{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:56:23Z","timestamp":1781880983549,"version":"3.54.5"},"reference-count":24,"publisher":"Wiley","issue":"3-4","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":52,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2025YFC3408700"],"award-info":[{"award-number":["2025YFC3408700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2025YFC3408701"],"award-info":[{"award-number":["2025YFC3408701"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Digest Diseases"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To explore the involvement of neutrophil dysregulation in Cronkhite\u2013Canada syndrome (CCS) and to identify serum biomarkers for its diagnosis and disease activity assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed comprehensive serum proteomic analysis using data\u2010independent acquisition (DIA) on samples from patients with active CCS (aCCS) and healthy controls (HCs). Candidate proteins were further evaluated by parallel reaction monitoring (PRM). An independent validation cohort including cases with aCCS, remitting CCS (rCCS), and HCs was then assessed using enzyme\u2010linked immunosorbent assay (ELISA). In addition, previously generated transcriptomic data and immunofluorescence staining of colonic polyps were used to assess local neutrophil extracellular trap (NET)\u2010related immune changes in intestinal tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Proteomic screening identified 362 differentially expressed proteins, and bioinformatic analysis consistently highlighted pathways related to neutrophil activation, acute inflammation, and NET formation. Key neutrophil\u2010associated proteins, including myeloperoxidase (MPO), lipocalin\u20102 (LCN2), and matrix metalloproteinase\u20109 (MMP\u20109), were significantly upregulated. PRM validated seven upregulated candidate proteins. In the independent validation cohort, compared with HCs, serum MPO\u2010DNA complexes, LCN2, and MMP\u20109 were significantly elevated in aCCS patients, whereas MPO\u2010DNA complexes and MMP\u20109 were significantly reduced in rCCS cases. Tissue\u2010level transcriptomic and immunofluorescence analyses further supported NET\u2010related immune activation in CCS colonic polyps. Receiver operating characteristic curve analysis demonstrated favorable diagnostic performance for these biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings support the involvement of neutrophil dysregulation and NET\u2010associated pathways in CCS pathobiology. Serum MPO\u2010DNA complexes, LCN2, and MMP\u20109 may serve as promising non\u2010invasive biomarkers for diagnosis and disease activity monitoring. Further studies incorporating disease control cohorts and mechanistic validation are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1751-2980.70046","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:06:01Z","timestamp":1776852361000},"page":"129-138","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Neutrophil Extracellular Trap\u2010Related Proteins Serving as Potential Diagnostic and Disease Activity Biomarkers of Cronkhite\u2013Canada Syndrome"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0206-318X","authenticated-orcid":false,"given":"Run Feng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Chinese Academy of Medical Sciences, Peking Union Medical College Hospital  Beijing China"},{"name":"Department of Internal Medicine Chinese Academy of Medical Sciences, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Fei","family":"Zhi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Chinese Academy of Medical Sciences, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng Zhu","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Chinese Academy of Medical Sciences, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"You","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2099-5140","authenticated-orcid":false,"given":"Shuang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Allergy Chinese Academy of Medical Sciences, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu Shi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Chinese Academy of Medical Sciences, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian Ming","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Chinese Academy of Medical Sciences, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4173-3169","authenticated-orcid":false,"given":"Qi Pu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Chinese Academy of Medical Sciences, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Chinese Academy of Medical Sciences, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing Nan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Chinese Academy of Medical Sciences, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0285-2966","authenticated-orcid":false,"given":"Ji","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Chinese Academy of Medical Sciences, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM195506162522401"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2014-202488"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-015-1107-7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2188\/jea.JE20190349"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcaf088"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00384\u2010023\u201004332\u2010w"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000167"},{"issue":"1","key":"e_1_2_9_9_1","first-page":"3","article-title":"Cronkhite\u2010Canada Syndrome: Epidemiological Study of 110 Cases Reported in Japan","volume":"64","author":"Goto 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