Microtubule affinity regulating kinase 4 (MARK4) plays a crucial role in the regulation of NOD-like receptor pyrin domain 3 (NLRP3) inflammasome activation, which leads to the generation of bioactive interleukin (IL)-1β and IL-18. E74-like ETS transcription factor 3 (ELF3) participates in endothelial inflammatory processes. We hypothesized that ELF3 modulates MARK4 expression in vascular endothelial cells, thus contributing to high glucose-mediated NLRP3 inflammasome activation. Plasma IL-1β, IL-18, NLRP3 inflammasome and MARK4 expression was increased in diabetic patients and rats. An in vitro study indicated that high glucose increased IL-1β and IL-18 expression and activated the NLRP3 inflammasome via upregulation of MARK4 in human umbilical vein endothelial cells (HUVECs). Furthermore, high glucose increased ELF3 expression. ELF3 downregulation reversed the effects of high glucose treatment. Accordingly, the effects of ELF3 overexpression were similar to those of high glucose treatment and were counteracted by siMARK4. Furthermore, ELF3 was found to interact with SET8. High glucose inhibited SET8 expression and histone H4 lysine 20 methylation (H4K20me1), a downstream target of SET8. Overexpression of SET8 inhibited high glucose-induced MARK4 expression and NLRP3 inflammasome activation. The effects of shSET8 were similar to those of high glucose treatment and were counteracted by siMARK4. A mechanistic study found that ELF3 and H4K20me1 were enriched in the MARK4 promoter region. si-ELF3 attenuated MARK4 promoter activity and augmented the inhibitory effect of SET8 on MARK4 promoter activity. Furthermore, SET8 downregulation and ELF3 upregulation were confirmed in diabetic patients and rats. In conclusion, ELF3 interacted with SET8 to modulate MARK4 expression, which participated in hyperglycaemia-mediated endothelial NLRP3 inflammasome activation.

Purpose: The influence of prior failed kidney transplants on outcomes of peritoneal dialysis (PD) is unclear. Thus, we conducted a systematic review and meta-analysis to compare the outcomes of patients initiating PD after a failed kidney transplant with those initiating PD without a prior history of kidney transplantation. Methods: We searched PubMed, Embase, CENTRAL, and Google Scholar databases from inception until 25 November 2020. Our meta-analysis considered the absolute number of events of mortality, technical failures, and patients with peritonitis, and we also pooled multi-variable adjusted hazard ratios (HR). Results: We included 12 retrospective studies. For absolute number of events, our analysis indicated no statistically significant difference in technique failure [RR, 1.14; 95% CI, 0.80-1.61; I 2 ¼52%; p ¼ 0.48], number of patients with peritonitis [RR, 1.13; 95% CI, 0.97-1.32; I 2 ¼5%; p ¼ 0.11] and mortality [RR, 1.00; 95% CI, 0.67-1.50; I 2 ¼63%; p ¼ 0.99] between the study groups. The pooled analysis of adjusted HRs indicated no statistically significant difference in the risk of technique failure [HR, 1.25; 95% CI, 0.88-1.78; I 2 ¼79%; p ¼ 0.22], peritonitis [HR, 1.04; 95% CI, 0.72-1.50; I 2 ¼76%; p ¼ 0.85] and mortality [HR, 1.24; 95% CI, 0.77-2.00; I 2 ¼66%; p ¼ 0.38] between the study groups. Conclusion: Patients with kidney transplant failure initiating PD do not have an increased risk of mortality, technique failure, or peritonitis as compared to transplant-naïve patients initiating PD. Further studies are needed to evaluate the impact of prior and ongoing immunosuppression on PD outcomes.

Objective. Chronic kidney disease (CKD) is a clinical collective term for kidney disease with glomerular filtration rate GFR < 60  mL/min for more than three months due to various factors and is usually associated with coronary heart disease and is also an independent risk factor for coronary heart disease. This study is aimed at systematically reviewing the influence of CKD on the outcomes of patients after percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs). Methods. The Cochrane Library, PubMed, Embase, China biomedical literature database (SinoMed), China National Knowledge Infrastructure, and Wanfang database were searched for case-control studies on the influence of CKD on outcomes after PCI for CTOs. After screening the literature, extracting data, and evaluating the quality of literature, RevMan 5.3 software was used for meta-analysis. Results. There were 11 articles with a total of 558,440 patients included. Meta-analysis results indicated that left ventricular ejection fraction (LVEF) level, diabetes, smoking, hypertension, coronary artery bypass grafting, angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), β-blockers, age, and renal insufficiency were the factors affecting outcomes after PCI for CTOs [risk ratio and 95% confidence interval were: 0.88 (0.86, 0.90), 0.96 (0.95, 0.96), 0.76 (0.59, 0.98), 1.39 (0.89, 2.16), 0.73 (0.38, 1.40), 0.24 (0.02, 3.9), 0.78 (0.77, 0.79), 0.81 (0.80, 0.82), and 1.50 (0.47, 4.79)]. Conclusion. LVEF level, diabetes, smoking, hypertension, coronary artery bypass grafting, ACEI/ARB, β-blockers, age, renal insufficiency, etc. are important risk factors for outcomes after PCI for CTOs. Controlling these risk factors is of great significance for the prevention, treatment, and prognosis of CKD.

Hyperglycaemia‐mediated endothelial‐to‐mesenchymal transition (EndMT) is involved in the occurrence and progression of cardiovascular complications in diabetic patients. Previous studies reported that AKT serine/threonine kinase 3 (AKT3) and Bric‐a‐brac/Tramtrack/Broad (BTB) and cap'n'collar (CNC) homology 1 (bach1) participates in endothelial injury and epithelial‐to‐mesenchymal transition. In the present study, we proposed that bach1 regulates AKT3 transcription, thus involved in hyperglycaemia‐mediated EndMT in vascular endothelium. Our results indicated that hyperglycaemia/high glucose increased AKT3 expression and induced EndMT in aorta of diabetic rats and hyperglycaemic human umbilical vein endothelial cells (HUVECs). Moreover, inhibition of AKT3 expression reversed high glucose‐mediated EndMT in HUVECs. Further, hyperglycaemia/high glucose augmented bach1 expression in aorta of diabetic rats and hyperglycaemic HUVECs. Furthermore, si‐bach1 countered high glucose‐induced AKT3 expression and EndMT in HUVECs. In addition, the effect of bach1 overexpression is similar to that of high glucose treatment, which was reversed by si‐AKT3. ChIP assays found bach1 enriched in the promoter region of AKT3. Bach1 overexpression augmented AKT3 promoter activity, which lost after specific binding site mutation. Bach1 was involved in hyperglycaemia‐induced EndMT via modulation of AKT3 transcription.