The efficacy and safety of vonoprazan in quadruple therapy for Helicobacter pylori eradication: a comparative study.

Background: The efficacy and optimal dose of the new acid-suppressant vonoprazan (VPZ) for quadruple therapy remain uncertain. This study aimed to compare the efficacy and safety of 20 mg VPZ daily (VOD) and 20 mg VPZ twice daily (VTD) with a proton pump inhibitor (PPI) twice daily in quadruple therapy. Methods: We retrospectively analyzed the data of 954 patients treated with quadruple therapy to eradicate Helicobacter pylori. Eradication rates and adverse events were compared between the VOD and VTD groups, and between the VOD and PPI groups. Multivariate analysis was conducted to identify the predictors of eradication failure. Results: Eradication was successful in 875 (91.7%) of the 954 patients. The total, initial, and rescue eradication rates in the VOD group were 92.1%, 93.3%, and 77.8%, respectively. In both the crude and multivariate analyses, the VOD group showed eradication rates comparable to those of the VTD and PPI groups (all P > 0.05). Age > 60 years (odds ratio [OR] = 2.165, P = 0.012) and use of rescue therapy (OR = 3.496, P < 0.001) were independent risk factors for eradication failure, whereas VPZ at a low dosing frequency of 20 mg daily was not. A total of 787 patients (82.5%) were followed up (mean follow-up time, 6.7 ± 2.0 months). Compared with the VOD group, the VTD group was more likely to experience adverse events (OR = 2.073, P = 0.035). Conclusion: VPZ at a low dose of 20 mg daily is an effective and safe component of the quadruple therapy for H.pylori eradication.

Construction of a hepatocytes-related and protein kinase–related gene signature in HCC based on ScRNA-Seq analysis and machine learning algorithm

With recent advancements in single-cell sequencing and machine learning methods, new insights into hepatocellular carcinoma (HCC) progression have been provided. Protein kinase–related genes (PKRGs) affect cell growth, differentiation, apoptosis, and signaling during HCC progression, making the predictive relevance of PKRGs in HCC highly necessary for personalized medicine. In this study, we analyzed single-cell data of HCC and used the machine learning method of LASSO regression to construct PKRG prediction models in six major cell types. CDK4 and AURKB were found to be the best PKRG prognostic signature for predicting the overall survival of HCC patients (including TCGA, ICGC, and GEO datasets) in hepatocytes. Independent clinical factors were further screened out using the COX regression method, and a nomogram combining PKRGs and cancer status was created. Treatment with Palbociclib (CDK4 Inhibitor) and Barasertib (AURKB Inhibitor) inhibited HCC cell migration. Patients classified as PKRG high- or low-risk groups showed different tumor mutation burdens, immune infiltrations, and gene enrichment. The PKRG high-risk group showed higher tumor mutation burdens and gene set enrichment analysis indicated that cell cycle, base excision repair, and RNA degradation pathways were more enriched in these patients. Additionally, the PKRG high-risk group demonstrated higher infiltration levels of Naïve CD8+ T cells, Endothelial cells, M2 macrophage, and Tregs than the low-risk group. In summary, this study established the hepatocytes-related PKRG signature for prognostic stratification at the single-cell level by using machine learning algorithms in HCC and identified potential HCC treatment targets based on the PKRG signature. (AU)

Dynamic alterations in metabolomics and transcriptomics associated with intestinal fibrosis in a 2,4,6-trinitrobenzene sulfonic acid-induced murine model.

BACKGROUND & AIMS: Intestinal fibrosis is a common and severe complication of inflammatory bowel disease without clear pathogenesis. Abnormal expression of host genes and metabolic perturbations might associate with the onset of intestinal fibrosis. In this study, we aimed to investigate the relationship between the development of intestinal fibrosis and the dynamic alterations in both fecal metabolites and host gene expression. METHODS: We induced intestinal fibrosis in a murine model using 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS-treated or control mice were sacrificed after 4 and 6 weeks of intervention; alterations in colonic genes and fecal metabolites were determined by transcriptomics and metabolomics, respectively. Differential, tendency, enrichment, and correlation analyses were performed to assess the relationship between host genes and fecal metabolites. RESULTS: RNA-sequencing analysis revealed that 679 differential genes with enduring changes were mainly enriched in immune response-related signaling pathways and metabolism-related biological processes. Among them, 15 lipid metabolism-related genes were closely related to the development of intestinal fibrosis. Moreover, the fecal metabolic profile was significantly altered during intestinal fibrosis development, especially the lipid metabolites. Particularly, dynamic perturbations in lipids were strongly associated with alterations in lipid metabolism-related genes expression. Additionally, six dynamically altered metabolites might serve as biomarkers to identify colitis-related intestinal fibrosis in the murine model. CONCLUSIONS: Intestinal fibrosis in colitis mice might be related to dynamic changes in gene expression and metabolites. These findings could provide new insights into the pathogenesis of intestinal fibrosis.

Construction of a hepatocytes-related and protein kinase-related gene signature in HCC based on ScRNA-Seq analysis and machine learning algorithm.

With recent advancements in single-cell sequencing and machine learning methods, new insights into hepatocellular carcinoma (HCC) progression have been provided. Protein kinase-related genes (PKRGs) affect cell growth, differentiation, apoptosis, and signaling during HCC progression, making the predictive relevance of PKRGs in HCC highly necessary for personalized medicine. In this study, we analyzed single-cell data of HCC and used the machine learning method of LASSO regression to construct PKRG prediction models in six major cell types. CDK4 and AURKB were found to be the best PKRG prognostic signature for predicting the overall survival of HCC patients (including TCGA, ICGC, and GEO datasets) in hepatocytes. Independent clinical factors were further screened out using the COX regression method, and a nomogram combining PKRGs and cancer status was created. Treatment with Palbociclib (CDK4 Inhibitor) and Barasertib (AURKB Inhibitor) inhibited HCC cell migration. Patients classified as PKRG high- or low-risk groups showed different tumor mutation burdens, immune infiltrations, and gene enrichment. The PKRG high-risk group showed higher tumor mutation burdens and gene set enrichment analysis indicated that cell cycle, base excision repair, and RNA degradation pathways were more enriched in these patients. Additionally, the PKRG high-risk group demonstrated higher infiltration levels of Naïve CD8+ T cells, Endothelial cells, M2 macrophage, and Tregs than the low-risk group. In summary, this study established the hepatocytes-related PKRG signature for prognostic stratification at the single-cell level by using machine learning algorithms in HCC and identified potential HCC treatment targets based on the PKRG signature.

Risk factors and clinical outcomes of incomplete endoscopic resection of small rectal neuroendocrine tumors in southern China: a 9-year data analysis.

Background: The histologically complete resection (CR) rate of small rectal neuroendocrine tumors (RNETs) is unsatisfactory at the first endoscopy. Risk factors and clinical outcomes associated with incomplete resection (IR) have not been explicitly elucidated. This study aims to explore the relevant factors of IR. Methods: This retrospective study reviewed patients with small RNETs (≤10 mm) in eight centers from January 2013 to December 2021. Clinicopathological characteristics and clinical outcomes were compared between the CR and IR groups, and the polypectomy and advanced treatment groups. Results: Of the 326 patients included, 83 (25.5%) were diagnosed with IR. Polypectomy (odds ratio [OR] = 16.86), a central depression (OR = 7.50), and treatment in the early period (OR = 2.60) were closely associated with IR. Further analysis revealed that an atypical hyperemic appearance (OR = 7.49) and treatment in the early period (OR = 2.54) were significantly associated with the inappropriate use of polypectomy (both P < 0.05). In addition, a total of 265 (81.3%) were followed up with a median follow-up period of 30.9 months. No death, metastasis, or recurrence was found during the follow-up period. Conclusions: Polypectomy, a central depression, and treatment in the early period were risk factors for IR. Further, an atypical hyperemic appearance and treatment in the early period were significant predisposing factors for inappropriate choice of polypectomy. For histologically incompletely resected small RNETs, follow-up may be a safe and feasible alternative to rigorous salvage therapy.

Predictors for Submucosal Fibrosis in Patients With Superficial Squamous Esophageal Neoplasia Undergoing Endoscopic Submucosal Dissection.

INTRODUCTION: Submucosal fibrosis greatly hinders the success of endoscopic submucosal dissection (ESD). This study determined ESD outcomes in patients with esophageal submucosal fibrosis and further explored the predictors. METHODS: We retrospectively analyzed 163 patients with superficial squamous esophageal neoplasia. The degree of submucosal fibrosis was classified as follows: F0, none; F1, mild; and F2, severe. ESD outcomes as a function of the degree of submucosal fibrosis and biopsy were determined. The potential predictors of submucosal fibrosis were analyzed. RESULTS: En bloc resection, R0 resection, and procedure time were significantly different between the F0-F2 groups (P = 0.009, P = 0.002, and P < 0.001, respectively). Perforation and immediate bleeding rates of F2 were significantly higher than the F0/F1 groups (P < 0.001 and P < 0.001, respectively). However, the nonbiopsy group vs the biopsy group and the delayed ESD group (postbiopsy >21 days) vs the early ESD group (postbiopsy ≤21 days) showed no statistical differences regarding the en bloc resection, R0 resection, and ESD complications (all P > 0.05). Further analysis indicated that it was not the biopsy history and delayed ESD (both P > 0.05), rather submucosal invasion vs intramucosal tumor (odds ratio = 4.534, P = 0.003) and current smoker vs nonsmoker (odds ratio = 2.145, P = 0.043) were independent risk factors for endoscopic submucosal fibrosis. DISCUSSION: Esophageal submucosal fibrosis was shown to be closely related to unsatisfactory ESD outcomes. Biopsy history and delayed ESD had no adverse effect on submucosal fibrosis and ESD outcomes. Submucosal invasion and current cigarette smoking were predictors of submucosal fibrosis.

Clinicopathological features and outcomes of esophageal lesions containing a basal layer type squamous cell carcinoma component.

PURPOSE: Basal layer type squamous cell carcinoma (BLSCC) is a unique type of squamous cell carcinoma (SCC), characterized by high-grade dysplastic cells occupying the lower half of the epithelium. So far, such special lesions do not seem to attract much attention. The aim of this study was to investigate the clinicopathological features and prognosis of esophageal squamous carcinoma lesions with a BLSCC component. MATERIALS AND METHODS: Between January 2011 and January 2018, 96 patients with esophageal squamous cell carcinoma underwent endoscopic submucosal resection in our hospital were retrospectively analyzed. Patients were divided into BLSCC or typical SCC groups according to the presence or absence of a BLSCC component. The endoscopic findings were compared between the two groups. Furthermore, patients were followed up until October 2018 to compare recurrence rates. RESULTS: BLSCC components were detected in 32 (33.3%, 32/96) lesions. Among them, 13 (40.62%, 13/32) were BLSCC predominant. The intraepithelial papillary capillary loops of 7 pure BLSCC showed type B1 under narrow-band imaging. Single-factor and multivariate analyses indicated that five or more independently scattered, deep-stained spots in iodine-unstained areas were significantly predictive of the presence of BLSCC components (OR=4.837, P=0.015). All patients of typical SCC group survived, but one of BLSCC group died for distant metastases during the follow-up period. The 1-year cumulative recurrence rate (CRR) of BLSCC group were 3.4%, lower than that of typical SCC group (7.1%). Although no significant difference of CRR was seen between the two groups (P>0.05), the 2-year CRR of BLSCC group increased to 11.9%, being higher than that of typical SCC group (7.1%). CONCLUSION: The presence of multiple, scattered stained spots in iodine-unstained areas was predictive of BLSCC components. Such lesion should be treated actively and subject to a more rigorous follow-up protocol due to a higher likelihood of late recurrence.

Association between three exonuclease 1 polymorphisms and cancer risks: a meta-analysis.

To date, the results of studies exploring the relation between exonuclease 1 (Exo1) polymorphisms and cancer risks have differed. In this study, we performed a meta-analysis to investigate the effect of the three most extensively studied Exo1 polymorphisms (Pro757Leu, Glu589Lys, and Glu670Gly) on cancer susceptibility. The related studies published before August 5, 2015, were collected by searching the PubMed and EMBASE databases. We found 16 publications containing studies that were eligible for our study, including 10 studies for Pro757Leu polymorphism (4,093 cases and 3,834 controls), 12 studies for Glu589Lys polymorphism (6,479 cases and 6,550 controls), and 7 studies for Glu670Gly polymorphism (3,700 cases and 3,496 controls). Pooled odds ratios and 95% confidence intervals were used to assess the strength of the associations, and all the statistical analyses were calculated using the software program STATA version 12.0. Our results revealed that the Pro757Leu polymorphism was significantly associated with a reduced cancer risk, whereas an inverse association was found for the Glu589Lys polymorphism. Furthermore, subgroup analysis of smoking status indicated that the Glu589Lys polymorphism was significantly associated with an increased cancer risk in smokers, but not in nonsmokers. However, no evidence was found for an association between the Glu670Gly polymorphism and cancer risk. In conclusion, this meta-analysis suggests that the Pro757Leu polymorphism may provide protective effects against cancer, while the Glu589Lys polymorphism may be a risk factor for cancer. Moreover, the Glu670Gly polymorphism may have no influence on cancer susceptibility. In the future, large-scaled and well-designed studies are needed to achieve a more precise and comprehensive result.