Background: The roles of circRNA and N6‐methyladenosine (m⁶A) methylation in Crohn's disease (CD) have drawn much attention. Therefore, this investigation aimed to discover how the m⁶A modification of circRNAs contributes to CD progression.Methods: The study performed circRNA sequencing on colon samples from four CD patients and four normal controls (NCs) to screen for dysregulated circRNAs. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to validate the candidate circRNA expression and determine its correlation to CD‐associated inflammatory indicators. In vivo and in vitro investigations were conducted to examine the functions and pathways of circPRKAR1B in CD, besides investigating the m⁶A modification role in circRNA expression modulation.Results: The RNA‐seq revealed that hsa_circ_0008039 (circPRKAR1B) was the most significant upregulated circRNA and was identified as the candidate circRNA for further examinations. Relative circPRKAR1B expression was significantly upregulated in CD colon tissues and closely related to CD‐associated inflammatory indices. The circPRKAR1B expression and function were regulated by methyltransferase‐like 3 (METTL3)‐mediated m⁶A methylation. In vitro studies indicated that circPRKAR1B promoted pyroptosis mediated by NLRP3 inflammasome (NLRP3; nucleotide‐binding oligomerization domain, leucine‐rich repeat and pyrin domain‐containing 3) and impaired autophagy by interacting with the RNA‐binding protein (RBP) SPTBN1, (SPTBN1; spectrin beta, non‐erythrocytic 1). The in vivo investigations revealed the treatment effects of si‐circPRKAR1B and si‐METTL3 in colitis models of IL‐10‐deficient mice.Conclusion: Our study reveals that METTL3‐mediated m⁶A modification of circPRKAR1B promotes Crohn's colitis by aggravating NLRP3 inflammasome‐mediated pyroptosis via autophagy impairment in colonic epithelial cells.

Postoperative severe complications are always associated with prolonged hospital stays, increased economic burdens, and poor prognoses in patients with colorectal cancer (CRC). This present study aimed to investigate potential risk factors including serum albumin (Alb) for severe complications in CRC patients. Eligible patients with primary CRC undergoing elective laparoscopic colectomy from July 2015 to July 2017 were included. Postoperative severe complications were defined as grade III and IV according to the Clavien–Dindo classification. ∆Alb was defined as (preoperative Alb − nadir Alb within POD2)/preoperative Alb × 100%. The baseline characteristics, intraoperative data, and laboratory data were obtained from the database for the analysis. Univariate and multivariate logistic regression analyses were utilized for the assessment of the association between risk factors and postoperative severe complications. The predictive value of ∆Alb for postoperative severe complications was evaluated by receiver operating characteristic (ROC) curve analysis. A total of 193 patients were finally included in the analysis data set, of which 38 (19.7%) patients had postoperative severe complications. In the final multivariate logistic regression analysis, ∆Alb was the only independent factor associated with postoperative severe complications (OR 1.66, 95%CI 1.18–2.33, p = 0.003). The area under the curve (AUC) of ∆Alb was 0.916, with the sensitivity and specificity of 0.842 and 0.858 (p < 0.001). The ∆Alb was an independent risk factor for severe complications in CRC patients after curative laparoscopic surgery.

This study aimed to at explore exploring the biological functions of dysregulated circRNA in Crohn’s disease (CD) pathogenesis, with the overarching goal of and providing potential novel therapeutic targets. CircRNA microarray and quantitative real time-polymerase chain reaction (qRT-PCR) analyses were performed to investigate and verify the candidate dysregulated circRNA. The Next, clinical, in vivo, and in vitro studies were performed to investigate explore the biological function and mechanisms of the candidate circRNA in CD. The therapeutic effect of poly (lactic-co-glycolic acid)-microspheres (PLGA MSs)-carried oe-circGMCL1 in experimental colitis models of IL-10 knock-out mice was assessed. CircGMCL1 was identified as the candidate circRNA by microarray and qRT-PCR analyses. Results showed that circGMCL1 expression was negatively correlated with CD-associated inflammatory indices, suggesting that it is a CD-associated circRNA. Microarray and bioinformatics analyses identified miR-124-3p and Annexin 7 (ANXA7) as its downstream mechanisms. The in vitro studies revealed that circGMCL1 mediates its effects on autophagy and NLRP3 inflammasome-mediated pyroptosis in epithelial cells through the ceRNA network. Moreover, the in vivo studies identified the therapeutic effect of PLGA MSs-carried oe-circGMCL1 in experimental colitis models. This study suggests that circGMCL1 protects intestinal barrier function against Crohn’s colitis through alleviating NLRP3 inflammasome-mediated epithelial pyroptosis by promoting autophagy through regulating ANXA7 via sponging miR-124-3p. Therefore, circGMCL1 can serve as a potential biological therapeutic target for Crohn’s colitis.

Numerous studies have explored the association between circular RNAs (circRNAs) and Crohn’s disease (CD). However, the pathological role, biological functions, and molecular mechanisms of circRNAs in CD have not been fully elucidated. The circRNA microarray analysis was performed to identify deregulated circRNAs in colon tissues. The identified circRNA were verified through quantitative real time-polymerase chain reaction (qRT-PCR). In vivo and in vitro functional studies were performed to verify the role of circSMAD4 in CD and investigate the mechanisms involved. We found that circSMAD4 was the most significantly upregulated circRNA. The expression level of circSMAD4 was positively correlated with levels of inflammatory factors. Overexpression of circSMAD4 impaired tight junction (TJ) proteins and enhanced apoptosis of epithelial cells. These effects were reversed by treatment with miR-135a-5p mimic. Mechanistic studies showed that circSMAD4 exerts its effects on CD by “sponging” miR-135a-5p to regulate Janus kinase 2 (JAK2). Si-circSMAD4 delivery through microspheres ameliorated experimental colitis and protected the intestinal barrier function in IL-10 knock-out mice. This study shows that circSMAD4 regulates the progression of experimental colitis via the miR-135a-5p/JAK2 signaling axis and it may be a potential therapeutic target.

Background: This study aimed to investigate the mechanisms by which PANoptosis of intestinal epithelial cells (IECs) promotes Crohn's disease (CD) progression.

Background: This study aimed to investigate the association between enhanced recovery after surgery (ERAS) nursing program and stoma-related complications (SRCs) and prognosis in patients with low rectal cancer (LRC) undergoing abdominoperineal resection with sigmoidostomy. Methods: LRC patients who underwent elective abdominoperineal resection with sigmoidostomy between May 2016 and May 2019 were retrospectively enrolled. The occurrence of early major or minor SRCs (within postoperative 30 days) was set as the primary end-point. Clinicopathological variables and laboratory tests were compared between patients with or without SRCs. The univariate and multivariate logistic regression analyses were performed to investigate risk factors for SRCs. Hospitalization satisfaction-related and prognosis-related variables were compared between LRC patients with or without ERAS nursing program. Results: A total of 288 patients were enrolled and the incidence of SRCs was 26.7% (77/288). ERAS nursing program was the only independent risk factor for SRCs in LRC patients (OR 2.04, 95%CI 1.31–3.12, P = 0.016) by the multivariate logistic regression analysis. Moreover, ERAS nursing program was associated with higher hospitalization satisfaction rate, faster bowel function recovery, better psychological status, and higher quality of life. Conclusions: ERAS nursing program was a protective factor for SRCs and associated with improved prognosis in LRC patients undergoing elective abdominoperineal resection with sigmoidostomy.