INTRODUCTION: No study has investigated the efficacy and safety of vonoprazan-amoxicillin dual therapy compared with bismuth quadruple therapy (B-quadruple). This study aimed to evaluate the efficacy and safety of 10-day vonoprazan-amoxicillin dual therapy as a first-line treatment of Helicobacter pylori infection compared with B-quadruple and to explore the optimal dosage of amoxicillin in the dual therapy. METHODS: A total of 375 treatment-naive, H. pylori-infected subjects were randomly assigned in a 1:1:1 ratio into 3 regimen groups including VHA-dual (vonoprazan 20 mg twice/day + amoxicillin 750 mg 4 times/day), VA-dual (vonoprazan 20 mg + amoxicillin 1,000 mg twice/day), and B-quadruple (esomeprazole 20 mg + bismuth 200 mg + amoxicillin 1,000 mg + clarithromycin 500 mg twice/day). Eradication rates, adverse events (AEs), and compliance were compared between 3 groups. RESULTS: The eradication rates of B-quadruple, VHA-dual, and VA-dual were 90.9%, 93.4%, and 85.1%, respectively, by per-protocol analysis; 89.4%, 92.7%, and 84.4%, respectively, by modified intention-to-treat analysis; 88.0%, 91.2%, and 82.4%, respectively, by intention-to-treat analysis. The efficacy of the VHA-dual group was not inferior to the B-quadruple group (P < 0.001), but VA-dual did not reach a noninferiority margin of −10%. The AEs rates of the B-quadruple group were significantly higher than those of the VHA-dual (P = 0.012) and VA-dual (P = 0.001) groups. There was no significant difference in medication compliance among 3 treatment groups (P = 0.995). CONCLUSIONS: The 10-day VHA-dual therapy provided satisfactory eradication rates of >90%, lower AEs rates, and similar adherence compared with B-quadruple therapy as a first-line therapy for H. pylori infection. However, the efficacy of VA-dual therapy was not acceptable.

Background: Exosomes are essential for tumor growth, metastasis, and are used as novel signaling molecules in targeted therapies. Therefore, exosomal miRNAs can be used in new diagnostic and therapeutic approaches due to their involvement in the development of cancers. However, the detailed biological function, potential molecular mechanism and clinical application of exo-miR-15b-3p in gastric cancer (GC) remains unclear. Methods: miR-15b-3p mRNA levels in tissues, serum, cells and exosomes were analyzed using qRT-PCR assays. qRT-PCR, immunohistochemical and western blotting analyses were utilized for the determination of DYNLT1 expression. The interrelationship connecting miR-15b-3p with DYNLT1 was verified using Dual-luciferase report, western blotting and qRT-PCR assays. Fluorescent PKH-26 or GFP-Lv-CD63 labeled exosomes, as well as Cy3-miR-15b-3p, were utilized to determine the efficacy of the transfer of exo-miR-15b-3p between BGC-823 and recipient cells. Several in vitro assays and xenograft tumor models were conducted to determine exo-miR-15b-3p impact on GC progression. Results: This is the first study to confirm high miR-15b-3p expression in GC cell lines, tissues and serum. Exosomes obtained from 108 GC patient serum samples and GC cell-conditioned medium were found to show upregulation of exo-miR-15b-3p, with the area under the ROC curve (AUC) being 0.820 [0.763–0.876], which is superior to the AUC of tissues and serum miR-15b-3p (0.674 [0.600–0.748] and 0.642 [0.499–0.786], respectively). In addition, high exo-miR-15b-3p expression in serum was found to accurately predict worse overall survival. SGC-7901 and GES-1 cells are capable of internalizing BGC-823 cell-derived exosomes, allowing the transfer of miR-15b-3p. Migration, invasion, proliferation and inhibition of apoptosis in vitro and in vivo were enhanced by exo-miR-15b-3p, by restraining DYNLT1, Cleaved Caspase-9 and Caspase-3 expression. Conclusions: This study identified a previously unknown regulatory pathway, exo-miR-15b-3p/DYNLT1/Caspase-3/Caspase-9, which promotes GC development and GES-1 cell malignant transformation. Therefore, serum exo-miR-15b-3p may be a potential GC diagnosis and prognosis biomarker, which can be used in precise targeted GC therapy.

Background. Lymph node metastasis (LNM) is the most important risk factor for endoscopic treatment in early gastric cancer (EGC) patients. We aimed to investigate the rate of LNM, the risk factors, and the prognosis of EGC patients with LMN. Methods. A total of 10,039 patients who underwent gastrectomy with lymphadenectomy were reviewed between January 2010 and December 2015 at Jiangsu Province Hospital in China. Among them, we identified 1004 (10%) EGCs. First, endoscopic and clinicopathological features related to LNM were analyzed, and then risk factors for LNM were identified using univariate and multivariate analysis. Finally, the short- and long-term outcomes were compared between the groups. Results. LNM occurred in 123 (12.3%) EGCs. Most of EGCs were male (n=720, 71.7%) and mean age was 59.65 ± 11.09 years. The rate of H. pylori infection was 78.0% (783/1004). LNM was significantly associated with age, sex, location, lesion size, macroscopic type, depth of invasion, differentiation type, histological morphology, lymphovascular invasion (LVI), and TMN stage. By multivariate analysis, significant independent risk factors for LNM in EGC were identified as following: male sex (OR 2.365, P=0.035), age ≦ 40 (OR 0.055, P=0.012), depressed type (OR 2.721, P=0.013), submucosa invasion (OR 2.987, P=0.032), LVI (OR 5.186, P=0.003), tumor located in corpora (OR 8.904, P=0.047), and in angle (OR 12.998, P=0.024). 86.5% were successfully followed up for 3 years. The overall 1- and 3-year survival rates in LNM group were 100% and 91.1%, respectively, and those with no LNM were 100% and 100%, respectively. Conclusion. EGCs were investigated in 10.0% of gastric cancer, which LNM occurred in 12.3% of EGC. Independent risk factors of LNM included male sex, age (>40), the depth of invasion, LVI, and tumor located in corpora or angle. The 3-year overall survival rate was greater in EGC patients without LNM.

This research aimed to investigate the expression and function of FAM83A in the proliferation and metastasis in head and neck squamous cell carcinoma (HNSCC). FAM83A mRNA and protein expressions in HNSCC were detected in primary HNSCC samples and cell lines. The associations between FAM83A expression and clinicopathologic variables were evaluated through tissue microarrays. Besides, FAM83A knockdown and overexpression cell lines were constructed to assess cell growth and metastasis in vitro and the relationship between FAM83A and epithelial-mesenchymal transition (EMT). Furthermore, two models of xenograft tumors in nude mice were used to assess the tumorigenicity and metastasis ability of FAM83A in vivo. In the present study, overexpression of FAM83A in HNSCC samples was significantly associated with tumor size, lymph node status and clinical tumor stages. Mechanically, FAM83A could promote HNSCC cell growth and metastasis by inducing EMT via activating Wnt/β-catenin signaling pathway. Rescue experiment demonstrated the inhibition of β-catenin could counteract the function of FAM83A. Also, the FAM83A knockdown could suppress tumor growth and distant metastasis in the xenograft animal models of HNSCC. In conclusion, this study identifies FAM83A as an oncogene of HNSCC. This study provides new insights into the molecular pathways that contribute to EMT in HNSCC. We revealed a previously unknown FAM83A-Wnt–β-catenin signaling axis involved in the EMT of HNSCC. There may be a potential bi-directional signaling loop between FAM83A and Wnt/β-catenin signaling pathway in HNSCC.

Background Symptomatic epiphrenic diverticula are mostly treated with laparoscopic diverticulectomy. Our study aimed to demonstrate the safety and efficacy of submucosal tunneling endoscopic septum division (STESD) for treatment of symptomatic epiphrenic diverticula. Methods Data from patients with epiphrenic diverticula who had undergone STESD were retrospectively reviewed. The parameters analyzed were the modified Eckardt score, total procedure time, length of hospital stay (LOS), number of clips used, adverse events, and patient satisfaction. Results A total of eight patients (5 men; mean [standard deviation (SD)] age 66.25 [7.17] years) were enrolled in our study. The mean (SD) size of epiphrenic diverticula was 3.68 (1.59) cm. The mean (SD) procedure time was 52.87 (22.47) minutes, with a median number of six clips being applied. The modified Eckardt score significantly decreased post-procedure (P < 0.001). The mean (SD) LOS was 5.87 (0.83) days. No adverse events or symptom recurrences were reported. Conclusion STESD is a safe and effective technique to be performed in the submucosal tunnel for the management of patients with epiphrenic diverticula. ^* Equal first authors