Claudin-6 is down-regulated in gastric cancer and its potential pathway.

Claudins are indispensible in modulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. In order to verify the function of claudin-6 in the development of gastric cancer, we investigated claudin-6 expression in different gastric disease tissues. Moreover, we further explored whether overexpression of claudin-6 altered proliferation, apoptosis, migration, invasiveness, differentiation in BGC-823 cells and the potential mechanism. Immunohistochemistry was performed to detect the in situ expression of claudin-6 in different gastric disease tissues; moreover, cell culture, real-time PCR and western blot were used to evaluate the effect of overexpression of claudin-6 in vitro and the related mechanism. The results of immunohistochemical staining showed that the positivity of claudin-6 was significantly higher in superficial gastritis than that in gastric cancer. Overexpression of claudin-6 induced differentiation of BGC-823 cells by inhibiting the JNK pathway. However, it had no effect on proliferation, apoptosis, migration or invasiveness in vitro. The expression of claudin-6 was decreased in gastric cancer. Overexpression of claudin-6 induced differentiation of gastric cancer cells by inhibiting the JNK pathway.

The Possible Anti-Inflammatory Effect of Dehydrocostus Lactone on DSS-Induced Colitis in Mice.

BACKGROUND: Dehydrocostus lactone (DL), one of the main active constituents in Aucklandia lappa Decne. (Muxiang), reported to have anti-inflammatory, antiulcer, and immunomodulatory properties. However, the effect of DL on ulcerative colitis (UC) has not been reported. To analyze the anti-inflammatory potential role of DL in UC, we provide a mechanism for the pharmacological action of DL. METHODS: The experimental model of UC was induced by using oral administration of 2% dextran sulfate sodium (DSS) with drinking water in BALB/c mice. Mesalazine (Mes, 0.52 g/kg/d), DL-high doses (DL-H, 20 mg/kg/d), DL-middle doses (DL-M, 15 mg/kg/d), DL-low doses (DL-L, 10 mg/kg/d) were gavaged once a day from day 4 to day 17. Disease activity index (DAI) was calculated daily. On day 18, mice were rapidly dissected and the colorectal tissues were used to detect the levels of UC-related inflammatory cytokines (TNF-α, IL-1ß, MCP-1, MPO, SOD, IL-6, IL-17, and IL-23), IL-6/STAT3 inflammatory signaling pathway (iNOS, COX2, IL-6, GP130, L-17, and IL-23), and colorectal mucosal barrier-related regulatory factors (MUC2, XBP1s, and α, IL-1. RESULTS: DL reduced the colorectal inflammation histological assessment, decreased UC-related inflammatory cytokines (TNF-α, IL-1ß, MCP-1, MPO, SOD, IL-6, IL-17, and IL-23), IL-6/STAT3 inflammatory signaling pathway (iNOS, COX2, IL-6, GP130, L-17, and IL-23), and colorectal mucosal barrier-related regulatory factors (MUC2, XBP1s, and α, IL-1. CONCLUSIONS: DL possessed the potential of anti-inflammatory effect to treated colitis. The protective mechanism of DL may involve in reducing inflammation and improving colorectal barrier function via downregulating the IL-6/STAT3 signaling.

Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Ulcerative colitis (UC) patients have an increased risk for the development of colorectal cancer (CRC). Our aim was to assess the risk of CRC in UC patients compared with disease extent, disease duration, and geographic variation. METHODS: In this systematic review and meta-analysis, we searched PubMed, scientific meetings, and the bibliographies of identified articles, with English language restrictions for studies published from 1988 to 2018, and assessed the risk of CRC in UC patients. Patients with Crohn's disease, family history of CRC, and colorectal adenomatous polyp (CAP) were excluded from this research. The study was registered with PROSPERO, number CRD42018102213. FINDINGS: We included 58 studies that included 267566 UC patients. Extensive UC and left-sided UC had a higher risk of CRC than proctitis UC. Geography also played a role in UC-associated CRC development. The time of malignant transformation in Asian UC patients started after 10-20 years of this disease duration. North American UC-associated CRC patients significantly increased in more than 30 years of this disease duration. CONCLUSION: In a systematic review of the literature, we found that disease extent, disease duration, and geography were strong, independent risk factors in UC-associated CRC development.

Traditional Chinese medicine (Xiaoai Jiedu Decoction) as an adjuvant treatment for prevention new colorectal adenomatous polyp occurrence in post-polypectomy: Study protocol for a randomized controlled trial.

BACKGROUND: Colorectal Adenomatous Polyp (CAP) was one precursor of colorectal cancer (CRC) and having a high chance of developing into CRC. There was a lack of conclusive chemoprevention evidences to prevention new CAP occurrence in post-polypectomy. Xiaoai Jiedu Decoction, Chinese National Medical Professor (Zhou Zhongying)'s experience formula, has been used to treat new CAP occurrence in post-polypectomy from the 20th century in China. However, clinical research of Xiaoai Jiedu Decoction in the treatment of CAP recurrence was lack. We design this study to evaluate the efficacy and safety of Xiaoai Jiedu Decoction in the treatment of new CAP occurrence in post-polypectomy on colonoscopy. METHODS/DESIGN: A randomized, controlled, blind and multicenter trial to evaluate the efficacy and safety of Xiaoai Jiedu Decoction is proposed. CAP patients (after complete polypectomy under colonoscopy) will be randomly assigned into Xiaoai Jiedu Decoction group and Xiaoai Jiedu Decoction mimetic agent group. Patients will receive 6-course treatments and a 2-year follow-up. Follow-up colonoscopy will be anticipated to perform in 1 and 2 years after the baseline examinations. The primary outcome measure is the new CAP occurrence in 1 and 2 years. The secondary outcome measure is the occurrence of advanced adenoma in 1 and 2 years. DISCUSSION: This study will provide objective evidences to evaluate the efficacy and safety of Xiaoai Jiedu Decoction as an adjuvant treatment for new CAP occurrence in post-polypectomy. TRIAL REGISTRATION: NCT03616444.

Consensus on the digestive endoscopic tunnel technique.

With the digestive endoscopic tunnel technique (DETT), many diseases that previously would have been treated by surgery are now endoscopically curable by establishing a submucosal tunnel between the mucosa and muscularis propria (MP). Through the tunnel, endoscopic diagnosis or treatment is performed for lesions in the mucosa, in the MP, and even outside the gastrointestinal (GI) tract. At present, the tunnel technique application range covers the following: (1) Treatment of lesions originating from the mucosal layer, e.g., endoscopic submucosal tunnel dissection for oesophageal large or circular early-stage cancer or precancerosis; (2) treatment of lesions from the MP layer, per-oral endoscopic myotomy, submucosal tunnelling endoscopic resection, etc.; and (3) diagnosis and treatment of lesions outside the GI tract, such as resection of lymph nodes and benign tumour excision in the mediastinum or abdominal cavity. With the increasing number of DETTs performed worldwide, endoscopic tunnel therapeutics, which is based on DETT, has been gradually developed and optimized. However, there is not yet an expert consensus on DETT to regulate its indications, contraindications, surgical procedure, and postoperative treatment. The International DETT Alliance signed up this consensus to standardize the procedures of DETT. In this consensus, we describe the definition, mechanism, and significance of DETT, prevention of infection and concepts of DETT-associated complications, methods to establish a submucosal tunnel, and application of DETT for lesions in the mucosa, in the MP and outside the GI tract (indications and contraindications, procedures, pre- and postoperative treatments, effectiveness, complications and treatments, and a comparison between DETT and other operations).

Role of gastroscopic biopsy of gastric ulcer margins and healed sites in the diagnosis of early gastric cancer: A clinical controlled study of 513 cases.

The present case study aimed to evaluate the effect of gastroscopic biopsy of gastric ulcer margins and healed sites in the diagnosis of early gastric cancer. A total of 513 patients who were diagnosed with gastric ulcers using gastroscopy between January 1999 and December 2013 were included in the present study and were divided into either the experimental or the control group. In the control group, samples were only taken from the ulcer margin, whereas in the experimental group samples were taken from the ulcer margin and from the ulcer base. In the experimental group, a routine biopsy of the ulcer margin was performed on first examination, and recheck by gastroscopy was performed from the second week. For ulcers that remained unhealed, a biopsy of the ulcer margin was subsequently conducted; however, for healed or almost healed ulcers, a biopsy of the ulcer base was conducted. The duration of follow-up by gastroscopy ranged between 1 week and 24 months. For the control group, a biopsy of the ulcer margin was conducted using the conventional method. The detection rate of the experimental group was 3.88% (9/232), with 4 cases of gastric cancer confirmed from examinations of the ulcer base. The detection rate of the control group was 1.07% (3/281), which was significantly decreased compared with that of the experimental group (P=0.0345). Overall, patients who underwent regular follow-up gastroscopy following treatment exhibited a markedly increased detection rate of early gastric cancer, suggesting that early cancer may occur in healed gastric ulcer sites.

Prophylactic somatostatin can reduce incidence of post-ERCP pancreatitis: multicenter randomized controlled trial.

BACKGROUND AND STUDY AIM: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains the most common complication of ERCP. Somatostatin may inhibit pancreatic secretion and has been tested for PEP prophylaxis. However, the results of previous studies are inconsistent. The aim of the current study was to investigate whether somatostatin can reduce the incidence of PEP. PATIENTS AND METHODS: The study was a multicenter, open-label, randomized controlled trial. A total of 908 patients with normal amylase levels who were undergoing ERCP were randomized to receive somatostatin 250 µg bolus injection before ERCP and 250 µg/hour intravenous infusion for 11 hours after ERCP (somatostatin group) or no somatostatin treatments (control group). The incidences of PEP and hyperamylasemia were compared in the two groups. RESULTS: The full analysis set included 900 patients (445 in the somatostatin group, 455 in the control group). PEP developed in 34 patients (7.5 %) in the control group (95 % confidence interval [CI] 5.4 % - 10.3 %) and in 18 patients (4.0 %) in the somatostatin group (95 %CI 2.6 % - 6.3 %; P = 0.03). Hyperamylasemia occurred in 46 patients (10.1 %) in the control group (95 %CI 7.7 % - 13.2 %) and in 27 patients (6.1 %) in the somatostatin group (95 %CI 4.2 % - 8.7 %; P = 0.03). No perforation or death occurred during the study. CONCLUSIONS: This study showed that somatostatin was effective and safe for the prevention of PEP and hyperamylasemia in ERCP patients.(ClinicalTrials.gov number, NCT01431781).