{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T23:15:03Z","timestamp":1779318903730,"version":"3.51.4"},"reference-count":26,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"unspecified","delay-in-days":33,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700451"],"award-info":[{"award-number":["81700451"]}],"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":["82070532"],"award-info":[{"award-number":["82070532"]}],"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":["82370522"],"award-info":[{"award-number":["82370522"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Unit of Minimally Invasive Pediatric Surgery on Diagnosis and Treatment, Chinese Academy of Medical Sciences","award":["2021RU015"],"award-info":[{"award-number":["2021RU015"]}]},{"name":"Beijing Municipal Administration of Hospitals Incubating Program","award":["PX2020054"],"award-info":[{"award-number":["PX2020054"]}]},{"name":"Beijing Municipal Administration of Hospitals Incubating Program","award":["PX2022054"],"award-info":[{"award-number":["PX2022054"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["World Jnl Ped Surgery"],"accepted":{"date-parts":[[2025,6,2]]},"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Hirschsprung\u2019s disease (HSCR) is a functional obstruction of the gastrointestinal tract characterized by abdominal distension, constipation, and vomiting. The protein zonulin serves as a biomarker for intestinal permeability. We sought to explore the changes in plasma zonulin levels in patients with HSCR and to assess its predictive role in the development of postoperative Hirschsprung-associated enterocolitis (HAEC).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>There are 60 patients with HSCR were recruited for this study, categorized into short-segment disease (S-HSCR) (<jats:italic>n<\/jats:italic>=33), long-segment disease (L-HSCR) (<jats:italic>n<\/jats:italic>=15), and total colonic aganglionosis (TCA) (<jats:italic>n<\/jats:italic>=12). Venous blood samples were taken from all participants before and after pull-through surgery. Plasma concentrations of zonulin were determined using an ELISA. Immunohistochemistry (IHC) analysis was conducted to evaluate the expression of zonula occludens-1 (ZO-1) and occludin in colonic tissues. Hematoxylin and Eosin stained (H&amp;E-stained) sections were used to evaluate the degree of inflammation in the dilated (ganglionic) segment. Postoperative outcomes were assessed through a combination of online questionnaires and telephone interviews. Diagnostic threshold for HAEC was based on clinical symptom sets and the HAEC scoring system developed previously.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Preoperative zonulin levels in patients with TCA were statistically lower than those in patients with S-HSCR (<jats:italic>p<\/jats:italic>=0.008) and L-HSCR (<jats:italic>p<\/jats:italic>=0.028). The incidence of postoperative HAEC was 16.7%, 57.1%, and 14.3% in TCA, L-HSCR, and S-HSCR groups, respectively. Patients who experienced an increase in plasma zonulin levels of more than 1.5 times those on the first day after surgery had a higher risk of developing HAEC (<jats:italic>p<\/jats:italic>=0.005). IHC staining further confirmed decreased expression of ZO-1 and occludin in colonic tissues of patients with HSCR who experienced postoperative HAEC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Preoperative zonulin levels were lowest in the TCA group. The change in zonulin levels on the first day after surgery can serve as a useful indicator for predicting the risk of postoperative HAEC occurrence.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/wjps-2025-001057","type":"journal-article","created":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T09:30:13Z","timestamp":1751707813000},"page":"e001057","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Predictive value of plasma zonulin for postoperative Hirschsprung-associated enterocolitis"],"prefix":"10.1136","volume":"8","author":[{"given":"Lihua","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruijie","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agostino","family":"Pierro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1921-4979","authenticated-orcid":false,"given":"Qi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,7,5]]},"reference":[{"key":"2025091622201742000_8.3.e001057.1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41572-023-00465-y","article-title":"Hirschsprung 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