{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:20:30Z","timestamp":1793658030764,"version":"4.5.1"},"reference-count":25,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7252113"],"award-info":[{"award-number":["7252113"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970495"],"award-info":[{"award-number":["81970495"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2507302"],"award-info":[{"award-number":["2023YFC2507302"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Peking Union Medical College Hospital Talent Cultivation Program","award":["Category D, UHB11899"],"award-info":[{"award-number":["Category D, UHB11899"]}]},{"name":"The National HighLevel Hospital Clinical Research Funding","award":["2025-PUMCH-A-101"],"award-info":[{"award-number":["2025-PUMCH-A-101"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therap Adv Gastroenterol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Although endoscopic remission is a primary therapeutic target in ulcerative colitis (UC), a meaningful proportion of patients with endoscopic healing still experience clinical relapse (CR). Histologic activity and epithelial barrier dysfunction may help explain this residual risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To develop and internally assess an exploratory tissue-based risk prediction model combining histologic activity with epithelial barrier and immunoregulatory markers for relapse risk stratification in UC patients with endoscopic healing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Multicenter prospective observational cohort study with internal model assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Consecutive UC patients with confirmed endoscopic remission (Mayo Endoscopic Subscore 0 or 1) were followed for 12\u2009months. Baseline colonic biopsies were assessed using the Nancy Histological Index (NHI) and immunohistochemical quantification of vitamin D receptor (VDR), Claudin-2, and mucin-2 (MUC-2). A prespecified four-marker logistic regression model was developed using these tissue-based predictors. Model performance was described by receiver operating characteristic analysis, calibration assessment, 1000-sample bootstrap internal validation, and exploratory therapeutic subgroup analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Among 145 patients, 36 (24.8%) experienced CR within 12\u2009months. In the final four-marker model, higher Claudin-2 and NHI were associated with increased relapse risk, whereas higher VDR and MUC-2 expression were protective. The model showed high apparent discrimination in the development cohort (area under the curve (AUC)\u2009=\u20090.968, 95% confidence interval: 0.943\u20130.992). Bootstrap internal validation yielded an optimism-corrected AUC of 0.957, Brier score of 0.075, calibration intercept of \u22120.067, and calibration slope of 0.827. A data-derived Youden cut-off of 0.379 classified 39 patients as higher risk, of whom 32 relapsed, and 106 patients as lower risk, of whom 4 relapsed. These estimates reflect internal model performance and should be interpreted cautiously because of the limited number of events and absence of external validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>A tissue-based model integrating Claudin-2, VDR, MUC-2, and NHI may help identify UC patients with different relapse risks despite endoscopic healing. These findings are exploratory and hypothesis-generating, and external validation with standardized biomarker quantification is required before clinical implementation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17562848261465757","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T16:29:57Z","timestamp":1784651397000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of a tissue-based risk prediction model combining histology and barrier biomarkers for clinical relapse in ulcerative colitis with endoscopic healing"],"prefix":"10.1177","volume":"19","author":[{"given":"Yubin","family":"Cao","sequence":"first","affiliation":[{"name":"Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9092-7592","authenticated-orcid":false,"given":"Xiaoyin","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonglin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Daqing People\u2019s Hospital, Daqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Peking University Third Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2986-7324","authenticated-orcid":false,"given":"Hong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.7861\/clinmed.2021-0080"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.101866"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.06.043"},{"issue":"9","key":"e_1_3_5_5_2","first-page":"1976","article-title":"The relapse rate of inflammatory bowel disease (IBD) in patients who discontinue anti-TNF therapy: a systematic review and meta-analysis","volume":"53","author":"Ebrahimi F","year":"2024","unstructured":"Ebrahimi F, Torkian S, Zare-Farashbandi E, et al. The relapse rate of inflammatory bowel disease (IBD) in patients who discontinue anti-TNF therapy: a systematic review and meta-analysis. Iran J Public Health 2024; 53(9): 1976\u20131991.","journal-title":"Iran J Public Health"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2021.1840976"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.15389"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.12.031"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-310187"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2016.418"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2024.2326838"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12876-022-02157-5"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006451107"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i11.3117"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.20517\/mrr.2025.96"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-147-8-200710160-00010"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjaf106"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000235"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-68372-0"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.848344"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803124105"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1407597111"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18010157"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S363840"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65842"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep10642"}],"container-title":["Therapeutic Advances in Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17562848261465757","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17562848261465757","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17562848261465757","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T05:06:34Z","timestamp":1787288794000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17562848261465757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":25,"alternative-id":["10.1177\/17562848261465757"],"URL":"https:\/\/doi.org\/10.1177\/17562848261465757","relation":{},"ISSN":["1756-2848","1756-2848"],"issn-type":[{"value":"1756-2848","type":"print"},{"value":"1756-2848","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"article-number":"17562848261465757"}}