Preserved mucosa unroofing facilitated closure of a large gastric defect after endoscopic full-thickness resection.

A 58-year-old woman was found to have a submucosal bulging lesion in the anterior wall of the gastric fundus during a screening esophagogastroscopy. Endosonographic evaluation revealed it to be a 3.1×2.5cm, hypoechoic mass originating from muscularis propria (MP). Endoscopic full-thickness resection (EFR) was attempted. After submucosal injection, a four-fifth circumferential mucosal incision was made around the lesion. Submucosal dissection was performed to unroof the overlying mucosa, which was preserved via the remaining one-fifth circumferential mucosal edge. Thus a mucosal flap was created and turned aside to expose the mass. En bloc resection of the lesion resulted in a 3.5*3.0cm full-thickness defect . The mucosal flap was flipped back and the defect was almost fully covered. Therefore, closure of the defect was accomplished by simply clipping the two edges of the initially incised mucosa. The patient was discharged 2 days later without discomfort. Histopathology confirmed a gastrointestinal stromal tumor (GIST), prognostic group 1.

Removal of an impacted apricot pit from a scarring duodenal stenosis using endoscopic retrograde cholangiopancreatography (ERCP) stone extraction technique.

A 66-year-old man presented with repeated vomiting for 5 days. Initial gastroscopy showed gastric retention while computed tomography (CT) revealed a 1.8*1.1 cm, oval-shaped, high-density object in the duodenum. Considering his past medical history of a surgical repair for duodenal ulcer perforation 20 years ago, a diagnosis of foreign body (FB) impaction causing gastric outlet obstruction was established. After gastric lavage, a second gastroscopy was performed. A brownish round FB impacted upon scarring stenoses at the junction of the 1st and 2nd part of duodenum was visualized after advancement of the scope with effort through a deformed pylorus. Attempts to capture the FB using a polypectomy snare failed because the snare loop could not be advanced across the stenotic impaction site to allow adequate opening. A grasper was also ineffective due to the smooth surface of the FB. Then the ERCP stone extraction technique was applied. Directed by the adjustable tip of a sphincterotome which was introduced through the same gastroscope, a guidewire passed with little resistance over the impaction site for an adequate length. Subsequently, an extraction balloon was advanced through the guidewire with slight inflation to avoid injury to the stenotic duodenal wall and fully inflated in the distal lumen. Gradual balloon deflation and withdrawal applied simultaneously achieved successful removal of the BF, which was identified as an apricot pit. The patient resumed his diet of soft food immediately after the procedure without complaint of any discomfort.

Endoscopic submucosal excavation of a rectal submucosal tumor assisted by a curvilinear echoendoscope.

A 62-year-old woman undergoing screening colonoscopy was found to have a submucosal protrusion in the mid-rectum. Evaluation with a curvilinear echoendoscope revealed it to be a 1.8×1.1cm, hypoechoic mass originating from muscularis propria (MP) . Endoscopic submucosal excavation (ESE) was attempted, but despite adequate dissection of the submucosa, the mass remained poorly defined appearing as a slight elevation in the background of flat muscle. Repeat visualization of the lesion status post submucosal dissection was performed with the curvilinear echoendoscope. A biopsy forceps was introduced as a movable landmark which could be visualized on both synchronized endosonographic and optical views, so as to clearly identify the margin of the lesion . Incision of the MP overlying the identified margin allowed for precise exposure of the mass, which was further excavated and finally resected.

Hepatic abscess occurred one year after endoscopic transmural management of an infected, walled-off pancreatic necrosis.

A 46-year-old man underwent endoscopic ultrasound (EUS)-guided transgastric drainage with subsequent direct endoscopic necrosectomy (DEN) for an infected walled-off pancreatic necrosis (WOPN). Following treatment, he improved clinically with resolution of fever and substantial reduction in size of the WOPN. He was discharged with indwelling plastic stents which were to be removed after complete resolution of the WOPN. Follow-up CT and EUS 1 months later showed spontaneous stents dislodgement and a residual pancreatic fluid collection (PFC) measuring 4.0×2.3cm, for which re-intervention was technically demanding due to the small size. As he was asymptomatic, a decision was made to manage him expectantly for spontaneous resolution of the residual PFC. However, against our expectation, 1 year later he presented with recurrent fever to 40.1 °C. An hepatic abscess was identified on CT scan, which also revealed the residual PFC, though it was further reduced in size. After one month of antibiotic treatment, follow-up CT revealed that the hepatic abscess had resolved. Concurrently, complete resolution of residual PFC was also observed. EUS-guided drainage/debridement is a first-line therapy for WOPN. Remnant PFC due to premature stent dislodgement may persist as an insidious source of infection in which dormant pathogens may become reactivated sometime and culminate in a flare-up. Since the venous drainage of the pancreatic region ends up in the portal vein, occurrence of the hepatic abscess in the presence of the residual PFC should be considered as causal rather than coincidental. At least we couldn't help arousing a high suspicion of their cause-and-effect relationship. Therefore, despite its being technically challenging, timely reintervention with measures such as EUS-guided needle puncture and irrigation so as to thoroughly eradicate the residual PFC burden should be advocated to reduce the likelihood of late on-set local or distant infection.

Secoisolariciresinol diglucoside induces pyroptosis by activating caspase-1 to cleave GSDMD in colorectal cancer cells.

Secoisolariciresinol diglucoside (SDG) is the main component of lignans with various biological activities, including anticancer activity. However, whether SDG has obvious anticancer effects on colorectal cancer (CRC) is unclear. Pyroptosis, a form of programmed cell death, has received increasing attention in cancer-related research. In this study, we aimed to test the anticancer properties and relatecd functional mechanisms of SDG. we found that SDG not only inhibited the cell viability of HCT116 cells, but also induced HCT116 cells to swell with apparent large bubbles, which are typical signs of pyroptosis. Furthermore, SDG induced cell pyroptosis by enhancing cleavage of the N-terminal fragment of gasdermin D (GSDMD) in CRC cells, accompanied by increased caspase-1 cleavage. Consistent with this, SDG-induced GSDMD-N-terminal fragment cleavage and pyroptosis were reduced by siRNA-mediated silencing of caspase-1 or treatment with the specific caspase-1 inhibitor VX-765 treatment, suggesting that active caspase-1 further induces pyroptosis. A mechanistic study showed that SDG induced reactive oxygen species (ROS) accumulation and inhibits phosphatidylinositol 3-kinase (PI3K) phosphorylation and increases pyroptosis, while increasing GSDMD and caspase-1 cleavage and enhancing expression of BCL2-associated X (BAX), which could be rescued by the ROS scavenger (NAC), suggesting that SDG-induced GSDME-dependent pyroptosis is related to the ROS/PI3K/AKT/BAX-mitochondrial apoptotic pathway. In vivo results showed that SDG significantly inhibited tumor growth and induced pyroptosis in the HCT116-CRC nude mouse model. In conclusion, our findings suggest that the anticancer activity of SDG in CRC is associated with the induction of GSDMD-dependent pyroptosis by SDG through the generation of ROS/P13K/AKT/BAK-mitochondrail apoptosis pathway, providing insights into SDG in its potential new application in cancer treatment.

The prospective multiple-centre randomized controlled clinical study of high-dose amoxicillin-proton pump inhibitor dual therapy for H. pylori infection in Sichuan areas.

OBJECTIVES: To evaluate the safety and efficacy of high-dose amoxicillin-proton pump inhibitor dual therapy, and to provide a new eradication regimen as a first-line option for patients with H. pylori infection. METHODS: A total of 971 H. pylori positive patients who received initial treatment were recruited from March to August 2020, and randomly divided into treatment group and control group. The treatment group received of 20 mg esomeprazole four times daily and 750 mg amoxicillin four times daily for 14 days. Control group received of 220 mg bismuth potassium citrate twice daily, 20 mg esomeprazole twice daily, 1000 mg amoxicillin twice daily and 250 mg clarithromycin capsule twice daily for 14 days. Four weeks after the end of treatment, the urea breath test was reviewed to detect whether H. pylori was eradicated. RESULTS: There were no statistical differences in age, gender, the total clinical symptom scores before and after initial treatment, the compliance, and the degree of remission of symptoms before and after initial treatment between the two groups. The eradication rates of H. pylori between dual therapy and quadruple therapy were 88.31% and 85.26% (p=.158) by intention-to-treat (ITT) analysis, 88.66% and 85.44% (p=.186) by modified intention-to-treat (mITT) analysis, and 91.63% and 90.60% (p=.116) by PP analysis, respectively. Adverse events in dual therapy group were significantly lower than quadruple therapy group (13.3% vs. 28.2% (p<.01)). CONCLUSIONS: For the initial treatment of H. pylori infection, the high-dose dual therapy regimen has the same efficacy as the bismuth-containing quadruple therapy regimen, good compliance, less adverse reactions and high safety, so it can be recommended as the empirical first-line treatment regimen for the eradication of H. pylori (KY2019173).

Fishbone foreign body ingestion in duodenal papilla: a cause of abdominal pain resembling gastric ulcer.

BACKGROUND: Foreign body ingestion is a common clinical problem. The upper esophagus is the most common site of foreign body, accounting for more than 75% of all cases, but cases with a foreign body in the duodenal papilla or common bile duct are rarely reported. CASE PRESENTATION: Herein, we report a rare case that a patient's abdominal pain resembling gastric ulcer was caused by a 3 cm long fishbone inserted into the duodenal papilla. CONCLUSION: Fishbone inserted into the duodenal papilla can cause an abdominal pain resembling gastric ulcer. Endoscopy is useful for the diagnosis and treatment of fishbone ingestion in clinical.

Efficacy and Safety of Vonoprazan-Based versus Proton Pump Inhibitor-Based Triple Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Clinical Trials.

AIMS: To compare the efficacy and safety of vonoprazan-based versus proton pump inhibitor (PPI)-based triple therapy in the eradication of Helicobacter pylori. METHODS: We performed a systematic search in PubMed, Embase, and the Cochrane Library databases for relevant randomized controlled trials up to March 2019. Studies were included if they compared the efficacy and safety of H. pylori eradication of vonoprazan-based and PPI-based triple therapy. RESULTS: Three studies with 897 patients were evaluated in this meta-analysis. The H. pylori eradication rate of vonoprazan-based triple therapy was higher than that of PPI-based triple therapy as first-line regimens (intention-to-treat analysis: pooled eradication rates, 91.4% vs 74.8%; odds ratio [OR], 3.68; 95% confidence interval (CI): [1.87-7.26]; P<0.05). The incidence of adverse events in vonoprazan-based triple therapy was lower than that in PPI-based triple therapy (pooled incidence, 32.7% vs 40.5%; OR, 0.71; 95%CI: [0.53-0.95]; P<0.05). CONCLUSIONS: Efficacy of vonoprazan-based triple therapy is superior to that of PPI-based triple therapy for first-line H. pylori eradication. Additionally, vonoprazan-based triple therapy is better tolerated than PPI-based triple therapy.

MicroRNA-147b Promotes Proliferation and Invasion of Human Colorectal Cancer by Targeting RAS Oncogene Family (RAP2B).

BACKGROUND: MicroRNAs (miRNAs), a class of small-regulatory RNA molecules, were closely involved in the pathogenesis of a broad-spectrum of colorectal cancer (CRC). But role of miR-147b in CRC still remains unclear. METHODS: Real-time RT-PCR or Western blotting was utilized to detect the expressions of miR-147b and RAP2B in CRC cell lines and tissues. Luciferase reporter assays were conducted to detect the associations between miR-147b and 3'UTRs of RAP2B. A series of assays were performed to evaluate the effect of miR-147b on proliferation, migration, and invasion of CRC in vitro and in vivo. RESULTS: We found that the level of miR-147b was significantly lower in CRC tissues than in normal tissues (p = 0.0006). Enforced expression of miR-147b led to suppression of CRC cell proliferation in vitro and tumor growth in vivo. Specifically, miR-147b promoted proliferation by arresting CRC cells in the G1/G0 phase. Mechanically, RAP2B was identified as a direct target gene of miR-147b and RAP2B rescued the suppression of proliferation and invasion reduced by miR-147b in CRC cells. CONCLUSIONS: miR-147b not only plays important roles in the regulation of cell proliferation and tumor growth in CRC, which might be a potential prognostic marker or therapeutic target for CRC.

Bcl­2 associated athanogene 4 promotes proliferation, migration and invasion of gastric cancer cells.

Currently, with the increase of morbidity and mortality rate, gastric cancer (GC) is attracting increasing attention in China. Bcl­2­associated athanogene 4 (BAG4) has been identified as a tumor promoter in several tumors, but its role in GC remains unknown. The present study aimed to detect the expression of BAG4 and determine its function in the progression of GC. The results from reverse transcription­quantitative polymerase chain reaction and western blotting revealed that BAG4 was markedly upregulated in highly metastatic cell lines (SGC7901 and MGC803), compared with the lower­metastatic cell lines (AGS and BGC823). Through Cell Counting Kit­8, cell cycle, apoptosis, Transwell and colony formation assays, BAG4 was demonstrated to promote the proliferation, migration and invasion of GC cells in vitro. Additionally, in vivo assays further certified that BAG4 can increase the proliferation and invasion of GC cells. In conclusion, these findings implicate BAG4 as a potential therapeutic target for GC.

[Effects of Erk signal transduction on the cell cycle of rat hepatic stellate cells stimulated by acetaldehyde].

OBJECTIVE: To investigate the effect of PD98059 on the proliferation and cell cycle of rat hepatic stellate cells (HSCs) stimulated by acetaldehyde and explore its mechanism. METHODS: Rat HSCs stimulated by acetaldehyde were incubated with different concentrations of PD98059. Cell proliferation was assessed by MTT colorimetric assay. Cell cycle was analysed by flow cytometry. The mRNA of cyclin D1 and CDK4 were examined by RT-PCR. RESULTS: 20, 50, 100 micromol/L PD98059 could significantly inhibit the proliferation of HSCs stimulated by acetaldehyde in a does-dependent manner (0.109+/-0.020, 0.081+/-0.010 and 0.056+/-0.020 vs 0.146+/-0.030, F=31.385, P<0.05) and provoke G0/G1 phase arrest of HSCs stimulated by acetaldehyde in a does-dependent manner (61.9%+/-6.3%, 64.1%+/-3.3% and 70.9%+/-4.8% vs 55.2%+/-4.4%, F=16.402, P<0.05). 50, 100 micromol/L PD98059 could markedly inhibit cyclin D1 mRNA expression of HSC stimulated by acetaldehyde (0.56+/-0.04 and 0.46+/-0.03 vs 0.65+/-0.07, F=68.758, P<0.05) and CDK4 mRNA expression (0.39+/-0.07 and 0.33+/-0.05 vs 0.50+/-0.06, F=29.406, P<0.05). CONCLUSION: The Erk signal transduction pathway plays an important role in regulating the proliferation and cell cycle of rat hepatic stellate cells stimulated by acetaldehyde, which may be partly related to its regulative effect on the expression of cyclin D1 gene and CDK4 gene