Helicobacter pylori infection exacerbates metabolic dysfunction-associated steatotic liver disease through lipid metabolic pathways: a transcriptomic study.

BACKGROUND: The relationship between Helicobacter pylori (H. pylori) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted increased clinical attention. However, most of those current studies involve cross-sectional studies and meta-analyses, and experimental mechanistic exploration still needs to be improved. This study aimed to investigate the mechanisms by which H. pylori impacts MASLD. METHODS: We established two H. pylori-infected (Cag A positive and Cag A negative) mouse models with 16 weeks of chow diet (CD) or high-fat diet (HFD) feeding. Body weight, liver triglyceride, blood glucose, serum biochemical parameters, inflammatory factors, and insulin resistance were measured, and histological analysis of liver tissues was performed. Mouse livers were subjected to transcriptome RNA sequencing analysis. RESULTS: Although H. pylori infection could not significantly affect serum inflammatory factor levels and serum biochemical parameters in mice, serum insulin and homeostatic model assessment for insulin resistance levels increased in CD mode. In contrast, H. pylori Cag A + infection significantly aggravated hepatic pathological steatosis induced by HFD and elevated serum inflammatory factors and lipid metabolism parameters. Hepatic transcriptomic analysis in the CD groups revealed 767 differentially expressed genes (DEGs) in the H. pylori Cag A + infected group and 1473 DEGs in the H. pylori Cag A- infected group, and the "nonalcoholic fatty liver disease" pathway was significantly enriched in KEGG analysis. There were 578 DEGs in H. pylori Cag A + infection combined with the HFD feeding group and 820 DEGs in the H. pylori Cag A- infected group. DEGs in the HFD groups were significantly enriched in "fatty acid degradation" and "PPAR pathway." Exploring the effect of different Cag A statuses on mouse liver revealed that fatty acid binding protein 5 was differentially expressed in Cag A- H. pylori. DEG enrichment pathways were concentrated in the "PPAR pathway" and "fatty acid degradation." CONCLUSIONS: Clinicians are expected to comprehend the impact of H. pylori on MASLD and better understand and manage MASLD. H. pylori infection may exacerbate the development of MASLD by regulating hepatic lipid metabolism, and the H. pylori virulence factor Cag A plays a vital role in this regulation.

Factors associated with peroral endoscopic myotomy for achalasia outcomes: systematic review and meta-analysis.

BACKGROUND: Peroral endoscopic myotomy (POEM) is an emerging effective treatment for achalasia. However, a significant proportion of patients do not respond well to the treatment. After over a decade of clinical practice, potential risk factors associated with POEM failure have been identified. This meta-analysis aimed to summarize the evidence of risk factors for POEM failure. METHODS: A systematic literature search was conducted on PubMed, Embase, Web of Science, and Cochrane Library from inception to June 10th, 2022. We included English studies that reported POEM outcomes in achalasia patients and identified risk factors for POEM failure. Relevant information was extracted and analyzed using fixed- or randomized-effect models to pool the effect size. RESULTS: A total of 27 studies comprising 9371 patients with achalasia were included in this review. The pooled failure rate was 8% (90% CI 7%-10%). We identified sigmoid esophagus (OR 1.90, 95% CI 1.45-2.47), type I achalasia (OR 1.30, 95% CI 1.04-1.63), and type III achalasia (OR 1.26, 95% CI 0.89-1.78) were associated with a worse clinical response. Conversely, type II achalasia was associated with a better response (OR 0.59, 95% CI 0.47-0.75). Prior treatment with Heller myotomy (OR 5.75, 95% CI 3.97-8.34) and prior balloon dilation (OR 1.18, 95% CI 1.07-1.29) were also associated with a higher risk of clinical failure. CONCLUSION: Our meta-analysis results demonstrated that sigmoid esophagus, manometric achalasia subtype, and prior treatment were associated with POEM failure. This information could be used to guide treatment decisions and improve the success rate of POEM in achalasia patients.

Risk Factors for Rebleeding After Endoscopic Injection of Cyanoacrylate Glue for Gastric Varices: A Systematic Review and Meta-Analysis.

BACKGROUND: Rebleeding is a significant complication of endoscopic injection of cyanoacrylate in gastric varices in cirrhotic patients. AIM: This systematic review and meta-analysis aimed to evaluate the efficiency of endoscopic cyanoacrylate injection and summarized the risk factors for rebleeding. METHODS: Databases were searched for articles published between January 2012 and December 2022. Studies evaluating the efficiency of endoscopic injection of cyanoacrylate glue for gastric varices and the risk factors for rebleeding were included. RESULTS: The final analysis included data from 24 studies. The hemostatic rates ranged from 65 to 100%. The pooled rate of gastric varices recurrence was 34% [95% CI 21-46, I2 = 61.4%], early rebleeding rate was 16% [95% CI 11-20, I2 = 37.4%], late rebleeding rate was 39% [95% CI 36-42, I2 = 90.9%], mild and moderate adverse events rate were 28% [95% CI 24-31, I2 = 91.6%], 3% [95% CI - 2 to 8, I2 = 15.3%], rebleeding-related mortality rate was 6% [95% CI 2-10, I2 = 0%], all-cause mortality rate was 17% [95% CI 12-22, I2 = 63.6%]. Independent risk factors for gastric variceal rebleeding included portal venous thrombosis, ascites, cyanoacrylate volume, fever/systemic inflammatory response syndrome, red Wale sign, previous history of variceal bleeding, active bleeding and paragastric veins. The use of proton pump inhibitors could be a protective factor. CONCLUSIONS: Endoscopic cyanoacrylate glue injection is an effective and safe treatment for gastric varices. Cirrhotic patients with the above risk factors may benefit from treatment aimed at reducing portal hypertension, antibiotic prophylaxis, and anticoagulation if they meet the indications.

Risk factors for positive resection margins after endoscopic resection for gastrointestinal neuroendocrine tumors.

BACKGROUND: In recent years, the incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has remarkably increased due to the widespread use of screening gastrointestinal endoscopy. Currently, the most common treatments are surgery and endoscopic resection. Compared to surgery, endoscopic resection possesses a higher risk of resection margin residues for the treatment of GI-NETs. METHODS: A total of 315 patients who underwent surgery or endoscopic resection for GI-NETs were included. We analyzed their resection modality (surgery, ESD, EMR), margin status, Preoperative marking and Prognosis. RESULTS: Among 315 patients included, 175 cases underwent endoscopic resection and 140 cases underwent surgical treatment. A total of 43 (43/175, 24.57%) and 10 (10/140, 7.14%) patients exhibited positive resection margins after endoscopic resection and surgery, respectively. Multivariate regression analysis suggested that no preoperative marking and endoscopic treatment methods were risk factors for resection margin residues. Among the patients with positive margin residues after endoscopic resection, 5 patients underwent the radical surgical resection and 1 patient underwent additional ESD resection. The remaining 37 patients had no recurrence during a median follow-up of 36 months. CONCLUSIONS: Compared with surgery, endoscopic therapy has a higher margin residual rate. During endoscopic resection, preoperative marking may reduce the rate of lateral margin residues, and endoscopic submucosal dissection may be preferred than endoscopic mucosal resection. Periodical follow-up may be an alternative method for patients with positive margin residues after endoscopic resection.

Efficacy and Safety of Vonoprazan-Based Quadruple Therapy for the Eradication of Helicobacter pylori in Patients with Peptic Ulcers: A Pooled Analysis of Two Randomized, Double-Blind, Double-Dummy, Phase 3 Trials.

Helicobacter pylori eradication is crucial in the treatment of peptic ulcers caused by H. pylori infection, a disease highly prevalent in Asia. We present a pooled analysis of two randomized, double-blind, double-dummy, phase 3 studies evaluating the efficacy and safety of vonoprazan-based bismuth-containing quadruple therapy for H. pylori eradication. Patients aged ≥18 years with endoscopically confirmed duodenal or gastric ulcers were randomized 1 : 1 to receive vonoprazan 20 mg or lansoprazole 30 mg once daily for up to 6 (duodenal ulcers) or 8 weeks (gastric ulcers). H. pylori-positive patients received vonoprazan- or lansoprazole-based bismuth-containing quadruple therapy for the first 2 weeks. H. pylori eradication was determined using the carbon-13 urea breath test at a follow-up visit 4 weeks post-treatment. The H. pylori eradication rate was 90.6% with vonoprazan vs. 85.2% with lansoprazole (difference: 5.4%; 95% confidence interval (CI): -0.1, 10.8). H. pylori eradication rates were 7.1% (95% CI: 1.4, 12.8) and 12.6% (95% CI: 3.9, 22.0) higher in patients aged <65 years and current smokers, respectively, with vonoprazan vs. lansoprazole. In the Chinese subpopulation, the H. pylori eradication rate was 92.0% with vonoprazan vs. 86.0% with lansoprazole (difference: 6.1%; 95% CI: 0.5, 11.7). Treatment-emergent adverse events occurred in 72.7 vs. 62.6% of H. pylori-positive patients at baseline in the vonoprazan vs. lansoprazole arm. H. pylori eradication with vonoprazan-based quadruple therapy was noninferior to lansoprazole-based quadruple therapy and exceeded 90%, a clinically relevant threshold for determining the efficacy of H. pylori eradication regimens (ClinicalTrials.gov identifier: NCT03050359; NCT03050307).

Indoleacrylic acid produced by Parabacteroides distasonis alleviates type 2 diabetes via activation of AhR to repair intestinal barrier.

BACKGROUND: Anti-inflammatory therapy is an effective strategy in the treatment of type 2 diabetes (T2D). Studies found that inflammatory responses in vivo were strongly associated with defects in the mucosal barrier function of the gut epithelium. While some microbial strains could help repair the intestinal mucosa and maintain the integrity of the intestinal barrier, the specific mechanisms remain to be fully elucidated. The present study investigated the effects of Parabacteroides distasonis (P. distasonis) on the intestinal barrier and the inflammation level in T2D rats and explored the specific mechanisms. RESULTS: By analyzing the intestinal barrier function, the inflammatory conditions, and the gut microbiome, we found that P. distasonis could attenuate insulin resistance by repairing the intestinal barrier and reducing inflammation caused by the disturbed gut microbiota. We quantitatively profiled the level of tryptophan and indole derivatives (IDs) in rats and fermentation broth of the strain, demonstrating that indoleacrylic acid (IA) was the most significant factor correlated with the microbial alterations among all types of endogenous metabolites. Finally, we used molecular and cell biological techniques to determine that the metabolic benefits of P. distasonis were mainly attributed to its ability to promote IA generation, active the aryl hydrocarbon receptor (AhR) signaling pathway, and increase the expression level of interleukin-22 (IL-22), thus enhancing the expression of intestinal barrier-related proteins. CONCLUSIONS: Our study revealed the effects of P. distasonis in the treatment of T2D via intestinal barrier repairment and inflammation reduction and highlighted a host-microbial co-metabolite indoleacrylic acid that could active AhR to perform its physiological effects. Our study provided new therapeutic strategies for metabolic diseases by targeting the gut microbiota and tryptophan metabolism.

Unsupervised Clustering-Assisted Method for Consensual Quantitative Analysis of Methanol-Gasoline Blends by Raman Spectroscopy.

Methanol-gasoline blends have emerged as a promising and environmentally friendly bio-fuel option, garnering widespread attention and promotion globally. The methanol content within these blends significantly influences their quality and combustion performance. This study explores the qualitative and qualitative analysis of methanol-gasoline blends using Raman spectroscopy coupled with machine learning methods. Experimentally, methanol-gasoline blends with varying methanol concentrations were artificially configured, commencing with initial market samples. For qualitative analysis, the partial least squares discriminant analysis (PLS-DA) model was employed to classify the categories of blends, demonstrating high prediction performance with an accuracy of nearly 100% classification. For the quantitative analysis, a consensus model was proposed to accurately predict the methanol content. It integrates member models developed on clustered variables, using the unsupervised clustering method of the self-organizing mapping neural network (SOM) to accomplish the regression prediction. The performance of this consensus model was systemically compared to that of the PLS model and uninformative variable elimination (UVE)-PLS model. Results revealed that the unsupervised consensus model outperformed other models in predicting the methanol content across various types of methanol gasoline blends. The correlation coefficients for prediction sets consistently exceeded 0.98. Consequently, Raman spectroscopy emerges as a suitable choice for both qualitative and quantitative analysis of methanol-gasoline blend quality. This study anticipates an increasing role for Raman spectroscopy in analysis of fuel composition.

Complex duodenal fistula after cholecystectomy successfully treated with endoscopic suturing.

We reported a 47-year-old female with a history of laparoscopic cholecystectomy presented with a complex duodenal fistula. The bleeding artery embolization and endoscopic suture of the duodenal fistula were performed successfully. We highlight the endoscopic tissue clip suture as a safe and feasible option when surgery is too risky.

Safety and efficacy of ESD for laterally spreading tumors with hemorrhoids close to the dentate line.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a curative treatment for laterally spreading tumors (LSTs). However, the outcomes of ESD for LSTs with hemorrhoids remain largely unknown. Our study aimed to evaluate the usefulness of ESD in managing LSTs with hemorrhoids. MATERIAL AND METHODS: We retrospectively collected 418 consecutive LST patients treated with ESD between 2011 and 2023. A retrospective comparative analysis was conducted. RESULTS: There were 85 patients included in the hemorrhoids group and 333 patients included in the other group. The en-bloc resection rate, R0 resection rate, and curative resection rate were comparable in these two groups (p > 0.05). The LSTs with hemorrhoids have a significantly higher intraoperative bleeding rate during ESD when compared to the other group (12.9% vs. 5.4%, p = 0.028). Rates of intraoperative perforation and anal pain in the hemorrhoid group were significantly higher than those in the no-hemorrhoid group (2.4% vs. 0%, p = 0.041; 9.4% vs.0.6%, p < 0.001; respectively). Moreover, most of the related manifestations caused by hemorrhoids were relieved to various degrees after ESD. CONCLUSIONS: ESD is a safe and effective treatment strategy for LSTs with hemorrhoids. A multi-center and prospective study should be conducted in the future to validate our results.

Endoscopic ultrasound-guided bite-on-bite biopsy and endoscopic ultrasound-guided fine-needle aspiration in the diagnosis of gastric tumors with negative malignant endoscopy biopsies: a retrospective cohort study.

BACKGROUND: Specific types of gastric tumors, including gastric linitis plastica and lymphoma, may cause extensive deep-layer infiltration, impeding an accurate diagnosis with endoscopic biopsy. This study aims to evaluate the efficacy of endoscopic ultrasound (EUS)-guided bite-on-bite biopsy and EUS-guided fine-needle aspiration (EUS-FNA) in diagnosing gastric malignancies with negative endoscopic biopsies. METHODS: We retrospectively analyzed suspicious malignant gastric lesion cases in our hospital from October 2017 to August 2023. Clinical manifestations, radiographical examinations, endoscopic examinations, histopathological results, and therapeutic strategies were recorded and analyzed. RESULTS: Forty malignant gastric tumor cases with negative endoscopic biopsies were incorporated into our study. EUS-guided bite-on-bite biopsy was performed in 16 cases exclusively, whereas 17 patients received EUS-FNA exclusively, and seven patients underwent both simultaneously. Among the 23 patients who received the EUS-guided bite-on-bite biopsy, 22 (95.7%) were diagnosed with malignancies. Among the 24 patients who received EUS-FNA, a total of 19 cases with malignancies (79.2%) were confirmed by EUS-FNA (p = 0.11): 13 gastric adenocarcinomas, five metastatic malignancies, and one malignant stromal tumor. No adverse events were observed in any of the cases. CONCLUSIONS: EUS-guided bite-on-bite biopsy and EUS-FNA possess their advantages and disadvantages. EUS-guided bite-on-bite biopsy could serve as a reliable diagnostic method for shallow lesions with negative malignant endoscopic biopsies.

Utilizing circulating tumour DNA as a prognostic predictor of gastric cancer: a meta-analysis.

Background: Circulating tumour DNA (ctDNA) has demonstrated robust diagnostic accuracy in several digestive cancers. However, the prognostic role of ctCDNA in gastric cancer (GC) is still controversial. This systematic review and meta-analysis aimed to evaluate the prognostic value of ctDNA in GC.Methods: PubMed, Web of Science and Cochrane databases were searched to identify studies reporting the use of ctDNA to predict GC outcome and all relevant studies published until November 2022 were enrolled for our analysis. Data were extracted by two authors independently and statistic analysis was conducted by R program with 'meta' and 'metafor' packages.Results: A total of 34 qualified articles with 5091 subjects were incorporated into our meta-analysis. The corresponding Hazard ratio (HR) of overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) were 2.74 (95% CI:2.24-3.35), 3.13 (95% CI:2.08-4.72) and 3.04 (95% CI:2.46-3.76), respectively, in GC patients.Conclusion: Blood-based ctDNA assay would be a potential novel biomarker for GC evaluation and prediction.Simple Summary: This is the integrated meta-analysis on the association of circulating tumour DNA (ctDNA) and prognosis of gastric cancer (GC) with an increasing number of studies exploring the prognostic value of GC in the last few years, which depicted that the detection of ctDNA could be a promising predictor in GC patients.

Association between the Systemic Immune-Inflammation Index and Thyroid Function in U.S. Adults.

Background: The systemic immune-inflammation index (SII) is used as an indicator of prognosis for a wide range of diseases. Thyroid function has been found to be strongly associated with inflammation. The purpose of this investigation was to analyze the correlation between SII and various thyroid functions. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. The association between SII and thyroid function was analyzed using weighted univariate and multivariate linear regression analyses. Subgroup analyses, interaction tests, and weighted restricted cubic spline (RCS) regression analyses were also employed to test this correlation. Results: Of the 6,875 participants (age ≥ 20 years), the mean age was 46.87 ± 0.40 years. The adjusted model showed that lnSII was negatively correlated with FT3 (ß = -0.0559, 95% CI -0.1060 to -0.0059,) and FT3/FT4 (ß = -0.0920, 95% CI -0.1667 to -0.0173,). There was a positive correlation between lnSII and TT4 (ß = 0.1499, 95% CI 0.0722-0.2276,). In subgroup analyses, lnSII still independently affected a wide range of thyroid functions. Weighted RCS analysis showed a nonlinear relationship between FT3 and lnSII. Conclusion: Close relationships exist between SII and a variety of thyroid functions. SII can be used as an indicator to predict thyroid dysfunction. Control of inflammatory activity may be a protective measure against thyroid dysfunction. More large-scale prospective studies are necessary to further explore the correlation between SII and thyroid function and the role of obesity in this.

The correlation of two bone turnover markers with bone mineral density: a population-based cross-sectional study.

OBJECTIVE: Exploring the correlation between bone turnover marks (BTMs) with lumbar BMD in middle-aged populations. METHODS: The cross-sectional analysis fetched data came from NHANES. The level of serum bone alkaline phosphatase (sBAP) and urinary N-telopeptide (uNTx) were regarded as representative of bone turnover. Lumbar BMD was the outcome of the study. Multivariable linear regression models were utilized to detect the correlation of sBAP and uNTx with Lumbar BMD. RESULTS: The level of sBAP and uNTx was negatively correlated with lumbar BMD in every multivariable linear regression. For sBAP, this inverse correlation was stable in both men and women (P < 0.01). uNTx indicated a negative association after all relevant covariables were adjusted (P < 0.01). The men group remained the negative correlation in gender subgroup analysis (P < 0.01). CONCLUSION: This study indicated that the increased level of sBAP and uNTx associated with lumbar BMD decreased among middle-aged adults. This correlation could prompt researchers to explore further the relationship between bone turnover rate and BMD, which may provide information for the early detection of BMD loss and provide a new strategy for clinical practice.

Peroral Endoscopic Myotomy for Achalasia in Older Adults: A Retrospective Analysis of 39 Cases with a Minimum Follow-Up of 5 Years.

Peroral endoscopic myotomy (POEM) has demonstrated favorable short-term safety and efficacy in older adults, while a comprehensive understanding of the long-term outcomes were vague. We aimed to evaluate clinical outcomes in older adults' 5-year postop after undergoing POEM to treatment achalasia. Older adults from a single hospital who received POEM between January 2010 and January 2017 were analyzed. Older persons were reached to evaluate their symptoms at present and encouraged repeat examinations for objective follow-up. The clinical success, POEM-related indicators, POEM-related adverse events, and quality of life were assessed. Thirty-nine older adults with a mean age of 70.82 ± 4.72 who underwent POEM were studied at a mean 84.23 ± 25.06 month follow-up. The preoperative diagnosis was achalasia type I in 7 older adults, achalasia type II in 26 older adults, and achalasia type III in 2 older adults. Sixteen older adults had prior treatment and 21 older adults suffered from comorbidities. The median operative time was 50 (25-120) minutes, and perioperative adverse events were recorded in four older adults. The current Eckardt scores were significantly lower than that before POEM (2.08 ± 2.12 vs. 6.58 ± 1.78, P < 0.001). Besides, long-term clinical success was gained in 66.7% of older adults. Three older adults received postop treatment for symptom recurrence. Ultimately, 80.6% of old adults expressed satisfaction with POEM, while 27.8% of older adults suffered from symptomatic reflux. In conclusion, POEM can provide symptomatic improvement in a large proportion of older adults with achalasia at 5-year postop.

Endoscopic submucosal dissection for giant colorectal laterally spreading tumor 33 cm in diameter.

A 77-year-old male presented with recurrent diarrhea for more than 2 years, aggravated and a 1-month history of a rectal mass. High-definition white light colonoscopy showed an approximately circumferential elevated lesion from about 12 cm from the anus to the dentate line, with surface nodules of different sizes, some surfaces slightly congested, and internal hemorrhoids. The patient was diagnosed with a giant laterally spreading tumor-granular nodular mixed type (LST-G-M) of the rectum with the possibility of local malignant transformation and treated with single-tunnel assisted endoscopic submucosal dissection (ESD) at the patient's request. Histopathology of the specimen showed villous tubular adenoma with local carcinogenesis, 33*12cm in size, negative margins, no lymphovascular invasion. No bleeding or perforation was observed during or after procedure, and no stenosis was scrutinized at 2 months later.

Coexisting achalasia and leiomyoma misdiagnosed as the submucosal tumor, successfully treated by simultaneous peroral endoscopic myotomy and submucosal tunneling endoscopic resection in the same tunnel.

Peroral endoscopic myotomy (POEM) is a safe and effective method in the treatment of achalasia. Meanwhile, submucosal tunneling endoscopic resection (STER) is a common endoscopic method for the treatment of submucosal tumors (SMT) in the upper digestive tract. However simultaneous POEM and STER for coexisting achalasia and esophageal SMT is rarely reported. A 40-year-old woman underwent esophagoscopy after dysphagia and vomiting for 20 years. The protruding submucosal lesion with normal overlying mucosa was found in the lower part of the esophagus, nearing cardia. Considering the persistent swallowing discomfort and vomiting symptoms, the patient underwent esophageal manometry and barium esophagram, and was finally diagnosed as achalasia with esophageal submucosal tumor. Finally, POEM and STER were performed simultaneously on the patient in the same tunnel. The patient was followed up for 4 months without recurrence or complaints. We herein report a case of achalasia with esophageal leiomyoma who underwent POEM and STER in the same tunnel to remove the mass and relieve the symptoms.

Research progress in cuproptosis in liver cancer. / é“œæ­»äº¡åœ¨è‚ç™Œä¸­çš„ç ”ç©¶è¿›å±•.

Copper, like iron, is an essential trace metal element for human cells. The role of iron overload and ferroptosis has been gradually clarified in tumors, but the role of copper overload and cuproptosis is still being explored. Cuproptosis is a novel mode of cell death, secondary to impaired mitochondrial function induced by copper overload, and characterized by copper-dependent and programmed. The excessive copper leads to protein toxicity stress by binding to sulfhydryl proteins in the tricarboxylic acid (TCA) cycle of mitochondria, disrupting cellular homeostasis and triggering cuproptosis. Copper accumulation has carcinogenic effects on normal cells, dual effects on tumor cells. Liver cancer is one of the most common malignant tumors in China and even globally, with hepatocellular carcinoma (HCC) being the most common histological subtype. Copper exhibits dualism in HCC, as it both contributes to the growth and invasion of HCC cells, and exerts anticancer effects by inducing cuproptosis. Also, cuproptosis-related genes can be the evaluation of immunotherapy effect and the construction of prognostic models. Clarifying the role of copper death in liver cancer can help explore new methods for liver cancer screening, treatment, and prognosis evaluation.

MiR-196a promotes the proliferation and migration of esophageal cancer via the UHRF2/TET2 axis.

The aim of this study was to investigate the functions and molecular mechanism of miR-196a in esophageal cancer (EC). miR-196a as well as UHRF2 and TET2 mRNA and protein levels in EC tissues and cells were detected using quantitative real-time PCR or western blot, respectively. Cell proliferation was evaluated via MTT assay. Transwell assays were used to detect cell migration. In addition, the targeted relationship between miR-196a and UHRF2 was assessed through a dual luciferase reporter assay. Enzyme-linked immunosorbent assay was performed to detect the levels of the cytosine intermediates 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). We found increased miR-196a expression in EC tissues and cells but decreased UHRF2 and TET2 expression. Next, functional experiments showed that knockdown of miR-196a or UHRF2 overexpression suppress EC cell proliferation and migration. miR-196a negatively regulates TET2 expression by directly targeting UHRF2. UHRF2 overexpression decreased 5mC levels but increased 5hmC levels. Furthermore, TET2 downregulation reversed the functions of miR-196a inhibition on EC cell proliferation and migration. Collectively, our study suggested that miR-196a was closely related to the progression of EC possibly by regulating the UHRF2/TET2 axis. Thus, miR-196a represents a potential new EC therapeutic target.

Safety and efficacy of surgical and endoscopic resection in the treatment of duodenal subepithelial lesions.

BACKGROUND: Duodenal subepithelial lesions (D-SELs) are rare and their resection is challenging. Unfortunately, data on surgical and endoscopic resection of D-SELs are scarce. This study aimed to assess the safety and efficacy of surgical resection and endoscopic resection (ER) for D-SELs. METHODS: We retrospectively analyzed clinical data of patients with non-ampullary D-SELs who underwent ER or surgery and compared the outcomes between ER and surgery with no/low-risk SELs over 15 mm from March 2010 to August 2020. Clinicopathologic findings, procedure-related parameters, and follow-up data were analyzed. RESULTS: A total of 107 patients (108 lesions) were enrolled; 52 patients (53 lesions) received ER and 55 patients (55 lesions) received surgery. In ER group, en bloc resection rate and R0 resection rate were 94 and 89%, respectively. Major adverse events rate was 6%. One (2%) patient experienced local recurrence. In surgery group, R0 resection was achieved in all cases. Major adverse events rate was 20%. Recurrence rate and distant metastases rate were 4 and 8%, respectively. One (2%) patient died from septicemia during follow-up. Thirty-three patients in each group were enrolled in the comparison. There were no significant differences in age, sex, lesion size and location (P > 0.05). More histologically GISTs and muscularis propria-originated lesions were treated by surgery (P < 0.05). ER was significantly associated with a shorter operation time, shorter hospital stay, lower cost, less estimated blood loss, and lower major adverse events rate compared to the surgery group (P < 0.05). However, R0 resection rate, mortality, recurrence rate, and metastases rate were not significant different (P > 0.05). CONCLUSIONS: ER is an effective and safe treatment modality for selected patients with non-ampullary D-SELs by expert endoscopists. Surgery is a radical method for D-SELs that should be reserved for D-SELs not amenable to ER.

Successful endoscopic removal of a giant duodenal bulb mass.

A 53-year-old man presented to our hospital for resection of a duodenal mass because of the increasing diameter. Esophagogastroduodenoscopy revealed a giant oval mass in the back wall of duodenal bulb, which was protruded to the second part of duodenum(Figure 1). Endoscopic ultrasonography (EUS) revealed a submucosal mass with heterogeneous echogenicity and regular shape(Figure 2). Eventually, the patient received endoscopic submucosal dissection (ESD) after signing informed consent. The mass was resected completely and measured 6.0×4.2×3.0 cm [Figure 3]. Histopathological examination revealed a brunner's gland adenoma. There was no complication besides minor intraoperative bleeding. Both surgery and endoscopic resection (ER) are alternative treatments for duodenal adenoma, but the best way remains controversial. Due to the thin wall, narrow cavity and plentiful vascular network of the duodenal bulb, ER is challenging because of the technical difficulty and probability of perforation and bleeding [1]. Our previous study found that ER is an effective and safe way for treating duodenal adenoma on experienced hands, and ER possesses several advantages over surgical resection for selected patients [2，3]. In the present case, we removed the giant BGA by ESD, as far as we know, this is the largest yet removed by ER.