03 to 0.53, P=0.026) and the proportion of CD45RA+CD28⁻CD8+T cells (IVW: β=0.41, 95%CI: 0.02 to 0.79, P=0.04). N2,N2-dimethylguanosine level was positively correlated with CD45RA+CD28⁻CD8+T cell absolute count (IVW: β=2.53, 95%CI: 0.51 to 4.55, P=0.014). Reverse MR analysis revealed an increase in the absolute count of CD45RA+CD28⁻CD8+T cells was causally associated with a reduction in carnitine levels (IVW: β=-0.000 03, 95%CI: -0.000 062 to 0.000 004, P=0.024). All sensitivity analyses supported the robustness of the main findings.

Conclusion

There are bidirectional causal associations between uremia-related toxins and metabolites and CD8+T cell senescence, providing novel causal insights and potential intervention targets for immune dysfunction in uremic patients.

uremia-related toxins and metabolites  /  CD8+ T cell senescence  /  Mendelian randomization analysis
孙跃文, 蓝琦港, 赵景宏. 肉碱与犬尿氨酸驱动CD8+T细胞衰老：一项双向孟德尔随机化研究阐释尿毒症免疫紊乱新机制. 陆军军医大学学报, 2026 , 48 (5) : 543 -550 . DOI: 10.16016/j.2097-0927.202512135
Yuewen SUN, Qigang LAN, Jinghong ZHAO. Carnitine and kynurenine drive CD8+T cell senescence: a bidirectional Mendelian randomization study elucidates novel mechanisms of uremia-associated immune dysregulation[J]. Journal of Army Medical University, 2026 , 48 (5) : 543 -550 . DOI: 10.16016/j.2097-0927.202512135
正文
收起
慢性肾脏病（chronic kidney disease， CKD）是一种慢性进行性疾病，其特征是由于各种原因导致肾脏的结构和功能发生变化，其病程呈进行性发展，最终可进展为尿毒症，并严重威胁患者生存［1］。全球约有10%的成年人患有CKD，每年导致100万~200万人死亡，到2040年，CKD预计将成为全球第五大死亡原因［2］。肾功能丧失与体内慢性炎症状态和伴随的免疫系统受损密切相关，尿毒症相关的免疫系统缺陷对终末期肾脏病（end stage renal disease， ESRD）患者的发病率和死亡率都有广泛的临床影响［3］。目前，感染是导致CKD患者发病和死亡的主要原因，而T细胞免疫功能障碍特别是CD8+T细胞功能异常，如CD8+T细胞早衰等，已被认为是免疫功能障碍的重要表现之一［4］。衰老的CD8+T细胞可呈现出多种衰老特征，如CD28表达缺失、CD45亚型升高、终末分化亚群增多、端粒缩短、线粒体功能紊乱等［5］。然而，目前对尿毒症患者CD8+T细胞早衰的理解仍然有限，临床实践中仍缺乏更有效的治疗措施。因此，进一步探索CKD患者CD8+T细胞早衰的发病机制，对于改善尿毒症患者免疫功能及长期预后等目标具有重要意义。
代谢紊乱是尿毒症的核心病理特征之一。随着肾功能进行性减退，体内代谢废物排泄障碍，大量尿毒症相关毒素及代谢物在血液及组织中蓄积［6］，对多个器官系统和代谢通路产生负面影响，如心血管系统损伤、神经系统改变等［7-8］。尽管越来越多的证据表明，尿毒症相关毒素及代谢物与免疫功能障碍密切相关，如硫酸对甲酚与CKD的免疫缺陷状态特别是适应性免疫反应相关，而硫酸吲哚酚则反映了先天和适应性免疫系统的激活［9］。然而，尿毒症相关毒素及代谢物与CD8+T细胞早衰的因果关系仍不明确。
孟德尔随机化（Mendelian randomization， MR）是一种基于遗传变异的因果推断方法，利用遗传变异作为工具变量，可有效规避观察性研究中的混杂偏倚和反向因果偏倚，为暴露因素与结局间的因果关系提供可靠证据［10］。基于此，本研究采用双向MR设计，系统探究尿毒症相关毒素及代谢物与CD8+T细胞不同衰老亚型的因果关联，并通过反向MR分析验证因果关系方向。本研究旨在明确影响CD8+T细胞衰老的关键尿毒症相关毒素及代谢物靶点，揭示二者间的因果调控机制，并为尿毒症患者免疫功能紊乱的精准干预提供新的理论依据和潜在靶点。
1　材料与方法
收起
1.1　数据来源
本研究使用的数据来自全基因组关联研究（genome-wide association studies，GWAS）数据库（https://opengwas.io/）。由于使用公共数据库，伦理审查被豁免。本研究遵循了《流行病学观察性研究报告加强指南（STROBE指南）》［11］。所有数据的人群均来自欧洲［10］。10种尿毒症相关毒素及代谢物（肉碱、犬尿氨酸、白介素-6、总脂肪酸、N2，N2-二甲基鸟苷、尿素、骨钙素、苯乙酰谷氨酰胺、尿苷、内皮素-2）及4种CD8+T细胞衰老表型（终末分化CD8+T细胞比例、CD45RA+CD28-CD8+T细胞比例、CD45RA+CD28-CD8+T细胞绝对计数、CD28-CD8+T细胞比例）关联数据具体信息见表1。
1.2　研究方法
采用双向MR方法评估尿毒症相关毒素及代谢物与CD8+T细胞衰老的因果关系。以10种尿毒症相关毒素及代谢物作为暴露，4种CD8+T细胞衰老表型作为结局，进行两样本MR分析，研究二者是否存在因果关系。随后为有效验证因果关联方向、排除反向因果偏倚，将结局与暴露角色互换，进行了反向MR分析。单核苷酸多态性（single nucleotide polymorphism，SNP）被选为工具变量，用于研究尿毒症相关毒素及代谢物与CD8+T细胞衰老的关联。所有选定的SNP均符合3个基本假设：①SNP与研究的暴露因素显著相关；②SNP未与其他已知混杂因素相关；③SNP仅通过暴露因素来影响结果。从而排除水平多效性（图1）。
1.3　工具变量的筛选
为确保工具变量的强度与独立性，并同时保证SNP的数量足够，本研究的工具变量筛选严格遵守以下标准：①显著性阈值：选取与暴露因素显著关联的SNP，关联强度阈值设为P<5×10-6，以保证工具变量数量以及与暴露的强相关性［12］。②连锁不平衡（linkage disequilibrium， LD）剔除：使连锁不平衡系数R2设定为0.001，区域宽度设定为10 000 kb，即去除10 MB范围内与最显著SNP的R2>0.001的SNP。③最小等位基因频率（minor allele frequenc， MAF）：剔除MAF<0.01的SNP，避免低频SNP导致的效应估计偏倚，其公式为MAF=min（p， 1-p），其中p为该位点次要等位基因的计数/该位点所有等位基因的总计数。④F统计量：为评估关联强度，进一步排除弱工具变量对结果可能造成的偏倚，计算每个SNP的F统计量，公式为F=（R²/K）×［（n-K-1）/（1-R²）］，其中n为暴露因素数据的样本量，K为工具变量的数目，R2为工具变量解释暴露因素变异的比例，公式为R²=2×MAF×（1-MAF）×β²，当对应的F统计量>10时，该统计量被视为充分。此外，统一暴露与结局GWAS数据的等位基因编码（效应等位基因/非效应等位基因），剔除等位基因方向不一致或无法匹配的SNP。为剔除与潜在混杂因素相关的工具变量，本研究使用NIH提供的连锁不平衡性状关联工具（https://ldlink.nih.gov）对每个SNP的已知关联表型进行交叉检索。
1.4　敏感性分析
本研究采用留一法逐一剔除单个SNP后，重复MR分析，观察剔除前后的MR分析是否存在统计学差异，以此判断是否存在异常SNP，进而全面评估MR分析结果的稳定性及核心结论的可靠性。
1.5　统计学分析
采用R 4.5.1软件及Two Sample MR 0.6.6包进行MR分析，逆方差加权法（inverse variance weighted，IVW）作为主要分析方法，同时采用MR-Egger回归、加权中位数法、简单众数法及加权众数法等多种方法进行补充分析。最终结果以回归系数（β）及95%置信区间（confidence interval，CI）表示［13］。为评估反向因果关系，进行反向MR分析。使用Cochran’s Q检验来评估SNPs中的异质性（Q_pval<0.05）。若有SNP存在异质性，使用随机效应模型的IVW的结果。同时采用两种互补的方法评估水平多效性，其中MR-Egger截距检验用于检测均匀分布的水平多效性，检验回归截距是否显著偏离0（Pegger<0.05）。MR-PRESSO用于检测和校正由离群值驱动的水平多效性，P<0.05的SNP被剔除。此外，Steiger检验用于验证预设的从暴露到结局的因果方向是否得到遗传数据的支持。本研究采用Bonferroni方法校正，P<0.001 25（0.05/40）的关联是有力的关联证据。P<0.05表示差异具有统计学意义。
2　结果
收起
2.1　工具变量
所有纳入的SNP的F统计量>10且MAF<0.01。以尿毒症相关毒素及代谢物为暴露时，纳入141个符合标准的SNP，见表2。
2.2　尿毒症相关毒素及代谢物对CD8+T细胞衰老的影响
IVW结果显示，部分尿毒症相关毒素及代谢物与CD8+T细胞衰老存在显著因果关系（图2）。针对终末分化CD8+T细胞比例，血浆肉碱水平与犬尿氨酸水平存在正向因果效应（图2A）。针对CD45RA+CD28-CD8+T细胞绝对计数，只有血浆N2，N2-二甲基鸟苷水平存在正向因果效应（图2B）。针对CD28-CD8+T细胞比例的因果效应，血浆肉碱水平与白介素-6均存在正向因果效应（图2C）。针对CD45RA+CD28-CD8+T细胞比例，血浆肉碱水平存在正向因果效应（图2D）。而总脂肪酸、尿素、骨钙素、苯乙酰谷氨酰胺、尿苷、内皮素-2与CD8+T细胞衰老无显著关联。MR Egger、加权中位数法、简单众数法和加权众数法等其他方法的结果与IVW的方向一致。MR-Egger截距检验提示肉碱与CD28-CD8+T细胞比例可能存在潜在多效性，而MR-PRESSO全局检验和离群值检测却未发现显著离群值（P=0.845），同时Steiger方向性检验结果表明，遗传工具变量对肉碱的方差解释量（R²=0.315）显著高于对CD28-CD8+T细胞比例的方差解释量（R²=0.017），差异极显著（P=8.50×10⁻¹³⁰），且与补充MR分析结果一致（图2C）。留一法分析也证明了MR分析的稳健性。
2.3　CD8+T细胞衰老对尿毒症相关毒素及代谢物的影响
反向MR结果显示，CD8+T细胞衰老表型对犬尿氨酸、白介素-6、总脂肪酸、N2，N2-二甲基鸟苷、尿素、骨钙素、苯乙酰谷氨酰胺、尿苷、内皮素-2水平均未发现显著的因果关联（图3）。CD45RA+CD28-CD8+T细胞绝对计数对血浆肉碱水平存在负向因果效应，其散点图表明补充分析方法也支持这一结论（图4A）。留一法敏感性分析发现3个潜在异常SNP（rs12130486、rs201928503、rs111347604），但剔除上述SNP后，效应量方向未发生反转，提示该因果推断不受个别工具驱动，结果具有稳健性（图4B）。
3　讨论
收起
CKD患者的肾小球滤过率不可逆下降会增加其病死率，其中感染是重要死因之一［14］。尿毒症患者的免疫系统缺陷有着广泛的临床影响，其中T细胞功能状态显著影响患者的免疫功能及感染易感性［15］。尿毒症相关毒素及代谢物的积累是CKD的重要特征之一，可参与调控机体的免疫状态［16］。本研究明确了肉碱、犬尿氨酸、白介素-6及N2，N2-二甲基鸟苷对CD8+T细胞衰老表型有正向因果效应，同时CD8+T细胞衰老表型对血浆肉碱水平存在负向调控作用。本研究为深入理解尿毒症患者免疫功能异常的分子基础提供了新的线索，在一定程度上填补了该领域的空白。
3.1　部分尿毒症相关毒素及代谢物与CD8+T细胞衰老存在正向因果关系
本研究发现血浆肉碱水平升高与CD8+T细胞衰老表型存在正向因果关联。肉碱是转运活化酰基通过线粒体内膜的关键物质，在尿毒症患者体内会出现蓄积现象［17］。肉碱通过保护线粒体功能改善细胞能量代谢，并表现出抗氧化、抗炎以及抗肿瘤能力［18］。肉碱会干扰T细胞免疫，CKD患者的肉碱过度积累可能会引起其代谢紊乱，继而出现线粒体功能障碍，并通过氧化应激通路加速细胞衰老［19-20］。神经毒性犬尿氨酸代谢可直接损害线粒体功能，其代谢产物烟酰胺腺嘌呤二核苷酸与细胞衰老的关系已充分证实［21-22］。CKD患者犬尿氨酸的过度积累及代谢紊乱可能通过调控线粒体能量代谢以及烟酰胺腺嘌呤二核苷酸的合成来影响CD8+T细胞衰老。白介素-6与CD28-CD8+T细胞、CD45RA+CD28-CD8+T细胞比例的升高存在正向因果关联。白介素-6通过cGAS-STING-NFκB介导的非经典衰老通路维持衰老细胞状态［23-24］。因此CKD患者白介素-6的蓄积也可能通过激活衰老相关基因表达，促进CD8+T细胞衰老表型的形成。N2，N2-二甲基鸟苷是转运RNA中的一种转录后修饰核苷，主要功能是稳定转运RNA的高级结构［25］。本研究发现N2，N2-二甲基鸟苷与CD45RA+CD28-CD8+T细胞绝对计数的正向因果关联，但其具体作用机制尚需进一步实验验证。本研究未发现总脂肪酸、尿素等6种尿毒症相关毒素及代谢物与CD8+T细胞衰老存在显著因果关联。这可能是由于，这些“毒素”作为一类宽泛的代谢物集合，其内部不同组分的免疫调节作用可能相互拮抗，导致整体关联信号被稀释或者统计功效不足的可能。另一方面，在复杂的代谢-免疫网络中，这些传统毒素的微弱效应可能被更直接、更特异的代谢物所介导或掩盖，使其难以通过MR方法被发现。该结果也提示，相较于传统宽泛的功能类别划分，功能明确的代谢分子可能是更精准的免疫调节信号分子及潜在干预靶点。
3.2　部分尿毒症相关毒素及代谢物与CD8+T细胞衰老存在反向因果关系
本研究亦通过反向MR分析探索了免疫衰老表型对代谢物的潜在因果影响。CD45RA+CD28-CD8+T细胞绝对计数与肉碱水平呈负相关。然而，该效应的估计值极小，其95%CI接近零，不排除为统计噪声或多重检验校正后的偶然发现。其次，目前缺乏直接证据支持衰老CD8+T细胞能够负反馈调节肉碱代谢稳态。尽管如此，作为一种推测性的假说，本研究提出一种可能的机制：衰老T细胞通过分泌特定的衰老相关分泌表型因子，间接影响肝脏或肌肉等代谢组织的肉碱合成或转运，但亟须在更大规模队列和实验模型中予以验证［26-27］。
3.3　方法学优势与局限
本研究通过双向MR设计，一定程度上避免传统观察性研究中的混杂偏倚与反向因果关系的干扰，从而为尿毒症相关毒素及代谢物与CD8+T细胞衰老之间的因果推断提供了更为稳健的支持［28］。其次，通过严格筛选工具变量，并使用多种敏感性分析方法提高结果的可靠性和稳健性。另外，本研究不仅证实了尿毒症相关毒素及代谢物对CD8+T细胞衰老的驱动作用，还发现衰老CD8+T细胞可能参与调控代谢紊乱，这为理解二者之间复杂的调控网络提供了新的认识。最后，本研究聚焦于具有明确病理生理意义的尿毒症相关毒素及代谢物，使研究发现更贴合临床实际情况，也为未来针对尿毒症患者免疫功能异常的干预策略提供了参考依据。
当然，本研究亦存在局限性：①研究所用GWAS数据主要来源于欧洲人群，研究结果的外推性可能受到限制，未来需纳入亚洲人群等多种族数据进行验证；②MR分析基于“工具变量仅通过暴露影响结局”的排他性假设。尽管已通过多种方法评估了水平多效性，但MR方法本身基于的三大假设在理论上仍存在未被完全满足的可能，结果可能受到潜在未检测到的多效性SNP的轻微影响，未来研究需要通过多变量MR研究和实验验证等方法进一步排除混杂因素的干扰；③部分代谢物对应的工具变量数量较少，可能影响统计效力，尽管采用了Bonferroni校正，但报告的结果仍可能存在假阳性，需要在未来研究中通过独立样本和多方法验证加以确认；④MR分析仅能证实因果关联的存在，后续需通过细胞实验、动物模型等基础研究进一步验证代谢物调控CD8+T细胞衰老的机制；⑤研究未考虑代谢物之间的交互作用，尿毒症患者体内多种代谢物的协同蓄积可能对CD8+T细胞衰老产生联合影响，未来可通过多变量MR分析深入探究。
总而言之，本研究揭示了尿毒症相关毒素及代谢物与CD8+T细胞衰老之间的双向因果关系。这一发现不仅拓展了对尿毒症免疫功能障碍机制的认识，也为相关治疗策略的探索提示了潜在的研究方向。然而，从机制发现到临床转化仍需谨慎：①当前证据主要基于遗传学关联，进一步需要通过实验研究验证其内在的具体分子机制；②在尿毒症患者中调控肉碱等代谢物需综合考虑安全性，例如过量补充可能加重代谢负担，而降低水平又可能影响能量代谢；③针对已鉴定的其他代谢物，需评估其临床干预的可行性。未来研究应通过动物实验验证、临床前安全性评价以及针对尿毒症人群的干预性试验，系统评估这些代谢靶点的治疗潜力与风险。

文献
收起
参考文献 引证文献
排序方式：
1
FOREMAN K J， MARQUEZ N， DOLGERT A， et al. Forecasting life expectancy， years of life lost， and all-cause and cause-specific mortality for 250 causes of death： reference and alternative scenarios for 2016-40 for 195 countries and territories［J］. Lancet， 2018， 392（10159）： 2052-2090.
2
KOVESDY C P. Epidemiology of chronic kidney disease： an update 2022［J］. Kidney Int Suppl， 2022， 12（1）： 7-11.
3
CRÉPIN T， LEGENDRE M， CARRON C， et al. Uraemia-induced immune senescence and clinical outcomes in chronic kidney disease patients［J］. Nephrol Dial Transplant， 2020， 35（4）： 624-632.
4
WU W S， SONG A H， XIE K W， et al. Characteristics of T cell premature senescence in maintenance hemodialysis patients［J］. Inflamm Res， 2024， 73（8）： 1299-1309.
5
MITTELBRUNN M， KROEMER G. Hallmarks of T cell aging［J］. Nat Immunol， 2021， 22（6）： 687-698.
6
GLORIEUX G， BURTEY S， EVENEPOEL P， et al. A guide to uraemic toxicity［J］. Nat Rev Nephrol， 2026， 22（1）： 50-68.
7
GUO L， LI X T， GOULD T， et al. T cell aging and Alzheimer’s disease［J］. Front Immunol， 2023， 14： 1154699.
8
FURMAN D， CAMPISI J， VERDIN E， et al. Chronic inflammation in the etiology of disease across the life span［J］. Nat Med， 2019， 25（12）： 1822-1832.
9
VANHOLDER R， SCHEPERS E， PLETINCK A， et al. The uremic toxicity of indoxyl sulfate and p-cresyl sulfate： a systematic review［J］. J Am Soc Nephrol， 2014， 25（9）： 1897-1907.
10
LARSSON S C， BUTTERWORTH A S， BURGESS S. Mendelian randomization for cardiovascular diseases： principles and applications［J］. Eur Heart J， 2023， 44（47）： 4913-4924.
11
SKRIVANKOVA V W， RICHMOND R C， WOOLF B A R， et al. Strengthening the reporting of observational studies in epidemiology using Mendelian randomization： the STROBE-MR statement［J］. JAMA， 2021， 326（16）： 1614-1621.
12
BOWDEN J， DAVEY SMITH G， BURGESS S. Mendelian randomization with invalid instruments： effect estimation and bias detection through Egger regression［J］. Int J Epidemiol， 2015， 44（2）： 512-525.
13
LI X M， REN H， ZHANG Z， et al. Subjective sleep problems is associated with epigenetic age acceleration： a Mendelian randomization study［J］. J Army Med Univ， 2025， 47（19）： 2437-2445.
14
CHEIKH HASSAN H I， TANG M L， DJURDJEV O， et al. Infection in advanced chronic kidney disease leads to increased risk of cardiovascular events， end-stage kidney disease and mortality［J］. Kidney Int， 2016， 90（4）： 897-904.
15
WITNEY M J， CROFT N P， WONG Y C， et al. Apoxvirus model reveals general correlates of antigen presentation and immunogenicity for viral CD8+ T cell epitopes［J］. Sci Adv， 2025， 11（51）： eaea8105.
16
ROCCHETTI M T， COSOLA C， RANIERI E， et al. Protein-bound uremic toxins and immunity［J］. Methods Mol Biol， 2021， 2325： 215-227.
17
SCHOLTE H R， LUYT-HOUWEN I E， VAANDRAGER-VERDUIN M H. The role of the carnitine system in myocardial fatty acid oxidation： carnitine deficiency， failing mitochondria and cardiomyopathy［J］. Basic Res Cardiol， 1987， 82（Suppl 1）： 63-73.
18
DONISI I， BALESTRIERI A， DEL VECCHIO V， et al. L-carnitine and acetyl-l-carnitine induce metabolism alteration and mitophagy-related cell death in colorectal cancer cells［J］. Nutrients， 2025， 17（6）： 1010.
19
VAN DER WINDT G J W， EVERTS B， CHANG C H， et al. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development［J］. Immunity， 2012， 36（1）： 68-78.
20
MIWA S， KASHYAP S， CHINI E， et al. Mitochondrial dysfunction in cell senescence and aging［J］. J Clin Invest， 2022， 132（13）： e158447.
21
SAVITZ J. The kynurenine pathway： a finger in every pie［J］. Mol Psychiatry， 2020， 25（1）： 131-147.
22
CHINI C C S， CORDEIRO H S， LE KIM T， et al. NAD metabolism： Role in senescence regulation and aging［J］. Aging Cell， 2024， 23（1）： e13920.
23
VIL’NER G A， LITOV M B， PASSOV L B， et al. The complex adjustment system for the microprocessor units［J］. Med Tekh， 1990（2）： 32-34.
24
HERBSTEIN F， SAPOCHNIK M， ATTORRESI A， et al. The SASP factor IL-6 sustains cell-autonomous senescent cells via a cGAS-STING-NFκB intracrine senescent noncanonical pathway［J］. Aging Cell， 2024， 23（10）： e14258.
25
MATSUDA T， YAMAGAMI R， IHARA A， et al. A transfer RNA methyltransferase with an unusual domain composition catalyzes 2'-O-methylation at position 6 in tRNA［J］. Nucleic Acids Res， 2025， 53（13）： gkaf579.
26
FU Y H， DU M Y， CAO Z G， et al. PGC-1α attenuates TNF-α-induced inflammatory responses in OCCM-30 cells［J］. J Periodontal Res， 2022， 57（5）： 1024-1033.
27
KIM M S， SWEENEY T R， SHIGENAGA J K， et al. Tumor necrosis factor and interleukin 1 decrease RXRalpha， PPARalpha， PPARgamma， LXRalpha， and the coactivators SRC-1， PGC-1alpha， and PGC-1beta in liver cells［J］. Metabolism， 2007， 56（2）： 267-279.
28
王业，钟威，商微，等.子宫内膜异位症亚型与不孕症的因果关系：双向孟德尔随机化研究［J］.陆军军医大学学报，2025，47（16）：1962-1969.
WANG Y， ZHONG W， SHANG W， et al. Causal effects between different sub-phenotypes of endometriosis and female infertility： a bidirectional Mendelian randomization study［J］. J Army Med Univ， 2025， 47（16）： 1962-1969.
2026年第48卷第5期
PDF下载
51
23
引用本文
BibTeX
文章信息
doi: 10.16016/j.2097-0927.202512135
  • 接收时间：2025-12-24
  • 首发时间：2026-10-23
  • 出版时间：2026-03-15
补充材料
相关文章
文章信息
作者
出版历史
  • 收稿日期：2025-12-24
  • 修回日期：2026-01-26
基金
作者信息
    1陆军军医大学（第三军医大学）第二附属医院肾内科，肾脏病防治重庆市重点实验室，重庆市肾病与泌尿系统疾病临床医学研究中心，重庆

通讯作者:

赵景宏，E-mail：
ZHAO Jinghong， E-mail：
参考文献
分享链接
https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/10.16016/j.2097-0927.202512135
分享至
全文二维码

扫描看全文

引用本文
BibTeX
本文的引用情况
2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
关闭全屏
相关链接
论文
最新文章
热读文章
热点专题
内参
蓝皮书
产业发展报告
传播力报告
期刊分级目录
资讯
学术新闻
行业新闻
学术会议
行业会议
关于
关于我们
联系我们
北京市海淀区学院南路86号
100081
010-62662699（运营及技术支持）
qkjq@cast.org.cn

中国科学技术协会版权所有 京ICP 备10216604号-4 海淀分局备案 1101084647
科技导报社主办 中国科协信息中心技术支持