Background: Early-start peritoneal dialysis (PD) is an effective option for patients need unplanned dialysis. However, there are few studies on the long-term prognosis of early-start PD patients. Methods: In this retrospective study, 635 eligible patients from 1 March 1996 to 30 September 2016 were included, and divided into three groups according to the duration of break-in period: 3 days or less, 4-13 days and more than 14 days. Patients started PD within 2 weeks and after 2 weeks were defined as early-start and conventional-start, respectively. The primary outcome was all-cause mortality, and the secondary outcome measures were peritonitis free survival and technical survival. Mechanical and infectious complications in the first 180 days were also analyzed. Results: Early-start PD patients were more likely to have higher serum total carbon dioxide and creatinine levels and lower serum albumin, Kt/v, creatinine clearance (Ccr) and residual glomerular filtration rate (rGFR) levels at the start of PD. The median follow-up period was 30 months (interquartile range, 13-53 months). A worse survival was observed in the early-start group than that in the conventional-start group (p < 0.001), even adjustment for the covariates (HR 1.549, 95%CI 1.104-2.173, p ¼ 0.011). In the subgroup analysis, in patients commencing PD after 2006 early-start and conventional-start PD patients had comparable survival. No differences were observed in the rate of infectious and mechanical complications, peritonitis-free survival and technique survival between early-start and conventional-start PD patients. Conclusions: Early-start PD could be a safe and effective strategy for patients needing unplanned dialysis initiation with the progress of technology on PD.

Diabetic nephropathy (DN) is one of the leading causes of chronic kidney disease (CKD), during which hyperglycemia is composed of the major force for the deterioration to end-stage renal disease (ESRD). However, the underlying mechanism triggering the effect of hyperglycemia on DN is not very clear and the clinically available drug for hyperglycemia-induced DN is in need of urgent development. Here, we found that high glucose (HG) increased the activity of cyclin-dependent kinase 5 (CDK5) dependent on P35/25 and which upregulated the oxidative stress and apoptosis of mouse podocytes (MPC-5). TFP5, a 25-amino acid peptide inhibiting CDK5 activity, decreased the secretion of inflammation cytokines in serum and kidney, and effectively protected the kidney function in db/db mouse from hyperglycemia-induced kidney injuries. In addition, TFP5 treatment decreased HG-induced oxidative stress and cell apoptosis in MPC-5 cells and kidney tissue of db/db mouse. The principal component analysis (PCA) of RNA-seq data showed that MPC-5 cell cultured under HG, was well discriminated from that under low glucose (LG) conditions, indicating the profound influence of HG on the properties of podocytes. Furthermore, we found that HG significantly decreased the level of NGF and Sirt1, both of which correlated with CDK5 activity. Furthermore, knockdown of NGF was correlated with the decreased expression of Sirt1 while NGF overexpression leads to upregulated Sirt1 and decreased oxidative stress and apoptosis in MPC-5 cells, indicating the positive regulation between NGF and Sirt1 in podocytes. Finally, we found that K252a, an inhibitor of NGF treatment could undermine the protective role of TFP5 on hyperglycemia-induced DN in db/db mouse model. In conclusion, the CDK5-NGF/Sirt1 regulating axis may be the novel pathway to prevent DN progression and TFP5 may be a promising compound to improved hyperglycemia induced DN.

Recent advances of g-C3N4 including structure, preparation methods, exfoliation strategies and potential application in ammonium perchlorate are illustrated.

Islet β‐cell damage and dysfunction represent the pathophysiological basis of diabetes. Excessive activation of cyclin‐dependent kinase 5 (CDK5) is involved in the pathogenesis of type 2 diabetes mellitus (T2DM), although the exact mechanism remains unclear. Therefore, this study investigated the role of a CDK5 inhibitor (TFP5) in islet β‐cell damage under diabetic conditions by regulating the expression of CDK5 in vitro and in vivo. CDK5 was upregulated under high glucose conditions in vivo and in vitro, which resulted in inflammation, oxidative stress, and apoptosis of islet β‐cells, thereby decreasing insulin secretion. However, TFP5 treatment inhibited the overexpression of CDK5; reduced the inflammatory response, oxidative stress, and apoptosis of islet β cells; and restored insulin secretion. In conclusion, CDK5 is involved in islet β‐cell damage under high glucose conditions, and TFP5 may represent a promising candidate for the development of treatments for T2DM.