Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis.

BACKGROUND: Visceral adipose tissue (VAT) has been linked to the severe acute pancreatitis (SAP) prognosis, although the underlying mechanism remains unclear. It has been reported that pyroptosis worsens SAP. The present study aimed to verify whether mesenteric adipose tissue (MAT, a component of VAT) can cause secondary intestinal injury through the pyroptotic pathway. METHODS: Thirty-six male Sprague Dawley (SD) rats were divided into six different groups. Twelve rats were randomly divided into the SAP and control groups. We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats. Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution (PBS). The remaining twelve SAP rats were first injected with MAT B lymphocytes, and then with MCC950 (NLRP3 inhibitor) or PBS. We collected blood and tissue samples from pancreas, gut and MAT for analysis. RESULTS: Compared to the control rats, the SAP group showed inflammation in MAT, including higher expression of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), lower expression of IL-10, and histological changes. Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages. The SAP rats also exhibited intestinal injury, characterized by lower expression of zonula occludens-1 (ZO-1) and occludin, higher levels of lipopolysaccharide and diamine oxidase, and pathological changes. The expression of NLRP3 and n-GSDMD, which are responsible for pyroptosis, was increased in the intestine of SAP rats. The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT. The upregulation of pyroptosis reduced tight junction in the intestine, which contributed to the SAP progression, including higher inflammatory indicators and worse histological changes. The administration of MCC950 to SAP + MAT B rats downregulated pyroptosis, which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP. CONCLUSIONS: In SAP, MAT B lymphocytes aggravated local inflammation, and promoted the injury to the intestine through the enteric pyroptotic pathway.

Efficacy and safety of fecal microbiota transplantation for the induction of remission in active ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials.

Background: Fecal microbiota transplantation (FMT) is a novel management strategy for ulcerative colitis (UC). However, its effectiveness remains controversial. This study sought to assess the effectiveness of FMT in the treatment of active UC by performing a meta-analysis of randomized controlled trials (RCTs). Methods: We searched the Cochrane, Embase, PubMed, and Web of Science databases from their inception to December 2021. RCTs that recruited patients with active UC and treated them with FMT, a placebo or a suitable comparator were included in the meta-analysis. PICOS: Patients, active UC; Intervention, FMT; Control, placebo or a suitable comparator; Outcomes, remission rate; Studies, RCTs. The risk of bias assessment was performed with Revised Cochrane risk-of-bias tool (version 2). Meta-analyses of risk ratios (RRs) were performed to estimate the differences in remission rates and the risk of serious adverse events (SAEs) between the FMT-treated and control patients. Results: A total of 9 RCTs comprising 425 UC patients (213 FMT and 212 control) were included in the meta-analysis. The risk of bias was low in these RCTs. Clinical remission was observed in 86 of the 213 patients in the FMT groups and 47 of the 212 patients in the control groups [RR: 1.84; 95% confidence interval (CI): 1.37, 2.47; P<0.0001]. Clinical remission was better when the FMT delivery route was via the lower gut, the FMT dose was >300 grams, and the fecal specimen from multiple donors. Endoscopic remission (observed in 7 RCTs) was achieved in 33 of the 195 FMT-treated patients compared to 17 of the 194 control patients (RR: 1.94; 95% CI: 1.14, 3.31; P=0.01). SAEs were reported in 22 of the 213 FMT-treated patients but only 11 of the 212 control patients (RR: 2.05; 95% CI: 1.03, 4.09; P=0.04). Discussion: FMT is an effective treatment for patients with active UC. Significantly higher clinical and endoscopic remission rates are observed with FMT than with control treatments. However, FMT may cause a significantly higher incidence of SAEs than control treatments. Future studies should delineate the effects of donor selection, dosage, delivery route, and antibiotic pretreatment and should evaluate the safety profile of FMT.

Endoscopic submucosal tunnel dissection of upper gastrointestinal submucosal tumors: A comparative study of hook knife vs hybrid knife.

AIM: To compare the efficacy and safety of a hook knife (HO) with a hybrid knife (HK) during endoscopic submucosal tunnel dissection (ESTD) procedure. METHODS: Between August 2012 and December 2015, the ESTD procedure was performed for 83 upper GI submucosal lesions, which originated from the muscularis propria layer identified by upper endoscopy and endoscopic ultrasonography. Of these, 34 lesions were treated by a HO, whereas 49 lesions were treated by a HK. Data regarding age, gender, presenting symptoms, tumor location and size, procedure time, complications, en bloc resection rate and others were analyzed and compared between the two groups. RESULTS: There were no significant differences in the age, gender, presenting symptoms and tumor location between the two groups. ESTD was successfully completed in all the patients, and no case was converted to laparoscopy. The mean procedure time was significantly shorter in the HK group than in the HO group (41.3 ± 20.3 min vs 57.2 ± 28.0 min, P = 0.004). The mean frequency of device exchange was 1.4 ± 0.6 in the HK group and significantly less than 3.3 ± 0.6 in the HO group (P < 0.001). The differences in tumor size and histopathological diagnoses were not significant between the two groups (P = 0.813, P = 0.363, respectively). Both groups had an equal en bloc resection rate and complete resection rate. Additionally, the complication rate was similar between the two groups (P = 0.901). During the follow-up, no recurrence occurred in either group. CONCLUSION: We demonstrate for the first time that HO and HK do not differ in efficacy or safety, but HK reduces the frequency of device exchange and procedure time.

High-resolution manometric subtypes as a predictive factor for the treatment of achalasia: A meta-analysis and systematic review.

OBJECTIVE: To assess manometric subtypes as predictive factors for the treatment efficacies of pneumatic balloon dilatation (PBD) and laparoscopic Heller myotomy (LHM) in patients with achalasia. METHODS: A systematic search of the Pubmed, Embase and Cochrane Library database was conducted to identify relevant publications on high-resolution manometric subtypes and different therapies for achalasia with predefined inclusion and exclusion criteria. Data on the success rates after PBD or LHM for different manometric subtypes were extracted. The pooled odds ratio (OR) and 95% confidence interval (CI) for different manometric subtypes were estimated using STATA 13.0. RESULTS: In all, nine studies met the inclusion criteria. A total of 298 patients having achalasia receiving PBD and 429 undergoing LHM were included in the meta-analysis. The pooled OR between the subtypes of achalasia after PBD or LHM showed that the best and worse treatment outcomes were found in patients with type II and III achalasia, respectively (type I vs type II after PBD: OR 0.16, 95% CI 0.08-0.36, P = 0.000; type I vs type III after PBD: OR 3.64, 95% CI 1.55-8.53, P = 0.003; type II vs type III after PBD: OR 27.18, 95% CI 9.08-81.35, P = 0.000; type I vs type II after LHM: OR 0.26, 95% CI 0.12-0.56, P = 0.001; type I vs type III after LHM: OR 1.89, 95% CI 0.80-4.50, P = 0.148; type II vs type III after LHM: OR 6.86, 95% CI 2.72-17.28, P = 0.000). CONCLUSION: Type II achalasia shows the best prognosis after PBD and LHM, while type III achalasia has the worst prognosis.

Abnormal ß-catenin immunohistochemical expression as a prognostic factor in gastric cancer: a meta-analysis.

AIM: To evaluate the effect of ß-catenin immunohistochemical expression on the prognosis of gastric cancer (GC). METHODS: We searched Pubmed and Embase to identify eligible studies. The search ended on November 10, 2013, with no lower date limit. The citation lists associated with the studies were used to identify additional eligible studies. We included studies reporting sufficient information to estimate the HR and 95%CI, and information to estimate the OR in the analysis of clinicopathological features. The qualities of these studies were assessed using the Newcastle-Ottawa Quality Assessment Scale. HRs and ORs and their variance were calculated and pooled using Review Manager Version 5.2. RESULTS: A total of 24 studies were identified and comprised 3404 cases. ß-catenin expression was significantly correlated with poor overall survival (OS) in GC patients (HR = 1.85, 95%CI: 1.39-2.46), but showed a significant degree of heterogeneity (I (2) = 71%, P < 0.0001). Subgroup analysis indicated that an abnormal pattern of ß-catenin expression had an unfavorable effect on OS (HR = 1.79, 95%CI: 1.39-2.32). However, accumulation in the nucleus or loss of membrane did not influence the survival of GC patients independently. Moreover, the combined OR of ß-catenin indicated that ß-catenin expression was associated with Lauren classification (OR = 1.98, 95%CI: 1.19-3.29), lymph node metastasis (OR = 2.00, 95%CI: 1.44-2.77), distant metastasis (OR = 2.69, 95%CI: 1.35-5.38) and grade of differentiation (OR = 2.68, 95%CI: 1.66-4.34). ß-catenin expression did not correlate with TNM stage (OR = 1.34 95%CI: 0.96-1.86), the depth of invasion (OR = 1.48, 95%CI: 0.94-2.33) or vascular invasion (OR = 1.11, 95%CI: 0.70-1.76). CONCLUSION: Abnormal ß-catenin immunohistochemical expression may be associated with tumor progression and could be a predictive factor of poor prognosis in patients with GC.