Background: The triglyceride-glucose index (TyG) is a reliable predictor of non-alcoholic fatty liver disease (NAFLD). Its association with the severity of hepatic steatosis and liver fibrosis in NAFLD is poorly understood. This study evaluated the relationship between these factors in NAFLD. Methods: A total of 4784 participants who underwent ultrasonography were enrolled. Anthropometric and biochemical measurements were assessed. Participants with NAFLD were diagnosed by ultrasound. The degree of hepatic steatosis and liver stiffness was evaluated with transient elastography. Results: The TyG index was significantly correlated with the severity of hepatic steatosis and the presence of liver fibrosis in patients with NAFLD. TyG quartile values correlated with increasing prevalence of NAFLD (Q1 30.9%, Q2 53.3%, Q3 71.7%, and Q4 86.4%, P < 0.001) and with the presence of liver fibrosis (Q1 13.5%, Q2 17.6%, Q3 18.8%, and Q4 26.1%, P < 0.001). The AUROC for the TyG index to predict NAFLD was 0.761, resulting in a cut-off value of 8.7. However, the AUC value of the TyG index was 0.589 for liver fibrosis, which was insufficient to predict this condition. The adjusted odds of having hepatic steatosis or liver fibrosis were more strongly associated with TyG values compared with HOMA-IR. Conclusion: The TyG index is positively related to the severity of hepatic steatosis and the presence of liver fibrosis in NAFLD. The index also performed better than HOMA-IR.

Survivin is overexpressed in cancer cells and plays a crucial role in apoptosis evasion. YM155, a small-molecule inhibitor of survivin, could enhance the cytotoxicity of various DNA-damaging agents. Here, we evaluated the radiosensitizaion potential of YM155 in human esophageal squamous cell carcinoma (ESCC). Cell viability was determined by CCK8 assay. The radiosensitization effect of YM155 was evaluated by clonogenic survival and progression of tumor xenograft. Cell cycle progression was determined by flow cytometric analysis. Radiation-induced DNA double strand break (DSB) and homologous recombination repair (HRR) were detected by the staining of γ-H2AX and RAD51, respectively. Expression of survivin and cell cycle regulators was detected by Western blot analysis. YM155 induced radiosensitization in ESCC cell lines Eca109 and TE13, associated with the abrogation of radiation induced G₂/M checkpoint, impaired Rad51 focus formation, and the prolongation of γ-H2AX signaling. G₂/M transition markers, including the activation of cyclinB1/Cdc2 kinase and the suppression of Cdc2 Thr14/Tyr15 phosphorylation were induced by YM155 in irradiated cells. The combination of YM155 plus irradiation delayed the growth of ESCC tumor xenografts to a greater extent compared with either treatment modality alone. Our findings suggest that the abrogation of G₂ checkpoint and the inhibition of HRR contribute to radiosensitization by YM155 in ESCC cells.

Lipid ratios, for example total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C), are associated with type 2 diabetes mellitus (T2DM). However, the predictive values of lipid ratios in prediabetes remain unclear. The aims of this study were: 1) to investigate the association between lipid ratios and abnormal glucose tolerance; 2) to compare the predictive significance of lipid ratios with commonly used indicators of lipid variables in clinical practice in a Chinese population. The cross-sectional study enrolled 2680 participants from the Health Promotion Center of the First Affiliated Hospital of Nanjing Medical University. All participants received a 75 g oral glucose tolerance test. Blood samples were obtained at baseline and 120 min after glucose ingestion. Participants were classified as normal glucose tolerance (NGT), impaired glucose regulation (IGR), and T2DM. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression model. The receiver operating characteristic (ROC) curve was used to identify the cutoff points of lipid and lipid ratios. The area under the receiver operating characteristic curve (AUROC), sensitivity and specificity were calculated to estimate their diagnostic values. TC, TG, TC/HDL-C, TG/HDL-C and non-HDL-C were significantly correlated with both prediabetes and T2DM after adjustment for other risk factors such as blood glucose, whereas LDL-C was only positively correlated with prediabetes. TG and TG/HDL-C showed higher diagnostic values for prediabetes and T2DM than TC, LDL-C, HDL-C, TC/HDL-C and non-HDL-C, with the AUC values over 0.70. For predicting prediabetes, the optimal cutoff point was 1.36 mmol/l for TG and 1.13 for TG/HDL-C. For predicting T2DM, the optimal cutoff point was 1.46 mmol/l for TG and 1.22 for TG/HDL-C. Both TG and TG/HDL-C are promising biomarkers for distinguishing individuals with abnormal glucose tolerance, and can be used to predict prediabetes and T2DM in Chinese population.

Background: To investigate the associations of weight change patterns across adulthood with the risk of non-alcoholic fatty liver disease (NAFLD). Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 cycle, we performed a retrospective cohort study with 2212 non-obese participants aged 36 years old over. Weight change patterns were categorized as “stable non-obese”, “early adulthood weight gain”, “middle and late adulthood weight gain” and “revert to non-obese” according to the body mass index (BMI) at age 25, 10 years prior and at baseline. Vibration-controlled transient elastography (VCTE) was performed to diagnose NAFLD. Modified Poisson regression was used to quantify the associations of weight change patterns with NAFLD. Results: Compared with participants in the “stable non-obese” group, those who gained weight at early or middle and late adulthood had an increased risk of NAFLD, with an adjusted rate ratio (RR) of 2.19 (95% CI 1.64–2.91) and 1.92 (95% CI 1.40–2.62), respectively. The risk of NAFLD in “revert to the non-obese” group showed no significant difference with the stable non-obese group. If the association of weight change and NAFLD was causal, we estimated that 73.09% (95% CI 55.62–82.93%) of incident NAFLD would be prevented if the total population had a normal BMI across adulthood. Conclusions: Weight gain to obese at early or middle and late adulthood was associated with an evaluated risk of NAFLD. A large proportion would have been prevented with effective weight intervention.

The relationship between metabolically healthy obese individuals (MHO) and cardiovascular disease (CVD) risk is disputed. This study investigated the association of metabolically unhealthy non-obese(MUNO) individuals and MHO with arterial stiffness and 10-year CVD risk. A total of 13,435 participants were enrolled and further divided into the metabolically healthy non-obese (MHNO) phenotype (n = 4927), MUNO phenotype (n = 1971), MHO phenotype (n = 2537) and metabolically unhealthy obese (MUO) phenotype (n = 4000) according to body mass index (BMI) and metabolic status. We used brachial ankle pulse wave velocity (baPWV) to measure arterial stiffness and the Framingham risk score (FRS) to evaluate the 10-year CVD risk. The MUO and MUNO phenotypes had higher mean baPWV values than the MHO and MHNO phenotypes, regardless of age (1446.19 ± 233.65 vs. 1423.29 ± 240.72 vs. 1283.57 ± 213.77 vs. 1234.08 ± 215.99 cm/s, P < 0.001). Logistic regression analysis indicated that the MUNO and MUO phenotypes were independently correlated with elevated baPWV and 10-year CVD risk, while the MHO phenotype was independently associated with only the 10-year CVD risk. In metabolically healthy subjects, BMI showed a dose-dependent increase in the risk of elevated baPWV, with an adjusted OR of 1.007 (95% CI 1.004–1.010, P < 0.001). However, in metabolically unhealthy participants, the estimate for the relationship between elevated baPWV and BMI was nonsignificant. The MUNO phenotype exhibits increased arterial stiffness and 10-year CVD risk. However, BMI is positively and dose-dependently correlated with arterial stiffness only in metabolically healthy subjects. We speculate that metabolic status may be a strong confounder in the obesity–elevated baPWV association.