The efficacy and safety of fexuprazan in treating erosive esophagitis: a phase III, randomized, double-blind, multicenter study.

BACKGROUND AND AIM: Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS: This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS: A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION: This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.

Risk factors of recurrent choledocholithiasis following therapeutic endoscopic retrograde cholangiopancreatography.

BACKGROUND: The risk factors for the recurrent choledocholithiasis after endoscopic retrograde cholangiopancreatography (ERCP) have not been well studied. The aim of this study was to explore the risk factors of recurrent choledocholithiasis. METHODS: We carried out a retrospective analysis of data collected between January 1, 2010 and January 1, 2020. Univariate analysis and multivariate analysis were used to explore the independent risk factors of recurrent choledocholithiasis following therapeutic ERCP. RESULTS: In total, 598 patients were eventually selected for analysis, 299 patients in the recurrent choledocholithiasis group and 299 patients in the control group. The overall rate of recurrent choledocholithiasis was 6.91%. Multivariate analysis showed that diabetes [odds ratio (OR) = 3.677, 95% confidence interval (CI): 1.875-7.209; P < 0.001], fatty liver (OR = 4.741, 95% CI: 1.205-18.653; P = 0.026), liver cirrhosis (OR = 3.900, 95% CI: 1.358-11.201; P = 0.011), history of smoking (OR = 3.773, 95% CI: 2.060-6.908; P < 0.001), intrahepatic bile duct stone (OR = 4.208, 95% CI: 2.220-7.976; P < 0.001), biliary stent (OR = 2.996, 95% CI: 1.870-4.800; P < 0.001), and endoscopic papillary balloon dilation (EPBD) (OR = 3.009, 95% CI: 1.921-4.715; P < 0.001) were independent risk factors of recurrent choledocholithiasis. However, history of drinking (OR = 0.183, 95% CI: 0.099-0.337; P < 0.001), eating light food frequently (OR = 0.511, 95% CI: 0.343-0.760; P = 0.001), and antibiotic use before ERCP (OR = 0.315, 95% CI: 0.200-0.497; P < 0.001) were independent protective factors of recurrent choledocholithiasis. CONCLUSIONS: Patients with the abovementioned risk factors are more likely to have recurrent CBD stones. Patients who eat light food frequently and have a history of drinking are less likely to present with recurrent CBD calculi.

m1A methylation modification patterns and metabolic characteristics in hepatocellular carcinoma.

BACKGROUND: The dysregulation of RNA methylation has been demonstrated to contribute to tumorigenicity and progression in recent years. However, the alteration of N1-methyladenosine (m1A) methylation and its role in hepatocellular carcinoma (HCC) remain unclear. METHODS: We systematically investigated the modification patterns of 10 m1A regulators in HCC samples and evaluated the metabolic characteristics of each pattern. A scoring system named the m1Ascore was developed using principal component analysis. The clinical value of the m1Ascore in risk stratification and drug screening was further explored. RESULTS: Three m1A modification patterns with distinct metabolic characteristics were identified, corresponding to the metabolism-high, metabolism-intermediate and metabolism-excluded phenotypes. Patients were divided into high- or low-m1Ascore groups, and a significant survival difference was observed. External validation confirmed the prognostic value of the m1Ascore. A nomogram incorporating the m1Ascore and other clinicopathological factors was constructed and had good performance for predicting survival. Two agents, mitoxantrone and doxorubicin, were determined to be potential therapeutic drugs for the high-risk group. CONCLUSION: This study provided novel insights into m1A modification and metabolic heterogeneity in cancer, promoted risk stratification in the clinic from the perspective of m1A modification, and further guided individual treatment strategies.

Clinical applicability of a new scoring system for population-based screening and risk factors of gastric cancer in the Wannan region.

BACKGROUND: We aimed to evaluate the clinical applicability of a new scoring system that comprises the variables age, sex, pepsinogen ratio (PGR), gastrin-17 (G-17), and Helicobacter pylori (Hp) infection for gastric cancer (GC) screening in the Wannan region, China. We also explored the risk factors of GC in the Wannan region. METHODS: We prospectively enrolled asymptomatic participants from January 1, 2019 to June 30, 2021 at the First Affiliated Hospital of Wannan Medical College. We used a receiver operating characteristic (ROC) curve to estimate the screening value of combined measurements of pepsinogen I, PGII, PGR, G-17, and Hp. Univariate analysis and multivariate analysis were used to explore the independent risk factors of GC. RESULTS: A total of 25,194 asymptomatic patients were eventually screened. The area under the ROC curve (AUC) of combined measurements was 0.817 (95% confidence interval [CI] 0.721-0.913), the sensitivity was 81.5%, and the specificity was 77.8%. The detection rate of this new scoring system for GC screening in low-, medium-, and high-risk groups was 0%, 1.63%, and 9%, respectively (P < 0.001). Multivariate analysis showed that age (odds ratio [OR], 5.934; 95% CI 3.695-9.529; P < 0.001), sex (OR 5.721; 95% CI 2.579-12.695; P < 0.001), Hp infection (OR 1.992; 95% CI 1.255-3.163; P = 0.003), a history of smoking (OR 2.028; 95% CI 1.213-3.392; P = 0.007), consuming a high-salt diet (OR 2.877; 95% CI 1.807-4.580; P < 0.001), frequently eating pickled foods (OR 1.873; 95% CI 1.125-3.120; P = 0.016), and frequently eating fried foods (OR 2.459; 95% CI 1.384-4.369; P = 0.002) were independent risk factors for GC and precancerous lesions. However, frequent consumption of green vegetables (OR 0.388; 95% CI 0.242-0.620; P < 0.001) was an independent protective factor against GC and precancerous lesions. CONCLUSION: The new scoring system for GC screening was feasible in the Wannan region, especially in high-risk populations. Frequent consumption of green vegetables was an independent protective factor against GC and precancerous lesions.

Clinical characteristics and risk factors for upgraded pathology in patients with gastric intraepithelial neoplasia after endoscopic submucosal dissection.

BACKGROUND AND AIMS: The pathological results of endoscopic forceps biopsy (EFB) are frequently inconsistent with those after endoscopic submucosal dissection (ESD) in patients with gastric intraepithelial neoplasia (GIN). The aim of this study was to explore the risk factors for upgraded pathology after ESD in the Wannan region of Anhui Province, in order to guide the best clinical treatment of GIN. METHODS: A retrospective analysis was performed at the First Affiliated Hospital of Wannan Medical College. Univariate analysis and multivariate analysis were used to investigate the independent risk factors for pathology upgrade between EFB and ESD. RESULTS: In total, 215 patients who were initially diagnosed with GIN from EFB and subsequently received treatment with ESD were eventually selected for analysis. Age >60 years, a lesion located in upper 2/3 of the stomach, a lesion size of >2 cm, a lesion surface with redness and nodules and a lesion with irregular or absent microglands were significantly associated with the upgraded group after ESD. Multivariate analysis suggested that a lesion size of >2 cm (odds ratio [OR], 1.499; 95% confidence interval [CI], 1.222-1.909; P=0.026), a lesion surface with redness (OR, 1.508; 95%CI, 1.260-1.993; P=0.048) and nodules (OR, 1.390; 95%CI, 1.195-1.778; P=0.008) were independent predictors for the upgraded group. CONCLUSIONS: For patients with suspected GIN by EFB, a lesion size of >2 cm, a lesion surface with redness and nodules should be taken into account before deciding on the ESD.

Boerhaave's syndrome with rupture of the right wall of the esophagus after oral administration of sulfate solution.

A 63-year-old male took magnesium sulfate for bowel cleansing and subsequently developed severe nausea and vomiting. He then suffered from acute epigastric pain and compression pain in the right chest, with dyspnea, chest tightness and palpitation. Physical examination revealed subcutaneous emphysema in the neck, with crepitus and diminished breathing sounds on the right side of the chest. A thoracic computed tomography (CT) scan showed mediastinal emphysema, right-sided pleural effusion and pneumothorax.

Development and Validation of Prognostic Nomograms for Patients with Primary Gastrointestinal Non-Hodgkin Lymphomas.

BACKGROUND AND AIMS: The objective of this study was to construct and authenticate nomograms to project overall survival (OS) and cancer-specific survival (CSS) in primary gastrointestinal non-Hodgkin lymphomas (PGINHL). METHODS: Suitable patients were chosen from the Surveillance, Epidemiology and End Results database and Wannan Medical College Yijishan Hospital. The Cox regression model was used to acquire independent predictive factors to develop nomograms for projecting OS and CSS. The performance of the nomograms was validated using the Harrell's concordance index (C-index), calibration curves, and decision curve analysis (DCA) and was compared with that of the AJCC 7th staging system. Survival curves were obtained using the Kaplan-Meier method, while the log-rank test was used to compare the difference among the groups. RESULTS: The C-index of the nomograms for OS and CSS was 0.735 (95% CI = 0.719-0.751) and 0.761 (95% CI = 0.739-0.783), respectively, signifying substantial predictive accuracy. These outcomes were reproducible when the nomograms were used for the internal and external validation cohorts. Moreover, assessments of the C-index, AUC, and DCA between the nomogram results and the AJCC 7th staging system showed that the former was better for evaluation and was more clinically useful. CONCLUSIONS: We constructed the nomogram which could predict 1-, 3-, and 5-year OS and CSS of patients with PGINHL. Our nomogram showed good performance, suggesting that it can be used as an efficacious instrument for predictive assessment of patients with PGINHL.

Development and Validation of Prognostic Nomograms for Patients with Duodenal Neuroendocrine Neoplasms.

BACKGROUND This study was designed to predict prognosis of patients with primary duodenal neuroendocrine neoplasms (D-NENs) by developing nomograms. MATERIAL AND METHODS Patients diagnosed with D-NENs between 1988 and 2015 were queried from the SEER database and a total of 965 appropriate cases were randomly separated into the training and validation sets. Kaplan-Meier analysis was used to generated survival curves, and the difference among the groups was assessed by the log-rank test. Independent prognostic indicators were acquired by Cox regression analysis, and were used to develop predictive overall survival (OS) and cancer-specific survival (CSS) nomograms. Harrell's concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis (DCA) were used to assess the efficacy of nomograms. Tumor stage was regarded as a benchmark in predicting prognostic compared with the nomograms built in this study. RESULTS The C-index was 0.739 (0.690-0.788) and 0.859 (0.802-0.916) for OS and CSS nomograms, respectively. Calibration curves exhibited obvious consistency between the nomograms and the actual observations. In addition, C-index, AUC, and DCA were better than tumor stage in the evaluative performance of nomograms. CONCLUSIONS The nomograms were able to predict the 1-, 5-, and 10-year OS and CSS for D-NENs patients. The good performance of these nomograms suggest that they can be used for evaluating the prognosis of patients with D-NENs and can facilitate individualized treatment in clinical practice.

Clinicopathologic Characteristics and Risk Factors of Lymph Node Metastasis in Patients with Early Gastric Cancer in the Wannan Region.

BACKGROUND To date, there has been no agreement on the risk factors of lymph node metastasis (LNM) for early gastric cancer (EGC). The objective of this article was to investigate the risk factors of LNM in EGC in the Wannan region of Anhui Province and then to develop a regional practice guideline to manage EGC cases in this population. MATERIAL AND METHODS This retrospective analysis was performed from July 1, 2014 to June 30, 2017, at First Affiliated Hospital of Wannan Medical College. We explored the independent risk factors of LNM by using univariate analysis and multivariate analysis. RESULTS In total, 381 patients were selected for analysis. The LNM rate of EGC was 13.65% (52 out of 381 patients). Submucosal invasion, ulcer presence, undifferentiated tumor, vascular tumor thrombus, and neural invasion were significantly associated with LNM in EGC patients. Multivariate analysis suggested that depth of invasion (odds ratio [OR], 3.50; 95% confidence interval [CI], 1.45-8.42; P=0.005), vascular tumor thrombus (OR, 6.33; 95%CI, 2.31-17.31; P=0.001), and neural invasion (OR, 10.95; 95%CI, 3.29-36.41; P=0.001) were independent predictors of LNM in EGC patients CONCLUSIONS In the Wannan region of Anhui Province in China, depth of invasion, vascular tumor thrombus, and neural invasion were independent predictive risk factors for LNM in EGC patients. EGC patients with these risk factors for LNM are more likely to have LNM, and radical surgical procedure was more likely to be considered. With respective to EGC with submucosal invasion, the flat type pattern had a lower risk of LNM.

Indomethacin down-regulating HMGB1 and TNF-α to prevent pancreatitis after endoscopic retrograde cholangiopancreatography.

Background and aims: Several articles demonstrated that non-steroidal anti-inflammation drugs (NSAIDs) were effective in reducing the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (PEP). However, studies revealed inconsistent results. The mechanism of NSAIDs in preventing PEP is still little known. Therefore, the aim of our study was to evaluate the efficacy of NSAIDs for PEP prophylaxis and further to explore the mechanism of NSAIDs for prevention of PEP. Methods: Patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) were randomly assigned to receive 100 mg rectal indomethacin or glycerin suppository 15-20 min before ERCP. The primary outcome was the rate of PEP. And the levels of serum HMGB1 and TNF-α were also measured before ERCP and 3 and 24 h after ERCP. Univariate analysis and multivariate analysis were carried out to estimate the independent risk factors for PEP. Results: Totally, 100 patients were enrolled, 50 received indomethacin and 50 with placebo (glycerin suppository). PEP developed in six patients in indomethacin group and 16 in the control group, the difference was significant (p = .016). The levels of HMGB1 and TNF-α were significantly decreased in indomethacin group at 3 (p < .0001) and 24 h (p < .0001) after ERCP, compared to the control group. Multivariate analysis revealed that duration of ERCP (OR, 0.221; 95% CI, 0.072-0.680; p = .008) and usage of NSAIDs (OR, 0.278; 95% CI, 0.090-0.861; p = .026) were independent predictors of PEP. Conclusions: Rectal indomethacin could significantly reduce the risk of PEP by down-regulating the levels of HMGB1 and TNF-α.

ENDOANGEL improves detection of missed colorectal adenomas in second colonoscopy: A retrospective study.

The ENDOANGEL (EN) computer-assisted detection technique has emerged as a promising tool for enhancing the detection rate of colorectal adenomas during colonoscopies. However, its efficacy in identifying missed adenomas during subsequent colonoscopies remains unclear. Thus, we herein aimed to compare the adenoma miss rate (AMR) between EN-assisted and standard colonoscopies. Data from patients who underwent a second colonoscopy (EN-assisted or standard) within 6 months between September 2022 and May 2023 were analyzed. The EN-assisted group exhibited a significantly higher AMR (24.3% vs 11.9%, P = .005) than the standard group. After adjusting for potential confounders, multivariable analysis revealed that the EN-assisted group had a better ability to detect missed adenomas than the standard group (odds ratio = 2.89; 95% confidence interval = 1.14-7.80, P = .029). These findings suggest that EN-assisted colonoscopy represents a valuable advancement in improving AMR compared with standard colonoscopy. The integration of EN-assisted colonoscopy into routine clinical practice may offer significant benefits to patients requiring hospital resection of lesions following adenoma detection during their first colonoscopy.

Association between neutrophil to high-density lipoprotein cholesterol ratio and disease severity in patients with acute biliary pancreatitis.

BACKGROUND: The neutrophil to high-density lipoprotein cholesterol ratio (NHR) is independently associated with the severity of various diseases. However, its association with acute biliary pancreatitis (ABP) remains unknown. METHODS: This study included 1335 eligible patients diagnosed with ABP from April 2016 to December 2022. Patients were divided into low- and high-NHR level groups using an optimal cut-off value determined utilizing Youden's index. Multivariate logistic regression analysis was used to investigate the correlation between NHR and ABP severity. Multivariate analysis-based limited restricted cubic spline (RCS) method was used to evaluate the nonlinear relationship between NHR and the risk of developing moderate or severe ABP. RESULTS: In this study, multivariate logistic regression analysis indicated an independent association between NHR and ABP severity (p < .001). The RCS analysis showed a linear correlation between NHR and the risk of developing moderate or severe ABP (P for non-linearity > 0.05), and increased NHR was found to be independently associated with a more severe form of the disease. CONCLUSIONS: Our study suggests that NHR is a simple and practical independent indicator of disease severity, serving as a potential novel predictor for patients with ABP.

This study is the first to report on the independent association between the neutrophil to high-density lipoprotein cholesterol ratio (NHR) and acute biliary pancreatitis (ABP) severity.The restricted cubic spline analysis showed a linear correlation between NHR and the risk of developing moderate or severe ABP.Increased NHR levels are independently associated with a more severe degree of the disease.

Exploration and verification a 13-gene diagnostic framework for ulcerative colitis across multiple platforms via machine learning algorithms.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with intricate pathogenesis and varied presentation. Accurate diagnostic tools are imperative to detect and manage UC. This study sought to construct a robust diagnostic model using gene expression profiles and to identify key genes that differentiate UC patients from healthy controls. Gene expression profiles from eight cohorts, encompassing a total of 335 UC patients and 129 healthy controls, were analyzed. A total of 7530 gene sets were computed using the GSEA method. Subsequent batch correction, PCA plots, and intersection analysis identified crucial pathways and genes. Machine learning, incorporating 101 algorithm combinations, was employed to develop diagnostic models. Verification was done using four external cohorts, adding depth to the sample repertoire. Evaluation of immune cell infiltration was undertaken through single-sample GSEA. All statistical analyses were conducted using R (Version: 4.2.2), with significance set at a P value below 0.05. Employing the GSEA method, 7530 gene sets were computed. From this, 19 intersecting pathways were discerned to be consistently upregulated across all cohorts, which pertained to cell adhesion, development, metabolism, immune response, and protein regulation. This corresponded to 83 unique genes. Machine learning insights culminated in the LASSO regression model, which outperformed others with an average AUC of 0.942. This model's efficacy was further ratified across four external cohorts, with AUC values ranging from 0.694 to 0.873 and significant Kappa statistics indicating its predictive accuracy. The LASSO logistic regression model highlighted 13 genes, with LCN2, ASS1, and IRAK3 emerging as pivotal. Notably, LCN2 showcased significantly heightened expression in active UC patients compared to both non-active patients and healthy controls (P < 0.05). Investigations into the correlation between these genes and immune cell infiltration in UC highlighted activated dendritic cells, with statistically significant positive correlations noted for LCN2 and IRAK3 across multiple datasets. Through comprehensive gene expression analysis and machine learning, a potent LASSO-based diagnostic model for UC was developed. Genes such as LCN2, ASS1, and IRAK3 hold potential as both diagnostic markers and therapeutic targets, offering a promising direction for future UC research and clinical application.

Fibrinogen-to-Lymphocyte Ratio Was an Independent Predictor of Lymph Node Metastasis in Patients with Clinically Node-Negative Advanced-Stage Gastric Cancer.

Purpose: Various hematological indicators have been reported to predict lymph node metastasis (LNM) in gastric cancer (GC) patients, but the relationship between FLR and LNM has not been studied. Therefore, the aim of this study was to evaluate the role of preoperative fibrinogen-to-lymphocyte ratio (FLR) in predicting LNM in patients with clinically node-negative (cN0) advanced gastric cancer (AGC). Patients and Methods: We retrospectively reviewed 571 eligible patients with primary AGC adenocarcinoma who underwent radical gastrectomy (discovery cohort). Patients were divided into high and low FLR groups according to the optimal cutoff value determined by Youden index. FLR is an independent predictor of LNM determined by logistic regression and validated in the validation cohort of 207 patients. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of FLR for LNM. The nonlinear relationship between FLR and LNM risk was assessed using restricted cubic spline. Sensitivity analyses were performed according to FLR quartiles to further assess the robustness of the results. The nomogram was built based on FLR and clinicopathological characteristics, and was evaluated by calibration curves, ROC curve analysis and decision curve analysis. Results: In the discovery cohort, the area under the curve (AUC) value for FLR to predict LNM was 0.592. There is a linear relationship between the FLR value and the risk of LNM, and the risk of LNM increased with FLR value. High FLR level is an independent risk factor for LNM, and the results of sensitivity analysis robust this finding. The nomogram for individual risk assessment performed well. Furthermore, we verified the FLR was an independent predictor of LNM in the validation cohort. Conclusion: FLR was an independent predictor of LNM in patients with cN0 AGC.

A novel potential inflammation-nutrition biomarker for predicting lymph node metastasis in clinically node-negative colon cancer.

Background: The purpose of this study is to investigate the predictive significance of (platelet × albumin)/lymphocyte ratio (PALR) for lymph node metastasis (LNM) in patients with clinically node-negative colon cancer (cN0 CC). Methods: Data from 800 patients with primary CC who underwent radical surgery between March 2016 and June 2021 were reviewed. The non-linear relationship between PALR and the risk of LNM was explored using a restricted cubic spline (RCS) function while a receiver operating characteristic (ROC) curve was developed to determine the predictive value of PALR. Patients were categorized into high- and low-PALR cohorts according to the optimum cut-off values derived from Youden's index. Univariate and multivariate logistic regression analyses were used to identify the independent indicators of LNM. Sensitivity analysis was performed to repeat the main analyses with the quartile of PALR. Results: A total of eligible 269 patients with primary cN0 CC were retrospectively selected. The value of the area under the ROC curve for PALR for predicting LNM was 0.607. RCS visualized the uptrend linear relationship between PALR and the risk of LNM (p-value for non-linearity > 0.05). PALR (odds ratio = 2.118, 95% confidence interval, 1.182-3.786, p = 0.011) was identified as an independent predictor of LNM in patients with cN0 CC. A nomogram incorporating PALR and other independent predictors was constructed with an internally validated concordance index of 0.637. The results of calibration plots and decision curve analysis supported a good performance ability and the sensitivity analysis further confirmed the robustness of our findings. Conclusion: PALR has promising clinical applications for predicting LNM in patients with cN0 CC.

Development and validation of a predictive model associated with lymph node metastasis of gastric signet ring carcinoma patients.

The risk factors for lymph node metastasis (LNM) in patients with gastric signet ring cell carcinoma (GSRC) have not been well-defined. This study was designed to prognosticate LNM in patients with GSRC by constructing and verifying a nomogram. A total of 2789 patients with GSRC from the Surveillance, Epidemiology, and End Results (SEER) database and Yijishan Hospital of Wannan Medical College (YJS) were retrospectively reviewed. A predictive model was established using logistic regression based on the SEER cohort. The performance of the model was evaluated using the concordance index (C-index) and decision curve analysis (DCA). In addition, its robustness was validated using the YJS cohort. Four independent predictors of LNM were identified in the SEER cohort. Next, a nomogram was constructed by incorporating these predictors. The C-index were 0.800 (95% confidence interval [CI] = 0.781-0.819) and 0.837 (95% CI = 0.784-0.890) in the training and external validation cohorts, respectively. The outcomes of DCA supported good clinical benefits. The proposed model for evaluating the LNM in patients with GSRC can help to avoid the misdiagnosis risk of N-stage, assist to screen the population suitable for neoadjuvant therapy and help clinicians to optimize clinical decisions.

miRNA-223-3p regulates ECT2 to promote proliferation, invasion, and metastasis of gastric cancer through the Wnt/ß-catenin signaling pathway.

PURPOSE: Expression of the guanine nucleotide exchange factor epithelial cell transforming 2 (ECT2) is elevated in gastric cancer (GC) but its biological function in GC is poorly understood. MicroRNAs (miRNAs) have great potential as therapeutic targets for GC through their ability to modulate gene expression. In the present study, we sought to identify potential miRNA-mRNA-protein regulatory pathways that might control ECT2 expression and function in GC. METHODS: ECT2 expression was examined in clinical GC specimens by immunohistochemical staining, and protein levels were correlated with clinicopathological features and prognosis. TargetScan was used to identify potential ECT2 mRNA-complementary miRNAs, and the roles of ECT2 and miRNA-223-3p (miR-223-3p) in GC cell biology and signaling pathway activation were examined by targeted knockdown (KD) or overexpression (OE) of ECT2 and miR-223-3p in GC cell lines. A murine GC xenograft model was developed to explore the impact of ECT2 OE on tumor growth in vivo. RESULTS: ECT2 expression was significantly elevated in GC specimens compared with normal gastric tissues and the level correlated positively with depth of invasion, ulceration, vascular tumor thrombus, neural invasion, and lymph node metastasis (p < 0.05). ECT2 was an independent prognostic factor for overall survival of GC patients (high ECT2 expression v.s. low ECT2 expression: χ2 = 29.831, p < 0.001). ECT2 KD or miR-223-3p OE markedly suppressed the proliferation, migration, and invasion of GC cells in vitro, whereas ECT2 OE had the opposite effects. ECT2 OE also promoted the growth of GC tumors in vivo. Tumor expression of Wnt2, ß-catenin, and several downstream target proteins in GC cells were decreased by ECT2 KD or miR-223-3p OE but increased by ECT2 OE. CONCLUSIONS: miR-223-3p regulates ECT2 expression to promote tumorigenic behavior of GC via activation of the Wnt/ß-catenin signaling pathway, suggesting that ECT2 and miR-223-3p as potential therapeutic targets for GC.

ENDOANGEL versus water exchange for the detection of colorectal adenomas.

Background: Recently, the ENDOANGEL (EN) system, a computer-assisted detection technique, and water exchange (WE) assisted colonoscopy have both been shown to increase the colorectal adenoma detection rate (ADR). Objectives: The aim of this study was to compare the ADR between EN- and WE-assisted colonoscopy. Design: This was a retrospective study. Methods: Data from patients who underwent either EN- or WE-assisted colonoscopy between October 2021 and August 2022 were analysed consecutively. The primary outcome measure was the ADR. Results: The ADR was found to be similar between the EN and WE groups, with 80 out of 199 (40.2%) patients in the EN group compared to 78 out of 174 (44.8%) patients in the WE group [1.21; 95% confidence interval (CI), 0.80-1.83]. In the analysis using stabilized inverse probability treatment weighting after adjustment for confounding factors, both colonoscopy methods had similar performance in terms of ADR (1.41; 95% CI, 0.88-2.27). Conclusion: EN was found to be comparable to WE in terms of ADR during colonoscopy, and both methods may be effectively used in clinical practice.

Dissecting the association between gut microbiota and liver cancer in European and East Asian populations using Mendelian randomization analysis.

Background: Ample evidence suggests an important role of the gut microbiome in liver cancer, but the causal relationship between gut microbiome and liver cancer is unclear. This study employed Mendelian randomization (MR) analysis to examine the causal relationship between the gut microbiome and liver cancer in European and East Asian populations. Methods: We sourced genetic variants linked to gut microbiota from the MiBioGen consortium meta-analysis, and procured liver cancer genome-wide association study (GWAS) summary data from the FinnGen consortium and Biobank Japan. We employed the inverse variance weighted method for primary statistical analysis, fortified by several sensitivity analyses such as MR-PRESSO, MR-Egger regression, weighted median, weighted mode, and maximum likelihood methods for rigorous results. We also evaluated heterogeneity and horizontal pleiotropy. Results: The study examined an extensive set of gut microbiota, including 131 genera, 35 families, 20 orders, 16 classes, and 9 phyla. In Europeans, ten gut microbiota types displayed a suggestive association with liver cancer (p < 0.05). Notably, Oscillospira and Mollicutes RF9 exhibited a statistically significant positive association with liver cancer risk, with odds ratios (OR) of 2.59 (95% CI 1.36-4.95) and 2.03 (95% CI 1.21-3.40), respectively, after adjusting for multiple testing. In East Asians, while six microbial types demonstrated suggestive associations with liver cancer, only Oscillibacter displayed a statistically significant positive association (OR = 1.56, 95% CI 1.11-2.19) with an FDR < 0.05. Sensitivity analyses reinforced these findings despite variations in p-values. Conclusion: This study provides evidence for a causal relationship between specific gut microbiota and liver cancer, enhancing the understanding of the role of the gut microbiome in liver cancer and may offer new avenues for preventive and therapeutic strategies.

Behçet's disease with intestinal involvement: a case report and review of the literature.

BACKGROUND: Behçet's disease (BD) is a chronic systemic disease characterized by vasculitis as the basic pathological change. BD is rare, and gastrointestinal involvement occurs in 3% to 25% of affected patients. This article describes a rare case of intestinal BD along with a literature review of intestinal involvement in BD. CASE PRESENTATION: A 50-year-old Han woman from China presented with a > 6-month history of distending pain in the right upper abdomen. Because of mechanical obstruction secondary to stricture formation from an ileocecal ulcer, she underwent radical right colon resection, and postoperative pathologic examination indicated an ileocecal ulcer. The patient was readmitted to the hospital 6 months postoperatively for recurrence of the same symptoms. Colonoscopy indicated obvious narrowing of the anastomosis with an oval-shaped deep ulcer that could not be passed by the endoscope. Pathologic examination showed acute and chronic inflammation of the anastomotic mucosa and granulation tissue. In addition, gastroscopy showed a 3.0- × 4.0-cm giant ulcer at the junction of the descending bulb along with a sinus tract. Moreover, total gastrointestinal computed tomography angiography showed significant thickening of the intestinal wall near the transverse colon, forming a sinus tract at the junction of the antrum and duodenum with a length of about 1.3 cm and width of about 0.2 cm. Further inquiry regarding the patient's medical history revealed that she had developed repeated oral ulcers 3 years previously and repeated eye inflammation 5 years previously. Specimens of the right half of the colon removed 6 months previously were sent to Run Run Shaw Hospital Affiliated to Zhejiang University for consultation. The pathologic examination revealed vasculitis in the submucosa and subserosa, and the patient was finally diagnosed with BD. She began treatment with adalimumab, and repeat gastroenteroscopy revealed that the intestinal ulcer had significantly improved. CONCLUSIONS: An oval-shaped deep intestinal ulcer is a characteristic lesion in patients with BD and may involve the intestinal muscle layer. This case emphasizes that BD is a vasculitis affecting multiple organs and can present with a single, deep, clean-edged intestinal ulcer that penetrates the bowel wall to form a sinus tract. Therefore, careful examination and differential diagnosis should be carried out to prevent a poor prognosis. Adalimumab is effective for patients with intestinal BD.