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BackgroundThe interleukin-1 pathway has been linked to pancreatic diseases. We applied the Mendelian randomization approach to explore whether higher interleukin-1 receptor antagonist (IL-1RA) levels reduce the risk of acute and chronic pancreatitis and pancreatic cancer.MethodsGenetic variants associated with blood IL-1RA levels at the genome-wide significance level and located 5MB downstream or upstream of the IL1RN gene were extracted from a genome-wide meta-analysis of 21,758 participants. After pruning, genetic variants without linkage disequilibrium were used as genetic instrument for IL-1RA. Summary-level data on acute and chronic pancreatitis and pancreatic cancer were obtained from the UK Biobank and FinnGen studies. The associations were meta-analyzed for one outcome from two sources.ResultsGenetically predicted higher levels of IL-1RA were associated with a lower risk of acute and chronic pancreatitis and pancreatic cancer. In the meta-analysis of UK Biobank and FinnGen, the combined odds ratio was 0.87 (95% confidence interval [CI] 0.77-0.97, P=0.003) for acute pancreatitis, 0.73 (95% CI 0.65-0.82, P=2.93×10-8) for chronic pancreatitis, and 0.86 (95% CI 0.77-0.96, P=0.009) for pancreatic cancer per one standard deviation increment in genetically predicted levels of IL-1RA.ConclusionThis study suggests a protective role of IL-1RA in three major pancreatic diseases, which hints the therapeutic potentials of IL-1RA in pancreatic diseases.

BackgroundThe purpose of this paper is to develop and validate a standardized endoscopist acceptance scale for the implementation of artificial intelligence (AI) in gastrointestinal endoscopy.MethodsAfter investigating endoscopists who have previously used AI and consulting with AI experts, we developed a provisional scale to measure the acceptance of AI as used in gastrointestinal endoscopy that was then distributed to a sample of endoscopists who have used AI. After analyzing the feedback data collected on the provisional scale, we developed a new formal scale with four factors. Cronbach's alpha, confirmatory factor analysis (CFA), content validity, and related validity were conducted to test the reliability and validity of the formal scale. We also constructed a receiver operating characteristic (ROC) curve in order to determine the scale's ability to distinguish higher acceptance and satisfaction.ResultsA total of 210 valid formal scale data points were collected. The overall Cronbach's alpha was 0.904. All the factor loadings were >0.50, of which the highest factor loading was 0.86 and the lowest was 0.54 (AVE = 0.580, CR = 0.953). The correlation coefficient between the total score of the scale and the satisfaction score was 0.876, and the area under the ROC curve was 0.949 ± 0.031. Endoscopists with a score higher than 50 tend to be accepting and satisfied with AI.ConclusionThis study yielded a viable questionnaire to measure the acceptance among endoscopists of the implementation of AI in gastroenterology.

Numerous pieces of evidence have identified that the NLRP3 inflammasome plays a pivotal role in the development and pathogenesis of colitis. Targeting the NLRP3 inflammasome represents a potential therapeutic treatment. Our previous studies have suggested that acetylation of NLRP3 is indispensable to NLRP3 inflammasome activation, and some acetyltransferase inhibitors could suppress the NLRP3 inflammasome activation. Here, we identified that C646, an inhibitor of histone acetyltransferase p300, exerts anti-inflammatory effects in DSS-induced colitis mice by targeting the NLRP3 inflammasome. Mechanistically, C646 not only inhibits NF-κB activation, leading to the decreased expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and NLRP3, but also suppresses the NLRP3 inflammasome assembly by disrupting the interaction between NLRP3 and ASC. In addition, C646 attenuated the LPS-induced acute systemic inflammation model. Thus, our results demonstrate the ability of C646 to suppress the NLRP3 inflammasome activity and its potential application in the treatment of inflammatory bowel disease.