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This study investigates how diabetes promotes gallstone formation and elucidates the underlying mechanism.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods<\/jats:bold>\n                    : Data from the National Health and Nutrition Examination Survey and Mendelian randomization analyses were used to identify the causal relationship between diabetes and gallstones. Through the integration of multi\u2010omics sequencing and molecular dynamics simulation, CXCR2 was identified as a molecular bridge linking both diseases. Animal models were established, and Western blotting, reverse transcription quantitative polymerase chain reaction, and enzyme\u2010linked immunosorbent assay were employed to explore the relevant mechanisms.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : Clinical data demonstrated that diabetes is an independent risk factor for gallstones. Animal experiments revealed that diabetes upregulated the expression of CXCR2 in hepatic neutrophils, thereby promoting the formation of neutrophil extracellular traps (NETs). Excessive NETs disrupted the tight junctions between hepatocytes, allowing NETs to enter the bile and accelerate gallstone formation. Moreover, sarcosine inhibited CXCR2 expression, reduced NETs production, and decreased gallstone formation.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions<\/jats:bold>\n                    : Diabetes promotes NETs formation through CXCR2 activation, which damages the liver\u2010bile barrier and facilitates gallstone development. Sarcosine may serve as a potential therapeutic agent, providing a theoretical basis for clinical intervention.\n                  <\/jats:p>","DOI":"10.1002\/advs.202519500","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:16:14Z","timestamp":1771272974000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diabetes Mellitus Facilitates Gallstone Formation Through CXCR2\u2010NETs\u2013Mediated Liver\u2010Bile Barrier Damage"],"prefix":"10.1002","volume":"13","author":[{"given":"Chao","family":"Shi","sequence":"first","affiliation":[{"name":"Department of General Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery Ministry of Education, The First Affiliated Hospital of Harbin Medical University  Harbin 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