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.

Integrating TCGA and single-cell sequencing data for colorectal cancer: a 10-gene prognostic risk assessment model.

Colorectal cancer represents a significant health threat, yet a standardized method for early clinical assessment and prognosis remains elusive. This study sought to address this gap by using the Seurat package to analyze a single-cell sequencing dataset (GSE178318) of colorectal cancer, thereby identifying distinctive marker genes characterizing various cell subpopulations. Through CIBERSORT analysis of colorectal cancer data within The Cancer Genome Atlas (TCGA) database, significant differences existed in both cell subpopulations and prognostic values. Employing WGCNA, we pinpointed modules exhibiting strong correlations with these subpopulations, subsequently utilizing the survival package coxph to isolate genes within these modules. Further stratification of TCGA dataset based on these selected genes brought to light notable variations between subtypes. The prognostic relevance of these differentially expressed genes was rigorously assessed through survival analysis, with LASSO regression employed for modeling prognostic factors. Our resulting model, anchored by a 10-gene signature originating from these differentially expressed genes and LASSO regression, proved adept at accurately predicting clinical prognoses, even when tested against external datasets. Specifically, natural killer cells from the C7 subpopulation were found to bear significant associations with colorectal cancer survival and prognosis, as observed within the TCGA database. These findings underscore the promise of an integrated 10-gene signature prognostic risk assessment model, harmonizing single-cell sequencing insights with TCGA data, for effectively estimating the risk associated with colorectal cancer.

hsa_circ_0006916 promotes hepatocellular carcinoma progression by activating the miR-337-3p/STAT3 axis.

BACKGROUND: Circular RNAs (circRNAs) are thought to be involved in the development of various malignancies. The expression and function of hsa_circ_0006916, a newly identified circRNA, in hepatocellular carcinoma remain unclear. METHODS: Quantitative RT-PCR was used to detect hsa_circ_0006916 in hepatocellular carcinoma. In vitro function assays were conducted to explore growth and invasion of hepatocellular carcinoma cells. Next, the mechanism of hsa_circ_0006916 function in hepatocellular carcinoma was determined by luciferase reporter and RIP assays. RESULTS: Hsa_circ_0006916 was substantially overexpressed in hepatocellular carcinoma tissues and cells. High levels of hsa_circ_0006916 in hepatocellular carcinoma patients were associated with advanced clinical characteristics. Down-regulation of hsa_circ_0006916 decreased the growth and invasion of hepatocellular carcinoma cells in vitro. The results suggested that hsa_circ_0006916 acted as a sponge of miR-337-3p and had an important functional use in the regulation of STAT3 levels in hepatocellular carcinoma cells. Moreover, miR-337-3p inhibition or STAT3 overexpression abolished the effect of hsa_circ_0006916 suppression on the progression of hepatocellular carcinoma cells. CONCLUSIONS: Our data suggest a novel hsa_circ_0006916/miR-337-3p/STAT3 axis in hepatocellular carcinoma, and provide a new target for treatment.

A Multicenter, Randomized, Controlled Trial of Rebamipide Plus Lansoprazole for the Treatment of Postendoscopic Submucosal Dissection Ulcers.

OBJECTIVES: To evaluate the healing efficacy of rebamipide and lansoprazole combination therapy with lansoprazole alone for endoscopic submucosal dissection (ESD)-induced ulcers and clarify the ulcer healing-associated factors. METHODS: Three hundred patients were randomized into control and experimental groups after they underwent ESD. The patients received intravenous pantoprazole (30 mg) every 12 hours and oral rebamipide (100 mg, experimental group) or placebo (control group) 3 times daily on days 1-3. On days 4-56, patients received oral lansoprazole (30 mg daily) and rebamipide (100 mg) or placebo 3 times daily. Endoscopic evaluations were performed at postoperative weeks 4 and 8. RESULTS: At week 4, the ulcer reduction rate was significantly higher in the experimental than in the control group (0.97 ± 0.034 vs. 0.94 ± 0.078; P < 0.001). The ulcer healing (18.2% vs 20.3%; P = 0.669) and ulcer improvement rates (94.2% vs 88.7%; P = 0.109) in the 2 groups were not significantly different. At week 8, the ulcer healing and ulcer improvement rates were 90.6% and 100%, respectively, in both groups. Multivariate analysis showed that the combination treatment was an independent factor associated with ulcer area reduction after ESD. The maximum diameter of the initial ulcer (≥35.5 mm vs <35.5 mm) was an independent factor associated with the ulcer improvement rate after ESD. CONCLUSIONS: The rebamipide and lansoprazole combination therapy can help accelerate the reduction rate of post-ESD ulcer compared with the lansoprazole monotherapy at 4 weeks of therapy.

Clinical efficacy of endoscopic submucosal dissection in the treatment of early esophageal cancer and precancerous lesions.

OBJECTIVE: The objective of this study was to evaluate the clinical value of endoscopic submucosal dissection (ESD) in the treatment of early esophageal cancer and precancerous lesions. MATERIALS AND METHODS: We retrospectively analyzed 58 patients who suffered from early esophageal and precancerous lesions and received ESD in the First Affiliated Hospital of Zhengzhou University from February 2012 to January 2016. The clinical efficacy and safety of ESD in treating the early esophageal cancer and precancerous lesions was evaluated by analyzing the operation successful rate, postoperative pathology, complications, and follow-up data of patients who received ESD. RESULTS: For the 58 patients, ESD was successfully completed in 56 cases with a success rate of 96.6%, whereas ESD was unsuccessful in 2 cases. Invasive lesions were observed in the esophageal muscular layer of 1 patient. Consequently, surgery was terminated and this patient was transferred to thoracotomy surgical intervention involving radical resection of esophageal cancer. Esophageal perforation was observed during the annular incision of the esophageal mucosa in another patient with early-stage cancer. This perforation was occluded with an endoscopic titanium clip and surgery was terminated. Intraoperative blood loss in 56 patients was ranged from 10 to 90 mL with an average of 28.3 ± 17.2 mL. The diameter of ESD resection lesion was varied from 2 to 6.0 cm with an average of 3.4 ± 1.1 cm. For the 56 patients, enbloc resection was performed in 50 patients, with an enbloc resection rate of 89.3%. Complete lesion resection was performed in 49 patients, with a complete resection rate of 87.5%. For all patients, 36 manifested with severe atypical hyperplasia confirmed by postoperative pathology, 11 showed moderate atypical hyperplasia, 2 showed carcinoma insitu, and 7 presented with esophageal squamous cell carcinoma. In these 7 patients, 6 patients whose lesions limited to their mucosa were in the early stage of cancer while 1 patient with esophageal cancer involving the incisal edge, and the submucosal layer was subjected to additional surgical treatment. In addition, 1 patient experienced postoperative delayed hemorrhage (1.79%), 6 patients suffered from fever (10.71%), 33 patients reported substernal burning pain (58.93%) that mostly lasted 1-2 days before spontaneous remission, 1 patient was observed intraoperative perforation (1.79%), and 3 patients showed postoperative esophageal stenosis (5.36%), received multiple balloon dilatations, and consumed fluids afterward. Follow-up visits were facilitated for 49 patients for more than 1 year, and their median follow-up time was 36 months. Of these patients, recurrence was observed in 3 patients, with a recurrence rate of 6.1% (3/49). Of these 3 patients, 2 received surgical treatment and 1 underwent another endoscopic lesion resection. No patient died of esophageal cancer during follow-up. CONCLUSION: ESD was safe and reliable for the treatment of early esophageal cancer and precancerous lesions, and its recurrence and complication rates were low. Complete pathological information could be obtained after operation, which could be applied to assess patients' condition accurately.

RAB23, regulated by miR-92b, promotes the progression of esophageal squamous cell carcinoma.

RAB23, a member of Ras-related small GTPase family, has been reported to be up-regulated in several cancer types. However, its biological functions and the underlying molecular mechanisms for its oncogenic roles in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we have shown that the expression of RAB23 was elevated in ESCC tissues and ESCC cells. Overexpression of RAB23 promoted the growth and migration of the ESCC cells, while knocking down the expression RAB23 inhibited the growth, migration and metastasis of the ESCC cells. The molecular mechanism study showed that RAB23 activated beta-catenin/TCF signaling and regulated the expression of several target genes. In the further study, it was found that the expression of RAB23 was regulated by the miR-92b. Forced expression of MiR-92b decreased the mRNA and protein level of RAB23, and RAB23 rescued the biological functions of miR-92b. Taken together, this study revealed the oncogenic roles and the regulation of RAB23 in ESCC, suggesting RAB23 might be a therapeutic target.

The effect of polyene phosphatidyl choline intervention on nonalcoholic steatohepatitis and related mechanism.

Nonalcoholic steatohepatitis (NASH) has similar clinical pathological changes to alcoholic hepatitis. It shows increased incidence and young trend year by year. Polyene phosphatidyl choline (PPC) is widely used in clinic for liver disease treatment. The effect and mechanism of PPC on NASH have not been fully elucidated. Thirty healthy male Wistar rats were randomly equally divided into control, NASH group, and PPC group. NASH model was established by high fat diet. PPC was intraperitoneal injected to NASH rat from the second week at 80 mg/kg·d for three weeks. Body weight, liver weight index, ALT, AST, TG, and TC were tested. TNF-α and IL-1ß levels were detected by ELISA. NF-κB mRNA and protein expression in liver tissue were determined by real time PCR and Western blot. SOD activity and ROS content were measured by colorimetry. NASH rat presented significantly elevated body weight and liver weight index, increased ROS content, declined SOD activity, enhanced liver function and inflammatory factors expression, and upregulated NF-κB mRNA and protein levels compared with control (P < 0.05). PPC intervention obviously reduced body weight and liver weight index, declined ROS content, amplified SOD activity, decreased liver function, weakened inflammatory factor TNF-α and IL-1ß expression, and downregulated NF-κB mRNA and protein levels compared with NASH group (P < 0.05). PPC can play a treatment effect on NASH through regulating oxidative balance, inhibiting inflammatory factors and NF-κB signaling pathway.