Emerging evidence suggests that USP39 plays an important role in the development of hepatocellular carcinoma (HCC). However, the molecular mechanism by which USP39 promotes HCC progression has not been well defined, especially regarding its putative ubiquitination function. Zinc-finger E-box-binding homeobox 1 (ZEB1) is a crucial inducer of epithelial-to-mesenchymal transition (EMT) to promote tumor proliferation and metastasis, but the regulatory mechanism of ZEB1 stability in HCC remains enigmatic. Here, we reveal that USP39 is highly expressed in human HCC tissues and correlated with poor prognosis. Moreover, USP39 depletion inhibits HCC cell proliferation and metastasis by promoting ZEB1 degradation. Intriguingly, deubiquitinase USP39 has a direct interaction with the E3 ligase TRIM26 identified by co-immunoprecipitation assays and immunofluorescence staining assays. We further demonstrate that TRIM26 is lowly expressed in human HCC tissues and inhibits HCC cell proliferation and migration. TRIM26 promotes the degradation of ZEB1 protein by ubiquitination in HCC. Deubiquitinase USP39 and E3 ligase TRIM26 function in an antagonistic pattern, but not a competitive pattern, and play key roles in controlling ZEB1 stability to determine the HCC progression. In summary, our data reveal a previously unknown mechanism that USP39 and TRIM26 balance the level of ZEB1 ubiquitination and thereby determine HCC cell proliferation and migration. This novel mechanism may provide new approaches to target treatment for inhibiting HCC development by restoring TRIM26 or suppressing USP39 expression in HCC cases with high ZEB1 protein levels.

BackgroundThe occurrence of antibiotic‐resistant strains has been rapidly increasing due to the wide use of antibiotics. To evaluate the current effects of antibiotic resistance on Helicobacter pylori eradication efficacy, we conducted this systematic review and meta‐analysis.MethodsLiterature searches were conducted in the following databases: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Statistical analysis was performed using STATA version 12.0 (StataCorp LP, College Station, TX, USA).ResultsA total of 120 studies, including 28 707 patients, were assessed. Only first‐line therapy was considered. The pooled RR of eradication rate in patients with Helicobacter pylori strains sensitive versus resistant to clarithromycin was 0.682 (95% CI: 0.636‐0.731). The pooled RR of eradication rate in patients with Helicobacter pylori strains sensitive versus resistant to metronidazole was 0.843 (95% CI: 0.810‐0.877). The pooled RR of eradication rate in patients with Helicobacter pylori strains sensitive versus resistant to levofloxacin was 0.794 (95% CI: 0.669‐0.941). The pooled RR of eradication rate in patients with Helicobacter pylori strains sensitive versus resistant to dual clarithromycin and metronidazole was 0.674 (95% CI: 0.590‐0.770).ConclusionAntibiotic resistance causes a decrease in the eradication rate of H pylori today. Quadruple concomitant therapy may overcome the declining H pylori eradication rate caused by metronidazole‐only resistance.

Background & Aims The eradication rate of Helicobacter pylori (H pylori) has decreased largely because of the antibiotic resistance. We aimed to evaluate the effectiveness and safety of furazolidone‐containing quadruple regimens for H pylori eradication. Methods This was an observational study of furazolidone‐containing quadruple regimens for H pylori infection in real‐world settings. Data sets were collected from the medical records and telephone interviews of patients referred to a specialist clinic for suspected H pylori reinfection from January 1, 2015, to January 1, 2018, at the First Affiliated Hospital of Nanchang University. Main outcome measures were the eradication rate and adverse reactions during medication. Results Among 584 patients with H pylori infection that met the inclusion criteria, 561 (96.1%) were treated for the first time, 19 (3.3%) had one, and 4 (0.5%) had two or more prior to furazolidone‐containing quadruple regimens. The eradication rates for 10‐day and 14‐day regimens were 93.7% (95% CI: 91.5%‐95.9%) vs 98.2% (95% CI: 95.6%‐99.3%), respectively (P = 0.098). Adverse drug reactions occurred in 8.2% (48/584) with abdominal discomfort being the most common symptom. Overall adverse events with 10‐day regimens were lower than 14‐day regimens (6.1% vs 17.4%, P < 0.001). Logistic regression analysis indicated that poor adherence (adjusted odds ratio [AOR] = 46.5, 95% CI: 9.7‐222.4) was correlated with failed eradication. Adverse drug reactions during medication were related to smoking and tobacco status, alcohol intake history, regimens combined with tetracycline, and poor adherence (all P < 0.05). Conclusions Furazolidone‐containing quadruple regimens proved both safe and highly effective in a real‐world setting.

Background & Aims Developing countries are making efforts to improve health management. Practice deviating from the guideline means inefficient control. The study aims to investigate the management of Helicobacter pylori (H pylori) infection from a developing country perspective. Methods An authoritative survey was conducted in 14th (2014) and 17th (2017) Congress of Gastroenterology China, respectively. The Maastricht V/Florence consensus report was invoked as the evaluation criterion. Results A total of 4182 valid samples were included in this study. Most of the respondents (94%) updated knowledge by lectures. Respondents had a different awareness rate of H pylori‐related diseases, ranging from 45% to 95%. Up to 40% of the respondents did not follow the recommendations for the diagnosis. Choice accuracy of eradication regimens and antibiotic combinations was <70%. About 20% of the respondents did not pay attention to the confirmation after the eradication. The situation had been improved in 2017 when compared with that in 2014 (all P < .05). Multivariate logistic regression analysis revealed that influencing factors including nongastroenterologists, bachelor degree and below, the primary professional title, hospital location, and a small proportion of H pylori infection in daily practice related to the deviation of consensus (all P < .05). Conclusions Although the management of H pylori infection has been improved in a developing country, there is still a gap between the real‐world practices and the consensus. Influencing factors should be taken into account in decision‐making, and the corresponding population should be strengthened with precision training during the promotion of the guideline.