Expression of interleukin-22/STAT3 signaling pathway in ulcerative colitis and related carcinogenesis

AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.

Associations between the use of red yeast rice preparations and adverse health outcomes:An umbrella review of meta-analyses of randomized controlled trials

Background:Red yeast rice(RYR),a natural lipid-lowering agent,is widely used in clinical practice.However,the existing meta-analyses concerning the safety of RYR preparations have yielded inconsistent results,and the credibility of the evidence has not been quantified.Objective:This study was designed to evaluate the existing evidence and offer a comprehensive understanding of the associations between the use of RYR preparations and various adverse health outcomes.Search strategy:Seven literature databases were searched from inception to May 5,2023,using medical subject headings and free-text terms(e.g.,“red yeast rice,”“Xuezhikang,”and“Zhibitai”).Inclusion criteria:Meta-analyses that investigated and quantitatively estimated associations between the use of RYR preparations and adverse health outcomes were included in this study.Data extraction and analysis:Two researchers independently extracted data using a standardized data collection table;any disagreements were resolved by consulting a third researcher.Based on the participant,intervention,comparator and outcome(PICO)framework in each eligible meta-analysis,a series of unique associations between the use of RYR preparations and adverse health outcomes were determined.The associations’effect estimates were re-evaluated using random-effect models.Results:Fifteen meta-analyses,comprising 186(164 unique)randomized controlled trials,were identified.Based on A Mea Surement Tool to Assess Systematic Reviews version 2,3(20%)and 12(80%)of these meta-analyses had low and critically low confidence,respectively.A total of 61 unique associations between the use of RYR preparations and adverse health outcomes were extracted from eligible metaanalyses.Based on the random-effect models,10(16.4%)associations indicated a significant protective effect of RYR preparations against adverse health outcomes,while 5(8.2%)indicated an increased risk of adverse health outcomes related to uric acid,alanine transaminase and aspartate transaminase levels.The other 46(75.4%)associations showed no significant difference between the use of RYR preparations and control treatments.Regarding the credibility of the evidence,21(34.4%),34(55.7%)and 6(9.8%)associations showed moderate,low and very low credibility,respectively.Conclusion:The evidence examined in this study suggests that RYR preparations are safe;however,the credibility of the evidence was not high.Further high-quality evidence is required.

An M^([X])/G/1 Retrial G-queue with Single Vacation Subject to the Server Breakdown and Repair

An M[X]/G/1 retrial G-queue with single vacation and unreliable server is investigated in this paper. Arrivals of positive customers form a compound Poisson process, and positive customers receive service immediately if the server is free upon their arrivals; Otherwise, they may enter a retrial orbit and try their luck after a random time interval. The arrivals of negative customers form a Poisson process. Negative customers not only remove the customer being in service, but also make the server under repair. The server leaves for a single vacation as soon as the system empties. In this paper, we analyze the ergodical condition of this model. By applying the supplementary variables method, we obtain the steady-state solutions for both queueing measures and reliability quantities.