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.

Thyroid cancer is the most common malignancy of endocrine system, and papillary thyroid cancer (PTC) is the most common subtype. E2F8, a novel identified E2F family member, was reported to associate with progression of several human cancers, however, its clinical significance and biological role in PTC remain unknown. E2F8 or miR-144 expression profiles in PTC tissues were obtained from The Cancer Genome Atlas (TCGA) datasets, and the correlation of E2F8 expression with clinicopathological features was analyzed in a cohort PTC patients. The effects of E2F8 and miR-144 on proliferation were evaluated both in vitro and in vivo. Luciferase reporter assay was used to determine E2F8 was a direct target of miR-144. E2F8 was widely upregulated in PTC tissues, and overexpression of E2F8 was correlated with more aggressive clinicopathological features. In contrast, we found that silence of E2F8 significantly suppressed proliferation of PTC cells by inducing G1-phase arrest via downregulating Cyclin D1 (CCND1) both in vitro and in vivo. We also identified miR-144 as a tumor-suppressive microRNA that directly targeted E2F8 to inhibit proliferation of PTC cells in vitro and in vivo. Moreover, miR-144 was widely downregulated in PTC, where its expression correlated inversely with E2F8 expression. Our results demonstrate a new miR-144/E2F8/CCND1 regulatory axis controlling PTC development, which may offer a potential prognostic and therapeutic strategy. No applicable.

Objective: Chronic obstructive pulmonary disease (COPD) and pulmonary tuberculosis (PTB) share a number of common risk factors, including innate immunity-related genetic factors. In the present study, we compared the role of genetic variations of theTLR4gene in susceptibility to COPD and PTB and illuminated the underlying molecular mechanism of functional single-nucleotide polymorphisms (SNPs).Methods: A population-based case control study was performed in a Chinese Han population and included 152 COPD cases, 1601 PTB cases and 1727 controls. Five SNPs in theTLR4gene (rs10759932, rs2737190, rs7873784, rs11536889, and rs10983755) were genotyped using TaqMan allelic discrimination technology. We estimated the effects of SNPs using the odds ratio (OR) together with 95% confidence interval (CI). Dual-luciferase reporter vectors expressing different genotypes of SNPs were constructed and transfected into the human HEK 293 T cell line to explore their effects on potential transcription activity.Results: After Bonferroni correction, the genetic polymorphisms of all five SNPs remained significantly associated with COPD, while rs10759932 and rs2737190 were also associated with PTB. Compared with rs10759932-TT, individuals carrying TC (OR: 0.42, 95% CI: 0.28–0.64) or CC (OR: 0.24, 95% CI: 0.09–0.63) had a significantly reduced risk of COPD. However, individuals carrying TC (OR: 1.28, 95% CI: 1.11–1.49) or CC (OR: 1.26, 95% CI: 0.98–1.62) had an increased risk of PTB. The OR (95% CI) for allele rs10759932-C was 0.45 (0.32–0.62) for COPD and 1.18 (1.07–1.32) for PTB. For rs2737190, heterozygous AG was related to a decreased risk of COPD (OR: 0.32, 95% CI: 0.21–0.49) and an increased risk of PTB (OR: 1.30, 95% CI: 1.11–1.52). The dual-luciferase reporter assay showed decreased transcription activity caused by rs10759932-C and rs2737190-G.Conclusion: Genetic polymorphisms of rs10759932 and rs2737190 inTLR4are significantly related to both COPD and PTB but with inverse effects. The altered transcription activity caused by mutations in these two loci may partly explain the observed relationship.

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.

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.