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In this study, a comprehensive inventory of pre\u2010, intra\u2010, and postoperative clinical and biological data of two cohorts (62 pancreatic cancer [PCa] and 111 pancreatic ductal adenocarcinoma [PDAC]) which could induce POPF were retrospectively analyzed. Then, a total of 7644 genes correlated with HYAL\u20101 was predicted in PDAC tissues and the enriched pathway, kinase targets and biological process of those correlated genes were evaluated. Finally, a mouse pancreatic fistula (PF) model was first built and in vitro studies were performed to investigate the effects of HYAL\u20101 on PF progression. Our data indicated that preoperative serum HYAL\u20101 level, pancreatic fibrosis score, and pancreatic duct size were valuable factors for detecting POPF of Grade B and C. The serum HYAL\u20101 level of 2.07\u00a0mg\/ml and pancreatic fibrosis score of 2.5 were proposed as the cutoff values for indicating POPF. The bioinformatic analysis and in vitro\n                    <jats:italic>and<\/jats:italic>\n                    in vivo studies demonstrated that HYAL\u20101 facilitates pancreatic acinar cell autophagy via the dephosphorylation of adenosine 5\u2018\u2010monophosphate\u2010activated protein kinase (AMPK) and signal transducers and activators of transcription 3 (STAT3) signaling pathways, which exacerbate pancreatic secretion and inflammation. In summary, the preoperative serum HYAL\u20101 was a significant predictor for POPF in patients who underwent PD. Tumor\u2010induced HYAL\u20101 is one of core risk in accelerating PF and then promoting pancreatic secretion and acute inflammation response through the AMPK and STAT3\u2010induced autophagy.\n                  <\/jats:p>","DOI":"10.1096\/fj.201901583r","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T04:22:56Z","timestamp":1576729376000},"page":"2524-2540","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["HYAL\u20101\u2010induced autophagy facilitates pancreatic fistula for patients who underwent pancreaticoduodenectomy"],"prefix":"10.1096","volume":"34","author":[{"given":"Le","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pancreatic and Biliary Surgery The First Affiliated Hospital of Harbin Medical University Harbin 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