Sclerosing cholangitis, characterized by biliary inflammation, fibrosis, and stricturing, remains one of the most challenging conditions of clinical hepatology. Geniposide (GE) has anti-inflammatory, hepatoprotective, and cholagogic effects. Whether GE provides inhibition on the development of sclerosing cholangitis is unknown. Here, we investigated the role of GE in a mouse model in which mice were fed with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 4 weeks to induce sclerosing cholangitis. The results demonstrated that the increased hepatic gene expressions of pro-inflammatory (IL-6, VCAM-1, MCP-1, and F4/80) and profibrogenic markers (Col1α1, Col1α2, TGF-β, and α-SMA) in DDC feeding mice were reversed after treatment with GE. GE also suppressed expressions of CK19 and Ki67 in DDC-fed mice, suggesting that GE could ameliorate DDC-induced hepatocytes and cholangiocytes proliferation. In addition, GE significantly increased bile acids (BAs) secretion in bile, which correlated with induced expressions of hepatic FXR, BAs secretion transporters (BSEP, MRP2, MDR1, and MDR2), and reduced CYP7A1 mRNA expression. Furthermore, higher expressions of ileal FXR-FGF15 signaling and reduced ASBT were also observed after GE treatment. Taken together, these data showed that GE could modulate inflammation, fibrosis, and BAs homeostasis in DDC-fed mice, which lead to efficiently delay the progression of sclerosing cholangitis.

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PGC-1α and CARM1 interact with FXR to increase FXR-dependent BSEP expression upon GE treatment.

Objective To construct a scientific and comprehensive emergency preparedness evaluation index system of public for major emerging infectious diseases (MEIDs). Methods Based on the global national-level emergency preparedness index framework and a literature review, a preliminary index system was constructed. From June 2022 to September 2022, a panel of 20 experts from the fields of public health, infectious diseases, disease control, and psychology participated in the study. They rated the importance of pre-defined indicators using a five-point Likert scale. The index inclusion criteria were: mean scores of importance > 3.5, coefficient of variation < 2.5, and full mark rate > 20%. According to the feedback of each round of experts, the indicators of the index system were revised. Results After two rounds of expert consultation, the evaluation index system reached a consensus. The expert authority coefficient of consultation was 0.88 and 0.90. The Kendall’s coefficient of concordance of expert consultations was 0.294 and 0.322, respectively. The differences were statistically significant (P < 0.05). Finally, the emergency preparedness evaluation index system of public for major emerging infectious diseases was ultimately formed, including five first-level indicators, 20 second-level indicators and 53 third-level indicators. Conclusion The evaluation index system established by experts was reasonably scientific and could be used as a tool to evaluate the emergency preparedness of public for major emerging infectious diseases. At the same time, it could provide a reference for future education and training.