Background and aims: Sarcopenia is associated with worse prognosis for non-alcoholic fatty liver disease (NAFLD). However, disease progression in the MAFLD-related sarcopenia is largely unknown. We aimed to clarify the relationship between MAFLD and/or sarcopenia with mortality and liver fibrosis in the real world. Methods: A total of 13,692 individuals were selected from the third National Health and Nutrition Examination Surveys and linked mortality until December 2019. MAFLD is diagnosed based on a radiologically diagnosed hepatic steatosis and the presence of any one of the following three conditions: overweight/obesity, diabetes mellitus (DM), or metabolic dysregulation. Sarcopenia is defined by weight-adjusted skeletal muscle mass. Results: The mean age was 43.7 ± 15.97 years, and 47.3% of the individuals were male. MAFLD was diagnosed in 4207/13,692 (30.73%) participants, and the proportion of sarcopenic was 19.42% amongst subjects with MAFLD. The mean follow-up duration was of 23.7 ± 7.62 years. MAFLD (aHR 1.152, 95% CI 1.070–1.241) and sarcopenia (aHR 1.123, 95% CI 1.042–1.210) were related to increased all-cause mortality in MAFLD after adjustment for age, sex, race, marital status, education, and smoking. Stratified analysis revealed that MAFLD and sarcopenia additively increased the risk of mortality (aHR 1.247, 95% CI 1.132–1.373) and liver fibrosis (aOR 2.296, 95% CI 1.718–3.069 assessed by NFS score >0.676; aOR 2.218, 95% CI 1.788–2.752 assessed by FIB-4 score >1.3) in fully adjusted models (P < 0.001 for all). Conclusion: Sarcopenia in individuals with MAFLD portends increased mortality and significant liver fibrosis. Novel therapeutic strategies targeting at increasing skeletal muscle mass should be explored for patients with MAFLD.

Background/Aims: Diabetic nephropathy is the one of the most serious microvascular complications of diabetes mellitus, and “metabolic memory” plays a vital role in the development of diabetic complications. To investigate the effect of epigenetics on metabolic memory, we analyzed the impact of transient high-glucose stimulation on the secretion of inflammatory factors from rat glomerular mesangial cells. Methods: Rat glomerular mesangial cells (HBZY-1) were divided into three groups: high-glucose group (25 mM glucose), hypertonic group (5.5 mM glucose+19.5 mM mannitol), and normal-glucose control group (5.5 mM glucose). Mesangial cells were cultured in high-glucose, hypertonic, and normal-glucose media for 24 h and transitioned to normal-glucose culture for 24, 48, and 72 h. Then, protein, mRNA, and supernatants were harvested. The expression of monomethylated H3K4 was determined by western blot analysis, and the expression of the NF-κB subunit p65 and histone methyltransferase set7/9 was determined by quantitative real-time PCR. The expression of monocyte chemoattractant protein 1 (MCP-1) and vascular cell adhesion molecule 1 (VCAM-1) was detected by an enzyme-linked immunosorbent assay. Results: Compared with the control group, H3K4me1 expression was upregulated after transient high-glucose stimulation, gradually downregulated in the following 48 h (P < 0.05), and reached the level of the control group at 72 h (P > 0.05). The expression of set7/9 was increased after 24 h of high-glucose stimulation and the following 24 h and 48 h (P < 0.05); it then returned to the level of the control group at 72 h. Compared with the control group, the increased expression of p65, VCAM-1, and MCP-1 was sustained for at least 72 h in the high-glucose group. Conclusion: Transient high-glucose stimulation can induce the persistent secretion of inflammatory factors from rat glomerular mesangial cells via histone modification.

We examined the effects of coronary heart disease (CHD), hypertension and diabetes on the development of severe COVID-19. We performed a comprehensive, systematic literature search for studies published between December 2019 and July 5, 2020 in five databases. The prevalence of severe COVID-19 in patients with CHD, hypertension and diabetes was evaluated through a meta-analysis. Thirty-five articles with 8,170 patients were included, and all the available studies were case series. The pooled odds ratio for the development of severe COVID-19 was 3.21 for patients with CHD (fixed-effects model, 95% CI: 2.58-3.99), 2.27 for patients with hypertension (random-effects model, 95% CI: 1.79-2.90) and 2.34 for patients with diabetes (random-effects model, 95% CI: 1.79-3.05). The heterogeneity of the studies was moderate for the effect of CHD on COVID-19 severity, but was high for the effects of diabetes and hypertension. Funnel plots and Egger's tests revealed no publication bias in the CHD and hypertension analyses, but suggested publication bias in the diabetes analysis. This bias was corrected using the trim-and-fill method, and was ultimately found to have no effect on the results. Our findings suggest patients with CHD, hypertension and diabetes are at greater risk for developing severe COVID-19 than those without these conditions.