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Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury:A multicenter,double-blind,placebo-controlled,randomized trial

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Journal of Integrative Medicine 2024年第3期22卷 279-285页

作者： Jia-jia Wu Tian-yi Zhang Ying-hui Qi Min-yan Zhu Yan Fang Chao-jun Qi Li-ou Cao Ji-fang Lu Bo-han Lu Lu-min Tang Jian-xiao Shen Shan Mou Department of nephrology Molecular Cell Lab for Kidney DiseaseShanghai Peritoneal Dialysis Research CenterUremia Diagnosis and Treatment CenterRenji Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200127China Department of nephrology Shanghai Pudong New Area Punan HospitalShanghai 200125China Department of nephrology Ningbo Hangzhou Bay HospitalNingbo 315336Zhejiang ProvinceChina

Background:Yiqi Peiyuan(YQPY)prescription,a composite prescription of traditional Chinese medicine,has been used to prevent or delay the continued deterioration of renal function after acute kidney injury(AKI)in some institutions and has shown considerable efficacy.Objective:This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with AKI.Design,setting,participants and interventions:This is a prospective,double-blind,multicenter,randomized,and placebo-controlled clinical trial.A total of 144 enrolled participants were randomly allocated to two groups according to a randomization schedule.Participants,caregivers and investigators assessing the outcomes were blinded to group assignment.Patients in the YQPY group received 36 g YQPY granules twice a day for 28 days.Patients in the placebo group received a placebo in the same dose as the YQPY granules.Main outcome measures:The primary outcome was the change in the estimated glomerular filtration rate(eGFR)between baseline and after 4 and 24 weeks of treatment.The secondary outcomes were the change of serum creatinine(Scr)level between baseline and after treatment,and the incidence of endpoint events,defined as eGFR increasing by more than 25%above baseline,eGFR>75 mL/min per1.73 m2or the composite endpoint,which was defined as the sum of patients meeting either of the above criteria.Results:Data from a total of 114 patients(59 in the YQPY group and 55 in the control group)were analyzed.The mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two groups.In further subgroup analysis(22 in the YQPY group and 31 in the control group),the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m2in the YQPY group and 5.78 mL/min per1.73 m2in the placebo group,and the mean difference between groups was 21.61 mL/min per 1.73 m2(P<0.001).Thirteen(59.1%)patients in the YQPY group and 5(16.1%)in the placebo group reached the composite endpoints(P=0.002).Du

关键词： Chinese herbal medicine Randomized controlled trial Acute kidney injury Renal function

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Targeted therapies for lupus nephritis:Current perspectives and future directions

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Chinese Medical Journal 2024年第1期137卷 34-43页

作者： Xiuzhi Jia Yuewen Lu Xunhua Zheng Ruihan Tang Wei Chen Department of nephrology The First Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510080China NHC Key Laboratory of Clinical nephrology(Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhouGuangdong 510080China

Lupus nephritis(LN),a severe manifestation of systemic lupus erythematosus,poses a substantial risk of progression to end-stage renal disease,with increased mortality.Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids,mycophenolate mofetil,and calcineurin inhibitors.Although therapeutic regimens have evolved over the years,they have inherent limitations,including non-specific targeting,substantial adverse effects,high relapse rates,and prolonged maintenance and remission courses.These drawbacks underscore the need for targeted therapeutic strategies for LN.Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity.This review provides an overview of the current evidence on targeted therapies for LN,elucidates the biological mechanisms of responses and failure,highlights the challenges ahead,and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.

关键词： Lupus nephritis Molecular targeted therapies Adaptive immunity Immunity,Innate Cytokines

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Distribution of Traditional Chinese Medicine syndromes in diabetic kidney disease chronic kidney disease 1-5: a correlation study

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Journal of Traditional Chinese Medicine 2024年第3期44卷 572-580页

作者： LI Shuang DUAN Shuwei DONG Zheyi QU Yilun LUO Yayong KE Jianghua WANG Conghui PENG Yangzhi ZHOU Xuefeng CHEN Xiangmei Department of nephrology First Medical Center of Chinese PLA General HospitalNephrology Institute of the Chinese People's Liberation ArmyNational Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease Research School of Clinical Medicine Guangdong Pharmaceutical University Basic Medical College Chengdu University of Traditional Chinese Medicine

OBJECTIVE: To analyze the distribution of Traditional Chinese medicine(TCM) syndromes in patients with diabetic kidney disease(DKD) and its related factors.METHODS: We enrolled 435 patients with DKD, who were not undergoing dialysis, admitted to the Department of nephrology, First Medical Center, Chinese PLA General Hospital from April 2020 to August 2021.Analysis of their TCM syndromes and related factors was carried out.RESULTS: The 435 patients included 109, 117, 86, and 123 chronic kidney disease(CKD) 1-2, CKD3, CKD4, and CKD5 cases, respectively. With the progression of CKD1-5, the proportion of Yin deficiency and dry heat syndrome,and that of Qi and Yin deficiency syndrome showed a downward trend, whereas the proportion of spleen-kidney Yang deficiency, blood deficiency, blood stasis, water stagnation, and phlegm turbidity syndromes showed an upward trend; the differences were statistically significant(P < 0.05). Multivariate logistic regression analysis showed that Yin deficiency and dry heat syndrome was positively correlated with hemoglobin [odds ratio(OR) =1.022, P = 0.005], albumin(OR = 1.058, P = 0.006), and estimated glomerular filtration rate(eGFR)(OR = 1.020,P < 0.001) but negatively correlated with male sex(OR =0.277, P = 0.004). Qi and Yin deficiency syndrome was positively correlated with albumin(OR = 1.056, P < 0.001)and eGFR(OR = 1.008, P = 0.022) but negatively correlated with age(OR = 0.977, P = 0.023). Liver-kidney Yin deficiency syndrome was positively correlated with age(OR = 1.028, P = 0.021) and glycosylated hemoglobin(OR = 1.223, P = 0.007) but negatively correlated with total cholesterol(OR = 0.792, P = 0.006).Spleen-kidney Yang deficiency syndrome was negatively correlated with hemoglobin(OR = 0.977, P < 0.001),albumin(OR = 0.891, P < 0.001), and eGFR(OR = 0.978,P < 0.001) but positively correlated with high density lipoprotein(OR = 3.376, P = 0.001). CONCLUSION: With CKD1-5 progression, TCM syndromes changed from Yin deficiency and dry heat syndrome to syndrome of deficiency of both

关键词： albumins correlation of data diabetic nephropathies glomerular filtration rate hemoglobins syndrome and complex

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A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort

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Genes & Diseases 2024年第4期11卷 400-410页

作者： Han Chan Fenfen Ni Bo Zhao Huimin Jiang Juanjuan Ding Li Wang Xiaowen Wang Jingjing Cui Shipin Feng Xiaojie Gao Xueying Yang Huan Chi Hao Lee Xuelan Chen Xiaoqin Li Jia Jiao Daoqi Wu Gaofu Zhang Mo Wang Yupeng Cun Xiongzhong Ruan Haiping Yang Qiu Li Department of nephrology Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014China Department of nephrology Shenzhen Children's HospitalShenzhenGuangdong 518034China Department of nephrology Kunming Children's HospitalKunming Medical UniversityKunmingYunnan 650228China Department of nephrology Wuhan Children's HospitalTongji Medical College of Huazhong University of Science and TechnologyWuhanHubei 430015China Department of nephrology Chengdu Women and Children Central HospitalChengduSichuan 610073China Pediatric research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Department of nephrology John Moorhead Research LaboratoryUniversity College London Medical SchoolRoyal Free CampusUniversity College LondonLondon NW32PFUnited Kingdom

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the disease.We conducted a multicenter cohort study(360 patients and 1835 controls)combined with a GWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNPs)in ANKRD36 and ALPG was significant between SSNSWR and healthy controls,and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls.Interestingly,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR.No significant SNPs were observed between SSNSWR and SDNS/FRNS.Meanwhile,chromosome 2:171713702 in GAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;P=0.034).rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20%compared with the baseline in SDNS/FRNS patients(P=0.0001).Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA.Thus,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/FRNS.The study provides a novel approach for the GWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.

关键词： Frequentrelapse Genome-wide association study Human leukocyte antigen region Steroid-sensitive nephrotic syndrome

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Blood pressure targets in patients with chronic kidney disease:Comments and controversies

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Chinese Medical Journal 2024年第3期137卷 270-272页

作者： Ying Zheng Guangyan Cai Xiangmei Chen Department of nephrology First Medical Center of Chinese PLA General HospitalNational Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijing 100853China

According to the Global Burden of Disease Study 2017,there are 132 million patients with chronic kidney disease(CKD)in China,^([1])and the prevalence of hypertension in Chinese patients with CKD(67.3%)is significantly higher than that in the general population(23.2%).^([2,3])CKD is both a cause and a consequence of hypertension,and these two conditions form a vicious cycle that leads to the high prevalence rate of hypertension in patients with CKD.Uncontrolled hypertension accelerates the deterioration of renal function,which significantly increases the risk of developing end-stage renal disease(ESRD),as well as cardiovascular and cerebrovascular diseases,leading to poor patient outcomes.

关键词： patients Blood hypertension

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J-shaped association between dietary thiamine intake and the risk of cognitive decline in cognitively healthy,older Chinese individuals

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General Psychiatry 2024年第1期37卷 44-52页

作者： Chengzhang Liu Qiguo Meng Yuanxiu Wei Xinyue Su Yuanyuan Zhang Panpan He Chun Zhou Mengyi Liu Ziliang Ye Xianhui Qin Department of Epidemiology and Biostatistics School of Public HealthAnhui Medical UniversityHefeiAnhuiChina institute of Biomedicine Anhui Medical UniversityHefeiAnhuiChina Division of nephrology Nanfang HospitalSouthern Medical UniversityNational Clinical Research Center for Kidney DiseaseState Key Laboratory of Organ Failure ResearchGuangdong Provincial Institute of NephrologyGuangdong Provincial Key Laboratory of Renal Failure ResearchGuangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhouGuangdongChina

Background The prospective association of dietary thiamine intake with the risk of cognitive decline among the general older adults remains uncertain.Aims To investigate the association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals.Methods The study included a total of 3106 participants capable of completing repeated cognitive function tests.Dietary nutrient intake information was collected through 3-day dietary recalls and using a 3-day food-weighed method to assess cooking oil and condiment consumption.Cognitive decline was defined as the 5-year decline rate in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status-modified.Results The median follow-up duration was 5.9 years.There was a J-shaped relationship between dietary thiamine intake and the 5-year decline rate in global and composite cognitive scores,with an inflection point of 0.68 mg/day(95%confidence interval(Cl):0.56 to 0.80)and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.Before the inflection point,thiamine intake was not significantly associated with cognitive decline.Beyond the inflection point,each unit increase in thiamine intake(mg/day)was associated with a significant decrease of 4.24(95%Cl:2.22 to 6.27)points in the global score and 0.49(95%Cl:0.23 to 0.76)standard units in the composite score within 5 years.A stronger positive association between thiamine intake and cognitive decline was observed in those with hypertension,obesity and those who were non-smokers(all p<0.05).Conclusions This study revealed a J-shaped association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals,with an inflection point at 0.68 mg/day and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.

关键词： intake shaped cognitive

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Advanced Strategies for Overcoming Endosomal/Lysosomal Barrier in Nanodrug Delivery

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research 2024年第1期2023卷 315-337页

作者： Chong Qiu Fei Xia Junzhe Zhang Qiaoli Shi Yuqing Meng Chen Wang Huanhuan Pang Liwei Gu Chengchao Xu Qiuyan Guo Jigang Wang Artemisinin research Center and Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Department of nephrology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong 518020China

Nanocarriers have therapeutic potential to facilitate drug delivery,including biological agents,smallmolecule drugs,and nucleic acids.However,their efficiency is limited by several factors;among which,endosomal/lysosomal degradation after endocytosis is the most important.This review summarizes advanced strategies for overcoming endosomal/lysosomal barriers to efficient nanodrug delivery based on the perspective of cellular uptake and intracellular transport mechanisms.These strategies include promoting endosomal/lysosomal escape,using non-endocytic methods of delivery to directly cross the cell membrane to evade endosomes/lysosomes and making a detour pathway to evade endosomes/lysosomes.On the basis of the findings of this review,we proposed several promising strategies for overcoming endosomal/lysosomal barriers through the smarter and more efficient design of nanodrug delivery systems for future clinical applications.

关键词： somal drugs finding

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The burden of depression,anxiety and schizophrenia among the older population in ageing and aged countries:an analysis of the Global Burden of Disease Study 2019

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General Psychiatry 2024年第1期37卷 83-93页

作者： Ying Cheng Yu Fang Jinxin Zheng shiyang Guan Meiti Wang Wu Hong Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineShanghaiChina Department of nephrology Rujin HospitalInstitute of NephrologyInstitute of NephrologyShanghai Jiao Tong University School of MedicineShanghaiChina School of Global Health Chinese Center for Tropical Diseases ResearchShanghai Jiao Tong University School of MedicineShanghaiChina Department of Epidemiology and Biostatistics School of Public HealthAnhui Medical UniversityHefeiAnhuiChina

Background Depression,anxiety and schizophrenia among older persons have become global public health challenges.However,the burden of these disorders in ageing and aged countries has not been analysed.Aims To investigate the burden of depression,anxiety and schizophrenia among older adults in ageing and aged countries.Methods Using data from the Global Burden of Disease Study 2019,we calculated the estimated annual percentage change(EAPC)in the age-standardised incidence rates(ASiR)and age-standardised disability-adjusted life years(DALYs)rates(ASDR)for depression,anxiety and schizophrenia of older people in ageing countries(China,India,Indonesia)and aged countries(Japan,Italy,Portugal)between 1990 and 2019.Trends in incidence and DALYs were analysed by gender and age.Results In 2019,the highest incidence of depression,anxiety and schizophrenia in the older population in aged countries was in Japan(927271.3(752552.3-1125796.5),51498.2(37625.7-70487.3)and 126.0(61.0-223.2),respectively),while the highest incidence in ageing countries was in China(5797556.9(4599403.4-7133006.5),330256.1(246448.9-445987.4)and 1067.7(556.2-1775.9),respectively).DALYs for these disorders were similar,with the highest in Japan and China.From 1990 to 2019,the ASIR for depressive disorders decreased in aged countries but increased in ageing countries;the ASIR for anxiety disorders and schizophrenia declined in both ageing and aged countries.The ASDR for depressive disorders was consistent with the ASIR but not for anxiety disorders and schizophrenia.The ASIR for depressive disorders was higher in older women,while the opposite was observed in anxiety disorders and schizophrenia.Notably,the conditions of burden of depressive disorders,anxiety disorders and schizophrenia in the 65-70-year-old age group were the most burdensome.Conclusions The incidence and DALYs of these three mental disorders increased while exhibiting differences between ageing and aged countries.Raising awareness about formulating health policies for preventing and trea

关键词： schizophrenia burden ageing

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The key mediator of diabetic kidney disease:Potassium channel dysfunction

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Genes & Diseases 2024年第4期11卷 188-200页

作者： Jia Guo Chaojie Zhang Hui Zhao Yufan Yan Zhangsuo Liu nephrology research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province ZhengzhouHenan 450052China research Center for Kidney Disease ZhengzhouHenan 450052China

Diabetic kidney disease is a leading cause of end-stage renal disease,making it a global public health concern.The molecular mechanisms underlying diabetic kidney disease have not been elucidated due to its complex pathogenesis.Thus,exploring these mechanisms from new perspectives is the current focus of research concerning diabetic kidney disease.lon channels are important proteins that maintain the physiological functions of cells and organs.Among ion channels,potassium channels stand out,because they are the most common and important channels on eukaryotic cell surfaces and function as the basis for cell excitability.Certain potassium channel abnormalities have been found to be closely related to diabetic kid-ney disease progression and genetic susceptibility,such as KATp,Kca,Kir,and Kv.In this review,we summarized the roles of different types of potassium channels in the occurrence and devel-opment of diabetic kidney disease to discuss whether the development of DKD is due to potas-sium channel dysfunction and present new ideas for the treatment of DKD.

关键词： Channel dysfunction Diabetic kidney disease End-stage renal disease lon channel Potassium

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Single-cell transcriptomic analysis reveals transcript enrichment in oxidative phosphorylation,fluid sheer stress,and inflammatory pathways in obesity-related glomerulopathy

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Genes & Diseases 2024年第4期11卷 314-326页

作者： Yinyin Chen Yushun Gong Jia Zou Guoli Li Fan Zhang Yiya Yang Yumei Liang Wenni Dai Liyu He Hengcheng Lu Department of nephrology Hunan Provincial People's HospitalThe First Affliated Hospital of Hunan Normal UniversityHunan Clinical Research Center for Chronic Kidney DiseaseChangshaHunan 410000China Department of nephrology The Second Xiangya Hospital of Central South UniversityHunan Key Laboratory of Kidney Disease and Blood PurificationChangshaHunan 410011China Cardiovascular research Institute of Jiangxi Province Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeNanchangJiangxi 330006China

Obesity-related glomerulopathy(ORG)is an independent risk factor for chronic kid-ney disease and even progression to end-stage renal disease.Efforts have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG,but relatively little is known about cell-specific changes in gene expression.To define the transcriptomic landscape at single-cell resolution,we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA sequencing.We report for the first time that immune cells,including T cells and B cells,are decreased in ORG patients.Further analysis indicated that SPP1 was significantly up-regulated in T cells and B cells.This gene is related to inflammation and cell proliferation.Analysis of differential gene expression in glomerular cells(endothelial cells,mesangial cells,and podocytes)showed that these cell types were mainly enriched in genes related to oxidative phosphorylation,cell adhesion,thermogenesis,and inflammatory pathways(PI3K-Akt signaling,MAPK signaling).Furthermore,we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress pathway.Moreover,an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients,with major interactions between parietal epithelial cells and podocytes.Altogether,our identification of molecular events,cell types,and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.

关键词： Fluid shear stress Inflammation Obesity-related glomerulopathy Oxidative phosphorylation Single-cell RNA seq

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