{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:44:59Z","timestamp":1753879499439,"version":"3.41.2"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260448"],"award-info":[{"award-number":["82260448"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017691","name":"Guangxi Key Research and Development Program","doi-asserted-by":"publisher","award":["2021AB11027"],"award-info":[{"award-number":["2021AB11027"]}],"id":[{"id":"10.13039\/501100017691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inflammatory cytokines are key indicators affecting the development of ulcers of lower limb. The causal role of inflammatory cytokines in ulcers of lower limb and whether this can be mediated by metabolites remain unknown. We conducted a two\u2010step, two\u2010sample Mendelian randomization (MR) study to investigate the causal effect of inflammatory cytokines on ulcers of lower limb and the mediating role of metabolites in the association between inflammatory cytokines and ulcers of lower limb. MR analysis identified seven inflammatory cytokines (CCL19, IL\u201012\u03b2, MCP4, MIP1a, SCF, sirtuin2, and TNFSF9) that promote ulcers of lower limb. Additionally, 56 metabolites were found to be associated with ulcers of lower limb. Mediation MR indicated that the causal effect of sirtuin2 on ulcers of lower limb (total effect Inverse Variance Weighted [IVW]: odds ratio [OR]\u2009=\u20091.162, 95% confidence interval [CI] [1.051, 1.285], <jats:italic>p<\/jats:italic>\u2009=\u20090.003) is largely mediated by 4\u2010hydroxyphenylacetate (0.0185, 95% CI [\u22120.00278, 0.0397], accounting for 11.1% of the total effect).<\/jats:p>","DOI":"10.1111\/wrr.13243","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T08:34:52Z","timestamp":1736152492000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal relationship between inflammatory cytokines, metabolites, and ulcers of lower limb: A Mendelian randomization study"],"prefix":"10.1111","volume":"33","author":[{"given":"Yongjun","family":"Mo","sequence":"first","affiliation":[{"name":"Department of Bone and Joint Surgery (Guangxi Diabetic Foot Salvage Engineering Research Center\/Research Centre for Regenerative Medicine) The First Affiliated Hospital of Guangxi Medical University  Nanning Guangxi China"},{"name":"Department of Orthopedics Guigang People's Hospital  Guigang Guangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peilin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Bone and Joint Surgery (Guangxi Diabetic Foot Salvage Engineering Research Center\/Research Centre for Regenerative Medicine) The First Affiliated Hospital of Guangxi Medical University  Nanning Guangxi China"},{"name":"Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co\u2010Constructed by the Province and Ministry Guangxi Medical University  Nanning Guangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bone and Joint Surgery (Guangxi Diabetic Foot Salvage Engineering Research Center\/Research Centre for Regenerative Medicine) The First Affiliated Hospital of Guangxi Medical University  Nanning Guangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongzhen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Bone and Joint Surgery (Guangxi Diabetic Foot Salvage Engineering Research Center\/Research Centre for Regenerative Medicine) The First Affiliated Hospital of Guangxi Medical University  Nanning Guangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhanming","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Bone and Joint Surgery (Guangxi Diabetic Foot Salvage Engineering Research Center\/Research Centre for Regenerative Medicine) The First Affiliated Hospital of Guangxi Medical University  Nanning Guangxi 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First Affiliated Hospital of Guangxi Medical University  Nanning Guangxi China"},{"name":"Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qikai","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Bone and Joint Surgery (Guangxi Diabetic Foot Salvage Engineering Research Center\/Research Centre for Regenerative Medicine) The First Affiliated Hospital of Guangxi Medical University  Nanning Guangxi China"},{"name":"Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co\u2010Constructed by the Province and Ministry Guangxi Medical University  Nanning Guangxi 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