Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic ...Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.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
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
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
The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The thera...The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission.In patients with achieved long-term remission,the question of de-escalation or discontinuation of therapy arises,considering the possible side effects and economic burden of long-term therapy.For each of the drugs used in IBD(5-aminosalycaltes,immunomodulators,biological drugs,small molecules)there is a risk of relapse.Furthermore,studies show that more than 50%of patients who discontinue therapy will relapse.Based on the findings of large studies and meta-analysis,relapse of disease can be expected in about half of the patients after therapy withdrawal,in case of monotherapy with aminosalicylates,immunomodulators or biological therapy.However,longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor.It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking.Before making a decision on discontinuation of therapy,it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse.Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse.Several other predictive factors have also been identified,such as:High Crohn's disease activity index or Harvey Bradshaw index,younger age(<40 years),longer disease duration(>40 years),smoking,young age of disease onset,steroid use 6-12 months before cessation.An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs.The decision to discontinue therapy must be based on individual approach,taking into account the severity,extension,and duration of the disease,the possibility of side adverse effects,the risk of relapse,and patient’s preferences.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 Many guidelines have recommended renin-angiotensin system inhibitors(RASI)as the first-line treatment for patients with chronic kidney disease(CKD).We studied RASI prescription trends from 2010 to 2019,and ...BACKGROUND Many guidelines have recommended renin-angiotensin system inhibitors(RASI)as the first-line treatment for patients with chronic kidney disease(CKD).We studied RASI prescription trends from 2010 to 2019,and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients.AIM To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China.METHODS It was retrospectively,cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019.RASI prescribing trends were analyzed from 2010 to 2019,and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription.RESULTS A total of 35090 CKD patients were included,with 10043(28.6%)RASI prescriptions.Among these patients,18919(53.9%)met the criteria for RASI treatments based on the 2012 kidney disease:Improving global outcomes guidelines.Of these,7246(38.3%)patients received RASI prescriptions.RASI prescriptions showed an initial rapid increase from 2011 to 2012,reached its peak around 2015 and 2016,and then exhibited a subsequent slight decreasing trend.Both bivariate and multivariate analyses showed that several characteristics,including the male gender,age less than 60-year-old,nephrology department admission,lower CKD stage,history of hypertension or diabetes,proteinuria,glomerulonephritis as the CKD etiology,and non-acute kidney injury were associated with RASI prescriptions.CONCLUSION The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years.CKD patients with certain characteristics such as elderly age,advanced disease stage,surgery department admission,or acute kidney injury were less likely to receive RASI prescriptions.In the application of RASI in hospitalized CKD patients is insufficient.The actual clinical practice needs to be improved.The development of related research is helpful to guide the correct choice of clinical treatment strategy.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
Vascular calcification is a crucial risk factor that affects the incidence and mortality of cardiovascular disease in chronic kidney disease patients.Modern medicine relies on calcium-phosphorus binding agents,calcium...Vascular calcification is a crucial risk factor that affects the incidence and mortality of cardiovascular disease in chronic kidney disease patients.Modern medicine relies on calcium-phosphorus binding agents,calcium mimetics,active vitamin D,and hemodialysis to prevent and treat vascular calcification,however,their efficacy is unsatisfactory and adverse reactions often occur.Medical plant therapy can act as an integrative regulator in patients with chronic kidney disease-associated vascular calcification,which can significantly improve patients’symptoms,but its specific mechanism has not been fully elucidated yet.In this paper,we reviewed the domestic and international theoretical studies on the pathogenesis mechanism of chronic kidney disease-associated vascular calcification in recent years,summarized eight active ingredients of medicinal plants as well as four compound formulas for improving chronic kidney disease-associated vascular calcification,and explored the mechanism of action of herbal medicine,which will provide a new strategy for promoting the prevention and treatment of vascular calcification.展开更多
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive impairments in the initial stage, which lead to severe cognitive dysfunction in the later stage. Action observation therapy (AOT) is...Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive impairments in the initial stage, which lead to severe cognitive dysfunction in the later stage. Action observation therapy (AOT) is a multisensory cognitive rehabilitation technique where the patient initially observes the actions and then tries to perform. The study aimed to examine the impact of AOT along with usual physiotherapy interventions to reduce depression, improve cognition and balance of a patient with AD. A 67 years old patient with AD was selected for this study because the patient has been suffering from depression, dementia, and physical dysfunction along with some other health conditions like diabetes and hypertension. Before starting intervention, a baseline assessment was done through the Beck Depression Inventory (BDI) tool, the Mini-Cog Scale, and the Berg Balance Scale (BBS). The patient received 12 sessions of AOT along with usual physiotherapy interventions thrice a week for four weeks, which included 45 minutes of each session. After four weeks of intervention, the patient demonstrated significant improvement in depression, cognition, and balance, whereas the BDI score declined from moderate 21/63 to mild 15/63 level of depression. The Mini-Cog score improved from 2/5 to 4/5, and the BBS score increased from 18/56 to 37/56. It is concluded that AOT along with usual physiotherapy intervention helps to reduce depression, improve cognition and balance of people with AD.展开更多
Background:Diabetic kidney disease(DKD)is a microvascular complication of diabetes mellitus and is the main cause of end-stage renal failure.Suoquan pills(SQP)has a variety of pharmacological activities and multiple t...Background:Diabetic kidney disease(DKD)is a microvascular complication of diabetes mellitus and is the main cause of end-stage renal failure.Suoquan pills(SQP)has a variety of pharmacological activities and multiple therapeutic effects,and it is used clinically as a basic formula for the treatment of DKD.Methods:Public databases were used to identify SQP compounds and the potential targets of SQP and DKD.A drug-component-therapeutic target network was constructed.Protein-protein interaction network analysis,Gene Ontology functional analysis,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyse the potential molecular mechanisms of SQP based on common targets of drugs and diseases.Molecular docking simulations were conducted to confirm the binding abity of the core compounds to key targets.The efficacy and predicted molecular mechanisms of SQP were validated using cell counting kit-8 assay,flow cytometry,and western blotting with HK-2 cells as a model.Results:Network pharmacology analysis showed that 26 compounds and 207 potential targets of SQP were involved in the treatment of DKD;boldine,denudatin B,pinocembrin,kaempferoid,and quercetin were considered core compounds,and epidermal growth factor receptor(EGFR)and proto-oncogene,non-receptor tyrosine kinase(SRC)were considered key targets.Gene Ontology enrichment analysis indicated that protein phosphorylation and negative regulation of apoptotic processes are important biological processes in the treatment of DKD by SQP.Molecular docking confirmed the excellent binding abilities of boldine,denudatin B,kaempferide,and quercetin to EGFR and SRC.The results of in vitro experiments showed that treatment with an ethanolic extract of SQP significantly protected HK-2 cells from high glucose-induced cell damage.In addition,the SQP ethanol extract inhibited the phosphorylation of EGFR and SRC,suppressed the apoptosis rate,and regulated apoptosis-related proteins in HK-2 cells under high glucose stress.Conclusion:This study systematically and intuitively illustrated the possible pharmacological mechanisms of SQP against DKD through multiple components,targets,and signalling pathways,especially the inhibition of EGFR and SRC phosphorylation and apoptosis.展开更多
[Objectives]To evaluate the clinical efficacy and safety of Kunkui Kidney Preserving Paste in the treatment of diabetic kidney disease(DKD)patients with damp-heat stasis syndrome in the clinical proteinuria stage.[Met...[Objectives]To evaluate the clinical efficacy and safety of Kunkui Kidney Preserving Paste in the treatment of diabetic kidney disease(DKD)patients with damp-heat stasis syndrome in the clinical proteinuria stage.[Methods]Retrospective analysis was made on 30 patients with DKD who were diagnosed with damp-heat stasis syndrome in the clinical proteinuria stage from March 2021 to March 2023 in Jiangsu Province Hospital of Chinese Medicine,and who took Kunkui Kidney Preserving Paste continuously for six months.The urinary albumin/creatinine ratio(UACR),urinary complement C3,and urea nitrogen(BUN)of DKD patients before and after treatment were compared,and estimated glomerular filtration rate(eGFR),blood creatinine(Scr),and cystatin C(CysC)were estimated,and the therapeutic effects on renal function and urinary protein were evaluated.[Results]After treatment,UACR significantly decreased(P<0.01),and urinary complement C3 and Scr decreased(P<0.05),while other indicators showed no significant statistical difference(P>0.05).In terms of evaluating the efficacy of urinary protein therapy,8 cases showed recent relief;8 cases showed significant effect;9 cases were effective,and 5 cases were invalid after treatment,with a total effective rate of 83.33%.In terms of renal function efficacy evaluation,8 cases showed significant effect;4 cases were effective;11 cases were stable,and 7 cases were invalid,with a total effective rate of 76.67%.In the safety evaluation,there were no obvious adverse reactions.[Conclusions]The Kunkui Kidney Preserving Past has significant clinical efficacy and safety in treating DKD patients with damp-heat stasis syndrome in the clinical proteinuria period.It has significant advantages in reducing urinary protein and protecting renal function,which is worthy of clinical promotion.展开更多
With the increasing morbidity of diabetes mellitus (DM), diabetic kidney disease (DKD) has become the major reason causing chronic kidney disease (CKD) and end-stage renal disease (ESRD) over the world. However, curre...With the increasing morbidity of diabetes mellitus (DM), diabetic kidney disease (DKD) has become the major reason causing chronic kidney disease (CKD) and end-stage renal disease (ESRD) over the world. However, current treating strategy is aiming at blood glucose controlling and renin-angiotensin system (RAS) restricting which can’t effectively preventing the development of DKD. Recent research indicating that low level of inflammatory and activation of immune system play a significant role in occurrence and progression of DKD. Understanding of inflammatory cascade and its mechanism is conducive to discern novel target of DKD and contributing to design new treating strategy based on anti-inflammatory. For the past few years, an increasing number of evidences proved that Tradit Chin Med (TCM) could delay the progression of ESRD on the basis of inflammatory. In this review, we overview the protective effect against DKD-based renal injury of TCM monomer, offering novel ideas in drug discovery and in mechanism-related research.sd.展开更多
BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated...BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.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
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
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 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 Polycystic kidney disease(PKD)is the most common genetic cause of kidney disease.It is a progressive and irreversible condition that can lead to end-stage renal disease and many other visceral complications...BACKGROUND Polycystic kidney disease(PKD)is the most common genetic cause of kidney disease.It is a progressive and irreversible condition that can lead to end-stage renal disease and many other visceral complications.Current comprehensive data on PKD patterns in Africa is lacking.AIM To describe the prevalence and outcomes of PKD in the African population.METHODS A literature search of PubMed,African journal online,and Google Scholar databases between 2000 and 2023 was performed.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed to design the study.Clinical presentations and outcomes of patients were extracted from the included studies.RESULTS Out of 106 articles,we included 13 studies from 7 African countries.Ten of them were retrospective descriptive studies concerning 943 PKD patients with a mean age of 47.9 years.The accurate prevalence and incidence of PKD were not known but it represented the third causal nephropathy among dialysis patients.In majority of patients,the diagnosis of the disease was often delayed.Kidney function impairment,abdominal mass,and hypertension were the leading symptoms at presentation with a pooled prevalence of 72.1%(69.1-75.1),65.8%(62.2-69.4),and 57.4%(54.2-60.6)respectively.Hematuria and infections were the most frequent complications.Genotyping was performed in few studies that revealed a high proportion of new mutations mainly in the PKD1 gene.CONCLUSION The prevalence of PKD in African populations is not clearly defined.Clinical symptoms were almost present with most patients who had kidney function impairment and abdominal mass at the diagnostic.Larger studies including genetic testing are needed to determine the burden of PKD in African populations.展开更多
BACKGROUND Dietary fiber(DF)intake may have a protective effect against type 2 diabetes(T2D);however,its relationship with diabetic kidney disease(DKD)remains unclear.AIM To investigate the potential association betwe...BACKGROUND Dietary fiber(DF)intake may have a protective effect against type 2 diabetes(T2D);however,its relationship with diabetic kidney disease(DKD)remains unclear.AIM To investigate the potential association between DF intake and the prevalence of DKD in individuals diagnosed with T2D.METHODS This cross-sectional study used data from the National Health and Nutrition Examination Survey collected between 2005 and 2018.DF intake was assessed through 24-h dietary recall interviews,and DKD diagnosis in individuals with T2D was based on predefined criteria,including albuminuria,impaired glomerular filtration rate,or a combination of both.Logistic regression analysis was used to assess the association between DF intake and DKD,and comprehensive subgroup and sensitivity analyses were performed.RESULTS Among the 6032 participants,38.4%had DKD.With lower DF intake-T1(≤6.4 g/1000 kcal/day)-as a reference,the adjusted odds ratio for DF and DKD for levels T2(6.5-10.0 g/1000 kcal/day)and T3(≥10.1 g/1000 kcal/day)were 0.97(95%CI:0.84-1.12,P=0.674)and 0.79(95%CI:0.68-0.92,P=0.002),respectively.The subgroup analysis yielded consistent results across various demographic and health-related subgroups,with no statistically significant interactions(all P>0.05).CONCLUSION In United States adults with T2D,increased DF intake may be related to reduced DKD incidence.Further research is required to confirm these findings.展开更多
基金supported by the National Natural Science Foundation of China,No.31960120Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(both to ZW).
文摘Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.
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.
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The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission.In patients with achieved long-term remission,the question of de-escalation or discontinuation of therapy arises,considering the possible side effects and economic burden of long-term therapy.For each of the drugs used in IBD(5-aminosalycaltes,immunomodulators,biological drugs,small molecules)there is a risk of relapse.Furthermore,studies show that more than 50%of patients who discontinue therapy will relapse.Based on the findings of large studies and meta-analysis,relapse of disease can be expected in about half of the patients after therapy withdrawal,in case of monotherapy with aminosalicylates,immunomodulators or biological therapy.However,longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor.It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking.Before making a decision on discontinuation of therapy,it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse.Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse.Several other predictive factors have also been identified,such as:High Crohn's disease activity index or Harvey Bradshaw index,younger age(<40 years),longer disease duration(>40 years),smoking,young age of disease onset,steroid use 6-12 months before cessation.An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs.The decision to discontinue therapy must be based on individual approach,taking into account the severity,extension,and duration of the disease,the possibility of side adverse effects,the risk of relapse,and patient’s preferences.
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.
文摘BACKGROUND Many guidelines have recommended renin-angiotensin system inhibitors(RASI)as the first-line treatment for patients with chronic kidney disease(CKD).We studied RASI prescription trends from 2010 to 2019,and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients.AIM To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China.METHODS It was retrospectively,cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019.RASI prescribing trends were analyzed from 2010 to 2019,and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription.RESULTS A total of 35090 CKD patients were included,with 10043(28.6%)RASI prescriptions.Among these patients,18919(53.9%)met the criteria for RASI treatments based on the 2012 kidney disease:Improving global outcomes guidelines.Of these,7246(38.3%)patients received RASI prescriptions.RASI prescriptions showed an initial rapid increase from 2011 to 2012,reached its peak around 2015 and 2016,and then exhibited a subsequent slight decreasing trend.Both bivariate and multivariate analyses showed that several characteristics,including the male gender,age less than 60-year-old,nephrology department admission,lower CKD stage,history of hypertension or diabetes,proteinuria,glomerulonephritis as the CKD etiology,and non-acute kidney injury were associated with RASI prescriptions.CONCLUSION The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years.CKD patients with certain characteristics such as elderly age,advanced disease stage,surgery department admission,or acute kidney injury were less likely to receive RASI prescriptions.In the application of RASI in hospitalized CKD patients is insufficient.The actual clinical practice needs to be improved.The development of related research is helpful to guide the correct choice of clinical treatment strategy.
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.
文摘Vascular calcification is a crucial risk factor that affects the incidence and mortality of cardiovascular disease in chronic kidney disease patients.Modern medicine relies on calcium-phosphorus binding agents,calcium mimetics,active vitamin D,and hemodialysis to prevent and treat vascular calcification,however,their efficacy is unsatisfactory and adverse reactions often occur.Medical plant therapy can act as an integrative regulator in patients with chronic kidney disease-associated vascular calcification,which can significantly improve patients’symptoms,but its specific mechanism has not been fully elucidated yet.In this paper,we reviewed the domestic and international theoretical studies on the pathogenesis mechanism of chronic kidney disease-associated vascular calcification in recent years,summarized eight active ingredients of medicinal plants as well as four compound formulas for improving chronic kidney disease-associated vascular calcification,and explored the mechanism of action of herbal medicine,which will provide a new strategy for promoting the prevention and treatment of vascular calcification.
文摘Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive impairments in the initial stage, which lead to severe cognitive dysfunction in the later stage. Action observation therapy (AOT) is a multisensory cognitive rehabilitation technique where the patient initially observes the actions and then tries to perform. The study aimed to examine the impact of AOT along with usual physiotherapy interventions to reduce depression, improve cognition and balance of a patient with AD. A 67 years old patient with AD was selected for this study because the patient has been suffering from depression, dementia, and physical dysfunction along with some other health conditions like diabetes and hypertension. Before starting intervention, a baseline assessment was done through the Beck Depression Inventory (BDI) tool, the Mini-Cog Scale, and the Berg Balance Scale (BBS). The patient received 12 sessions of AOT along with usual physiotherapy interventions thrice a week for four weeks, which included 45 minutes of each session. After four weeks of intervention, the patient demonstrated significant improvement in depression, cognition, and balance, whereas the BDI score declined from moderate 21/63 to mild 15/63 level of depression. The Mini-Cog score improved from 2/5 to 4/5, and the BBS score increased from 18/56 to 37/56. It is concluded that AOT along with usual physiotherapy intervention helps to reduce depression, improve cognition and balance of people with AD.
基金supported by the grants from National Natural Science Foundation of China(No.82174334)Hainan Province in 2022 postgraduate innovation research projects(No.Qhys2022-273).
文摘Background:Diabetic kidney disease(DKD)is a microvascular complication of diabetes mellitus and is the main cause of end-stage renal failure.Suoquan pills(SQP)has a variety of pharmacological activities and multiple therapeutic effects,and it is used clinically as a basic formula for the treatment of DKD.Methods:Public databases were used to identify SQP compounds and the potential targets of SQP and DKD.A drug-component-therapeutic target network was constructed.Protein-protein interaction network analysis,Gene Ontology functional analysis,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyse the potential molecular mechanisms of SQP based on common targets of drugs and diseases.Molecular docking simulations were conducted to confirm the binding abity of the core compounds to key targets.The efficacy and predicted molecular mechanisms of SQP were validated using cell counting kit-8 assay,flow cytometry,and western blotting with HK-2 cells as a model.Results:Network pharmacology analysis showed that 26 compounds and 207 potential targets of SQP were involved in the treatment of DKD;boldine,denudatin B,pinocembrin,kaempferoid,and quercetin were considered core compounds,and epidermal growth factor receptor(EGFR)and proto-oncogene,non-receptor tyrosine kinase(SRC)were considered key targets.Gene Ontology enrichment analysis indicated that protein phosphorylation and negative regulation of apoptotic processes are important biological processes in the treatment of DKD by SQP.Molecular docking confirmed the excellent binding abilities of boldine,denudatin B,kaempferide,and quercetin to EGFR and SRC.The results of in vitro experiments showed that treatment with an ethanolic extract of SQP significantly protected HK-2 cells from high glucose-induced cell damage.In addition,the SQP ethanol extract inhibited the phosphorylation of EGFR and SRC,suppressed the apoptosis rate,and regulated apoptosis-related proteins in HK-2 cells under high glucose stress.Conclusion:This study systematically and intuitively illustrated the possible pharmacological mechanisms of SQP against DKD through multiple components,targets,and signalling pathways,especially the inhibition of EGFR and SRC phosphorylation and apoptosis.
基金Supported by the National Natural Science Foundation of China(82174293,82374355,82004286)Science and Technology Support Program of Jiangsu Province(ZD202208,ZT202206)Postgraduate Research and Practice Innovation Program of Jiangsu Province(SJCX22_0718).
文摘[Objectives]To evaluate the clinical efficacy and safety of Kunkui Kidney Preserving Paste in the treatment of diabetic kidney disease(DKD)patients with damp-heat stasis syndrome in the clinical proteinuria stage.[Methods]Retrospective analysis was made on 30 patients with DKD who were diagnosed with damp-heat stasis syndrome in the clinical proteinuria stage from March 2021 to March 2023 in Jiangsu Province Hospital of Chinese Medicine,and who took Kunkui Kidney Preserving Paste continuously for six months.The urinary albumin/creatinine ratio(UACR),urinary complement C3,and urea nitrogen(BUN)of DKD patients before and after treatment were compared,and estimated glomerular filtration rate(eGFR),blood creatinine(Scr),and cystatin C(CysC)were estimated,and the therapeutic effects on renal function and urinary protein were evaluated.[Results]After treatment,UACR significantly decreased(P<0.01),and urinary complement C3 and Scr decreased(P<0.05),while other indicators showed no significant statistical difference(P>0.05).In terms of evaluating the efficacy of urinary protein therapy,8 cases showed recent relief;8 cases showed significant effect;9 cases were effective,and 5 cases were invalid after treatment,with a total effective rate of 83.33%.In terms of renal function efficacy evaluation,8 cases showed significant effect;4 cases were effective;11 cases were stable,and 7 cases were invalid,with a total effective rate of 76.67%.In the safety evaluation,there were no obvious adverse reactions.[Conclusions]The Kunkui Kidney Preserving Past has significant clinical efficacy and safety in treating DKD patients with damp-heat stasis syndrome in the clinical proteinuria period.It has significant advantages in reducing urinary protein and protecting renal function,which is worthy of clinical promotion.
基金National Natural Science Foundation of China(No.82060851)Hainan Graduate Innovative Research Project A(No.HyYS2021A03)Hainan Graduate Innovative Research Project Class A(No.HYYS2021A35)。
文摘With the increasing morbidity of diabetes mellitus (DM), diabetic kidney disease (DKD) has become the major reason causing chronic kidney disease (CKD) and end-stage renal disease (ESRD) over the world. However, current treating strategy is aiming at blood glucose controlling and renin-angiotensin system (RAS) restricting which can’t effectively preventing the development of DKD. Recent research indicating that low level of inflammatory and activation of immune system play a significant role in occurrence and progression of DKD. Understanding of inflammatory cascade and its mechanism is conducive to discern novel target of DKD and contributing to design new treating strategy based on anti-inflammatory. For the past few years, an increasing number of evidences proved that Tradit Chin Med (TCM) could delay the progression of ESRD on the basis of inflammatory. In this review, we overview the protective effect against DKD-based renal injury of TCM monomer, offering novel ideas in drug discovery and in mechanism-related research.sd.
基金Supported by National Natural Science Foundation of China,No.81573695,No.81860894,and No.81674096Ningxia Key Research and Development Plan Project,No.2021BEG03106.
文摘BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.
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.
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.
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.
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.
文摘BACKGROUND Polycystic kidney disease(PKD)is the most common genetic cause of kidney disease.It is a progressive and irreversible condition that can lead to end-stage renal disease and many other visceral complications.Current comprehensive data on PKD patterns in Africa is lacking.AIM To describe the prevalence and outcomes of PKD in the African population.METHODS A literature search of PubMed,African journal online,and Google Scholar databases between 2000 and 2023 was performed.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed to design the study.Clinical presentations and outcomes of patients were extracted from the included studies.RESULTS Out of 106 articles,we included 13 studies from 7 African countries.Ten of them were retrospective descriptive studies concerning 943 PKD patients with a mean age of 47.9 years.The accurate prevalence and incidence of PKD were not known but it represented the third causal nephropathy among dialysis patients.In majority of patients,the diagnosis of the disease was often delayed.Kidney function impairment,abdominal mass,and hypertension were the leading symptoms at presentation with a pooled prevalence of 72.1%(69.1-75.1),65.8%(62.2-69.4),and 57.4%(54.2-60.6)respectively.Hematuria and infections were the most frequent complications.Genotyping was performed in few studies that revealed a high proportion of new mutations mainly in the PKD1 gene.CONCLUSION The prevalence of PKD in African populations is not clearly defined.Clinical symptoms were almost present with most patients who had kidney function impairment and abdominal mass at the diagnostic.Larger studies including genetic testing are needed to determine the burden of PKD in African populations.
文摘BACKGROUND Dietary fiber(DF)intake may have a protective effect against type 2 diabetes(T2D);however,its relationship with diabetic kidney disease(DKD)remains unclear.AIM To investigate the potential association between DF intake and the prevalence of DKD in individuals diagnosed with T2D.METHODS This cross-sectional study used data from the National Health and Nutrition Examination Survey collected between 2005 and 2018.DF intake was assessed through 24-h dietary recall interviews,and DKD diagnosis in individuals with T2D was based on predefined criteria,including albuminuria,impaired glomerular filtration rate,or a combination of both.Logistic regression analysis was used to assess the association between DF intake and DKD,and comprehensive subgroup and sensitivity analyses were performed.RESULTS Among the 6032 participants,38.4%had DKD.With lower DF intake-T1(≤6.4 g/1000 kcal/day)-as a reference,the adjusted odds ratio for DF and DKD for levels T2(6.5-10.0 g/1000 kcal/day)and T3(≥10.1 g/1000 kcal/day)were 0.97(95%CI:0.84-1.12,P=0.674)and 0.79(95%CI:0.68-0.92,P=0.002),respectively.The subgroup analysis yielded consistent results across various demographic and health-related subgroups,with no statistically significant interactions(all P>0.05).CONCLUSION In United States adults with T2D,increased DF intake may be related to reduced DKD incidence.Further research is required to confirm these findings.