1.Effects of seasonal changes on peritoneal dialysis associated peritonitis in peritoneal dialysis patients
Shaogui ZHANG ; Huiping ZHAO ; Bei WU ; Lixia LU ; Jie QIAO ; Chuncui MEN ; Li ZUO ; Mei WANG
Chinese Journal of Nephrology 2017;33(7):488-494
Objectives To investigate the effects of seasonal changes on peritoneal dialysis associated peritonitis (PDAP) in patients on peritoneal dialysis (PD),and to provide evidence for clinical prevention and treatment of PDAP.Methods All episodes of PD-related peritonitis during clinic follow-up in maintenance PD patients from Jan 1st,2007 to Dec 31st,2015 in Peking University People's Hospital were reviewed.The incidence of peritonitis,laboratory indexes,pathogens and clinical outcomes in different seasons were recorded and analyzed.One-way ANOVA and chi square test were employed to compare the incidence of PDAP and related data in different seasons,and Pearson correlation was used to analyze correlations between PDAP rate and monthly mean temperature and mean humidity.Results During nine years,a total of 119 PD patients occurred 190 times of peritonitis during home PD.The PDAP rate in summer was the highest,0.21 episodes/year,followed by spring (0.16 episodes/year) and autumn (0.16 episodes/risk year),but there was no significant difference among peritonitis rates in four seasons.There were significant positive correlation between monthly mean temperature,monthly mean humidity and the peritonitis rate (mean temperature:r=0.828,P < 0.01;mean humidity r=0.657,P < 0.05).(2) As for bacteria,in Summer the PDAP rate caused by Staphylococcus aureus and Coagulase negative staphylococcus (CoNS),and Gram-negative bacteria was higher than that in other seasons,but there was no statistical difference.There were significant positive correlation between monthly mean temperature,mean humidity and the rate of CoNS peritonitis (mean temperature:r=0.704,P < 0.05;mean humidity:r=0.607,P < 0.05).(3) There were no statistical difference among results of PD related peritonitis in different seasons about general situation,clinical manifestation,causes of peritonitis and laboratory index before peritonitis episodes.PD procedure-related problems were the main cause of peritonitis in summer and autumn.(4) The cure rate of all peritonitis was 90%.The highest cure rate was in autumn and winter,while the lowest cure rate was in summer,but no statistical difference.Among the peritonitis episodes with treatment failure,52.6% occurred in summer.Conclusions There is some correlation between the rate of PDAP and seasons.Higher temperature and higher humidity were significantly correlated with higher peritonitis rate,especially the rate of CoNS peritonitis.The prognosis of PDAP in summer was relatively poor,with higher proportion of hospitalization and lower cure rate.
2.High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice.
Xiaojuan CHAO ; Mengwei NIU ; Shaogui WANG ; Xiaowen MA ; Xiao YANG ; Hua SUN ; Xujia HU ; Hua WANG ; Li ZHANG ; Ruili HUANG ; Menghang XIA ; Andrea BALLABIO ; Hartmut JAESCHKE ; Hong-Min NI ; Wen-Xing DING
Acta Pharmaceutica Sinica B 2024;14(1):190-206
Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.