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Background: Vascular invasion is closely related to the prognosis of hepatocellular carcinoma (HCC). Increasing evidence suggests that miRNAs can serve as biomarks to predict prognosis in various tumors. Thus, the aim of this study was to develop a novel, vascular invasion-related miRNA signature for prediction of HCC prognosis.Methods: Differentially expressed miRNAs (DEMs) between HCC samples with vascular invasion and without vascular invasion were obtained from GSE67140. MiRNAs expression profiles and clinical information for 344 patients were collected from The Cancer Genome Atlas database, and the patients were randomized (1:1) to training set and validation set. LASSO regression model was employed to identify survival-associated DEMs and establish risk score in the training set. Moreover, risk score was verified in the validation set. And nomogram based on risk score and clinical information was constructed to improve the prediction of prognosis. Meanwhile, four online tools were used to predict target genes and enrichment analysis was utilized to explore the biological pathway of the miRNAs.Results: A novel three-miRNA signature was screened including hsa-mir-210, hsa-mir-149 and hsa-mir-99a, and risk score was established for HCC prognosis prediction. Patients were divided into the low-risk group and high-risk group according to risk score. High-risk group both have higher hazard of death compared with low-risk group in training set and validation set. And the 5-year AUC of risk score were 0.718, 0.674 and 0.697 in training set, validation set and the total set, respectively. The C-index of nomogram was 0.724, and calibration curves showed nomogram had high concordance to predict 1- ,3- , and 5-year survival rates among HCC patients. Furthermore, enrichment analysis identified several tumor-associated pathways including Ras signaling pathway, PI3K-Akt signaling pathway, and MAPK signaling pathway and so on, which may contribute to explain the potential molecular mechanisms of above miRNAs.Conclusion: This study developed a risk assessment model based on three miRNAs, which could accurately predict the prognosis of HCC.

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Background: Insulin resistance and hepatogenic diabetes are common complications in patients with liver cirrhosis. Previous studies have shown that reducing the fasting phase by supplying a late evening snack (LES) is a potential intervention to improve substrate utilization and liver function. However, the underlying mechanisms need to be further elucidated. The purpose of current meta-analysis is to evaluate effects of LES on glucose homeostasis in cirrhotic patients.Methods: Electronic databases including PubMed, Web of Science, and major scientific conference sessions were searched without language restriction and carried out on March 1, 2022 with an additional manual search of bibliographies of relevant articles. A total of 4145 studies were identified, and 10 studies were eligible for the meta-analysis, comprising 631 patients (319 in the LES group and 312 in the non-LES group). Subgroup analyses were performed to investigate the effect of LES on cirrhotic patients with or without diabetes.Results: Analysis showed that LES intervention had significant effects in cirrhotic patients for glycemic parameters on fasting plasma glucose, fasting insulin, and glycosylated hemoglobin respective effect sizes of −8.7, −0.86, and −0.76. Subgroup result revealed that the effect of LES on fasting plasma glucose is higher in cirrhotic patients with diabetes group than cirrhotic patients without diabetes group, and long-term LES supplementation (>2 months) was more beneficial to maintain glucose homeostasis in cirrhotic patients than that of short-term supplementation (<2 months). LES also had significant effect on nutritional metabolic parameters like including albumin and non-protein respiratory quotient.Conclusion: Meta-analysis indicated that LES not only improved malnutrition in cirrhotic patients with or without diabetes but also maintain glucose homeostasis in cirrhotic patients with diabetes. LES is a promising and simple intervention that beneficial to maintain glucose homeostasis in cirrhotic patients.Abbreviations: ALB = albumin, BCAA = branched-chain amino acid, CI = confidence interval, FINS = fasting serum insulin, FPG = fasting plasma glucose, HbA1c = glycosylated hemoglobin, HD = hepatogenic diabetes, HOMA-IR = homeostasis model assessment method for IR, IR = insulin resistance, LC = liver cirrhosis, LES = late evening snack, MD = mean difference, npRQ = non-protein respiratory quotient.