The PDIA3-STAT3 protein complex regulates IBS formation and development via CTSS/MHC-II pathway-mediated intestinal inflammation.

Irritable bowel syndrome (IBS) is a persistent functional gastrointestinal disorder characterised by abdominal pain and altered patterns of defecation. This study aims to clarify an increase in the expression and interaction of protein disulfide-isomerase A3 (PDIA3) and Signal Transducer and Activator of Transcription 3 (STAT3) within the membrane of dendritic cells (DCs) from individuals with IBS. Mechanistically, the heightened interaction between PDIA3 and STAT3 at the DC membrane results in reduced translocation of phosphorylated STAT3 (p-STAT3) into the nucleus. The reduction of p-STAT3 to nuclear transport subsequently increased the levels of cathepsin S (CTSS) and major histocompatibility complex class II (MHC-II). Consequently, activated DCs promote CD4+ T cell proliferation and cytokine secretion, including interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-9 (IL-9), and tumour necrosis factor-alpha (TNF-α), thereby contributing to the development of IBS. Importantly, the downregulation of PDIA3 and the administration of punicalagin (Pun), a crucial active compound found in pomegranate peel, alleviate IBS symptoms in rats, such as increased visceral hypersensitivity and abnormal stool characteristics. Collectively, these findings highlight the involvement of the PDIA3-STAT3 protein complex in IBS, providing a novel perspective on the modulation of immune and inflammatory responses. Additionally, this research advances our understanding of the role and mechanisms of PDIA3 inhibitors, presenting new therapeutic possibilities for managing IBS.

Endoscopic treatment of extreme esophageal stenosis complicated with esophagotracheal fistula: A case report.

BACKGROUND: At present, there is no unified and effective treatment for extreme corrosive esophageal stenosis (CES) with esophagotracheal fistula (ETF). This case had extreme and severe esophageal stenosis (ES) and ETF after ingesting an enzyme-based chemical detergent, resulting in a serious pulmonary infection and severe malnutrition. Upper gastrointestinal imaging showed that he had an ETF, and endoscopy showed that he had extreme and severe esophageal stricture. This case was complex and difficult to treat. According to the domestic and foreign literature, there is no universal treatment that is low-risk. CASE SUMMARY: A patient came to our hospital with extreme ES, an ETF, and severe malnutrition complicated with pulmonary tuberculosis 1 mo after the consumption of an enzyme-based detergent. The ES was serious, and the endoscope was unable to pass through the esophagus. We treated him by endoscopic incision method (EIM), esophageal stent placement (ESP), and endoscopic balloon dilation (EBD) by using the bronchoscope and gastroscope. This treatment not only closed the ETF, but also expanded the esophagus, with minimal trauma, greatly reducing the pain of the patient. According to the literature, there are no similar reported cases. CONCLUSION: We report, for the first time, a patient with extreme CES complicated with ETF, where the endoscope could not be passed through his esophagus but he could be examined by bronchoscopy and treated by EIM, ESP, and EBD.

Laparoscopic-assisted endoscopic full-thickness resection of a large gastric schwannoma: A case report.

BACKGROUND: Schwannomas, also known as neurinomas, are benign tumors derived from Schwann cells. Gastrointestinal schwannomas are rare and are most frequently reported in the stomach. They are usually asymptomatic and are difficult to diagnose preoperatively; however, endoscopy and imaging modalities can provide beneficial preliminary diagnostic data. There are various surgical options for management. Here, we present a case of a large gastric schwannoma (GS) managed by combined laparoscopic and endoscopic surgery. CASE SUMMARY: A 28-year-old woman presented with a 2-mo history of epigastric discomfort and a feeling of abdominal fullness. On upper gastrointestinal endoscopy and endoscopic ultrasonography, a hypoechogenic submucosal mass was detected in the gastric antrum: It emerged from the muscularis propria and projected intraluminally. Computed tomography showed a nodular lesion (4 cm × 3.5 cm), which exhibited uniform enhancement, on the gastric antrum wall. Based on these findings, a preliminary diagnosis of gastrointestinal stromal tumor was established, with schwannoma as a differential. Considering the large tumor size, we planned to perform endoscopic resection and to convert to laparoscopic treatment, if necessary. Eventually, the patient underwent combined laparoscopic and gastroscopic surgery. Immunohistochemically, the resected specimen showed positivity for S-100 and negativity for desmin, DOG-1, α-smooth muscle actin, CD34, CD117, and p53. The Ki-67 index was 3%, and a final diagnosis of GS was established. CONCLUSION: Combined laparoscopic and endoscopic surgery is a minimally invasive and effective treatment option for large GSs.

Peroral endoscopic longer vs shorter esophageal myotomy for achalasia treatment: A systematic review and meta-analysis.

BACKGROUND: Peroral endoscopic myotomy (POEM) has been demonstrated to be safe and effective in the treatment of achalasia. Longer myotomy is the standard POEM procedure for achalasia but when compared with shorter myotomy, its effectiveness is not as well known. AIM: To compare the clinical effectiveness of longer and shorter myotomy. METHODS: PubMed, EmBase, Cochrane Library, web of science and clinicaltrials.gov were queried for studies comparing shorter and longer POEM for achalasia treatment. The primary outcome was clinical success rate. Secondary outcomes comprised of operative time, adverse events (AEs) rate, gastroesophageal reflux disease (GERD) and procedure-related parameters. The Mantel-Haenszel fixed-effects model was primarily used for the analysis. Publication bias was assessed. RESULTS: Six studies were included in this analysis with a total of 514 participants. During the follow-up period of 1-28.7 mo, longer and shorter myotomy in treating achalasia showed similar excellent effectiveness [overall clinical success (OR = 1, 95%CI: 0.46-2.17, P = 1, I2: 0%; subgroup of abstract (OR = 1.19, 95%CI: 0.38 to 3.73; P = 0.76; I2: 0%); subgroup of full text (OR = 0.86 95%CI: 0.30 to 2.49; P = 0.78; I2: 0%)]. Shorter myotomy had significantly reduced mean operative time compared with the longer procedure. There were no statistically significant differences in AEs rates, including GERD (overall OR = 1.21, 95%CI: 0.76-1.91; P = 0.42; I2: 9%; subgroup of abstract OR = 0.77, 95%CI: 0.40-1.47; P = 0.43; I2: 0%; subgroup of full text OR = 1.91, 95%CI: 0.98-3.75; P = 0.06; I2: 0%), hospital stay (overall MD = -0.07, 95%CI: -0.30 to 0.16; P = 0.55; I2: 24%; subgroup of abstract MD = 0.20, 95%CI: -0.25 to 0.65; P = 0.39; I2: 0; subgroup of full text MD = -0.16, 95%CI: -0.42 to 0.10; P = 0.23; I2: 42%), and major bleeding (overall OR = 1.25, 95%CI: 0.58-2.71; P = 0.56; I2: 0%) between the two procedures. These differences remained statistically non-significant in all sensitivity analyses. CONCLUSION: POEM was effective in treating achalasia. Shorter and longer myotomy procedures provided similar therapeutic effects in terms of long-term effectiveness. In addition, shorter myotomy reduced the operative time.

Comparison of regional and local anesthesia for arteriovenous fistula creation in end-stage renal disease: a systematic review and meta-analysis.

BACKGROUND: Arteriovenous fistulae (AVF) are the hemodialysis access modality of choice for patients with end-stage renal disease. However, they have a high early failure rate. Good vascular access is essential to manage long-term hemodialytic treatment, but some anesthesia techniques directly affect venous diameter as well as intra- and post-operative blood flow. The main purpose of this meta-analysis was to compare the results of regional and local anesthesia (RA and LA) for arteriovenous fistula creation in end-stage renal disease. METHODS: We conducted a systematic review and meta-analysis to synthesize evidence from 7 randomized controlled trials (565 patients) and 1 observational study (408 patients) with the aim of evaluating the safety and efficacy of RA versus LA in surgical construction of AVF. RESULTS: Pooled data showed that RA was associated with higher primary patency rates than LA (odds ratio [OR], 1.88; 95% confidence interval [CI]: 1.24-2.84; P = 0.003; I2 = 31%). Additionally, brachial artery diameter was significantly increased in the RA versus LA group (mean difference [MD], 0.83; 95% CI: 0.75-0.92; P < 0.001; I2 = 97%) and the need for intra- as well as post-operative pain killers was significantly less (RA, P = 0.0363; LA, P = 0.0318). Moreover, operation duration was significantly reduced using RA versus LA (MD, - 29.63; 95% CI: - 32.78 - -26.48; P < 0.001; I2 = 100%). CONCLUSIONS: This meta-analysis suggests that RA is preferable to LA in patients with end-stage renal disease in guaranteeing AVF patency and increasing brachial artery diameter.

Long-Term Efficacy of Peroral Endoscopic Myotomy for Patients with Achalasia: Outcomes with a Median Follow-Up of 36 Months.

OBJECTIVE: This study aimed to evaluate the long-term efficacy of peroral endoscopic myotomy (POEM) for patients with achalasia. METHODS: Prospective data collected from 115 patients (median age 45 years; interquartile range 34-57) with achalasia who underwent POEM at the First Affiliated Hospital of ZheJiang Chinese Medical University with a median follow-up of 36 months were retrospectively analyzed. The Eckardt score and lower esophageal sphincter pressure changes were analyzed, and the gastroesophageal reflux was observed. RESULTS: During the final follow-up, the mean Eckardt score reduced from 7.5 ± 1.9 preoperatively to 2.3 ± 1.4 after 1 month of surgery (P < 0.001). Treatment success was observed in 91.3% [confidence interval (CI) 86.2-96.4], 90.3% (CI 84.8-95.8), 89.0% (CI 83.1-94.9), 83.7% (CI 75.7-91.7), and 80.1% (CI 69.7-90.5) of patients after 12, 24, 36, 48, and 60 months, respectively. A total of 16 (13.9%) failures occurred. Four patients were nonresponders (failure within 3 months), eight had an early recurrence (between 3 months and 3 years), and four had a late recurrence (after 3 years). Further, 21 (20.6%) patients had symptoms of reflux during the two-year follow-up. Only one patient with symptomatic reflux was newly added during the subsequent three-year follow-up. Moreover, 71 (61.7%) patients underwent gastroscopy after POEM, and 13 (18.3%) patients were diagnosed with reflux esophagitis. CONCLUSION: POEM is safe and effective in treating achalasia and has a favorable long-term efficacy.