{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:36:22Z","timestamp":1774431382723,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":83,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic foot ulcer (DFU), a severe complication of diabetes, impose substantial global health burdens. Dampness\u2013heat syndrome (DHS), a common syndrome in traditional Chinese medicine (TCM), is highly prevalent among DFU patients and closely correlated with treatment response and prognosis. However, the molecular biomarkers associated with DFU in patients with DHS remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Serum 4D\u2010data\u2010independent acquisition (DIA) proteomics was performed on 16 DFU\u2013DHS patients and six healthy controls (HCs). Differentially expressed proteins (DEPs) were screened by |fold change (FC)| &gt;\u20091.2 and\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein\u2013protein interaction (PPI) analyses were conducted. Key biomarkers were validated via enzyme\u2010linked immunosorbent assay (ELISA) in 28 independent DFU\u2013DHS cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 201 DEPs were identified between DFU\u2013DHS patients and HCs. Bioinformatics revealed DEPs enriched in lipid metabolism (high\u2010density lipoprotein [HDL] remodeling and cholesterol metabolism) and complement\u2013coagulation cascades. PPI network analysis revealed a core functional module centered on four proteins, APOA1, LCAT, PLTP, and CETP. ELISA validation confirmed the significant dysregulation of these four apolipoproteins in the independent DFU\u2013DHS cohort (all\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05 vs. HCs). The combination of the biomarkers APOA1, LCAT, PLTP, and CETP exhibited a high diagnostic efficacy for DFU\u2013DHS, with an area under the curve (AUC) of 0.9672 based on receiver operating characteristic (ROC) analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>To our knowledge, this is the first study to employ 4D\u2010DIA proteomics on DFU\u2013DHS. We identified four serum biomarkers (APOA1, LCAT, PLTP, and CETP) linked to dysregulated cholesterol metabolism in DFU\u2013DHS patients, which show diagnostic potential and provide insights for integrating TCM syndrome differentiation with precision medicine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/jdr\/6604989","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T07:01:47Z","timestamp":1774422107000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of Biomarkers in Diabetic Foot Ulcer Patients With Dampness\u2013Heat Syndrome Based on 4D\u2010DIA Proteomics Technology"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4549-0246","authenticated-orcid":false,"given":"Jinlun","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiming","family":"Ni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawei","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2552-4754","authenticated-orcid":false,"given":"Mingmei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-6987","authenticated-orcid":false,"given":"Cheng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"e_1_2_14_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1615439"},{"key":"e_1_2_14_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13169-8"},{"key":"e_1_2_14_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-015-0057-7"},{"key":"e_1_2_14_4_2","doi-asserted-by":"publisher","DOI":"10.2337\/dci22-0043"},{"key":"e_1_2_14_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.foot.2022.101909"},{"key":"e_1_2_14_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2019.107843"},{"key":"e_1_2_14_7_2","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S275814"},{"key":"e_1_2_14_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0216701"},{"key":"e_1_2_14_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0683-2"},{"key":"e_1_2_14_10_2","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v13.i10.851"},{"key":"e_1_2_14_11_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6390530"},{"key":"e_1_2_14_12_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/492193"},{"key":"e_1_2_14_13_2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/3585617"},{"key":"e_1_2_14_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-03110-9"},{"key":"e_1_2_14_15_2","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn501225-20220822-00354"},{"key":"e_1_2_14_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2024.100800"},{"key":"e_1_2_14_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40744-023-00636-z"},{"key":"e_1_2_14_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002843"},{"key":"e_1_2_14_19_2","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2023.1621"},{"key":"e_1_2_14_20_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/351601"},{"key":"e_1_2_14_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104916"},{"key":"e_1_2_14_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218075"},{"key":"e_1_2_14_23_2","doi-asserted-by":"publisher","DOI":"10.1159\/000478097"},{"key":"e_1_2_14_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-024-00601-0"},{"key":"e_1_2_14_25_2","doi-asserted-by":"publisher","DOI":"10.1590\/S1516-89132013005000013"},{"key":"e_1_2_14_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003224"},{"key":"e_1_2_14_27_2","doi-asserted-by":"publisher","DOI":"10.1517\/17530059.2.3.277"},{"key":"e_1_2_14_28_2","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2022.2027173"},{"key":"e_1_2_14_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/medicina58121866"},{"key":"e_1_2_14_30_2","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/5722131"},{"key":"e_1_2_14_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-019-4959-1"},{"key":"e_1_2_14_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109565"},{"key":"e_1_2_14_33_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/378790"},{"key":"e_1_2_14_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00569-6"},{"key":"e_1_2_14_35_2","doi-asserted-by":"publisher","DOI":"10.5704\/MOJ.2307.010"},{"key":"e_1_2_14_36_2","unstructured":"Yu-zhenW. 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