Haixu Wang

N6-methyladenosine (m 6 A) is a common form of mRNA modification regulated by m6A RNA methylation regulators and play an important role in the progression of gastric cancer (GC). However, the prognostic role of m 6 A-related lncRNA in gastric cancer has not been fully explored. This study aims at exploring the biological function and prognostic roles of the m 6 A-related lncRNA signature in gastric cancer. A total of 800 m6A-related lncRNAs were identified through Pearson correlation analysis between m6A regulators and all lncRNAs. Eleven m6A-related lncRNA signatures were identified through a survival analysis and the Kaplan-Meier (KM) curve analysis results suggest that patients in the low-risk group have a better overall survival (OS) and disease-free survival (DFS) outcome than the high-risk group. Also, the lncRNA signature can serve as an independent prognostic factor for OS and DFS. The gene set enrichment analysis (GSEA) result suggests that patients in the high-risk group were mainly enriched in the ECM receptor interaction, focal adhesion, and cytokine-cytokine receptor interaction pathway, while the low-risk group was characterized by the base excision repair pathway. We further constructed an individualized prognostic prediction model via the nomogram based on the independent prognostic factor for the OS and DFS, respectively. In addition, some candidate drugs aimed at GC risk group differentiation were identified using the Connective Map (CMAP) database. Lastly, four subgroups (C1, C2, C3, and C4) were identified based on the m6A-related lncRNA expression, through a consensus clustering algorithm. Among them, C1 and C2 have a greater likelihood to respond to immune checkpoint inhibitor immunotherapy, suggesting that the C1 and C2 subgroup might benefit from immunotherapy. In conclusion, the m6A-related lncRNA signature can independently predict the OS and DFS of GC and may aid in development of personalized immunotherapy strategies.

Laryngeal cancers are mostly squamous cell carcinomas. Although targeting radio-resistant cancer cells is important for improving the treatmental efficiency, the signaling pathway- and therapeutic strategy-related to laryngeal carcinoma still require further study. Galangin is an active pharmacological ingredient, isolated from propolis and Alpinia officinarum Hance, and has been reported to have anticancer and anti-oxidative properties through regulation of cell cycle, resulting in angiogenesis, apoptosis, invasion and migration without triggering any toxicity in normal cells. PI3K/AKT and p38 are important signaling pathways to modulate cancer cell apoptosis and proliferation through caspase-3, NF-κB and mTOR signal pathways. Autophagy is also enhanced by activating LC3s and Beclin 1. In the present study, galangin was found to suppress laryngeal cancer cell proliferation. Also, flow cytometry, immunohistochemical and western blot analysis indicated that cell apoptosis was induced for galangin administration, promoting caspase-3 expression through regulating PI3K/AKT/NF-κB. Furthermore, galangin inhibited laryngeal cancer cell proliferation, related to p38 inactivation by galangin treatment. Additionally, mTOR activation regulated by PI3K/AKT was reduced by galangin, suppressing cancer cell transcription and proliferation. Our data also indicated that the tumor volume and weight in nude mice were reduced for galangin use in vivo accompanied by Ki-67 decrease and TUNEL increase in tumor tissues. Together, our data indicated that galangin has a potential role in suppressing human laryngeal cancer via inhibiting tumor cell proliferation, activating apoptosis and autophagy, which were regulated by p38 and AKT/NF-κB/mTOR pathways, providing a therapeutic strategy for human laryngeal cancer treatment.

Abstract Background High morbidity and mortality due to carbapenem-resistant Gram-negative bacilli (CR-GNB) has led to the resurgence of polymyxin B (PMB) use in the last decade. The aim of our multicenter, real-world study was to evaluate the effectiveness and safety of PMB in the treatment of CR-GNB infections. Methods The real-world study included patients treated with intravenous PMB for at least 7 days during the period of October 2018 through June 2019. Associations between these clinical features and 28-day mortality or all-cause hospital mortality were explored through univariate analyses and multivariable logistic regression. Results The study included 100 patients. Many patients presented with combined chronic conditions, septic shock, mechanical ventilation, and the presence of Klebsiella pneumoniae . The mean duration of PMB therapy was 11 days (range 7–38 days). Temperature (38 °C vs 37.1 °C), white blood cells (14.13 × 10 9 /l vs 9.28 × 10 9 /l), C-reactive protein (103.55 ug/l vs 47.60 ug/l), procalcitonin (3.89 ng/ml vs 1.70 ng/ml) and APACHE II levels (17.75 ± 7.69 vs 15.98 ± 7.95) were significantly decreased after PMB treatment. The bacteria eradication rate was 77.65%. The overall mortality at discharge was 15%, and 28-day mortality was 40%. Major adverse reactions occurred in 16 patients. Nephrotoxicity was observed in 7 patients (7%). Conclusions Our results provide positive clinical and safety outcomes for PMB in the treatment of CR-GNB. Timely and appropriate use of PMB may be particularly useful in treating patients with sepsis in CR-GNB infections.

Vascular invasion (VI) in hepatocellular carcinoma (HCC) is an important clinical parameter to predict survival. In this study, we collected microRNA (miRNA) expression data from HCC patients using The Cancer Genome Atlas database and identified a novel miRNA signature associated with VI. First, we categorized HCC patients into groups with or without VI (VI+ and VI-). We identified three miRNAs (miRNA-210, miRNA-10b, and miRNA-9-1) that were associated with VI according to a Kaplan-Meier analysis. This three-miRNA signature exhibited good predictive ability for VI in patients with HCC according to a receiver operating characteristic curve analysis at 1, 3, and 5 years. Patients with HCC with a high risk score exhibited a trend toward worse outcomes as determined by multivariable Cox regression and stratified analyses. This three-miRNA signature provides an accurate prediction of VI and can be used as an independent prognostic indicator for predicting VI in HCC patients.

The gut microbiota has been implicated in the pathogenesis and progression of sepsis. Akkermansia muciniphila is considered to be a promising probiotic with reduced abundance in cecal ligation and puncture (CLP)-induced sepsis model, and its specific outer membrane protein (Amuc_1100) can partially recapitulate the probiotic function of Akkermansia muciniphila. However, its role in sepsis is unclear. This study aimed to investigate the effect of Amuc_1100 on the gut microbiota of septic rats, thereby improving the prognosis of septic acute lung injury (ALI). A total of 42 adult Sprague-Dawley (SD) rats were randomly divided into three groups: the sham control (SC group), the septic ALI induced by CLP method (CLP group), and administered Amuc_1100 by oral gavage (3 µg/d) for 7 d before the CLP procedure (AMUC group). The survival of the three groups was recorded and the feces and lung tissues of rats were collected 24 h after treatment for 16S rRNA sequencing and histopathological evaluation. Oral administration of Amuc_1100 improved the survival rate and alleviated lung histopathological damage induced by sepsis. Serum levels of pro-inflammatory cytokines and chemokines were substantially attenuated. Amuc_1100 significantly increased the abundance of some beneficial bacteria in septic rats. Additionally, the Firmicutes/Bacteroidetes ratio was low in septic rats, which was partially corrected by increasing Firmicutes and decreasing Bacteroidetes after oral administration of Amuc_1100 (p < 0.05). In addition, Escherichia-Shigella, Bacteroides, and Parabacteroides were relatively enriched in septic rats, while in the AMUC group, their abundance was restored to levels similar to that of the healthy group. Amuc_1100 protects against sepsis by enhancing beneficial bacteria and reducing potential pathogenic bacteria. These findings indicate that Amuc_1100 can blunt CLP-induced ALI through the modulation of gut microbiota, thereby providing a new promising therapeutic target in sepsis.