Background: Lipid metabolism plays an important role in viral infections. We aimed to assess the causal effect of lipid-lowering drugs (HMGCR inhibitiors, PCSK9 inhibitiors and NPC1L1 inhibitior) on COVID-19 outcomes using 2-sample Mendelian Randomization (MR) study. Methods: We used two kinds of genetic instruments to proxy the exposure of lipid-lowering drugs, including eQTLs of drugs target genes, and genetic variants within or nearby drugs target genes associated with LDL cholesterol from GWAS. Summary-data-based MR (SMR) and inverse-variance weighted MR (IVW-MR) were used to calculate the effect estimates. Results: SMR analysis found that a higher expression of HMGCR was associated with a higher risk of COVID-19 hospitalization (OR=1.38, 95%CI=1.06-1.81). Similarly, IVW-MR analysis observed a positive association between HMGCR-mediated LDL cholesterol and COVID-19 hospitalization (OR=1.32, 95%CI=1.00-1.74). No consistent evidence from both analyses was found for other associations. Conclusions: This 2-sample MR study suggested a potential causal relationship between HMGCR inhibition and the reduced risk of COVID-19 hospitalization. Funding: Fujian Province Major Science and Technology Program.

Background Metabolic associated fatty liver disease (MAFLD) is a new definition for liver disease associated with known metabolic dysfunction. Based on new diagnostic criteria, we aimed to investigate its prevalence and risk factors in Chinese population. Methods We conducted this study in a health examination population who underwent abdominal ultrasonography in China. The diagnosis of MAFLD was based on the new diagnostic criteria. The characteristics of the MAFLD population, as well as the associations between MAFLD and metabolic abnormalities, were explored. Mann–Whitney U test and chi-square test were performed to compare different variables. Binary logistic regression was used to determine the risk factors for MAFLD. Results Among 139,170 subjects, the prevalence of MAFLD was 26.1% (males: 35.4%; females: 14.1%). The prevalence based on female menopausal status, that is, premenopausal, perimenopausal, and postmenopausal, was 6.1%, 16.8%, and 30.2%, respectively. In different BMI groups (underweight, normal, overweight and obese), the prevalence was 0.1%, 4.0%, 27.4% and 59.8%, respectively. The proportions of abnormal metabolic features in the MAFLD group were significantly higher than those in the non-MAFLD group, as was the proportion of elevated alanine aminotransferase (ALT) (42.5% vs. 11%, P < 0.001). In nonobese individuals with MAFLD, the proportions of abnormal metabolic features were also all significantly higher than those in nonobese individuals without MAFLD. The prevalence of metabolic syndrome (MS), dyslipidaemia, and hyperuricaemia, respectively, in the MAFLD group (53.2%, 80.0%, and 45.0%) was significantly higher than that in the non-MAFLD group (10.1%, 41.7%, and 16.8%). Logistic regression revealed that age, BMI, waist circumference, ALT, triglycerides, fasting glucose, uric acid and platelet count were associated with MAFLD. Conclusions MAFLD is prevalent in China and varies considerably among different age, sex, BMI, and female menopausal status groups. MAFLD is related to metabolic disorders, especially obesity, while metabolic disorders also play important roles in the occurrence of MAFLD in nonobese individuals. MAFLD patients exhibit a high prevalence of MS, dyslipidaemia, hyperuricaemia, and elevated liver enzymes. MAFLD tends to coexist with systemic metabolic disorders, and a deep inner relationship may exist between MAFLD and MS. Metabolic disorders should be considered to improve the management of MAFLD.

Regional differences in rabbit atrial repolarization were investigated using a conventional microelectrode technique. A more rapid phase 1 repolarization (lower phase 1 amplitude) was seen in the left atrial (LA) roof area compared with the right atrial (RA) roof area: 54 +/- 10 vs. 82 +/- 6 mV at 1,000 ms (P < 0.001). In addition, action potential duration at 40 mV above the resting potential (APD40) was shorter in LA and was associated with a slower phase 3 repolarization rate. Furthermore, the recovery time constant of phase 1 amplitude at 500 ms was 0.9 +/- 0.2 s in LA and 3.5 +/- 1.5 s in RA (P < 0.001). Pacing cycle lengths (2,000, 1,500, 1,000, 800, and 500 ms) modulated phase 1 amplitude, APD40, and phase 3 rate in both regions. 4-Aminopyridine (4-AP; 1 mM), a selective transient outward current (I(to)) blocker, abolished cycle length dependence of the above action potential parameters and diminished the differences in electrophysiological properties between the two regions. 4-AP also flattened the restitution curve of phase 1 amplitude in both regions. In conclusion, the findings suggest that the different kinetics of I(to) play an important role in regional differences of atrial repolarization.

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