We conducted a meta-analysis to assess the association between patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism and nonalcoholic fatty liver disease (NAFLD) and its subtypes simple steatosis(SS) and nonalcoholic steatohepatitis (NASH). The study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models, with assessment for heterogeneity and publication bias. Twenty-three case-control studies involving 6071 NAFLD patients and 10366 controls were identified. The combined results showed a significant association between NAFLD risk and the rs738409 polymorphism in all genetic models (additive model: OR = 3.41, 95% CI = 2.57–4.52; P < 0.00001). In addition, evidence indicated that the rs738409 polymorphism was significantly associated with NASH in all genetic models (additive model: OR = 4.44, 95% CI = 3.39–5.82; P < 0.00001). The subgroup and sensitivity analyses showed that these changes were not influenced by the ethnicities and ages of subjects or by the source of controls. The rs738409 polymorphism was only significantly associated with risk of simple steatosis in the allele contrast and had no effect in the other genetic models. These findings suggest that the rs738409 polymorphism in PNPLA3 gene confers high cross-ethnicity risk for NAFLD and NASH development.

Observational studies have revealed that higher serum vitamin E concentrations and increased vitamin E intake and vitamin E supplementation are associated with beneficial effects on glycaemic control in type 2 diabetes mellitus (T2DM). However, whether vitamin E supplementation exerts a definitive effect on glycaemic control remains unclear. This article involves a meta-analysis of randomised controlled trials of vitamin E to better characterise its impact on HbA1c, fasting glucose and fasting insulin. PubMed, EMBASE and the Cochrane Library were electronically searched from the earliest possible date through April 2013 for all relevant studies. Weighted mean difference (WMD) was calculated for net changes using fixed-effects or random-effects models. Standard methods for assessing statistical heterogeneity and publication bias were used. Fourteen randomised controlled trials involving individual data on 714 subjects were collected in this meta-analysis. Increased vitamin E supplementation did not result in significant benefits in glycaemic control as measured by reductions in HbA1c, fasting glucose and fasting insulin. Subgroup analyses revealed a significant reduction in HbA1c (−0.58%, 95% CI −0.83 to −0.34) and fasting insulin (−9.0 pmol/l, 95% CI −15.90 to −2.10) compared with controls in patients with low baseline vitamin E status. Subgroup analyses also demonstrated that the outcomes may have been influenced by the vitamin E dosage, study duration, ethnic group, serum HbA1c concentration, and fasting glucose control status. In conclusion, there is currently insufficient evidence to support a potential beneficial effect of vitamin E supplementation on improvements of HbA1c and fasting glucose and insulin concentrations in subjects with T2DM.

BackgroundConflicting results have been obtained in trials that have evaluated the prophylactic efficacy of N‐acetylcysteine (NAC) pretreatment in the prevention of contrast‐induced nephropathy (CIN). In this meta‐analysis of randomized controlled trials, we aimed to assess the effectiveness of NAC treatment for the prevention of CIN.Methods and ResultsPubMed, EMBASE, and the Cochrane Library were electronically searched from inception to January 2016 for all relevant studies. The weighted relative risk (RR) and corresponding 95% CI for incident CIN were estimated using random effects models. Standard methods for assessing statistical heterogeneity and publication bias were used. The study included 11 480 participants and 1653 cases of CIN. The incidence of CIN was 12.8% in the NAC group versus 16.0% in the control group (RR: 0.76, 95% CI: 0.66–0.88, P=0.0002). In the patients undergoing coronary angiography, the incidence of CIN in the NAC group versus the control group was 13.7% versus 17.2% (RR: 0.74, 95% CI: 0.63–0.87, P=0.0002); in those undergoing peripheral angiography, the incidence was 6.4% versus 5.8% (RR: 1.00, 95% CI: 0.42–2.40, P=1.00); in those undergoing computed tomography, the incidence was 7.7% versus 14.8% (RR: 0.51, 95% CI: 0.29–0.89, P=0.02).ConclusionsOur meta‐analysis showed an inverse and significant association between NAC supplementation and risk of CIN in patients undergoing coronary angiography and computed tomography, while a protective role for NAC in patients undergoing peripheral angiography was not obvious.

Background:Cardiac arrhythmias can occur during pregnancy. Owing to radiation exposure and other uncertain risks for the mother and fetus, catheter ablation has rarely been performed and is often delayed until the postpartum period. We reported 2 pregnant women who were experiencing severe arrhythmias and were successfully ablated without fluoroscopic guidance. We also carried out a literature review of cases of pregnant women who underwent zero-fluoroscopy ablation.Methods and Results:One woman had drug-resistant and poorly tolerated frequent premature ventricular contraction (PVC) and ventricular tachycardia (VT). The other one had persistent and hardly terminated supraventricular tachycardia (SVT) via a right accessory pathway. The 2 patients were successfully underwent zero-fluoroscopy ablation guided by Ensite NavX system. The procedure time was 42 and 71 minutes, respectively.Conclusion:Catheter ablation of SVT or PVC/VT in pregnant patients can be safely and effectively performed with a completely zero-fluoroscopy approach guided by the Ensite NavX system. In the case of a drug refractory, life-threatening arrhythmia during pregnancy, catheter ablation may be considered.

Cytochrome P-450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play important roles in regulating cardiovascular functions. The anti-inflammatory, antiapoptotic, proangiogenic, and antihypertensive properties of EETs suggest a beneficial role for EETs in diabetic nephropathy. Endogenous EET levels are maintained by a balance between synthesis by CYP epoxygenases and hydrolysis by epoxide hydrolases into physiologically less active dihydroxyeicosatrienoic acids. Genetic disruption of soluble epoxide hydrolase (sEH/EPHX2) results in increased EET levels through decreased hydrolysis. This study investigated the effects of sEH gene disruption on diabetic nephropathy in streptozotocin-induced diabetic mice. Streptozotocin-induced diabetic manifestations were attenuated in sEH-deficient mice relative to wild-type controls, with significantly decreased levels of Hb A1c, creatinine, and blood urea nitrogen and urinary microalbumin excretion. The sEH-deficient diabetic mice also had decreased renal tubular apoptosis that coincided with increased levels of antiapoptotic Bcl-2 and Bcl-xl, and decreased levels of the proapoptotic Bax. These effects were associated with activation of the PI3K-Akt-NOS3 and AMPK signaling cascades. sEH gene inhibition and exogenous EETs significantly protected HK-2 cells from TNFα-induced apoptosis in vitro. These findings highlight the beneficial role of the CYP epoxygenase-EETs-sEH system in the pathogenesis of diabetic nephropathy and suggest that the sEH inhibitors available may be potential therapeutic agents for this condition.

Background Strong epidemiologic evidence indicates that green tea intake is protective against hyperlipidemia; however, randomized controlled studies have presented varying results. In the present study, we aimed to conduct a literature review and meta-analysis to assess the effect of green tea on blood lipids. Methods PubMed, Embase, and the Cochrane Library were electronically explored from inception to September 2019 for all relevant studies. Random effect models were used to estimate blood lipid changes between green tea supplementation and control groups by evaluating the weighted mean differences (WMD) with 95% confidence intervals (CIs). The risk of bias for study was assessed using the Cochrane tool. Publication bias was evaluated using funnel plots and Egger’s tests. Results Thirty-one trials with a total of 3321 subjects were included in the meta-analysis. In general, green tea intake significantly lowered the total cholesterol (TC); WMD: − 4.66 mg/dL; 95% CI: − 6.36, − 2.96 mg/dL; P < 0.0001) and low-density lipoprotein (LDL) cholesterol (WMD:− 4.55 mg/dL; 95% CI: − 6.31, − 2.80 mg/dL; P < 0.0001) levels compared with those in the control. Green tea consumption did not affect high-density lipoprotein (HDL) cholesterol; however, it reduced the triglycerides compared with that in the control (WMD: − 3.77 mg/dL; 95% CI: − 8.90, 1.37 mg/dL; P = 0.15). In addition, significant publication bias from funnel plots or Egger’s tests was not evident. Conclusions Collectively, consumption of green tea lowers LDL cholesterol and TC, but not HDL cholesterol or triglycerides in both normal weight subjects and those who were overweight/obese; however, additional well-designed studies that include more diverse populations and longer duration are warranted.

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Cytochrome P-450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) exert diverse biological activities, which include potent vasodilatory, anti-inflammatory, antiapoptotic, and antioxidatant effects, and cardiovascular protection. Liver has abundant epoxygenase expression and high levels of EET production; however, the roles of epoxygenases in liver diseases remain to be elucidated. In this study, we investigated the protection against high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) in mice with endothelial-specific CYP2J2 overexpression (Tie2-CYP2J2-Tr). After 24 wk of high-fat diet, Tie2-CYP2J2-Tr mice displayed attenuated NAFLD compared with controls. Tie2-CYP2J2-Tr mice showed significantly decreased plasma triglyceride levels and liver lipid accumulation, improved liver function, reduced inflammatory responses, and less increase in hepatic oxidative stress than wild-type control mice. These effects were associated with inhibition of NF-κB/JNK signaling pathway activation and enhancement of the antioxidant defense system in Tie2-CYP2J2-Tr mice in vivo. We also demonstrated that 14,15-EET treatment protected HepG2 cells against palmitic acid-induced inflammation and oxidative stress. 14,15-EET attenuated palmitic acid-induced changes in NF-κB/JNK signaling pathways, malondialdehyde generation, glutathione levels, reactive oxygen species production, and NADPH oxidase and antioxidant enzyme expression in HepG2 cells in vitro. Together, these results highlight a new role for CYP epoxygenase-derived EETs in lipotoxicity-related inflammation and oxidative stress and reveal a new molecular mechanism underlying EETs-mediated anti-inflammatory and antioxidant effects that could aid in the design of new therapies for the prevention and treatment of NAFLD.