The interplay between western diet and gut microbiota drives the development of non-alcoholic fatty liver disease and its progression to non-alcoholic steatohepatitis. However, the specific microbial and metabolic mediators contributing to non-alcoholic steatohepatitis remain to be identified. Here, a choline-low high-fat and high-sugar diet, representing a typical western diet, named CL-HFS, successfully induces male mouse non-alcoholic steatohepatitis with some features of the human disease, such as hepatic inflammation, steatosis, and fibrosis. Metataxonomic and metabolomic studies identify Blautia producta and 2-oleoylglycerol as clinically relevant bacterial and metabolic mediators contributing to CL-HFS-induced non-alcoholic steatohepatitis. In vivo studies validate that both Blautia producta and 2-oleoylglycerol promote liver inflammation and hepatic fibrosis in normal diet- or CL-HFS-fed mice. Cellular and molecular studies reveal that the GPR119/TAK1/NF-κB/TGF-β1 signaling pathway mediates 2-oleoylglycerol-induced macrophage priming and subsequent hepatic stellate cell activation. These findings advance our understanding of non-alcoholic steatohepatitis pathogenesis and provide targets for developing microbiome/metabolite-based therapeutic strategies against non-alcoholic steatohepatitis.

Albumin-to-alkaline phosphatase ratio (AAPR), a novel and economic serum biomarker, is associated with survival in patients with cancer. This study aimed to evaluate the potential role of AAPR as a prognostic indicator of solid cancers. This meta-analysis with trial sequential analysis of retrospective studies was designed to investigate the relationship between AAPR and overall survival (OS) in solid cancers. The meta-analysis included 5951 patients from 20 cohorts. The main predictor variable was AAPR, and the main outcome was OS. Statistical tests were performed using Stata 12.0, Revman 5.3, and R 3.6.1. Compared to patients with a lower AAPR, those with a higher AAPR had a better OS (hazard ratio [HR]: 0.50; 95% confidence interval [CI]: 0.43-0.58; p < 0.001). Subgroup analysis by tumor type indicated that a higher AAPR was associated with a better OS in non-small cell lung cancer (HR: 0.45; 95% CI: 0.26-0.78; p < 0.001), small cell lung cancer (HR: 0.60; 95% CI: 0.44-0.82; p < 0.001), hepatocellular carcinoma (HR: 0.49; 95% CI: 0.34-0.69; p < 0.001), pancreatic ductal adenocarcinoma (HR: 0.47; 95% CI: 0.31-0.71; p < 0.001), and nasopharyngeal carcinoma (HR: 0.42; 95% CI: 0.21-0.85; p = 0.016). Pretreatment AAPR may be a useful prognostic indicator in solid cancers.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadly tumors in digestive tract tumors. Although there has been advancement in PDAC treatment, its prognosis still remains unsatisfactory, mainly because of dismal diagnosis. This article aims to develop new prognostic factors related to energy metabolism in PDAC and to use these genes for novel risk stratification. Hundred fifty messenger RNA (mRNA) expression profiles and clinicopathological data of PDAC were downloaded from The Cancer Genome Atlas dataset. The glycolysis pathway was the significant pathway based on the gene set enrichment analysis. We chose the glycolysis pathway-related 176 genes for further analysis. Multivariate Cox regression analysis and forward stepwise Cox regression model established a novel three-gene glycolytic signature (including MET, B3GNT3, and SPAG4) for PDAC patients' prognosis prediction. All 150 patients were classified into two groups by the median risk score. High-risk group had a worse outcome compared to the low-risk group. The risk score was also significantly correlated with age and radiotherapy. A nomogram, including the glycolytic gene signature, has shown some clinical net benefit for overall survival prediction. We also validated the validity and reliability in the Puleo dataset. This novel gene expression signature may be involved in the pathophysiology and used for risk stratification and prognosis prediction in PDAC.

Background. Circular RNAs (circRNAs) have been shown to be involved in tumorigenesis. As a member of circRNAs, ciRS‐7 is thought to be a negative prognostic indicator in multiple types of cancer. The present study aimed to comprehensively explore the value of ciRS‐7 in tumor malignancy. Materials and Methods. A systematic review of PubMed, Web of Science, and the Cochrane library was carried out to examine the related studies. The pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated from the available publications by STATA 12.0. Subgroup analysis, publication bias, sensitivity analysis, and meta‐regression were conducted. Results. This meta‐analysis included 1,714 patients from 13 cohorts. The results suggested that high ciRS‐7 expression was significantly associated with overall survival (OS) (HR = 2.17, 95% CI = 1.50–3.15, P < 0.001) in various cancers. Stratified analyses indicated that elevated levels of ciRS‐7 appeared to be a powerful prognostic biomarker for patients with non‐small‐cell lung cancer (NSCLC) (HR: 2.50, 95% CI: 1.07–6.07, P = 0.035), colorectal cancer (CRC) (HR: 1.95, 95% CI: 1.34–2.84, P < 0.001), and gastric cancer (GC) (HR: 2.32, 95% CI: 1.48–3.64, P < 0.001). A similar effect was also observed in subgroup of sample size, analysis method, and cutoff value, except for ethnicity. The increased ciRS‐7 expression was associated with a higher tumor stage (OR = 2.30, 95% CI: 1.69–3.13, P < 0.001). Conclusions. High expression of ciRS‐7 has a significant correlation with the high stage in various cancers, and ciRS‐7 is intimately associated with an adverse OS in numerous cancers. Thus, ciRS‐7 may act as a potential biomarker for the development of malignancies.

Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with the highest mortality, and the incidence of brain metastasis (BM) is in high frequency. So far, prophylactic cranial irradiation (PCI) has been suggested as an effective treatment for preventing brain metastasis of SCLC. PCI has long been applied to limited-stage SCLC (LS-SCLC) patients who have achieved complete remission after radiotherapy and chemotherapy as a standard treatment. However, the neurocognitive decline is a major concern surrounding PCI. New therapeutic approaches targeting PCI-induced neurotoxicity, including hippocampal protection or memantine, have been increasingly incorporated into the therapeutic interventions of PCI. Helical tomotherapy, RapidArc, and Volumetric-modulated arc therapy (VMAT) with a head-tilting baseplate are recommended for hippocampal protection. Besides, in the MRI and immunotherapy era, the significance of PCI in SCLC patients is controversial. SCLC patients with PCI should be recruited in clinical trials since this is the only way to improve the existing standard of care. This review summarizes the current therapeutic strategy and dilemma over PCI for SCLC, providing a theoretical basis for clinical decision-making and suggestions for PCI practice in clinical.