{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:04:21Z","timestamp":1792785861012,"version":"4.5.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070570"],"award-info":[{"award-number":["82070570"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101192"],"award-info":[{"award-number":["82101192"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Science and Technology Innovation Initiative","award":["22S31903500"],"award-info":[{"award-number":["22S31903500"]}]},{"name":"Shanghai Science and Technology Innovation Initiative","award":["21SQBS02302"],"award-info":[{"award-number":["21SQBS02302"]}]},{"name":"Shanghai Baoshan District Science and Technology Foundation","award":["21-E-05"],"award-info":[{"award-number":["21-E-05"]}]},{"name":"Ren Ji Hospital Cultivated Funding for Clinical Research Innovation","award":["RJPY-LX-004"],"award-info":[{"award-number":["RJPY-LX-004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Perianal fistulizing Crohn\u2019s disease [pfCD] is a disabling phenotype of Crohn\u2019s disease [CD] with suboptimal outcomes. We assessed neutrophil extracellular traps [NETs] in perianal fistulas and implicated their roles in pfCD healing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with complex pfCD who developed preplaced seton drainage were recruited during the verified maintenance of remission in CD. Fistula tracts were sampled during definitive surgery plus seton removal. Patient demographics, CD classification, medication strategy and healing of pfCD were recorded. RNA sequencing was applied for transcriptomic profile analysis. NET components, including myeloperoxidase [MPO], neutrophil elastase [NE] and citrullinated histone H3 [CitH3], were identified using immunofluorescence. Serum infliximab [IFX], anti-IFX antibodies, and tissue levels of IFX, adalimumab [ADA], MPO and CitH3 were determined using enzyme-linked immunosorbent assays. Peptidyl arginine deiminase IV [PAD4], tumour necrosis factor [TNF]-\u03b1, and NE were detected using immunohistochemistry. Gene expression levels of PAD family members were assessed with quantitative PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-one patients were included, 15 of whom adopted IFX as maintenance treatment. RNA-sequencing revealed differences in neutrophil associated pathways between unhealed and healed fistulas. NET components [MPO\/NE\/CitH3] were detectable in the fistulas and were parallel with the levels of PAD4. Eleven of 21 [52%] patients experienced complete healing of the pfCD 108 weeks post-operatively. Fistula NETs were significantly increased in patients with unhealed pfCD. Increased NETs were associated with abundant TNF-\u03b1 production and the absence of IFX in fistulas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>NETs exist in pfCD fistulas, which are associated with unhealed post-operative fistulas in pfCD, suggesting their prognostic roles in pfCD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjac171","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T14:28:41Z","timestamp":1667399321000},"page":"580-592","source":"Crossref","is-referenced-by-count":19,"title":["Association of Neutrophil Extracellular Traps with Fistula Healing in Patients with Complex Perianal Fistulizing Crohn\u2019s Disease"],"prefix":"10.1093","volume":"17","author":[{"given":"Dongxing","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200127 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyu","family":"Qian","sequence":"additional","affiliation":[{"name":"Laboratory of Medicine, Baoshan Branch, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200444 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Cancer Institute; Shanghai Institute of Digestive Disease; Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Hong","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Cancer Institute; Shanghai Institute of Digestive Disease; Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyan","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Cancer Institute; Shanghai Institute of Digestive Disease; Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Baoshan Branch, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200444 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nailin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200127 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200127 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingkai","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Baoshan Branch, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200444 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyu","family":"Jia","sequence":"additional","affiliation":[{"name":"Laboratory of Medicine, Baoshan Branch, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200444 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200444 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Zhu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200127 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Shen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Ren Ji Hospital, School of Medicine, Shanghai Institute of Digestive 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200127 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"2023041916523144900_CIT0001","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1136\/gutjnl-2013-306709","article-title":"A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn\u2019s disease","volume":"63","author":"Gecse","year":"2014","journal-title":"Gut"},{"key":"2023041916523144900_CIT0002","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1136\/gutjnl-2017-314918","article-title":"Modern management of perianal fistulas in Crohn\u2019s disease: future 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