Molecular classification and clinical diagnosis of acute-on-chronic liver failure patients by serum metabolomics.

Prevalence of acute-on-chronic liver failure (ACLF) patients is growing worldwide, associating with multi-organ failure and high short-term mortality rates. ACLF can be of varying entity manifestation, whereas it remains poorly defined. Traditional Chinese medicine (TCM) stratifies ACLF into two types, damp hot (DH) and cold damp (CD), by seasoned TCM practitioners, for specific treatment with different TCMs. The biggest challenge for the outcome of TCM therapy is the accuracy of diagnosis. However, it is difficult to guarantee it due to lack of the molecule classification of ACLF. Herein, we recruited 58 subjects including 34 ACLF patients (18 DH and 16 CD) and 24 healthy controls, and analyzed serum metabolic profiles using untargeted ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomics approach. A total of 10 serum metabolites were found as potential biomarkers for diagnosis of ACLF. Among them, taurochenodesoxycholic acid (N3), glycyldeoxycholic acid (N5) and 12-HETE-GABA (N7), varied between two types of ACLF and can be merged as a combination marker to differentiate CD from DH patients with area under the receiver operating curve (AUC) of 0.928 (95 % CI 0.8-1). CD patients possessed comparatively higher bile acid metabolism and lower arachidonic acid metabolism compared with DH patients. The results provide not only serum molecules for early accurate diagnosis of ACLF patients, but also potential clinical biomarkers for classification of CD and DH types. The findings clarify that molecular markers will be objective criteria for diagnosis of clinical types in TCM practice.

The feasibility of two anthropometric indices to identify metabolic syndrome, insulin resistance and inflammatory factors in obese and overweight adults.

OBJECTIVES: A body shape index (ABSI) and body roundness index (BRI) were reported to predict diabetes and hypertension in general population, but their validity was regularly questioned. The aim of this study was to evaluate whether ABSI and BRI are the best anthropometric indices to reflect metabolic syndrome (MetS), insulin resistance (IR), and inflammatory factors in obese and overweight Chinese adults. METHODS: Cross-sectional data on sociodemographic, lifestyle, anthropometric indices, clinical characteristics, and biochemical measurements were collected for 1442 Chinese obese and overweight adults. Logistic regression analysis examined the associations between anthropometric indices with incidences of MetS and IR in both sexes. Furthermore, the correlation between anthropometric indices and inflammatory factors was assessed. RESULTS: Multivariate regression analysis depicting BRI and waist circumference (WC) were associated significantly with MetS and IR. BRI had the highest odds ratios (ORs) for IR and WC had the highest ORs for MetS in all anthropometric indices. However, ABSI did not exhibit any association between the MetS and IR. The ABSI adjusted regression coefficients (ß values) were 0.403 for high-sensitivity C reactive protein, 0.077 for tumor necrosis factor-α, and 0.022 for interleukin-6. BRI and WC were also significantly associated with three inflammatory factors. Comparing the lowest with the highest quintile, BRI had the largest ORs for MetS (OR, 5.778; 95% confidence interval [CI], 2.954-11.303; P < 0.01) and IR (OR, 6.212; 95% CI, 2.912-13.250; P < 0.01). CONCLUSION: Only BRI and WC, not ABSI, can significantly determine the presence of MetS and IR. BRI showed the optimal capability to identify IR in obese and overweight population.

Small dense low density lipoprotein-cholesterol and cholesterol ratios to predict arterial stiffness progression in normotensive subjects over a 5-year period.

BACKGROUND: Small dense low density lipoprotein-cholesterol (sdLDL-C), cholesterol ratios and carotid-femoral pulse wave velocity (cf-PWV) impart risk for all-cause morbidity and mortality independently of conventional cardiovascular disease (CVD) risk factors. This study was designed to identify feasible indicators for predicting arterial stiffness progression. METHODS: We followed up 816 normotensive participants without diabetes or CVD for nearly 5.0 years. Cholesterol parameters, ratios and other clinical and laboratory data were collected at baseline. cf-PWV were measured at baseline and the end of follow-up. RESULTS: PWV progression subjects had higher levels of PWV parameters, sdLDL-C and TG/HDL-C ratio. sdLDL-C and TG/HDL-C were significantly correlated with all PWV parameters. Multiple regression models showed that sdLDL-C was closely associated with follow-up PWV (ß = 0.222, p < 0.001) and △PWV (ß = 0.275, p < 0.001). TG/HDL-C was only one cholesterol ratios that associated with all PWV parameters. sdLDL-C (OR = 2.070, 95%CI: 1.162 to 3.688, p = 0.014) and TG/HDL-C (OR = 1.355, 95%CI: 1.136 to 1.617, p = 0.001) could significantly determine the progression of PWV after correction for covariates. High sd-LDL-C quantiles subjects were more likely to develop arterial stiffness progression than low quantiles (Tertiles 3 vs Tertiles1, RR = 2.867, 95%CI: 1.106 to 7.434, p = 0.03). CONCLUSION: We founded that sdLDL-C and TG/HDL-C ratio can independently predict arterial stiffness progression in normotensive subjects, and high level sdLDL-C and TG/HDL-C ratio were associated with a higher risk of arterial stiffness.

Autoantibodies against AT1 and α1-adrenergic receptors predict arterial stiffness progression in normotensive subjects over a 5-year period.

Arterial stiffness is an independent indicator of cardiovascular risk. Autoantibodies (AAs) against angiotensin AT1 receptor (AT1-AAs) and α1-adrenergic receptor (α1-AAs) are important in the pathogenesis of hypertension. We identified the types of AT1-AAs and α1-AAs in normotensive subjects, with the aim of determining whether these antibodies predict aortic stiffness progression. Carotid-femoral pulse wave velocity (cf-PWV) was used to measure aortic stiffness. Overall, 816 subjects (71% of those invited) underwent a medical examination and evaluation of aortic stiffness. The types of AT1-AAs and α1-AAs were measured at baseline. Meanwhile, plasma renin, angiotensin II (Ang II), and norepinephrine (NE) concentrations were measured at baseline and follow-up. Baseline mean cf-PWV was 9.90 ± 0.84 m/s and follow-up was 10.51 ± 1.12 m/s. The annualized ΔPWV was 0.12 ± 0.08 m/s/year. At the end of follow-up, 129 normotensive subjects developed hypertension and 144 subjects had PWV progression. After adjustment for covariates, AA type was independently associated with ΔPWV, annualized ΔPWV, and abnormal PWV. In our study, the risk of developing hypertension (RR =2.028, 95% CI: 1.227-3.351, P=0.006) and PWV progression (RR =2.910, 95% CI: 1.612-5.253, P<0.001) in AA-positive subjects was significantly higher than that in AA-negative subjects. Receiver operating characteristic (ROC) curve showed AA had an identify power to discriminate subjects with or without PWV and hypertension progression. We have shown for the first time that the types of A1-AAs and α1-AAs are independent predictors for aortic stiffness progression in normotensive subjects. Our data collectively support the utility of these AAs as potential markers of aortic stiffness.