Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Objective:To evaluate the efficacy and safety of triamcinolone acetonide-saline submucosal injection for prevention of esophageal stricture after endoscopic submucosal dissection (ESD) for extensive superficial esophageal neoplasms.Methods:A total of 75 patients who underwent ESD for superficial esophageal neoplasms involving larger than 2/3 of the esophageal circumference at the Department of Gastroenterology, Northern Jiangsu People's Hospital from January 2018 to December 2020 were enrolled. Patients were randomly assigned to triamcinolone acetonide-saline submucosal injection group (group A, n=25), triamcinolone acetonide injections immediately after ESD group (group B, n=25) and the control group undergoing only ESD (group C, n=25). Serial gastroscopy was performed to assess wound healing and esophageal stricture. Endoscopic balloon dilatation (EBD) was performed when patients experienced esophageal stricture. The completion of ESD, time of operation, the amount of triamcinolone acetonide, the incidences of esophageal stricture and the time of EBD treatment of the three groups were compared. Results:All ESD procedures were successfully performed without complications such as intraoperative perforation, massive bleeding or postoperative delayed perforation. The operation time of group A, B and C were 72.87±12.99 min, 94.15±14.22 min and 74.08±11.86 min, respectively, with significant difference ( F=20.925, P<0.001). In pairwise comparison the above indicator in group A and group C was significantly shorter than that of group B (LSD- t=5.759, P<0.001; LSD- t=5.432, P<0.001), but there was no difference between group A and group C (LSD- t=0.327, P=0.745). There was no significant difference in the amount of triamcinolone acetonide between group A and group B (125±15 mg VS 133±19 mg, t=1.673, P=0.101). The rates of wound healing under endoscopy after 1 month of group A, B and C were 76% (19/25), 84% (21/25), and 76% (19/25), respectively, with no significant difference ( χ2=0.636, P=0.728). The esophageal stricture rates were 52% (13/25) in both group A and B, and 84% (21/25) in group C, with significant difference among the three groups ( χ2=7.295, P=0.026), and group A and B showed a significantly lower stricture rate than that of group C ( P=0.015; P=0.015). The median time of EBD treatment of group A, B and C were 4 (range 0 to 9), 5 (range 0 to 13) and 9 (range 0 to 16), respectively, with significant difference ( H=17.58, P<0.001). In pairwise comparison the above indicator in group A and B was significantly less than that of group C ( H=23.96, P<0.001; H=19.00, P=0.002), but there was no significant difference between group A and group B ( H=4.96, P=0.407). Esophageal stricture was observed in all patients with circumferential mucosa resected in the three groups. But the times of EBD treatment were 6.90±1.10 in group A, 10.13±2.42 in group B and 15.29±0.76 in group C with significant difference ( F=57.754, P<0.001). In pairwise comparison the above indicator in group A was less than that in group B (LSD- t=4.294, P<0.001) and this indicator in group B was less than that in group C (LSD- t=6.294, P<0.001). Median EBD times in patients with non-circumferential mucosal defects in the three groups were 0 (range 0 to 9), 0 (range 0 to 6) and 8 (range 0 to10), respectively, with significant difference ( H=19.72, P<0.001). In pairwise comparison, the EBD time in group A and B was less than that in group C ( H=17.93, P<0.001; H=16.62, P<0.001), but there was no statistical difference between group A and B ( H=1.31, P=0.779). Conclusion:Triamcinolone acetonide-saline submucosal injection ESD can safely and effectively prevent esophageal stricture after ESD for large-area superficial esophageal neoplasms, reduce the operation time and time of EBD treatment in patients with circumferential mucosa defect compared with local injections of triamcinolone acetonide after ESD.