Synergistic Effects of Serum Uric Acid and Cardiometabolic Risk Factors on Early Stage Atherosclerosis: The Cardiometabolic Risk in Chinese Study

Objective: To comprehensively examine the associations of serum uric acid (SUA) with central and peripheral arterial stiffness in Chinese adults, and particularly assess the interactions between SUA and other cardiometabolic risk factors. Methods: The study included 3,772 Chinese men and women with carotid radial pulse wave velocity (crPWV), carotid femoral PWV (cfPWV), carotid artery dorsalis pedis PWV (cdPWV) and SUA measured. Results: After adjustment for age, sex, and BMI, the levels of SUA were significantly associated with increasing trend of cfPWV, crPWV and cdPWV (P for trend <0.0001). Further adjustment for heart rate (HR), blood pressure (BP) and lipids attenuated the associations with crPWV and cdPWV to be non-significant (P = 0.1, P = 0.099 respectively), but the association between SUV and cfPWV remained significant (P = 0.004). We found significant interactions between SUA and HR or BP in relation to cfPWV (P for interaction = 0.03, 0.003 respectively). The associations between SUA and cfPWV were more evident among individuals with higher HR or normal BP than those with lower HR or hypertension. Conclusions: SUA was associated with elevated aortic arterial stiffness in Chinese adults, independent of conventional cardiovascular risk factors. BP and HR might modify the deleterious effects of SUA

基于不同肌肉类型验证羊肉质量特征的蛋白质生物标志物

peer reviewedThis work investigated the ability of 8 potential biomarkers (phosphoglycerate kinase-1 (PGK1), pyruvate kinase-M2 (PKM2), phosphoglucomutase-1 (PGM1), β-enolase (ENO3, myosin-binding protein-C (MYBPC1), myosin regulatory light chain-2 (MYLPF), troponin C-1 (TNNC1) and troponin I-1 (TNNI1)) to characterize meat quality by analyzing their relative abundance and enzymatic activity. Two different meat quality groups (Quadriceps femoris (QF) and Longissimus thoracis (LT) muscles) were selected at 24 h postmortem from 100 lamb carcasses. The relative abundance of PKM2, PGK1, PGM1, ENO3, MYBPC1, MYLPF, and TNNI1 was significantly different between LT and QF muscle groups (P < 0.01). Moreover, PKM, PGK, PGM, and ENO activity in LT muscle group was significantly lower than that in QF muscle (P < 0.05). Suggesting that PKM2, PGK1, PGM1, ENO3, MYBPC1, MYLPF, and TNNI1 can be used as robust biomarkers of lamb meat quality, providing the reference for understanding the molecular mechanism of postmortem meat quality formation in future

Cytokeratin 18, alanine aminotransferase, platelets and triglycerides predict the presence of nonalcoholic steatohepatitis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the critical public health problems in China. The full spectrum of the disease ranges from simple steatosis and nonalcoholic steatohepatitis (NASH) to cirrhosis and hepatocellular carcinoma(HCC). The infiltration of inflammatory cells characterizes NASH. This characteristic contributes to the progression of hepatitis, fibrosis, cirrhosis, and HCC. Therefore, distinguishing NASH from NAFLD is crucial. OBJECTIVE AND METHODS: Ninety-five patients with NAFLD, 44 with NASH, and 51 with non-NASH were included in the study to develop a new scoring system for differentiating NASH from NAFLD. Data on clinical and biological characteristics, as well as blood information, were obtained. Cytokeratin-18 (CK-18) fragments levels were measured using an enzyme-linked immunosorbant assay. RESULTS: Several indexes show significant differences between the two groups, which include body mass index (BMI), waist-on-hip ratio (WHR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), platelets, uric acid (UA), hs-C-reactive protein (hs-CRP), triglycerides (TG), albumin (ALB), and CK-18 fragments (all P < 0.05). The CK-18 fragment levels showed a significant positive correlation with steatosis severity, ballooning, lobular inflammation, and fibrosis stage (all P < 0.05). Therefore, a new model that combines ALT, platelets, CK-18 fragments, and TG was established by logistic regression among NAFLD patients. The AUROC curve in predicting NASH was 0.920 (95% CI: 0.866 - 0.974, cutoff value = 0.361, sensitivity = 89%, specificity = 86%, positive predictive value = 89%, negative predictive value = 89%). CONCLUSION: The novel scoring system may be considered as a useful model in predicting the presence of NASH in NAFLD patients

Seismic Analysis of a Large LNG Tank Considering Different Site Conditions

Seismic resilience of critical infrastructure, such as liquefied natural gas (LNG) storage tanks, is essential to the safety and economic well-being of the general public. This paper studies the effect of different ground motions on large LNG storage tanks under four different site conditions. Key parameters of structural design and dynamic analysis, including von Mises stress of outer and inner tanks, tip displacement, and base shear, are analyzed to directly evaluate the safety performance of the large LNG tanks. Because the size of an LNG tank is too large to perform any experiments on a physical prototype, Smoothed Particle Hydrodynamics-Finite Element Method (SPH-FEM) simulation is used as a feasible and efficient method to predict its seismic response. First, the accuracy of the SPH-FEM method is verified by comparing sloshing frequencies obtained from theoretical formulation to experimental results and SPH-FEM models. Then, the seismic response of a real-life 160,000 m3 LNG prestressed storage tank is evaluated with different liquid depths under four site classes. Simulation results show that the tip displacements of the LNG tank at liquid levels of 25% and 50% under site class IV are nearly identical to that of 75% and 100% under site class II. In addition, the maximum von Mises stress of the inner tanks exceeds 500 MPa in all four site classes and jeopardizes the structural integrity of large LNG tanks. As a result, optimization of structural design and the establishment of an early warning system are imperative to the safety of LNG tanks at high liquid levels

Seismic Analysis of a Large LNG Tank Considering Different Site Conditions

Seismic resilience of critical infrastructure, such as liquefied natural gas (LNG) storage tanks, is essential to the safety and economic well-being of the general public. This paper studies the effect of different ground motions on large LNG storage tanks under four different site conditions. Key parameters of structural design and dynamic analysis, including von Mises stress of outer and inner tanks, tip displacement, and base shear, are analyzed to directly evaluate the safety performance of the large LNG tanks. Because the size of an LNG tank is too large to perform any experiments on a physical prototype, Smoothed Particle Hydrodynamics-Finite Element Method (SPH-FEM) simulation is used as a feasible and efficient method to predict its seismic response. First, the accuracy of the SPH-FEM method is verified by comparing sloshing frequencies obtained from theoretical formulation to experimental results and SPH-FEM models. Then, the seismic response of a real-life 160,000 m3 LNG prestressed storage tank is evaluated with different liquid depths under four site classes. Simulation results show that the tip displacements of the LNG tank at liquid levels of 25% and 50% under site class IV are nearly identical to that of 75% and 100% under site class II. In addition, the maximum von Mises stress of the inner tanks exceeds 500 MPa in all four site classes and jeopardizes the structural integrity of large LNG tanks. As a result, optimization of structural design and the establishment of an early warning system are imperative to the safety of LNG tanks at high liquid levels

MicroRNA-124a contributes to glucocorticoid resistance in acute-on-chronic liver failure by negatively regulating glucocorticoid receptor alpha

Introduction and objectives: Glucocorticoid resistance frequently associating with inflammation, may severely compromise the therapeutic effect of glucocorticoids. In this study, we aimed to investigate the regulation of glucocorticoid resistance by microRNA-124a (miR-124a) in patients with acute-on-chronic liver failure (ACLF). Materials and methods: The miR-124a levels and glucocorticoid receptor alpha (GRα) expressions in peripheral blood monocytes and liver tissues were measured by quantitative reverse transcription–polymerase chain reaction (qRT-PCR), flow cytometry, and western blot analyses in the following four groups: healthy controls (HC), moderate chronic hepatitis B (CHB) patients, hepatitis B virus-related ACLF (HBV-ACLF) patients, and alcohol-induced ACLF (A-ACLF) patients. In addition, the serum miR-124a levels and multiple biochemical indices were determined. The effects of miR-124a transfection on GRα expression were assayed by qRT-PCR and western blotting in U937 and HepG2 cells stimulated with lipopolysaccharide (LPS). Results: Compared with the CHB patients and HC, the miR-124a levels in HBV-ACLF and A-ACLF patients increased, while GRα expressions decreased. No significant differences in miR-124a levels and GRα expressions were observed between the HBV-ACLF and A-ACLF patients. For the ACLF patients, miR-124a level was negatively related to GRα expression in monocytes and positively correlated with the inflammatory factors such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). In U937 and HepG2 cells, LPS stimulated miR-124a levels but inhibited GRα expressions; meanwhile, increasing miR-124a levels reduced GRα expressions, and inhibiting miR-124a levels increased GRα expressions. Conclusions: This study provides evidence that GRα expression was negatively regulated by miR-124a, which primarily determines the extent of acquired glucocorticoid resistance in ACLF

The efficacy and safety of Nucleos(t)ide analogues in patients with spontaneous acute exacerbation of chronic hepatitis B: a systematic review and meta-analysis.

BACKGROUND: Spontaneous acute exacerbation (AE) of chronic hepatitis B (CHB) is often detrimental but sometimes leads to sustained immune control and disease remission. The efficacy and safety of nucleos(t)ide analogues (NAs) in patients with spontaneous AE of CHB remains unclear. METHODS: We performed a systematic review and meta-analysis of NAs in patients with spontaneous AE of CHB. We calculated pooled effects of NAs in these patients of each study and conducted quantitative meta-analysis, displaying results using Forest plots. RESULTS: 15 studies were included and substantial heterogeneity was noted in the inclusion/exclusion criteria and controls. Pooled data showed no benefit of lamivudine (LAM) vs. untreated controls for transplant-free survival in patients with spontaneous AE of CHB (OR = 0.98 (95% CI, 0.50-1.92; P = 0.956)), hepatic decompensation (OR = 0.94 (95% CI, 0.47-1.88; P = 0.862)) and liver failure owing to AE (OR = 2.30 (95% CI, 0.35-15.37; P = 0.387)) at 3 months. Entecavir achieved even higher short-term mortality than LAM. NAs led to rates of ALT normalization, undetectable HBV DNA, HBeAg loss, HBeAg seroconversion and drug resistance at 1 year in 88%, 61%, 46%, 35% and 5%. Pooled data also showed benefit favoring LAM vs. untreated controls for ALT normalization (OR = 1.98 (95% CI, 1.03-3.80; P = 0.039)) and undetectable HBV DNA (OR = 38.50 (95% CI, 7.68-192.99; P<0.001)) at 3 months. All NAs were relatively safe and well tolerated. CONCLUSION: NAs had no obvious impact on short-term survival in patients with AE of CHB, despite of possible better antiviral responses. We suggest additional studies to evaluate the efficacy of other NAs and early introduction of immunosuppressant in combination with NAs. We highlight developing prognostic models to identify predictors of mortality and disease progression for AE of CHB

Mesoporous Silica Coated Polydopamine Functionalized Reduced Graphene Oxide for Synergistic Targeted Chemo-Photothermal Therapy

The integration of different therapies into a single nanoplatform has shown great promise for synergistic tumor treatment. Herein, mesoporous silica (MS) coated polydopamine functionalized reduced graphene oxide (pRGO) further modified with hyaluronic acid (HA) (pRGO@MS-HA) has been utilized as a versatile nanoplatform for synergistic targeted chemo-photothermal therapy against cancer. A facile and green chemical method is adopted for the simultaneous reduction and noncovalent functionalization of graphene oxide (GO) by using mussel inspired dopamine (DA) to enhance biocompatibility and the photothermal effect. Then, it was coated with mesoporous silica (MS) (pRGO@MS) to enhance doxorubicin (DOX) loading and be further modified with the targeting moieties hyaluronic acid (HA). The pH-dependent and near-infrared (NIR) laser irradiation-triggered DOX release from pRGO@MS(DOX)-HA is observed, which could enhance the chemo-photothermal therapy effect. In vitro experimental results confirm that pRGO@MS(DOX)-HA exhibits good dispersibility, excellent photothermal property, remarkable tumor cell killing efficiency, and specificity to target tumor cells. In vivo antitumor experiments further demonstrated that pRGO@MS(DOX)-HA could exhibit an excellent synergistic antitumor efficacy, which is much more distinct than any monotherapy. This work presents a novel nanoplatform which could load chemotherapy drugs with high efficiency and be used as light-mediated photothermal cancer therapy agent.</p