Maternal QI in obese dams during gestation and lactation reduced birth weight and postnatal BW gain in the offspring, and helped to improve insulin sensitivity and lipid metabolism of the mature offspring via reducing ER stress and related inflammation in the liver and adipose tissue.

Cardiovascular disease (CVD) is a major contributor to the global burden of disease. Berberine, a long-standing, widely used, traditional Chinese medicine, is thought to have beneficial effects on CVD risk factors and in women with polycystic ovary syndrome. The mechanisms and effects, specifically in men, possibly via testosterone, have not been examined previously. To assess the effect of berberine on CVD risk factors and any potential pathway via testosterone in men, we conducted a randomized, double-blind, placebo-controlled, parallel trial in Hong Kong. In total, 84 eligible Chinese men with hyperlipidemia were randomized to berberine (500 mg orally, twice a day) or placebo for 12 weeks. CVD risk factors (lipids, thromboxane A2, blood pressure, body mass index and waist–hip ratio) and testosterone were assessed at baseline, and 8 and 12 weeks after intervention. We compared changes in CVD risk factors and testosterone after 12 weeks of intervention using analysis of variance, and after 8 and 12 weeks using generalized estimating equations (GEE). Of the 84 men randomized, 80 men completed the trial. Men randomized to berberine had larger reductions in total cholesterol (−0.39 mmol/L, 95% confidence interval (CI) −0.70 to −0.08) and high-density lipoprotein cholesterol (−0.07 mmol/L, 95% CI −0.13 to −0.01) after 12 weeks. Considering changes after 8 and 12 weeks together, berberine lowered total cholesterol and possibly low-density lipoprotein-cholesterol (LDL-c), and possibly increased testosterone. Changes in triglycerides, thromboxane A2, blood pressure, body mass index and waist–hip ratio after the intervention did not differ between the berberine and placebo groups. No serious adverse event was reported. Berberine is a promising treatment for lowering cholesterol. Berberine did not lower testosterone but instead may increase testosterone in men, suggesting sex-specific effects of berberine. Exploring other pathways and assessing sex differences would be worthwhile, with relevance to drug repositioning and healthcare.

OBJECTIVES: The risk of liver injury in patients with atrial fibrillation (AF) using nonvitamin K antagonist oral anticoagulants (NOACs) has not been previously examined using liver function tests as the primary outcome in the real-world setting. This study assessed the association between NOACs (dabigatran, rivaroxaban, apixaban) and warfarin and the risk of liver injury, as defined by laboratory tests. METHODS: Patients newly diagnosed with AF and prescribed NOACs or warfarin between 2010-2016, identified using the Hong Kong Clinical Database and Reporting System, were matched on age, sex, health status scores, comorbidities and medications by propensity score at a 1:1 ratio. Risk of liver injury, defined as laboratory test values >3 times the upper limit of normal of alanine aminotransferase or aspartate aminotransferase and >2 times the upper limit of normal of total bilirubin, was compared between NOAC and warfarin users using Cox proportional hazards regression. RESULTS: After propensity score matching, 13,698 patients were included, of which 141 (2.1%) NOAC users and 232 (3.4%) warfarin users developed liver injury. The hazard ratio (HR) for NOAC vs warfarin users was 0.71 (95% CI: 0.58-0.89). When comparing individual NOACs, only dabigatran (HR: 0.63; 95% CI: 0.48-0.82) was associated with a lower risk of liver injury. DISCUSSION: Among patients with atrial fibrillation, NOACs as a group, as well as dabigatran alone, were associated with a significantly lower risk of laboratory-based liver injury when compared to warfarin. However, liver injury occurs more frequently in real-world practice than in NOAC randomized controlled trials. Response to Reviewers: Dear Drs. Lacy and Spiegel, RE: Manuscript ID AJG-19-2621 -"Association Between Non-vitamin K Antagonist Oral Anticoagulants or Warfarin and Liver Injury: A Cohort Study": response to the reviewers' comments for the manuscript Thank you very much for the comments in the recent decision letter dated 3 February 2020. We appreciate this opportunity to further revise our manuscript. Our responses to the reviewers' comments are given point-by-point below in red. Editor/Editorial Board: 1.Please indicate if any subjects had cholestatic liver injury defined by R value or ratio of serum ALT to serum alkaline phosphatase as a multiple of upper limit of normal R<2. Thank you for your comment. To address this point, and several other comments regarding the clinical details of patients who experienced our outcome definition of liver injury, we have added an additional table to the main text (Table 2, p. 31). As per the EASL Clinical Practice Guidelines: Drug-induced liver injury, we have described the number (%) of patients with the primary outcome by their ALT/ALP ratio (R) (i.e. R ≤2 cholestatic pattern, R >2 to <5 mixed pattern, and R ≥5 hepatocellular pattern) on the outcome date. In the complete cohort, a total of 332 (64.7%) of patients had a cholestatic pattern of liver injury (208 [66.5%] warfarin users and 124 [62.0%] NOAC users). Further details by drug are...