BACKGROUND The association between congenital heart disease and chronic kidney disease is well known.Various mechanisms of kidney damage associated with congenital heart disease have been established.The etiology of k...BACKGROUND The association between congenital heart disease and chronic kidney disease is well known.Various mechanisms of kidney damage associated with congenital heart disease have been established.The etiology of kidneydisease has commonly been considered to be secondary to focal segmental glomerulosclerosis(FSGS),however,this has only been demonstrated in case reports and not in observational or clinical trials.AIM To identify baseline and clinical characteristics,as well as the findings in kidney biopsies of patients with congenital heart disease in our hospital.METHODS This is a retrospective observational study conducted at the Nephrology Depart-ment of the National Institute of Cardiology“Ignacio Chávez”.All patients over 16 years old who underwent percutaneous kidney biopsy from January 2000 to January 2023 with congenital heart disease were included in the study.RESULTS Ten patients with congenital heart disease and kidney biopsy were found.The average age was 29.00 years±15.87 years with pre-biopsy proteinuria of 6193 mg/24 h±6165 mg/24 h.The most common congenital heart disease was Fallot’s tetralogy with 2 cases(20%)and ventricular septal defect with 2(20%)cases.Among the 10 cases,one case of IgA nephropathy and one case of membranoproliferative glomerulonephritis associated with immune complexes were found,receiving specific treatment after histopathological diagnosis,delaying the initiation of kidney replacement therapy.Among remaining 8 cases(80%),one case of FSGS with perihilar variety was found,while the other 7 cases were non-specific FSGS.CONCLUSION Determining the cause of chronic kidney disease can help in delaying the need for kidney replacement therapy.In 2 out of 10 patients in our study,interventions were performed,and initiation of kidney replacement therapy was delayed.Prospective studies are needed to determine the usefulness of kidney biopsy in patients with congenital heart disease.展开更多
BACKGROUND Glomerular diseases rank third among the causes of chronic kidney disease worldwide and in Indonesia,and its burden continues to increase,especially regarding the sociodemographic index.Kidney biopsy remain...BACKGROUND Glomerular diseases rank third among the causes of chronic kidney disease worldwide and in Indonesia,and its burden continues to increase,especially regarding the sociodemographic index.Kidney biopsy remains the gold standard for the diagnosis and classification of glomerular diseases.It is crucial for developing treatment plans,determining the degree of histologic changes,and identifying disease relapse.AIM To describe the patterns of biopsy-proven kidney diseases in adult patients.METHODS We retrospectively reviewed the demographic,histopathologic,clinical,and laboratory data of 75 adult patients with biopsy-proven kidney diseases at our institution recorded from 2017 to 2022.RESULTS Among the patients,43(57.3%)were females,and the mean age was 31.52 years±11.70 years.The most common histopathologies were lupus nephritis(LN)(33.3%),minimal change disease(MCD)(26.7%),and focal segmental glomerulosclerosis(10.7%).LN(41.7%)was frequently diagnosed in women and MCD(28.1%)in men.The most common cause of nephritic syndrome was LN(36.7%)and of nephrotic syndrome was MCD(40%).CONCLUSION Different kidney disease patterns were observed in different sexes,age categories,clinical syndromes,and biopsy dates relative to the coronavirus disease 2019 pandemic.展开更多
BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differenti...BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.展开更多
BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated ...BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.展开更多
Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with...Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with CKD and its subtypes in China.Methods:The study included 475,376 adults from the China Kadoorie Biobank aged 30-79 years during 2004-2008 at baseline.An interviewer-administered questionnaire was used to collect the information about PA,which was quantified as metabolic equivalent of task hours per day(MET-h/day)and categorized into 4 groups based on quartiles.Cox regression was used to analyze the association between PA and CKD risk.Results:During a median follow-up of 12.1 years,5415 incident CKD cases were documented,including 1159 incident diabetic kidney disease(DKD)cases and 362 incident hypertensive nephropathy(HTN)cases.Total PA was inversely associated with CKD risk,with an adjusted hazard ratio(HR,95%confidence interval(95%CI))of 0.83(0.75-0.92)for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile.Similar results were observed for risk of DKD and HTN,and the corresponding HRs(95%CIs)were 0.75(0.58-0.97)for DKD risk and 0.56(0.37-0.85)for HTN risk.Increased nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD,with HRs(95%CIs)of 0.80(0.73-0.88),0.85(0.77-0.94),and 0.85(0.76-0.95)in the highest quartile,respectively.Conclusion:PA,including nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA,was inversely associated with the risk of CKD,including DKD,HTN,and other CKD,and such associations were dose dependent.展开更多
Diabetic kidney disease(DKD)is a common complication of diabetes mellitus that contributes to the risk of end-stage kidney disease(ESKD).Wide glycemic var-iations,such as hypoglycemia and hyperglycemia,are broadly fou...Diabetic kidney disease(DKD)is a common complication of diabetes mellitus that contributes to the risk of end-stage kidney disease(ESKD).Wide glycemic var-iations,such as hypoglycemia and hyperglycemia,are broadly found in diabetic patients with DKD and especially ESKD,as a result of impaired renal metabolism.It is essential to monitor glycemia for effective management of DKD.Hemoglobin A1c(HbA1c)has long been considered as the gold standard for monitoring glycemia for>3 months.However,assessment of HbA1c has some bias as it is susceptible to factors such as anemia and liver or kidney dysfunction.Continuous glucose monitoring(CGM)has provided new insights on glycemic assessment and management.CGM directly measures glucose level in interstitial fluid,reports real-time or retrospective glucose concentration,and provides multiple glycemic metrics.It avoids the pitfalls of HbA1c in some contexts,and may serve as a precise alternative to estimation of mean glucose and glycemic variability.Emerging studies have demonstrated the merits of CGM for precise monitoring,which allows fine-tuning of glycemic management in diabetic patients.Therefore,CGM technology has the potential for better glycemic monitoring in DKD patients.More research is needed to explore its application and management in different stages of DKD,including hemodialysis,peritoneal dialysis and kidney transplantation.展开更多
BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To i...BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD.METHODS This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023.A questionnaire was formulated by literature review and expert consultation and included questions about age,sex,education level,per capita monthly household income,marital status,living condition,payment method,and hypertension.RESULTS Logistic regression analysis showed that patients aged 60-79 years[odds ratio(OR)=1.561,P=0.015]and≥80 years(OR=1.760,P=0.013),participants with middle to high school education(OR=0.820,P=0.027),divorced or widowed individuals(OR=1.37,P=0.032),self-funded patients(OR=2.368,P=0.008),and patients with hypertension(OR=2.011,P=0.041)had a higher risk of cognitive impairment.The risk of cognitive impairment was lower for those with a college degree(OR=0.435,P=0.034)and married individuals.CONCLUSION The risk factors affecting cognitive dysfunction are age,60-79 years and≥80 years;education,primary school education or less;marital status,divorced or widowed;payment method,selffunded;hypertension;and CKD.展开更多
Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Review...Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases.This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases,including Alzheimer's disease,Huntington's chorea,and Parkinson's disease.This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states.Therefore,inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.展开更多
Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exoso...Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.展开更多
Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signalin...Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.展开更多
Background:Climate change profoundly shapes the population health at the global scale.However,there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease...Background:Climate change profoundly shapes the population health at the global scale.However,there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease(CKD).Methods:In the present study,we studied the association of heat exposure with hospitalizations for cause-specific CKD using a national inpatient database in China during the study period of hot season from 2015 to 2018.Standard time-series regression models and random-effects Meta-analysis were developed to estimate the city-specific and national averaged associations at a 7 lag-day span,respectively.Results:A total of 768,129 hospitalizations for CKD was recorded during the study period.The results showed that higher temperature was associated with elevated risk of hospitalizations for CKD,especially in sub-tropical cities.With a 1℃ increase in daily mean temperature,the cumulative relative risks(RR)over lag 0-7 d were 1.008[95% confidence interval(CI)1.003-1.012]for nationwide.The attributable fraction of CKD hospitalizations due to high temperatures was 5.50%.Stronger associations were observed among younger patients and those with obstructive nephropathy.Our study also found that exposure to heatwaves was associated with added risk of hospitalizations for CKD compared to non-heatwave days(RR=1.116,95%CI 1.069-1.166)above the effect of daily mean temperature.Conclusions:Short-term heat exposure may increase the risk of hospitalization for CKD.Our findings provide insights into the health effects of climate change and suggest the necessity of guided protection strategies against the adverse effects of high temperatures.展开更多
Chronic kidney disease(CKD)is a major health concern today,requiring early and accurate diagnosis.Machine learning has emerged as a powerful tool for disease detection,and medical professionals are increasingly using ...Chronic kidney disease(CKD)is a major health concern today,requiring early and accurate diagnosis.Machine learning has emerged as a powerful tool for disease detection,and medical professionals are increasingly using ML classifier algorithms to identify CKD early.This study explores the application of advanced machine learning techniques on a CKD dataset obtained from the University of California,UC Irvine Machine Learning repository.The research introduces TrioNet,an ensemble model combining extreme gradient boosting,random forest,and extra tree classifier,which excels in providing highly accurate predictions for CKD.Furthermore,K nearest neighbor(KNN)imputer is utilized to deal withmissing values while synthetic minority oversampling(SMOTE)is used for class-imbalance problems.To ascertain the efficacy of the proposed model,a comprehensive comparative analysis is conducted with various machine learning models.The proposed TrioNet using KNN imputer and SMOTE outperformed other models with 98.97%accuracy for detectingCKD.This in-depth analysis demonstrates the model’s capabilities and underscores its potential as a valuable tool in the diagnosis of CKD.展开更多
Chronic kidney disease is commonly diagnosed in dogs,and clinical signs may be aggravated when infected agents are involved.In this case report,33 dogs with chronic kidney disease were clinically evaluated and serolog...Chronic kidney disease is commonly diagnosed in dogs,and clinical signs may be aggravated when infected agents are involved.In this case report,33 dogs with chronic kidney disease were clinically evaluated and serologically tested for Leptospira spp.,Ehrlichia canis,and Anaplasma phagocytophilum.The seroprevalence for Leptospira spp.was 39.4%.The most frequent serovars found were Pyrogenes,Canicola,Bratislava and Australis,with serological titers between 1:100 to 1:800.Clinical signs included fever,depression,decreased body condition,vomiting and hema‑turia.Signifcant laboratory fndings were anemia,leukocytosis,thrombocytopenia,increased liver enzymes,urea and creatinine,hyperbilirubinemia and hyperphosphatemia.All leptospira seronegative dogs were positive for one or both monitored homoparasites(i.e.,E.canis and A.phagocytophilum);only three leptospira seropositive dogs were positive for one or both hemoparasites.Findings also suggest that endemic hemoparasites of dogs should be moni‑tored in dogs with a kidney condition for a better clinical picture of the patients and therapeutic approach.展开更多
AIM:To investigate whether retinal nerve fiber layer defects(RNFLDs)is a potential risk factor for chronic kidney disease(CKD)in Chinese adults.METHODS:The Kailuan Eye Study was a populationbased study that included 1...AIM:To investigate whether retinal nerve fiber layer defects(RNFLDs)is a potential risk factor for chronic kidney disease(CKD)in Chinese adults.METHODS:The Kailuan Eye Study was a populationbased study that included 14440 participants.All participants underwent detailed assessments,RNFLDs were diagnosed using color fundus photographs.RESULTS:Overall,12507 participants[8533 males(68.23%)]had complete systemic examination data and at least one evaluable fundus photograph.RNFLDs were found in 621 participants[5.0%;95%confidence interval(CI):4.6%-5.34%],and 70 cases of multiple RNFLDs were found(11.27%).After adjusting multiple factors,RNFLDs was significantly associated with CKD severity,the ORs of CKD stage 3,stage 4 and stage 5 were 1.698,4.167,and 9.512,respectively.Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors,the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively.Furthermore,2294 participants had CKD(18.34%,95%CI:17.68%-18.99%).After adjusting for other factors,CKD presence was significantly correlated with the presence of RNFLDs.CONCLUSION:The strongest risk factors for RNFLDs are CKD and hypertension.Conversely,RNFLDs can be an ocular feature in patients with CKD.Fundoscopy can help detect systemic diseases,and assessment for RNFLDs should be considered in CKD patients.展开更多
Chaperone-mediated autophagy is one of three types of autophagy and is characterized by the selective degradation of proteins.Chaperone-mediated autophagy contributes to energy balance and helps maintain cellular home...Chaperone-mediated autophagy is one of three types of autophagy and is characterized by the selective degradation of proteins.Chaperone-mediated autophagy contributes to energy balance and helps maintain cellular homeostasis,while providing nutrients and support for cell survival.Chaperone-mediated autophagy activity can be detected in almost all cells,including neurons.Owing to the extreme sensitivity of neurons to their environmental changes,maintaining neuronal homeostasis is critical for neuronal growth and survival.Chaperone-mediated autophagy dysfunction is closely related to central nervous system diseases.It has been shown that neuronal damage and cell death are accompanied by chaperone-mediated autophagy dysfunction.Under certain conditions,regulation of chaperone-mediated autophagy activity attenuates neurotoxicity.In this paper,we review the changes in chaperone-mediated autophagy in neurodegenerative diseases,brain injury,glioma,and autoimmune diseases.We also summarize the most recent research progress on chaperone-mediated autophagy regulation and discuss the potential of chaperone-mediated autophagy as a therapeutic target for central nervous system diseases.展开更多
Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effec...Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.展开更多
Acute kidney injury(AKI)and chronic kidney disease(CKD)are significant public health issues associated with a long-term increase in mortality risk,resulting from various etiologies including renal ischemia,sepsis,drug...Acute kidney injury(AKI)and chronic kidney disease(CKD)are significant public health issues associated with a long-term increase in mortality risk,resulting from various etiologies including renal ischemia,sepsis,drug toxicity,and diabetes mellitus.Numerous preclinical models have been developed to deepen our understanding of the pathophysiological mechanisms and therapeutic approaches for kidney diseases.Among these,rodent models have proven to be powerful tools in the discovery of novel therapeutics,while the development of kidney organoids has emerged as a promising advancement in the field.This review provides a comprehensive analysis of the construction methodologies,underlying biological mechanisms,and recent therapeutic developments across different AKI and CKD models.Additionally,this review summarizes the advantages,limitations,and challenges inherent in these preclinical models,thereby contributing robust evidence to support the development of effective therapeutic strategies.展开更多
In this editorial,we comment on the article by Zhang et al.Chronic kidney disease(CKD)presents a significant challenge in managing glycemic control,especially in diabetic patients with diabetic kidney disease undergoi...In this editorial,we comment on the article by Zhang et al.Chronic kidney disease(CKD)presents a significant challenge in managing glycemic control,especially in diabetic patients with diabetic kidney disease undergoing dialysis or kidney transplantation.Conventional markers like glycated haemoglobin(HbA1c)may not accurately reflect glycemic fluctuations in these populations due to factors such as anaemia and kidney dysfunction.This comprehensive review discusses the limitations of HbA1c and explores alternative methods,such as continuous glucose monitoring(CGM)in CKD patients.CGM emerges as a promising technology offering real-time or retrospective glucose concentration measure-ments and overcoming the limitations of HbA1c.Key studies demonstrate the utility of CGM in different CKD settings,including hemodialysis and peritoneal dialysis patients,as well as kidney transplant recipients.Despite challenges like sensor accuracy fluctuation,CGM proves valuable in monitoring glycemic trends and mitigating the risk of hypo-and hyperglycemia,to which CKD patients are prone.The review also addresses the limitations of CGM in CKD patients,emphasizing the need for further research to optimize its utilization in clinical practice.Altogether,this review advocates for integrating CGM into managing glycemia in CKD patients,highlighting its superiority over traditional markers and urging clinicians to consider CGM a valuable tool in their armamentarium.展开更多
Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor dete...Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.展开更多
BACKGROUND Diabetic kidney disease(DKD)is a prevalent complication of diabetes that often requires hemodialysis for treatment.In the field of nursing,there is a growing recognition of the importance of humanistic care...BACKGROUND Diabetic kidney disease(DKD)is a prevalent complication of diabetes that often requires hemodialysis for treatment.In the field of nursing,there is a growing recognition of the importance of humanistic care,which focuses on the holistic needs of patients,including their emotional,psychological,and social well-being.However,the application of humanistic nursing in the context of hemodialysis for DKD patients remains relatively unexplored.AIM To explore the experience of humanistic nursing in hemodialysis nursing for DKD patients.METHODS Ninety-six DKD patients treated with hemodialysis from March 2020 to June 2022 were included in the study and divided into the control cluster(48 cases)and the study cluster(48 cases)according to different nursing methods;the control cluster was given routine nursing and the study cluster was given humanized nursing.The variances of negative emotion mark,blood glucose,renal function,the incidence of complications,life mark and nursing satisfaction before and after nur-sing were contrasted between the two clusters.RESULTS No significant difference in negative emotion markers between the two clusters were observed before nursing(P>0.05),and the negative emotion markers of the two clusters decreased after nursing.The Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale markers were lower in the study cluster than the control cluster.The healing rate of patients in the study cluster was significantly higher than the control cluster(97.92%vs 85.42%,P<0.05).Blood glucose parameters were not significantly different between the groups prior to nursing(P>0.05).However,after nursing,blood urea nitrogen and serum creatinine(SCr)levels in the study cluster were lower than those in the control cluster(P<0.05).The incidence rate of complications was significantly lower in the study group compared to the control cluster(6.25%vs 20.83%,P<0.05).There was no significant difference in the life markers between the two clusters before nursing.While the life markers increased after nursing for both groups,the 36-item health scale markers in the study cluster were higher than those within the control cluster(P<0.05).Finally,the nursing satisfaction rate was 93.75% in the study cluster,compared to 75% in the control cluster(P<0.05).CONCLUSION In hemodialysis for DKD patients,the implementation of humanistic nursing achieved ideal results,effectively reducing patients’psychological negative emotion markers so that they can actively cooperate with the diagnosis and nursing,facilitate the control of blood glucose and the maintenance of residual renal function,reduce the occurrence of complications,and finally enhance the life quality and nursing satisfaction of patients.It is worthy of being widely popularized and applied.展开更多
文摘BACKGROUND The association between congenital heart disease and chronic kidney disease is well known.Various mechanisms of kidney damage associated with congenital heart disease have been established.The etiology of kidneydisease has commonly been considered to be secondary to focal segmental glomerulosclerosis(FSGS),however,this has only been demonstrated in case reports and not in observational or clinical trials.AIM To identify baseline and clinical characteristics,as well as the findings in kidney biopsies of patients with congenital heart disease in our hospital.METHODS This is a retrospective observational study conducted at the Nephrology Depart-ment of the National Institute of Cardiology“Ignacio Chávez”.All patients over 16 years old who underwent percutaneous kidney biopsy from January 2000 to January 2023 with congenital heart disease were included in the study.RESULTS Ten patients with congenital heart disease and kidney biopsy were found.The average age was 29.00 years±15.87 years with pre-biopsy proteinuria of 6193 mg/24 h±6165 mg/24 h.The most common congenital heart disease was Fallot’s tetralogy with 2 cases(20%)and ventricular septal defect with 2(20%)cases.Among the 10 cases,one case of IgA nephropathy and one case of membranoproliferative glomerulonephritis associated with immune complexes were found,receiving specific treatment after histopathological diagnosis,delaying the initiation of kidney replacement therapy.Among remaining 8 cases(80%),one case of FSGS with perihilar variety was found,while the other 7 cases were non-specific FSGS.CONCLUSION Determining the cause of chronic kidney disease can help in delaying the need for kidney replacement therapy.In 2 out of 10 patients in our study,interventions were performed,and initiation of kidney replacement therapy was delayed.Prospective studies are needed to determine the usefulness of kidney biopsy in patients with congenital heart disease.
文摘BACKGROUND Glomerular diseases rank third among the causes of chronic kidney disease worldwide and in Indonesia,and its burden continues to increase,especially regarding the sociodemographic index.Kidney biopsy remains the gold standard for the diagnosis and classification of glomerular diseases.It is crucial for developing treatment plans,determining the degree of histologic changes,and identifying disease relapse.AIM To describe the patterns of biopsy-proven kidney diseases in adult patients.METHODS We retrospectively reviewed the demographic,histopathologic,clinical,and laboratory data of 75 adult patients with biopsy-proven kidney diseases at our institution recorded from 2017 to 2022.RESULTS Among the patients,43(57.3%)were females,and the mean age was 31.52 years±11.70 years.The most common histopathologies were lupus nephritis(LN)(33.3%),minimal change disease(MCD)(26.7%),and focal segmental glomerulosclerosis(10.7%).LN(41.7%)was frequently diagnosed in women and MCD(28.1%)in men.The most common cause of nephritic syndrome was LN(36.7%)and of nephrotic syndrome was MCD(40%).CONCLUSION Different kidney disease patterns were observed in different sexes,age categories,clinical syndromes,and biopsy dates relative to the coronavirus disease 2019 pandemic.
基金Supported by the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China,No.LHDMZ22H050001the Construction of Key Projects by Zhejiang Provincial Ministry,No.WKJ-ZJ-2302+3 种基金the Zhejiang Province Chinese Medicine Modernization Program,No.2020ZX001the Key Project of Scientific Research Foundation of Chinese Medicine,No.2022ZZ002the“Pioneer”and“LeadingGoose”R&D Program of Zhejiang,No.2022C03118 and 2023C03075the Key Project of Basic Scientific Research Operating Funds of Hangzhou Medical College,No.KYZD202002.
文摘BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.
基金Supported by the Nature Science Foundation of Hebei Province,No.H2023104011.
文摘BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.
基金supported by National Natural Science Foundation of China(82192900,82192901,82192904,81941018,and 91846303)Peking University Medicine Seed Fund for Interdisciplinary Research(BMU2022MX025)+5 种基金the Fundamental Research Funds for the Central Universitiessupported by a grant from the Kadoorie Charitable Foundation in Hong Kongsupported by grants from the UK Wellcome Trust(212946/Z/18/Z,202922/Z/16/Z,104085/Z/14/Z,and 088158/Z/09/Z)the National Key R&D Program of China(2016YFC0900500)National Natural Science Foundation of China(81390540)Chinese Ministry of Science and Technology(2011BAI09B01)。
文摘Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with CKD and its subtypes in China.Methods:The study included 475,376 adults from the China Kadoorie Biobank aged 30-79 years during 2004-2008 at baseline.An interviewer-administered questionnaire was used to collect the information about PA,which was quantified as metabolic equivalent of task hours per day(MET-h/day)and categorized into 4 groups based on quartiles.Cox regression was used to analyze the association between PA and CKD risk.Results:During a median follow-up of 12.1 years,5415 incident CKD cases were documented,including 1159 incident diabetic kidney disease(DKD)cases and 362 incident hypertensive nephropathy(HTN)cases.Total PA was inversely associated with CKD risk,with an adjusted hazard ratio(HR,95%confidence interval(95%CI))of 0.83(0.75-0.92)for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile.Similar results were observed for risk of DKD and HTN,and the corresponding HRs(95%CIs)were 0.75(0.58-0.97)for DKD risk and 0.56(0.37-0.85)for HTN risk.Increased nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD,with HRs(95%CIs)of 0.80(0.73-0.88),0.85(0.77-0.94),and 0.85(0.76-0.95)in the highest quartile,respectively.Conclusion:PA,including nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA,was inversely associated with the risk of CKD,including DKD,HTN,and other CKD,and such associations were dose dependent.
基金Supported by Natural Science Foundation of Zhejiang Province,No.LY23H050005and Zhejiang Medical Technology Project,No.2022RC009.
文摘Diabetic kidney disease(DKD)is a common complication of diabetes mellitus that contributes to the risk of end-stage kidney disease(ESKD).Wide glycemic var-iations,such as hypoglycemia and hyperglycemia,are broadly found in diabetic patients with DKD and especially ESKD,as a result of impaired renal metabolism.It is essential to monitor glycemia for effective management of DKD.Hemoglobin A1c(HbA1c)has long been considered as the gold standard for monitoring glycemia for>3 months.However,assessment of HbA1c has some bias as it is susceptible to factors such as anemia and liver or kidney dysfunction.Continuous glucose monitoring(CGM)has provided new insights on glycemic assessment and management.CGM directly measures glucose level in interstitial fluid,reports real-time or retrospective glucose concentration,and provides multiple glycemic metrics.It avoids the pitfalls of HbA1c in some contexts,and may serve as a precise alternative to estimation of mean glucose and glycemic variability.Emerging studies have demonstrated the merits of CGM for precise monitoring,which allows fine-tuning of glycemic management in diabetic patients.Therefore,CGM technology has the potential for better glycemic monitoring in DKD patients.More research is needed to explore its application and management in different stages of DKD,including hemodialysis,peritoneal dialysis and kidney transplantation.
文摘BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD.METHODS This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023.A questionnaire was formulated by literature review and expert consultation and included questions about age,sex,education level,per capita monthly household income,marital status,living condition,payment method,and hypertension.RESULTS Logistic regression analysis showed that patients aged 60-79 years[odds ratio(OR)=1.561,P=0.015]and≥80 years(OR=1.760,P=0.013),participants with middle to high school education(OR=0.820,P=0.027),divorced or widowed individuals(OR=1.37,P=0.032),self-funded patients(OR=2.368,P=0.008),and patients with hypertension(OR=2.011,P=0.041)had a higher risk of cognitive impairment.The risk of cognitive impairment was lower for those with a college degree(OR=0.435,P=0.034)and married individuals.CONCLUSION The risk factors affecting cognitive dysfunction are age,60-79 years and≥80 years;education,primary school education or less;marital status,divorced or widowed;payment method,selffunded;hypertension;and CKD.
基金supported partly by the National Natural Science Foundation of China,Nos.32161143021 and 81271410the Natural Science Foundation of Henan Province of China,No.182300410313(all to JW)。
文摘Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases.This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases,including Alzheimer's disease,Huntington's chorea,and Parkinson's disease.This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states.Therefore,inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.
基金supported by grants from the Department of Science and Technology of Sichuan Province,Nos.2021ZYD0093(to LY),2022YFS0597(to LY),2021YJ0480(to YT),and 2022ZYD0076(to JY)。
文摘Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.
基金supported by the National Natural Science Foundation of China,Nos.82230042 and 81930029(to ZY),U2004201(to FG and RYP)the China Postdoctoral Science Foundation,No.2020M683748(to RYP)。
文摘Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.
基金This study was supported by the National Natural Science Foundation of China(82003529,72125009)the National Key Research and Development Program of the Ministry of Science and Technology of China(2019YFC2005000)+4 种基金the Chinese Scientific and Technical Innovation Project 2030(2018AAA0102100)the National High Level Hospital Clinical Research Funding(“Star of Outlook”Scientific Research Project of Peking University First Hospital,2022XW06)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-046)the Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)the PKU-Baidu Fund(2020BD004,2020BD005 and 2020BD032).
文摘Background:Climate change profoundly shapes the population health at the global scale.However,there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease(CKD).Methods:In the present study,we studied the association of heat exposure with hospitalizations for cause-specific CKD using a national inpatient database in China during the study period of hot season from 2015 to 2018.Standard time-series regression models and random-effects Meta-analysis were developed to estimate the city-specific and national averaged associations at a 7 lag-day span,respectively.Results:A total of 768,129 hospitalizations for CKD was recorded during the study period.The results showed that higher temperature was associated with elevated risk of hospitalizations for CKD,especially in sub-tropical cities.With a 1℃ increase in daily mean temperature,the cumulative relative risks(RR)over lag 0-7 d were 1.008[95% confidence interval(CI)1.003-1.012]for nationwide.The attributable fraction of CKD hospitalizations due to high temperatures was 5.50%.Stronger associations were observed among younger patients and those with obstructive nephropathy.Our study also found that exposure to heatwaves was associated with added risk of hospitalizations for CKD compared to non-heatwave days(RR=1.116,95%CI 1.069-1.166)above the effect of daily mean temperature.Conclusions:Short-term heat exposure may increase the risk of hospitalization for CKD.Our findings provide insights into the health effects of climate change and suggest the necessity of guided protection strategies against the adverse effects of high temperatures.
基金funded by Princess Nourah bint Abdulrahman University Researchers Supporting Project Number PNURSP2024R333,Princess Nourah bint Abdulrahman University,Riyadh,Saudi Arabia.
文摘Chronic kidney disease(CKD)is a major health concern today,requiring early and accurate diagnosis.Machine learning has emerged as a powerful tool for disease detection,and medical professionals are increasingly using ML classifier algorithms to identify CKD early.This study explores the application of advanced machine learning techniques on a CKD dataset obtained from the University of California,UC Irvine Machine Learning repository.The research introduces TrioNet,an ensemble model combining extreme gradient boosting,random forest,and extra tree classifier,which excels in providing highly accurate predictions for CKD.Furthermore,K nearest neighbor(KNN)imputer is utilized to deal withmissing values while synthetic minority oversampling(SMOTE)is used for class-imbalance problems.To ascertain the efficacy of the proposed model,a comprehensive comparative analysis is conducted with various machine learning models.The proposed TrioNet using KNN imputer and SMOTE outperformed other models with 98.97%accuracy for detectingCKD.This in-depth analysis demonstrates the model’s capabilities and underscores its potential as a valuable tool in the diagnosis of CKD.
文摘Chronic kidney disease is commonly diagnosed in dogs,and clinical signs may be aggravated when infected agents are involved.In this case report,33 dogs with chronic kidney disease were clinically evaluated and serologically tested for Leptospira spp.,Ehrlichia canis,and Anaplasma phagocytophilum.The seroprevalence for Leptospira spp.was 39.4%.The most frequent serovars found were Pyrogenes,Canicola,Bratislava and Australis,with serological titers between 1:100 to 1:800.Clinical signs included fever,depression,decreased body condition,vomiting and hema‑turia.Signifcant laboratory fndings were anemia,leukocytosis,thrombocytopenia,increased liver enzymes,urea and creatinine,hyperbilirubinemia and hyperphosphatemia.All leptospira seronegative dogs were positive for one or both monitored homoparasites(i.e.,E.canis and A.phagocytophilum);only three leptospira seropositive dogs were positive for one or both hemoparasites.Findings also suggest that endemic hemoparasites of dogs should be moni‑tored in dogs with a kidney condition for a better clinical picture of the patients and therapeutic approach.
基金Supported by the National Natural Science Foundation of China(No.82220108017,No.82141128)the Capital Health Research and Development of Special(No.2020-1-2052)Science&Technology Project of Beijing Municipal Science&Technology Commission(No.Z201100005520045,No.Z181100001818003).
文摘AIM:To investigate whether retinal nerve fiber layer defects(RNFLDs)is a potential risk factor for chronic kidney disease(CKD)in Chinese adults.METHODS:The Kailuan Eye Study was a populationbased study that included 14440 participants.All participants underwent detailed assessments,RNFLDs were diagnosed using color fundus photographs.RESULTS:Overall,12507 participants[8533 males(68.23%)]had complete systemic examination data and at least one evaluable fundus photograph.RNFLDs were found in 621 participants[5.0%;95%confidence interval(CI):4.6%-5.34%],and 70 cases of multiple RNFLDs were found(11.27%).After adjusting multiple factors,RNFLDs was significantly associated with CKD severity,the ORs of CKD stage 3,stage 4 and stage 5 were 1.698,4.167,and 9.512,respectively.Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors,the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively.Furthermore,2294 participants had CKD(18.34%,95%CI:17.68%-18.99%).After adjusting for other factors,CKD presence was significantly correlated with the presence of RNFLDs.CONCLUSION:The strongest risk factors for RNFLDs are CKD and hypertension.Conversely,RNFLDs can be an ocular feature in patients with CKD.Fundoscopy can help detect systemic diseases,and assessment for RNFLDs should be considered in CKD patients.
基金supported by the National Nature Science Foundation of China,Nos.81871603(to XZ)and 82171322(to ZF)Discipline Boost Program of the First Affiliated Hospital of Air Force Military Medical University,No.XJZT21J08(to XZ)the Natural Science Foundation of Shaanxi Province of China,No.2022KJXX-102(to ZF)。
文摘Chaperone-mediated autophagy is one of three types of autophagy and is characterized by the selective degradation of proteins.Chaperone-mediated autophagy contributes to energy balance and helps maintain cellular homeostasis,while providing nutrients and support for cell survival.Chaperone-mediated autophagy activity can be detected in almost all cells,including neurons.Owing to the extreme sensitivity of neurons to their environmental changes,maintaining neuronal homeostasis is critical for neuronal growth and survival.Chaperone-mediated autophagy dysfunction is closely related to central nervous system diseases.It has been shown that neuronal damage and cell death are accompanied by chaperone-mediated autophagy dysfunction.Under certain conditions,regulation of chaperone-mediated autophagy activity attenuates neurotoxicity.In this paper,we review the changes in chaperone-mediated autophagy in neurodegenerative diseases,brain injury,glioma,and autoimmune diseases.We also summarize the most recent research progress on chaperone-mediated autophagy regulation and discuss the potential of chaperone-mediated autophagy as a therapeutic target for central nervous system diseases.
基金supported by the grants from National Natural Science Foundation of China(No.82174334)Hainan Provincial Key Laboratory of Tropical Brain Science Research and Transformation Research Project(JCKF2021001)Innovative Research Projects for Graduate Students(HYYS2021B01).
文摘Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.
基金supported by the Zhejiang Provincial Natural Science Foundation of China(LZ22H050001)National Natural Science Foundation of China(82270704,81970573)+1 种基金“Lingyan”R&D Research and Development Project(2024C03165)Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents。
文摘Acute kidney injury(AKI)and chronic kidney disease(CKD)are significant public health issues associated with a long-term increase in mortality risk,resulting from various etiologies including renal ischemia,sepsis,drug toxicity,and diabetes mellitus.Numerous preclinical models have been developed to deepen our understanding of the pathophysiological mechanisms and therapeutic approaches for kidney diseases.Among these,rodent models have proven to be powerful tools in the discovery of novel therapeutics,while the development of kidney organoids has emerged as a promising advancement in the field.This review provides a comprehensive analysis of the construction methodologies,underlying biological mechanisms,and recent therapeutic developments across different AKI and CKD models.Additionally,this review summarizes the advantages,limitations,and challenges inherent in these preclinical models,thereby contributing robust evidence to support the development of effective therapeutic strategies.
文摘In this editorial,we comment on the article by Zhang et al.Chronic kidney disease(CKD)presents a significant challenge in managing glycemic control,especially in diabetic patients with diabetic kidney disease undergoing dialysis or kidney transplantation.Conventional markers like glycated haemoglobin(HbA1c)may not accurately reflect glycemic fluctuations in these populations due to factors such as anaemia and kidney dysfunction.This comprehensive review discusses the limitations of HbA1c and explores alternative methods,such as continuous glucose monitoring(CGM)in CKD patients.CGM emerges as a promising technology offering real-time or retrospective glucose concentration measure-ments and overcoming the limitations of HbA1c.Key studies demonstrate the utility of CGM in different CKD settings,including hemodialysis and peritoneal dialysis patients,as well as kidney transplant recipients.Despite challenges like sensor accuracy fluctuation,CGM proves valuable in monitoring glycemic trends and mitigating the risk of hypo-and hyperglycemia,to which CKD patients are prone.The review also addresses the limitations of CGM in CKD patients,emphasizing the need for further research to optimize its utilization in clinical practice.Altogether,this review advocates for integrating CGM into managing glycemia in CKD patients,highlighting its superiority over traditional markers and urging clinicians to consider CGM a valuable tool in their armamentarium.
基金Supported by the National Natural Science Foundation of China,No.82100883the Research Project of Educational Commission of Jilin Province of China,No.JJKH20231214KJ.
文摘Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.
基金Supported by 2021 Wuxi Nursing Association Nursing Scientific Research Project Fund,No.Q202106.
文摘BACKGROUND Diabetic kidney disease(DKD)is a prevalent complication of diabetes that often requires hemodialysis for treatment.In the field of nursing,there is a growing recognition of the importance of humanistic care,which focuses on the holistic needs of patients,including their emotional,psychological,and social well-being.However,the application of humanistic nursing in the context of hemodialysis for DKD patients remains relatively unexplored.AIM To explore the experience of humanistic nursing in hemodialysis nursing for DKD patients.METHODS Ninety-six DKD patients treated with hemodialysis from March 2020 to June 2022 were included in the study and divided into the control cluster(48 cases)and the study cluster(48 cases)according to different nursing methods;the control cluster was given routine nursing and the study cluster was given humanized nursing.The variances of negative emotion mark,blood glucose,renal function,the incidence of complications,life mark and nursing satisfaction before and after nur-sing were contrasted between the two clusters.RESULTS No significant difference in negative emotion markers between the two clusters were observed before nursing(P>0.05),and the negative emotion markers of the two clusters decreased after nursing.The Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale markers were lower in the study cluster than the control cluster.The healing rate of patients in the study cluster was significantly higher than the control cluster(97.92%vs 85.42%,P<0.05).Blood glucose parameters were not significantly different between the groups prior to nursing(P>0.05).However,after nursing,blood urea nitrogen and serum creatinine(SCr)levels in the study cluster were lower than those in the control cluster(P<0.05).The incidence rate of complications was significantly lower in the study group compared to the control cluster(6.25%vs 20.83%,P<0.05).There was no significant difference in the life markers between the two clusters before nursing.While the life markers increased after nursing for both groups,the 36-item health scale markers in the study cluster were higher than those within the control cluster(P<0.05).Finally,the nursing satisfaction rate was 93.75% in the study cluster,compared to 75% in the control cluster(P<0.05).CONCLUSION In hemodialysis for DKD patients,the implementation of humanistic nursing achieved ideal results,effectively reducing patients’psychological negative emotion markers so that they can actively cooperate with the diagnosis and nursing,facilitate the control of blood glucose and the maintenance of residual renal function,reduce the occurrence of complications,and finally enhance the life quality and nursing satisfaction of patients.It is worthy of being widely popularized and applied.