Comparison of vonoprazan and proton pump inhibitors for the treatment of gastric endoscopic submucosal dissection-induced ulcer: an updated systematic review and meta-analysis.

BACKGROUND: Both vonoprazan and proton pump inhibitors (PPIs) are currently used to treat artificial ulcers after gastric endoscopic submucosal dissection. However, evidence-based medicine proving the efficacy of vonoprazan is still lacking. Therefore, this meta-analysis aimed to compare the efficacy of vonoprazan and PPIs for the treatment of artificial ulcers after gastric endoscopic submucosal dissection. METHODS: The PubMed, EMBASE and Cochrane Library databases were searched up to September 2023 for related randomized controlled trials (RCTs). RCTs that compared the efficacy of vonoprazan and PPIs in treating artificial gastric ulcers after gastric endoscopic submucosal dissection were included. Two independent reviewers screened the included studies, extracted the data and assessed the risk of bias. The following outcomes were extracted for comparison: ulcer healing rate, ulcer shrinkage rate, delayed postoperative bleeding rate, and ulcer perforation rate. RESULTS: Nine randomized controlled trials involving 926 patients were included. The pooled results showed that vonoprazan had a significantly lower rate of delayed postoperative bleeding than did PPIs (RR = 0.46; 95% CI = 0.23-0.91; P = 0.03). No significant differences were found in terms of ulcer healing, shrinkage rates, or ulcer perforation rates between vonoprazan and PPIs. CONCLUSIONS: Compared with PPIs, vonoprazan is superior at reducing delayed postoperative bleeding after endoscopic submucosal dissection. However, further studies are needed to prove the efficacy of vonoprazan. SYSTEMATIC REVIEW REGISTRATION: Identifier CRD42024509227.

Residual refinement for interactive skin lesion segmentation.

BACKGROUND: Image segmentation is a difficult and classic problem. It has a wide range of applications, one of which is skin lesion segmentation. Numerous researchers have made great efforts to tackle the problem, yet there is still no universal method in various application domains. RESULTS: We propose a novel approach that combines a deep convolutional neural network with a grabcut-like user interaction to tackle the interactive skin lesion segmentation problem. Slightly deviating from grabcut user interaction, our method uses boxes and clicks. In addition, contrary to existing interactive segmentation algorithms that combine the initial segmentation task with the following refinement task, we explicitly separate these tasks by designing individual sub-networks. One network is SBox-Net, and the other is Click-Net. SBox-Net is a full-fledged segmentation network that is built upon a pre-trained, state-of-the-art segmentation model, while Click-Net is a simple yet powerful network that combines feature maps extracted from SBox-Net and user clicks to residually refine the mistakes made by SBox-Net. Extensive experiments on two public datasets, PH2 and ISIC, confirm the effectiveness of our approach. CONCLUSIONS: We present an interactive two-stage pipeline method for skin lesion segmentation, which was demonstrated to be effective in comprehensive experiments.

PEA­15 contributes to the clinicopathology and AKT­regulated cisplatin resistance in gastric cancer.

Phosphoprotein enriched in astrocytes 15 (PEA­15) plays an important role in controlling biological behaviors of cancer cells. In the present study, we demonstrated that PEA­15 was overexpressed in gastric cancer tissues and associated with tumor staging, differentiation, pathological types and the prognosis of patients. Gastric cancer cells expressed variable levels of PEA­15 and its bi­phosphorylation forms, p­PEA­15 (Ser104) and p­PEA­15 (Ser116). To gain insight into the functional role of PEA­15, we generated cells stably depleted of PEA­15 and resistant to cisplatin (CDDP) from human gastric cancer cells. PEA­15 depletion inhibited cell proliferation by reducing cyclin D1 expression through the extracellular signal­regulated kinase (ERK) pathway, resulting in cell cycle arrest at the G1 phase, and induced apoptosis by activating caspase­8. PEA­15 depletion also enhanced the inhibitory effect of CDDP that caused cell cycle arrest at the S phase and also enhanced the pro­apoptotic activity of CDDP in vitro and in animal models of tumorigenesis and therapeutic effects. PEA­15 and its phosphorylated forms were overexpressed in CDDP­resistant cells, which had higher levels of p­AKT. Specific inhibition of AKT by MK2206 reduced the expression of p­PEA­15 at the Ser116 residue, resulting in sequential downregulation of p­ERK1/2, cyclin D1 and caspase­8 activation. However, depletion of PEA­15 had little effect on AKT expression or phosphorylation, or its downstream factors including p27, glycogen synthase kinase 3ß and caspase­9, indicating that the regulatory effects between PEA­15 and AKT were unidirectional. In summary, the results indicated that PEA­15 expression was associated with clinicopathology and prognosis in gastric cancer and was regulated by AKT to participate in CDDP resistance, indicating that it may be a potential target for overcoming CDDP resistance in the treatment of gastric cancer.

miR-129-3p inhibits NHEJ pathway by targeting SAE1 and represses gastric cancer progression.

Gastric cancer (GC) is one of the leading malignancies worldwide and is also a leading cause of cancer-related mortality. Micro RNA (miRNA) is a group of short non-coding RNAs modulating gene expression through targeting the 3'UTR of genes. Peripheral blood exosome miRNAs are relatively stable and might be used as biomarkers for clinical diagnosis. In this study, we found a reduced level of miR-129-3p in GC tumor when compared with adjacent non-tumor tissues, and the peripheral blood exosome miR-129-3p level was also reduced when compared with healthy controls. Subsequently, we identified that miR-129-3p repressed the expression of SUMO-activating enzyme subunit 1 (SAE1) directly through targeting 3'UTR. miR-129-3p also inhibited the sumoylation modification of XRCC4 which disturbed the nuclear localization of XRCC4 and induced more DNA damage in GC cells. Furthermore, overexpression of miR-129-3p induced more cell apoptosis and inhibited GC cell proliferation, migration and invasion, indicating miR-129-3p is a powerful anti-tumor miRNA and has potential for GC treatment.

Mir-483 inhibits colon cancer cell proliferation and migration by targeting TRAF1.

MicroRNAs are important regulators during human growth and development. Emerging evidence indicates that microRNAs play important roles in colorectal cancer. The aim of this study is to reveal the biological function and direct target gene of miR-483 in colorectal cancer. The biological function of miR-483 on the proliferation and migration of colon cancer cells was then examined by Edu assay and transwell assay, respectively. Our findings revealed that miR-483 mimic could significantly inhibit cell proliferation and migration. The target gene of miR-483 was predicted by target scan software and identified by a dual fluorescence reporter system which showed that TRAF1 was a direct target gene of miR-483 in SW480 cell line. These data suggest that miR-483 is a colorectal cancer suppressor which could inhibit cell proliferation and migration, possibly via targeting TRAF1. The miR-483 could be a potential treatment target for colorectal cancer.

Clinical manifestations and endoscopic presentations of gastric lymphoma: a multicenter seven year retrospective survey.

BACKGROUND AND AIM: To improve the diagnostic rate of gastric lymphoma by analyzing clinical and endoscopic features of patients with gastric lymphoma and suspected gastric lymphoma. METHODS: Clinical and endoscopic records of 35 patients with gastric lymphoma (positive group) and 133 patients with suspected gastric lymphoma but subsequent non-malignant pathology (negative group) were analyzed retrospectively. Data from another 99 gastric lymphoma patients with malignant pathology but nonspecific endoscopy (endoscopy non-suspect group) were analyzed. RESULTS: Abdominal pain was the predominant symptom reported in both the positive and negative lymphoma groups, representing 60.0 and 52.5%, respectively. No significant differences in age, sex and clinical manifestations in subjects from the two groups were found. In the positive group, 54.3% were ulcerative; 34.3%, infiltrative; 8.5%, polypoid; and 2.9%, granulonodular. In the negative group, 52.6% were infiltrative; 42.1%, ulcerative; 4.5%, granulonodular; and 0.75%, polypoid. The endoscopic results varied between the two groups (p < 0.05). In the non-suspect group, 66.7% were ulcerative; 17.2%, infiltrative; 14.1%, polypoid; and 2.0%, granulonodular. With regards to histology, diffuse large B cell lymphoma was the most common subtype. The sensitivity of endoscopy was 60% for detecting malignancy and 21% for gastric lymphoma. CONCLUSION: The present study suggests that gastric lymphoma and suspected gastric lymphoma have similar clinical features. Gastric lymphoma presented mainly as macroscopic ulcerative lesions, whereas suspected gastric lymphoma appeared mainly as infiltrative lesions. Although the diagnostic rate of gastric lymphoma was relatively low (21%), it can be identified by endoscopy (60%). To improve diagnosis, repetitive endoscopic biopsies should be performed and novel endoscopic techniques developed in the future.

5-Azacytidine suppresses EC9706 cell proliferation and metastasis by upregulating the expression of SOX17 and CDH1.

5-Azacytidine is a well-known anticancer drug that is clinically used in the treatment of breast cancer, melanoma and colon cancer. It has been reported that 5-azacytidine suppresses the biological behavior of esophageal cancer cells. However, corresponding mechanisms remain unclear. In this study, using Transwell invasion and cell proliferation assays, we demonstrated that 5-azacytidine significantly inhibited the metastasis and proliferation of EC9706 cells, and upregulated the expression of cadherin 1 (CDH1) and SRY-box containing gene 17 (SOX17). Moreover, the inhibition of the metastasis of the 5-azacytidine-treated EC9706 cells was impaired following transfection with siRNA targeting CDH1 (CDH1 siRNA), and the inhibition of cell proliferation was attenuated following the downregulation of SOX17 by siRNA targeting SOX17 (SOX17 siRNA). Furthermore, 5-azacytidine remarkably reduced the CDH1 and SOX17 promoter methylation levels, suggesting that 5-azacytidine upregulates the expression of SOX17 and CDH1 by inhibiting the methylation of the SOX17 and CDH1 promoter. The findings of our study confirm that 5-azacytidine suppresses the proliferation and metastasis of EC9706 esophageal cancer cells by upregulating the expression of CDH1 and SOX17. The expression levels of CDH1 and SOX17 negatively correlate with the promoter methylation levels. CDH1 and SOX17 are potential indicators of the clinical application of 5-azacytidine.

Analysis of the causes and clinical characteristics of jejunoileal hemorrhage in China: a multicenter 10 year retrospective survey.

BACKGROUND: A retrospective study was performed to assess the causes, diagnostic methods for, and clinical features of, jejunoileal hemorrhage in Shandong province, China and to derive recommendations for management of this condition from these data. METHODS: We performed a retrospective systematic collection of data from between January 1999 and December 2008 in seven cities in Shandong province, China, identified 72 patients with jejunoileal hemorrhage and analyzed the relevant clinical data. RESULTS: Overall, tumors were the most common cause of jejunoileal hemorrhage (42 patients, 58.3%). The causes of this condition were significantly different (P < 0.05) in male and female patients. In male patients, the commonest factors were tumor (52.2%), enteritis (17.4%) and angiopathy (15.2%). However, in female patients, tumors accounted for a greater proportion of cases (18/26, 69.2%). In 38 cases (52.8%) the diagnosis was made by intraoperative enteroscopy or laparotomy, in 14 by capsule endoscopy and in the remainder by radiological methods. The most frequent presentation was melena (62.7%), followed by maroon stools (26.9%) and hematochezia (9.0%). Of the 72 patients,laparotomy is the main treatment method. CONCLUSION: Tumor, enteritis and angiopathy and diverticular disease are the most common causes of jejunoileal hemorrhage in Shandong province, China. The main clinical manifestations are bloody stools, most commonly in the form of melena, with or without abdominal pain. We recommend that female patients over the age of 40 with jejunoileal hemorrhage accompanied by abdominal pain should undergo urgent further assessment because of the strong probability of jejunoileal tumor.