Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.

基于HRP系统的医用耗材精细化管理模式实践探索

目的在医用耗材零加成、疾病诊断相关分组付费改革的实施背景下,探索医用耗材精细化管理模式,为公立医院高质量发展提供保障。方法以北京市某公立三级综合医院为研究对象,基于医院资源规划(Hospital Resource Planning,HRP)系统物资管理模块信息联通形成的数据,以规范临床用耗行为为导向,探索在医院运营管理委员会、医用耗材管理委员会领导下,以物资管理部门为主导,与医务、护理、医保、绩效等管理部门协同联动,以“精细管理、控制成本、优化结构”的理念为主线,对医用耗材目录、医用耗材申领、医用耗材消耗以及医用耗材监测进行精细化管理的模式。比较2023年2-7月与2021年同期的耗材成本、收入结构,来检验基于HRP系统的精细化管理模式的实践成效。结果经实践,该院医用耗材管理相关人员的精细化管理意识提升;2023年2-7月百元医疗收入消耗卫生材料(不含药品收入)相较2021年同期明显降低,差异有统计学意义(P<0.001),耗材成本控制初见成效;2023年2-7月医院耗占比相较2021年同期明显降低,医疗服务收入占比相较2021年同期明显升高,差异均有统计学意义(均P<0.001),收入结构有所改善。结论基于HRP系统的医用耗材精细化管理模式,可有效控制成本,促进收入结构优化,降低管理风险,可为公立医院耗材控制提供参考。

Evaluation of Glutathione Peroxidase Enzymatic Activity in Seminal Plasma of Patients Treated at the Institute Pasteur in Cote d’Ivoire

Glutathione peroxidase (GPx) is an antioxidant that plays an important role in the maintenance of male fertility. The aim of this study was to compare the profile of enzymatic activity of glutathione peroxidase in the seminal plasma of normozoosperm and those of pathological sperm. Thus, the activity of glutathione peroxidase was determined in the seminal plasma of 20 normozoosperms, 9 azoosperms and 31 oligoasthenoteratozoosperms. It was 37.58 ± 3.14 U/L in normozoosperms, 39.39 ± 2.27 U/L in oligoasthenoteratozoosperms, and 29.77 ± 2.62 U/L in azoosperms. The mean GPx enzyme activity of normozoosperms did not differ significantly from that of oligoasthenoteratozoosperms and azoosperms. In contrast, comparison of enzyme activity between abnormal sperms gave a significant difference. This study showed that glutathione peroxidase enzymatic activity is not related to sperm quality.

基于HRP技术的医院智慧报销管理系统的建设与实践

随着医疗保险制度的改革和发展,医院报销管理系统在医疗机构中扮演着越来越重要的角色。文章基于HRP系统的理论框架,探讨了医院报销管理系统的建设与实践。研究旨在通过医院智慧报销管理系统的建设,提升医院的精细化管理水平,推动医院高质量发展,以费用报销为抓手,实现与全面预算、经济合同、资产物资、人力资源等子系统的互联互通、数据共享,实现医院运营管理一体化、信息化、数字化。

Evaluation of combined detection of nuclear factor erythroid 2-related factor 2 and glutathione peroxidase 4 in primary hepatic carcinoma and preliminary exploration of pathogenesis

This study aims to analyze the clinical significance and mechanism of nuclear factor erythroid 2-related factor 2(NRF2)and glutathione peroxidase 4(GPX4)in primary hepatic carcinoma(PHC).Methods:The expression of NRF2 and GPX4 in peripheral blood of patients with PHC was determined to analyze the diagnostic value of the two combined for PHC.The prognostic significance of NRF2 and GPX4 was evaluated by 3-year followup.Human liver epithelial cells THLE-2 and human hepatocellular carcinoma cells HepG2 were purchased,and the expression of NRF2 and GPX4 in the cells was determined.NRF2 and GPX4 aberrant expression vectors were constructed and transfected into HepG2,and changes in cell proliferation and invasion capabilities were observed.Results:The expression of NRF2 and GPX4 in patients with PHC was higher than that in patients with LC or VH(p<0.05),and the two indicators combined was excellent in diagnosing PHC.Moreover,patients with high expression of NRF2 and GPX4 had a higher risk of death(p<0.05).In in vitro experiments,both NRF2 and GPX4 expression was elevated in HepG2(p<0.05).HepG2 activity was enhanced by increasing the expression of the two,vice versa(p<0.05).Conclusion:NRF2 and GPX4 combined is excellent in diagnosing PHC,and promotes the malignant development of PHC.

Glutathione peroxidase mimicry of diphenyl diselenide: Plausible contribution of proteins’ thiols

Organoseleniums are a class of compounds attracting attention across the globe owing to their Glutathione peroxidase(GPx)mimicry,which confers on them a strong antioxidant activity.Diphenyl diselenide(DPDS)is an Organoselenium whose GPx mimetic property has been suggested to rely on the oxidation of non-protein or protein thiols critical to the activities of some sulfhydryl enzymes.This study,therefore investigated the GPx mimic/antioxidant property of DPDS as well as the role of thiols of two key sulfhydryl enzymes,cerebral Na^(+)/K^(+)-ATPase(sodium pump)and hepatic delta-aminolevulinic acid dehydratase(δ-ALAD)in the GPx mimicry of DPDS.Albino Wistar rats were euthanized,and the liver and brain were removed and used to assay for the effect of DPDS on lipid peroxidation induced by two prooxidants[Fe2^(+)(10μM)and H2O2,(1 mM)]as well as the activities of the sulfhydryl enzymes.The results revealed that DPDS profoundly(P<0.05)counteracted Fe2^(+)and H2O2-induced lipid peroxidation in the rats’hepatic and cerebral tissues.Furthermore,the results of assay systems for lipid peroxidation and sodium pump revealed that DPDS inhibited Na^(+)/K^(+)-ATPase and lipid peroxidation in the brain tissue homogenates in the same reaction system.A similar result was obtained in the assay system for lipid peroxidation and hepaticδ-ALAD as DPDS simultaneously inhibited the enzyme’s activity and lipid peroxidation.This suggests that the GPx mimetic property of DPDS may be linked to the enzymes’loss of activity,which further validates the suggestions that the enzymes’inhibition,as well as the antioxidant action of DPDS,rely on the oxidation of critical thiols of the enzymes.However,the GPx mimicry of DPDS should be investigated in the presence of thiol-blocking or oxidizing agents in biological systems in order to further ascertain the role of protein thiols.

HRP系统在公立医院固定资产管理中的应用研究

本文结合公立医院自身发展,分析HRP系统在固定资产管理中存在的基础数据信息缺乏统一标准、业务流程缺乏整体规划、数据挖掘不充分等问题,针对性地提出制定统一标准化信息、规范各部门各业务模块管理流程、重视数据准确性互通性等对策建议,推动信息一体化建设,从而有效助力公立医院固定资产的精细化管理。

HRP系统在医院财务管理中的应用研究

随着信息技术的快速发展,医院财务管理面临越来越多的挑战,如资金利用效率低、成本控制不够精准等。基于此,概述了HRP系统,阐述了HRP系统在医院财务管理中的作用,分析了HRP系统在医院财务管理中面临的挑战,提出了应用建议。

基于HRP环境背景下医院预算管理思路探究

在我国医疗改革持续深入的时代环境下,越来越多的医院增强了对预算管理工作的重视程度,也能够在日常的管理工作中采用更为现代化的模式提升这一工作的质量。HRP是新时期医疗行业主要使用的管理模式,其与医院的管理工作形成了更为紧密的联系。基于HRP环境背景下优化医院的预算管理工作,不仅可以提升医院预算管理工作的效益,还可以使医院实现可持续发展。本文将依据相关研究成果以及工作实践经验,从多个角度分析并探讨了HRP环境背景下医院预算管理中存在的问题、管理架构的主要内容以及优化措施。最终希望通过本文的分析探讨,能够使广大医院预算管理工作的相关参与主体有所启发。

HRP环境下医院财务内部控制优化分析

随着医疗行业的快速发展和HRP系统的广泛应用,医院财务内部控制面临着新的挑战和机遇。文章通过分析HRP环境下医院财务内部控制的优势与特征,探讨了在HRP环境下医院财务内部控制的优化分析,根据HRP环境下医院财务内部控制的情况提出了相应的优化措施,旨在提高医院财务内部控制的效率和效果,确保医院的财务安全和稳定发展。

HRP环境下管理会计与内部控制在医院财务管理工作中的融合分析

HRP环境下医院能否运用科学的管理理论和方法,提高医院的竞争力,已经是医院未来可持续发展的重要课题。当前,医院财务管理面临着诸多问题,在管理会计与内部控制有效融合的情况下,可有效提升医院财务管理水平,优化资源配置,以及提高经济效益和社会效益。本文将从HRP环境的特征出发,探讨管理会计与内部控制在医院财务管理工作中的融合路径。

基于HRP系统的N医院全面预算管理研究

医院全面预算管理信息化已经成为趋势,文章以N医院进行研究,以医院资源计划系统(Hospital Resource Planning,简称HRP)为工具,对研究我国公立医院全面预算管理有重要的现实意义。结合N医院现状及存在问题,构建并实施了HRP系统下的全面预算管理体系,提升N医院全面预算管理水平。基于HRP系统对预算各方面工作提出实施方案,优化全面预算管理工作、加强医院资金合理化管控、解决目前N医院全面预算管理存在的问题。

HRP背景下公立医院预算信息化实施路径

随着医疗体制改革的深入推进,医院管理现代化已成为公立医院不可或缺的任务之一。尤其是基于HRP系统背景来看,公立医院加快了信息化管理体系建设进程。预算作为医院管理的重要组成部分,信息化的推进可以提高医院管理的效率和精度,从而解决这些问题。通过预算信息化,医院可以实现预算编制、执行、监控和分析等管理环节的自动化,提高管理效率,优化管理流程,实现医院管理的现代化。文章先对HRP系统进行了阐述,分析了HRP背景下研究公立医院推进预算信息化的重要意义,以及当前公立医院预算管理中存在的问题,再以Q医院为例,提出具体的实施路径,以期为提高公立医院预算管理水平提供一些参考借鉴。

HRP环境下医院成本核算和绩效分配的改进与完善

近年来,越来越多的公立医院开始建设和应用HRP系统,将各种医疗系统信息资源进行整合,协调统筹人力资源管理、财务管理、物流资产管理、成本管理、绩效管理等各项工作,搭建具有医院特色的一体化运营管理平台,更好地服务医院精细化管理,促进医院高质量发展。本文从某三甲公立医院HRP系统的实际运行情况出发,对成本管理和绩效管理中的应用成果及存在的问题进行详细分析,探究未来的优化策略。

基于HRP系统的医用检验试剂精细化管理实践探索

在现代化医院高质量发展的要求下,医用检验试剂的管理直接影响着诊疗服务质量以及医院成本管控。本文基于医院HRP系统,借助信息化技术支持,通过业务流程再造革新医用检验试剂管理方式,形成了计划与采购、供应与验收、领用与库存三大主要功能的可追溯、可视化的全流程精细化管理模式。HRP系统能有效提高工作效率,降低医院人工成本、试剂浪费成本,促进医院信息化建设和精细化管理水平显著提升。

Effects of Hg^(2+) on Isozymes of Peroxidase,Catalase and Superoxide Dismutase in Wheat Seedlings

[Objective] This work was aimed to explore the mechanism of Hg2+ toxicity on plants.[Method]Activities of peroxidase(POD),catalase(CAT)and superoxide dismutase(SOD)were investigated in wheat(Triticum aestivum L.)seedlings under Hg2+ stress at different concentrations.[Result]① There were no obvious effects on the growth of seedlings when the concentration of Hg2+ was lower than 0.10 mmol/L.However,toxic effects on the growth of seedling were observed when the concentration of Hg2+ was higher than 0.10 mmol/L.② Different tissues showed different resistant ability in response to Hg2+ stress.The leaves and roots of wheat seedlings were more insensitive to Hg2+ toxicity.③ CAT was more sensitive to Hg2+ stress compared to POD and SOD.[Conclusion]The toxic effect was related to the concentration of Hg2+(0.10 mmol/L).The higher concentration of Hg2+ could affect the expression of POD,CAT,and SOD isozymes in the leaves,roots of wheat seedlings and germinated seeds,which further affect the normal metabolism of membrane lipid and inhibit the growth of wheat seedlings at last.

Effects of Catalase and Ascorbate Peroxidase on the Root Growth of Rice under Cadmium Stress

[Objective] The research aimed to study the correlations between catalase（CAT） and ascorbate peroxidase（ASP） and the growth and development of rice roots under cadmium stress.[Method] Taking rice variety Zhonghua No.11 as materials,the changes of rice seedlings under the treatment conditions of Cd,Cd＋CAT inhibitor,Cd＋APX inhibitor were studied.[Result] Under Cd stress,inhibition of CAT activity caused the significant inhibition on the growth of aerial parts,decreased the number of adventitious roots and lateral roots,but it can significant promote the elongation growth of adventitious roots and lateral roots.Moreover,the length of the first lateral root from root tip on the primary roots and adventitious roots was also increased than control.When APX activity was inhibited,the growth changes of rice were similar with that treated by CAT inhibitor.[Conclusion] CAT and APX may play important roles in the regulation of rice root system growth in both non-stress and Cd-stressed rice

Hydrogen Peroxide Sensor Based on Horseradish Peroxidase Combined with CaCO_3 Microspheres and Gold Nanoparticles

Direct electrochemistry and electrocatalysis of horseradish peroxidase（HRP） were achieved by entrapping the enzyme between CaCO3 microspheres and gold nanoparticles through forming sandwich configuration （CaCO3-HRP-AuNPs）. Polyanion, poly（styrene sulfonate）（PSS）, was hybrid with CaCO3 microspheres to increase the surface negative charges for binding with HRP through electrostatic interaction. After the bioconjugate CaCO3 PSS-HRP was entrapped in chitosan based sol-gel（CS-GPTMS） film, HRP was encapsulated by in situ formation of an outer layer of AuNPs through electrochemical reduction of HAuCl4. The composite film containing AuNPs, CaCO3-PSS-HRP bioconjugates and CS-GPTMS can provide favorable microenvironment for HRP to perform direct electron transfer at glassy carbon electrode（GCE）. HRP retained its bioelectrocatalytic activity and lead to sensitive and fast amperometric response for the determination of H2O2. H2O2 could be detected in a very wide linear range from 5.0×10-6 mol/L to 7.1×10-2 mol/L. The sandwich configuration of CaCO3-biomolecules-AuNPs could serve as a versatile platform for enzyme immobilization and biosensing.

Regulation of Heat Shock Factor AtHsfA1a on Ascorbate Peroxidase under Heat Stress in Arabidopsis thaliana

[Objective] This study was conducted to investigate the regulation of heat shock factor AtHsfA1a on ascorbate peroxidase under heat stress in Arabidopsis thaliana. [Method] After heat stress treatment on transgenetic A. thaliana with silenced endogenetic AtHsfA1a gene and wild A. thaliana plants as materials, the change in activity of APX enzyme was analyzed by spectrophotometry, the expression level of APX gene was investigated by real-time fluorescent quantitative PCR, and the binding condition of AtHsfAla with the promoter region of APX gene was analyzed by chromatin immunoprecipitation assay. [Result] The activity and mRNA level of APX in plants with silenced endogenetic AtHsfAla gene were higher than those in wild plants. Fragments of the promoter region of APX gene were not screened from the plants with silenced endogenetic AtHsfA1a gene, but found in wild plants. [Conclusion] This study provides a theoretical basis for the understanding of the important role of AtHsfAla in resistance to stress in plant, and is of great significance to the revealing of mechanism of resistance to stress in plant.

基于HRP的公立医院内部控制体系建设研究

内部控制体系建设是公立医院实现高质量发展的重要手段,医院资源计划(HRP)有助于公立医院内部控制水平的提升。但公立医院HRP建设面临着一些问题,包括建设周期过长、观念转变困难、系统功能缺失、模块工作受限、业务流程不畅及系统风险增加等。医院基于HRP的内部控制体系建设有助于在有限的资源下更有效地发挥管理效能并控制风险。其主要建设步骤有识别资源、确定医院内部流程、确定控制点、设计内部控制措施和监管等。可以通过加强系统培训、提升内部控制认识,强化系统流程管控作用、控制减少风险发生,完善制度建设、规范内部控制质量等手段,发挥HRP在内部控制管理中的作用,整合利用医院内部资源,达到打破“信息孤岛”、控制医院成本和增加医院效益的总体目标。