BACKGROUND The understanding of bile acid(BA)and unsaturated fatty acid(UFA)profiles,as well as their dysregulation,remains elusive in individuals with type 2 diabetes mellitus(T2DM)coexisting with non-alcoholic fatty...BACKGROUND The understanding of bile acid(BA)and unsaturated fatty acid(UFA)profiles,as well as their dysregulation,remains elusive in individuals with type 2 diabetes mellitus(T2DM)coexisting with non-alcoholic fatty liver disease(NAFLD).Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM.AIM To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM.METHODS A training model was developed involving 399 participants,comprising 113 healthy controls(HCs),134 individuals with T2DM without NAFLD,and 152 individuals with T2DM and NAFLD.External validation encompassed 172 participants.NAFLD patients were divided based on liver fibrosis scores.The analytical approach employed univariate testing,orthogonal partial least squares-discriminant analysis,logistic regression,receiver operating characteristic curve analysis,and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers.RESULTS Compared to HCs,both T2DM and NAFLD groups exhibited diminished levels of specific BAs.In UFAs,particular acids exhibited a positive correlation with NAFLD risk in T2DM,while theω-6:ω-3 UFA ratio demonstrated a negative correlation.Levels ofα-linolenic acid andγ-linolenic acid were linked to significant liver fibrosis in NAFLD.The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients.CONCLUSION This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM,proposing their potential as biomarkers in the pathogenesis of NAFLD.展开更多
This research examines the contentious issue of euthanasia and physician-assisted suicide in the context of China's unique conditions.Historically,the debate over euthanasia has been influenced by moral philosophy...This research examines the contentious issue of euthanasia and physician-assisted suicide in the context of China's unique conditions.Historically,the debate over euthanasia has been influenced by moral philosophy and ethics,and euthanasia is illegal in China at present.The research explores the difficulty in making euthanasia legalized across five key dimensions:financial,medical,social,legal,and psychological factors.We conclude that while there is a desire among some terminally ill patients for euthanasia,the current situation in China makes it unsuitable for legalization.The profound question of one's right to die remains a significant moral and judicial challenge,indicating the need for continued dialogue and nuanced understanding of this complex issue.展开更多
Objective Idiopathic nephrotic syndrome(INS)is the most common glomerular disease in children.Toll-like receptors(TLRs)have been reported to be associated with response to steroid treatment in children with INS.Nevert...Objective Idiopathic nephrotic syndrome(INS)is the most common glomerular disease in children.Toll-like receptors(TLRs)have been reported to be associated with response to steroid treatment in children with INS.Nevertheless,the correlation between TLR genes and the progression of INS has not yet been clarified.The present study aimed to investigate the association of single-nucleotide polymorphisms(SNPs)in TLR2,TLR4,and TLR9 with susceptibility to INS as well as the clinical phenotyping of steroid responsiveness in Chinese children with INS.Methods A total of 183 pediatric inpatients with INS were included and given standard steroid therapy.Based on their clinical response to steroids,the patients were classified into three groups:steroid-sensitive nephrotic syndrome(SSNS),steroid-dependent nephrotic syndrome(SDNS),and steroid-resistant nephrotic syndrome(SRNS).A total of 100 healthy children were employed as controls.The blood genome DNA was extracted from each participant.Six SNPs(rs11536889,rs1927914,rs7869402,rs11536891,rs352140,and rs3804099)in TLR2,TLR4,and TLR9 were selected and detected by multiplex polymerase chain reaction with next-generation sequencing to assess TLR gene polymorphisms.Results Among the 183 patients with INS,89(48.6%)had SSNS,73(39.9%)had SDNS,and 21(11.5%)had SRNS.No significant difference was found in the genotype distribution between healthy children and patients with INS.However,the genotype and allele frequencies of TLR4 rs7869402 were significantly different between SRNS and SSNS.Compared with patients with the C allele and CC genotype,patients with the T allele and CT genotype had an increased risk of SRNS.Conclusion TLR4 rs7869402 affected the steroid response in Chinese children with INS.It might be a predictor for the early detection of SRNS in this population.展开更多
Background and objective Maintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer.PR-Set7(also known as Set8)is a cell cycle regulated enzyme that ca...Background and objective Maintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer.PR-Set7(also known as Set8)is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20(H4K20me1)to promote chromosome condensation and prevent DNA damage.Recent studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA damage.This might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA damage.Methods We developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A.We have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in vivo.With this model,staining of PR-Set7 in the preneoplastic and tumor lesions in Adeno Cre-induced mouse lungs was performed.Meanwhile we identified higher protein level changes ofγ-tubulin and pericentrin by IHC.Results The level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A.We also identified higher levels of the proteins pericentrin andγ-tubulin in Cul4A mouse lungs induced by Adeno Cre.Conclusion PR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model.展开更多
BACKGROUND The development of precision medicine is essential for personalized treatment and improved clinical outcome,whereas biomarkers are critical for the success of precision therapies.AIM To investigate whether ...BACKGROUND The development of precision medicine is essential for personalized treatment and improved clinical outcome,whereas biomarkers are critical for the success of precision therapies.AIM To investigate whether iCEMIGE(integration of CEll-morphometrics,MIcro-biome,and GEne biomarker signatures)improves risk stratification of breast cancer(BC)patients.METHODS We used our recently developed machine learning technique to identify cellular morphometric biomarkers(CMBs)from the whole histological slide images in The Cancer Genome Atlas(TCGA)breast cancer(TCGA-BRCA)cohort.Multivariate Cox regression was used to assess whether cell-morphometrics prognosis score(CMPS)and our previously reported 12-gene expression prognosis score(GEPS)and 15-microbe abundance prognosis score(MAPS)were independent prognostic factors.iCEMIGE was built upon the sparse representation learning technique.The iCEMIGE scoring model performance was measured by the area under the receiver operating characteristic curve compared to CMPS,GEPS,or MAPS alone.Nomogram models were created to predict overall survival(OS)and progress-free survival(PFS)rates at 5-and 10-year in the TCGA-BRCA cohort.RESULTS We identified 39 CMBs that were used to create a CMPS system in BCs.CMPS,GEPS,and MAPS were found to be significantly independently associated with OS.We then established an iCEMIGE scoring system for risk stratification of BC patients.The iGEMIGE score has a significant prognostic value for OS and PFS independent of clinical factors(age,stage,and estrogen and progesterone receptor status)and PAM50-based molecular subtype.Importantly,the iCEMIGE score significantly increased the power to predict OS and PFS compared to CMPS,GEPS,or MAPS alone.CONCLUSION Our study demonstrates a novel and generic artificial intelligence framework for multimodal data integration toward improving prognosis risk stratification of BC patients,which can be extended to other types of cancer.展开更多
Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal involvement.However,there are few studies on the risk factors...Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal involvement.However,there are few studies on the risk factors and predictive models for renal outcomes of AAV in children.Methods Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively.The risk factors and predictive model of end-stage renal disease(ESRD)in AAV were explored.Results Renal involvement was the most typical manifestation(95.5%),and the crescent was the predominant pathological lesion(84.9%).The estimated glomerular filtration rate(eGFR)was evaluated in 114 patients,of whom 59.6%developed ESRD,and the median time to ESRD was 3.20 months.The eGFR[P=0.006,odds ratio(OR)=0.955,95%confidence interval(CI)=0.924–0.987]and the percentages of global glomerulosclerosis(pGGS;P=0.018,OR=1.060,95%CI=1.010–1.112)were independent risk factors for ESRD of renal biopsy.Based on the pGGS and eGFR at renal biopsy,we developed three risk grades of ESRD and one predictive model.The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades(P<0.001).Compared with serum creatinine at baseline,the predictive model had higher accuracy(0.86 versus 0.58,P<0.001)and a lower coefficient of variation(0.07 versus 0.92)in external validation.Conclusions Renal involvement is the most common manifestation of pediatric AAV in China,of which more than half deteriorates into ESRD.The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.展开更多
Background Clinical studies suggest that the dysfunction of T cells and B cells may play an essential role in the pathogenesis of idiopathic nephrotic syndrome(INS),but laboratory evidence is lacking.Therefore,this st...Background Clinical studies suggest that the dysfunction of T cells and B cells may play an essential role in the pathogenesis of idiopathic nephrotic syndrome(INS),but laboratory evidence is lacking.Therefore,this study explored T-cell receptor(TCR)and B-cell receptor(BCR)profiling in children with idiopathic nephrotic syndrome.Methods High-throughput sequencing technology was used to profile the TCR and BCR repertoires in children with INS.Peripheral blood was collected from ten INS patients,including five vinculin autoantibody-positive patients and five vin-culin autoantibody-negative patients,before and after treatment.TCR and BCR libraries were constructed by 5'-RACE and sequenced by a DNBSEQ-T7 sequencer,and sequence analyses were performed using ReSeqTools,FastP,MiXCR,and VDJtools.Results The TRA(T-cell receptorα),TRG(T-cell receptor y),and IGH(immunoglobulin heavy chain)repertoires of the INS group were occupied by highly abundant clonotypes,whereas small clonotypes occupied the healthy group,especially TRA.A significant increase in the Shannon-Weaver index was observed for the TRA and TRG repertoires after treatment in vinculin autoantibody-negative patients,but a significant increase in the IGH repertoire after treatment was observed in vinculin autoantibody-positive patients.The frequency of some V-J pairs was significantly enriched in steroid-sensitive nephrotic syndrome patients.The usage frequency of the V and J genes was skewed in patients,which seemed not related to immunosuppressive therapy.However,after effective treatment,dynamic changes in the size of the individual clonotype were observed.Conclusion T-cell and B-cell immunity contribute to the pathogenesis of different INSs.展开更多
Background:Henoch-Schönlein purpura(HSP)is one of the most common vasculitides in children.It is manifested by skin purpura,arthritis,abdominal pain,renal involvement,etc.Typically,HSP is considered to be self-li...Background:Henoch-Schönlein purpura(HSP)is one of the most common vasculitides in children.It is manifested by skin purpura,arthritis,abdominal pain,renal involvement,etc.Typically,HSP is considered to be self-limiting,although renal involvement(HSP purpura nephritis,HSPN)is the principal cause of morbidity from this disease.For this reason,it is important to clarify the mechanism of onset and clinical manifestations of HSPN and to ascertain the most appropriate treatment for HSPN.In this article,we review the updated pathophysiology and treatment strategies for HSPN.Data sources:We searched databases including PubMed,Elsevier and Wanfang for the folowing key words:Henoch-Schönlein purpura,nephritis,mechanism and treatment,and we selected those publications written in English that we judged to be relevant to the topic of this review.Results:Based on the data present in the literature,we reviewed the following topics:1)the possible pathogenesis of HSPN:several studies suggest that immunoglobulin A immune complexes deposit in the mesangium and induce renal injury;2)multiple-drug treatment for HSPN:although there have been few evidence-based treatment strategies for HSPN,several studies have suggested that immunosuppressive drugs and multiple drug combination therapy were effective in ameliorating proteinuria and histological severity.Conclusions:HSPN is a severe disease of childhood.To better understand this disease,detailed investigations into the pathogenesis of HSPN and prospective randomized controlled treatment studies on children with severe HSPN are needed.展开更多
Background Idiopathic nephrotic syndrome is a common form of glomerular nephropathy in children,with an incidence rate of 1.15-16.9/100,000 depending on different nationalities and ethnicities.The etiological factors ...Background Idiopathic nephrotic syndrome is a common form of glomerular nephropathy in children,with an incidence rate of 1.15-16.9/100,000 depending on different nationalities and ethnicities.The etiological factors and mechanisms of childhood idiopathic nephrotic syndrome have not yet been fully elucidated.This review summarizes the progress of the immunopathogenesis of idiopathic nephrotic syndrome in children.Data sources We review the literature on the immunopathogenesis of idiopathic nephrotic syndrome in children.Databases including Medline,Scopus,and Web of Science were searched for studies published in any language with the terms"chil-dren","idiopathic nephrotic syndrome","immunopathogenesis","T cells","circulating permeability factors",and"B cells".Results Dysfunction in T lymphocytes and pathogenic circulatory factors were indicated to play key roles in the pathogenesis of idiopathic nephrotic syndrome.Recently,some studies have shown that cellular immune dysfunction may also be involved in the pathogenesis of idiopathic nephrotic syndrome.Conclusions Both T-and B-cell dysfunction may play significant roles in the pathogenesis of idiopathic nephrotic syndrome,like two sides of one coin,but the role of B cell seems more important than T cells.展开更多
Background:Congenital nephrotic syndrome(CNS),defined as heavy proteinuria,hypoalbuminemia,hyperlipidemia and edema presenting in the first 0-3 months of life,may be caused by congenital syphilis,toxoplasmosis,or cong...Background:Congenital nephrotic syndrome(CNS),defined as heavy proteinuria,hypoalbuminemia,hyperlipidemia and edema presenting in the first 0-3 months of life,may be caused by congenital syphilis,toxoplasmosis,or congenital viral infections(such as cytomegalovirus).However,the majority of CNS cases are caused by monogenic defects of structural proteins that form the glomerular fi ltration barrier in the kidneys.Since 1998,an increasing number of genetic defects have been identifi ed for their involvements in the pathogenesis of CNS,including NPHS1,NPHS2,WT1,PLCE1,and LAMB2.Data sources:We searched databases such as PubMed,Elsevier and Wanfang with the following key words:congenital nephrotic syndrome,proteinuria,infants,neonate,congenital infection,mechanism and treatment;and we selected those publications written in English that we judged to be relevant to the topic of this review.Results:Based on the data present in the literature,we reviewed the following topics:1)Infection associated CNS including congenital syphilis,congenital toxoplasmosis,and congenital cytomegalovirus infection;2)genetic CNS including mutation of NPHS1(Nephrin),NPHS2(Podocin),WT1,LAMB2(Laminin-β2),PLCE1(NPHS3);3)Other forms of CNS including maternal systemic lupus erythematosus,mercury poisoning,renal vein thrombosis,neonatal alloimmunization against neutral endopeptidase.Conclusions:At present,the main challenge in CNS is to identify the cause of disease for individual patients.To make a definitive diagnosis,with the exclusion of infection-related CNS and maternal-associated disorders,pathology,family history,inheritance mode,and other accompanying congenital malformations are sometimes,but not always,useful indicators for diagnosing genetic CNS.Next-generation sequencing would be a more effective method for diagnosing genetic CNS in some patients,however,there are still some challenges with next-generation sequencing that need to be resolved in the future.展开更多
Background Huaiqihuang(HQH)granule is a traditional Chinese herbal complex that has been used as an adjuvant treatment in clinics for the primary nephrotic syndrome(PNS)for many years.However,the effectiveness and saf...Background Huaiqihuang(HQH)granule is a traditional Chinese herbal complex that has been used as an adjuvant treatment in clinics for the primary nephrotic syndrome(PNS)for many years.However,the effectiveness and safety of HQH have not been systematically discussed.This review aimed to evaluate the effectiveness and safety of HQH in paediatric patients with PNS.Methods The following databases were searched from inception to Mar 2019:MEDLINE,Cochrane Library,EMBASE,CNKI,Wanfang Database,the Chinese Scientific Journal Database and the Chinese biomedical literature service system.All the randomized controlled trials(RCTs)eligible for inclusion were included.The primary outcomes were relapse,infection,remission and adverse events.The secondary outcomes included serum immunoglobulin levels(IgA,IgG or IgM),T-lymphocyte subtype(CD3+,CD4+,CD8+,CD4+/CD8+),IL-10,TNF-α,TNF-γ,total cholesterol and time of proteinuria turning negative.Results Fourteen RCTs(885 patients)were identified.Treatment with HQH reduced the chance of relapse[relative risk(RR):0.47;95%CI:0.34,0.66;P<0.001]and infections(RR:0.47;95%Cl:0.35,0.62;P<0.001).No significant difference was found in adverse events.HQH also increased the serum levels of IgA[weighted mean difference(WMD):0.40;95%Cl:0.20,0.60;P<0.001]and IgG(WMD:1.58;95%Cl:1.38-1.78;P<0.001),as well as CD4+[standard mean difference(SMD):0.90;95%Cl:0.12-1.68;P=0.02],CD3+(WMD:4.04;95% CI:3.27-4.82;P<0.001),and the CD4^(+)/CD8^(+)ratio(WMD:0.31;95% CI:0.21-0.41;P<0.001),but decreased the level of CD8+cells(WMD:-3.39;95% CI:-5.73-1.05;P=0.004).No statistically significant difference was found in IgM(WMD:0.05;95% CI:-0.13,0.24;P=0.57).Conclusions HQH could reduce the rate of relapse and the frequency of infection in children with PNS.No apparent adverse effects were found.Moreover,the beneficial influence of HQH may act through immunomodulation.Additional multi-center,large-sample,high-quality studies are needed to confirm the effectiveness and safety of HQH.展开更多
Background Dent disease is a rare tubulopathy characterized by manifestations of proximal tubular dysfunction,which occurs almost exclusively in males.It mainly presents symptoms in early childhood and may progress to...Background Dent disease is a rare tubulopathy characterized by manifestations of proximal tubular dysfunction,which occurs almost exclusively in males.It mainly presents symptoms in early childhood and may progress to end-stage renal failure between the 3rd and 5th decades of human life.According to its various genetic basis and to clinical signs and symp-toms,researchers define two forms of Dent disease(Dent diseases 1 and 2)and suggest that these forms are produced by mutations in the CLCN5 and OCRL genes,respectively.Dent diseases 1 and 2 account for 60% and 15% of all Dent disease cases,and their genetic cause is generally understood.However,the genetic cause of the remaining 25% of Dent disease cases remains unidentified.Data sources All relevant peer-reviewed original articles published thus far have been screened out from PubMed and have been referenced.Results Genetic testing has been used greatly to identify mutation types of CLCN5 and OCRL gene,and next-generation sequencing also has been used to identify an increasing number of unknown genotypes.Gene therapy may bring new hope to the treatment of Dent disease.The abuse of hormones and immunosuppressive agents for the treatment of Dent disease should be avoided to prevent unnecessary harm to children.Conclusions The current research progress in classification,genetic heterogeneity,diagnosis,and treatment of Dent disease reviewed in this paper enables doctors and researchers to better understand Dent disease and provides a basis for improved prevention and treatment.展开更多
Introduction Idiopathic nephrotic syndrome(INS)is one of the most common renal diseases in the pediatric population,which is characterized by massive proteinuria,hypoalbuminemia,edema,and hyperlipidemia[1].
Background Hereditary renal tubular disease can cause hypercalciuria,acid-base imbalance,hypokalemia,hypomagnesemia,rickets,kidney stones,etc.If these diseases are not diagnosed or treated in time,they can cause kidne...Background Hereditary renal tubular disease can cause hypercalciuria,acid-base imbalance,hypokalemia,hypomagnesemia,rickets,kidney stones,etc.If these diseases are not diagnosed or treated in time,they can cause kidney damage and electrolyte disturbances,which can be detrimental to the maturation and development of the child.Glomerular involvement in renal tubular disease patients has only been considered recently.Methods We screened 71 papers(including experimental research,clinical research,etc.)about Dent's disease,Gitelman syndrome,and cystinosis from PubMed,and made reference.Results Glomerular disease was initially underestimated among the clinical signs of renal tubular disease or was treated merely as a consequence of the tubular damage.Renal tubular diseases affect glomerular podocytes through certain mechanisms resulting in functional damage,morphological changes,and glomerular lesions.Conclusions This article focuses on the progress of changes in glomerular podocyte function in Dent disease,Gitelman syndrome,and cystinosis for the purposes of facilitating clinically accurate diagnosis and scientific treatment and improving prognosis.展开更多
Background Calcineurin inhibitors(CNIs)are commonly given to transplant recipients of kidneys and other solid organs and to patients with immune disorders,such as steroid-resistant nephrotic syndrome,steroid-dependent...Background Calcineurin inhibitors(CNIs)are commonly given to transplant recipients of kidneys and other solid organs and to patients with immune disorders,such as steroid-resistant nephrotic syndrome,steroid-dependent nephrotic syndrome,and frequent relapse nephrotic syndrome.Although CNIs remain the most effective available immunosuppressant agent,there is clinical concern regarding possible long-term nephrotoxicity.This concern is especially significant in children who have a longer life expectancy and greater growth rate.Data sources In this review,we analyzed the literatures to identify original articles that examined use of CNIs in children who received organ transplantation and nephropathy to assess the available evidence of their nephrotoxicity.PubMed,Elsevier,and Tompson ISI Web of Knowledge were searched for identifying relevant papers.Results Clinical research supports the presence of CNI-related nephrotoxicity.However,some researchers have questioned the prevalence and seriousness of chronic CNIs nephrotoxicity,especially because the pathological lesions typically associ-ated with long-term CNI use are nonspecific.Many researchers have focused on early markers of CNI nephrotoxicity,and the methods that may help prevent and manage nephrotoxicity.Conclusions Future research should focus on investigating early markers of CNI nephrotoxicity and strategies for improved immunosuppressant therapy,and developing alternative treatments.CNI-mediated nephrotoxicity should always be taken seriously in clinic.展开更多
Acute kidney injury (AKI) is a global public health concern with rapid decline in glomerular filtration rate and signifi-cant increase in serum creatinine and blood urea nitrogen, which is an independent risk factor f...Acute kidney injury (AKI) is a global public health concern with rapid decline in glomerular filtration rate and signifi-cant increase in serum creatinine and blood urea nitrogen, which is an independent risk factor for short-term and long-term mortality (1, 2)In addition to kidney disease, AKI can occur secondary to a variety of diseases, such as multi-organ dysfunction, respiratory distress syndrome, sepsis, losing of gastrointestinal fluids, cardiac surgery, using of nephrotoxic drugs and tumors. The most common causes for AKI of children include sepsis, ischemia and reperfusion injury and tubulointerstitial lesions (3)Additionally, morbidity and mortality were high in critically ill patients, especially for those who were admitted to pediatric intensive care unit (PICU) and underwent cardiac surgery (2–4)Although renal replacement therapies have greatly improved and can pro-vide relief for most patients, the mortality remained high for critically ill children as high as 10%, about six times higher than non-AKI patients (2)In the past few years, studies have reported that even mild elevation of serum creatinine levels may increase the risk of complications and mortality (5)In a prospective cohort study, 10.3% of survivors from AKI in the PICU eventually progress to chronic kidney disease [6].展开更多
Despite tremendous efforts to fight cancer,it remains a major public health problem and a leading cause of death worldwide.With increased knowledge of cancer pathways and improved technological platforms,precision the...Despite tremendous efforts to fight cancer,it remains a major public health problem and a leading cause of death worldwide.With increased knowledge of cancer pathways and improved technological platforms,precision therapeutics that specifically target aberrant cancer pathways have improved patient outcomes.Nevertheless,a primary cause of unsuccessful cancer therapy remains cancer drug resistance.In this review,we summarize the broad classes of resistance to cancer therapy,particularly pharmacokinetics,the tumor microenvironment,and drug resistance mechanisms.Furthermore,we describe how bacterial-mediated cancer therapy,a bygone mode of treatment,has been revitalized by synthetic biology and is uniquely suited to address the primary resistance mechanisms that confound traditional therapies.Through genetic engineering,we discuss how bacteria can be potent anticancer agents given their tumor targeting potential,anti-tumor activity,safety,and coordinated delivery of anti-cancer drugs.展开更多
Introduction To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis(PMNE),a new modified 3-day weekend frequency-volume chart(FVC)was designed,and the compliance and val...Introduction To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis(PMNE),a new modified 3-day weekend frequency-volume chart(FVC)was designed,and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society(ICCS)recommended voiding diary.Methods A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary.The primary outcome measure was the compliance,assessed by comparing the completing index and the quality score of diaries between two groups.The secondary outcome measure was the validity,evaluated by comparing the constituent of subtypes,micturition parameters and response rate to desmopressin.Results Among the 1200 participants enrolled in the study,447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary.The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group.In addition,there was no significant difference between these two groups in the subtype classification,or in the response rate to desmopressin.Conclusions The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.展开更多
To the Editor:As the coronavirus disease 2019(COVID-19)pandemic continues to expand in many countries,and the more transmissible variants emerged,the second wave could be more severe and result in a greater peak of in...To the Editor:As the coronavirus disease 2019(COVID-19)pandemic continues to expand in many countries,and the more transmissible variants emerged,the second wave could be more severe and result in a greater peak of infection and mortality.There is an urgent need to develop effective vaccines,which remains a critical tool to control the pandemic.Vaccination is equally important in areas where outbreaks persist and in well-controlled countries.展开更多
Background:Hemolytic uremic syndrome (HUS) is a main cause of acute renal failure in children.This study aimed to analyze the clinical characteristics of HUS.Methods:A retrospective analysis was performed in 46 childr...Background:Hemolytic uremic syndrome (HUS) is a main cause of acute renal failure in children.This study aimed to analyze the clinical characteristics of HUS.Methods:A retrospective analysis was performed in 46 children with sporadic HUS.Results:Of the 46 HUS patients,20 (43.5%) were diarrhea-related HUS,and 26 (56.5%) were atypical HUS.Anemia,edema,oliguria,hemoglobinuria and hypertension were the most common manifestations.Thrombocytopenia,hyponatremia,hypocalcemia,hyperkalemia,metabolic acidosis,increased fibrinogen and hypocomplementemia were found in most patients.The age of onset (younger than 2 years or not,P=0.009),the duration of oliguria or anuria (more than one week or not,P=0.005),accompanied with extrarenal complications or not (P=0.005),dialysis and plasma exchange (P=0.04) were associated with the mortality rate.Conclusion:The age of onset younger than 2 years,oliguria/anuria more than 1 week,and associated with extrarenal complications were predictive factors of poor prognosis.展开更多
基金Supported by the Scientific Research Projects of Jiangsu Provincial Health and Health Commission,No.ZDB2020034 and No.M2021056.
文摘BACKGROUND The understanding of bile acid(BA)and unsaturated fatty acid(UFA)profiles,as well as their dysregulation,remains elusive in individuals with type 2 diabetes mellitus(T2DM)coexisting with non-alcoholic fatty liver disease(NAFLD).Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM.AIM To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM.METHODS A training model was developed involving 399 participants,comprising 113 healthy controls(HCs),134 individuals with T2DM without NAFLD,and 152 individuals with T2DM and NAFLD.External validation encompassed 172 participants.NAFLD patients were divided based on liver fibrosis scores.The analytical approach employed univariate testing,orthogonal partial least squares-discriminant analysis,logistic regression,receiver operating characteristic curve analysis,and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers.RESULTS Compared to HCs,both T2DM and NAFLD groups exhibited diminished levels of specific BAs.In UFAs,particular acids exhibited a positive correlation with NAFLD risk in T2DM,while theω-6:ω-3 UFA ratio demonstrated a negative correlation.Levels ofα-linolenic acid andγ-linolenic acid were linked to significant liver fibrosis in NAFLD.The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients.CONCLUSION This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM,proposing their potential as biomarkers in the pathogenesis of NAFLD.
文摘This research examines the contentious issue of euthanasia and physician-assisted suicide in the context of China's unique conditions.Historically,the debate over euthanasia has been influenced by moral philosophy and ethics,and euthanasia is illegal in China at present.The research explores the difficulty in making euthanasia legalized across five key dimensions:financial,medical,social,legal,and psychological factors.We conclude that while there is a desire among some terminally ill patients for euthanasia,the current situation in China makes it unsuitable for legalization.The profound question of one's right to die remains a significant moral and judicial challenge,indicating the need for continued dialogue and nuanced understanding of this complex issue.
基金This study was funded by the Science and Technology Projects of Zhejiang Province(No.LGC21H200004)the Key Research and Development Plan of Zhejiang Province(No.2019C03028)the Medical Scientific Projects from Health Department of Zhejiang Province(No.2018KY455)。
文摘Objective Idiopathic nephrotic syndrome(INS)is the most common glomerular disease in children.Toll-like receptors(TLRs)have been reported to be associated with response to steroid treatment in children with INS.Nevertheless,the correlation between TLR genes and the progression of INS has not yet been clarified.The present study aimed to investigate the association of single-nucleotide polymorphisms(SNPs)in TLR2,TLR4,and TLR9 with susceptibility to INS as well as the clinical phenotyping of steroid responsiveness in Chinese children with INS.Methods A total of 183 pediatric inpatients with INS were included and given standard steroid therapy.Based on their clinical response to steroids,the patients were classified into three groups:steroid-sensitive nephrotic syndrome(SSNS),steroid-dependent nephrotic syndrome(SDNS),and steroid-resistant nephrotic syndrome(SRNS).A total of 100 healthy children were employed as controls.The blood genome DNA was extracted from each participant.Six SNPs(rs11536889,rs1927914,rs7869402,rs11536891,rs352140,and rs3804099)in TLR2,TLR4,and TLR9 were selected and detected by multiplex polymerase chain reaction with next-generation sequencing to assess TLR gene polymorphisms.Results Among the 183 patients with INS,89(48.6%)had SSNS,73(39.9%)had SDNS,and 21(11.5%)had SRNS.No significant difference was found in the genotype distribution between healthy children and patients with INS.However,the genotype and allele frequencies of TLR4 rs7869402 were significantly different between SRNS and SSNS.Compared with patients with the C allele and CC genotype,patients with the T allele and CT genotype had an increased risk of SRNS.Conclusion TLR4 rs7869402 affected the steroid response in Chinese children with INS.It might be a predictor for the early detection of SRNS in this population.
基金support from the Kazan, Mc Clain, Abrams, Fernandez, Lyons, Greenwood, Harley & Oberman Foundation, Incthe Estate of Robert Griffiths+3 种基金the Jeffrey and Karen Peterson Family FoundationPaul and Michelle Zygielbaumthe Estate of Norman Mancinithe Barbara Isackson Lung Cancer Research Fund
文摘Background and objective Maintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer.PR-Set7(also known as Set8)is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20(H4K20me1)to promote chromosome condensation and prevent DNA damage.Recent studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA damage.This might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA damage.Methods We developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A.We have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in vivo.With this model,staining of PR-Set7 in the preneoplastic and tumor lesions in Adeno Cre-induced mouse lungs was performed.Meanwhile we identified higher protein level changes ofγ-tubulin and pericentrin by IHC.Results The level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A.We also identified higher levels of the proteins pericentrin andγ-tubulin in Cul4A mouse lungs induced by Adeno Cre.Conclusion PR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model.
基金Supported by This work was supported by the Department of Defense(DoD)BCRP,No.BC190820the National Cancer Institute(NCI)at the National Institutes of Health(NIH),No.R01CA184476+1 种基金MCIN/AEI/10.13039/501100011039,No.PID2020-118527RB-I00,and No.PDC2021-121735-I00the“European Union Next Generation EU/PRTR.”the Regional Government of Castile and León,No.CSI144P20.Lawrence Berkeley National Laboratory(LBNL)is a multi-program national laboratory operated by the University of California for the DOE under contract DE AC02-05CH11231.
文摘BACKGROUND The development of precision medicine is essential for personalized treatment and improved clinical outcome,whereas biomarkers are critical for the success of precision therapies.AIM To investigate whether iCEMIGE(integration of CEll-morphometrics,MIcro-biome,and GEne biomarker signatures)improves risk stratification of breast cancer(BC)patients.METHODS We used our recently developed machine learning technique to identify cellular morphometric biomarkers(CMBs)from the whole histological slide images in The Cancer Genome Atlas(TCGA)breast cancer(TCGA-BRCA)cohort.Multivariate Cox regression was used to assess whether cell-morphometrics prognosis score(CMPS)and our previously reported 12-gene expression prognosis score(GEPS)and 15-microbe abundance prognosis score(MAPS)were independent prognostic factors.iCEMIGE was built upon the sparse representation learning technique.The iCEMIGE scoring model performance was measured by the area under the receiver operating characteristic curve compared to CMPS,GEPS,or MAPS alone.Nomogram models were created to predict overall survival(OS)and progress-free survival(PFS)rates at 5-and 10-year in the TCGA-BRCA cohort.RESULTS We identified 39 CMBs that were used to create a CMPS system in BCs.CMPS,GEPS,and MAPS were found to be significantly independently associated with OS.We then established an iCEMIGE scoring system for risk stratification of BC patients.The iGEMIGE score has a significant prognostic value for OS and PFS independent of clinical factors(age,stage,and estrogen and progesterone receptor status)and PAM50-based molecular subtype.Importantly,the iCEMIGE score significantly increased the power to predict OS and PFS compared to CMPS,GEPS,or MAPS alone.CONCLUSION Our study demonstrates a novel and generic artificial intelligence framework for multimodal data integration toward improving prognosis risk stratification of BC patients,which can be extended to other types of cancer.
基金approved by the Ethics Committee of the Children’s Hospital of Chongqing Medical University(approval Number:149/2022)other enrolled centers.This study was registered at the Chinese Clinical Trial Registry(registered number:ChiCTR2000034203).
文摘Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal involvement.However,there are few studies on the risk factors and predictive models for renal outcomes of AAV in children.Methods Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively.The risk factors and predictive model of end-stage renal disease(ESRD)in AAV were explored.Results Renal involvement was the most typical manifestation(95.5%),and the crescent was the predominant pathological lesion(84.9%).The estimated glomerular filtration rate(eGFR)was evaluated in 114 patients,of whom 59.6%developed ESRD,and the median time to ESRD was 3.20 months.The eGFR[P=0.006,odds ratio(OR)=0.955,95%confidence interval(CI)=0.924–0.987]and the percentages of global glomerulosclerosis(pGGS;P=0.018,OR=1.060,95%CI=1.010–1.112)were independent risk factors for ESRD of renal biopsy.Based on the pGGS and eGFR at renal biopsy,we developed three risk grades of ESRD and one predictive model.The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades(P<0.001).Compared with serum creatinine at baseline,the predictive model had higher accuracy(0.86 versus 0.58,P<0.001)and a lower coefficient of variation(0.07 versus 0.92)in external validation.Conclusions Renal involvement is the most common manifestation of pediatric AAV in China,of which more than half deteriorates into ESRD.The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.
基金supported by the Natural Science Foundation of Zhejiang Province(LY22H050001)the National Natural Science Foundation of China(82270741,U20A20351)+1 种基金the Key Project of Provincial Ministry Coconstruction,Health Science,and Technology Project Plan of Zhejiang Province(WKJ-ZJ-2128)Yiluqihang Shenmingyuanyang Medical Development and Scientific Research Fund Project on Kidney Diseases(SMYY20220301001).
文摘Background Clinical studies suggest that the dysfunction of T cells and B cells may play an essential role in the pathogenesis of idiopathic nephrotic syndrome(INS),but laboratory evidence is lacking.Therefore,this study explored T-cell receptor(TCR)and B-cell receptor(BCR)profiling in children with idiopathic nephrotic syndrome.Methods High-throughput sequencing technology was used to profile the TCR and BCR repertoires in children with INS.Peripheral blood was collected from ten INS patients,including five vinculin autoantibody-positive patients and five vin-culin autoantibody-negative patients,before and after treatment.TCR and BCR libraries were constructed by 5'-RACE and sequenced by a DNBSEQ-T7 sequencer,and sequence analyses were performed using ReSeqTools,FastP,MiXCR,and VDJtools.Results The TRA(T-cell receptorα),TRG(T-cell receptor y),and IGH(immunoglobulin heavy chain)repertoires of the INS group were occupied by highly abundant clonotypes,whereas small clonotypes occupied the healthy group,especially TRA.A significant increase in the Shannon-Weaver index was observed for the TRA and TRG repertoires after treatment in vinculin autoantibody-negative patients,but a significant increase in the IGH repertoire after treatment was observed in vinculin autoantibody-positive patients.The frequency of some V-J pairs was significantly enriched in steroid-sensitive nephrotic syndrome patients.The usage frequency of the V and J genes was skewed in patients,which seemed not related to immunosuppressive therapy.However,after effective treatment,dynamic changes in the size of the individual clonotype were observed.Conclusion T-cell and B-cell immunity contribute to the pathogenesis of different INSs.
基金supported by grants from the National Natural Science Foundation of China(Grant.81270792,81470939 and 81170664)State"1025"Science and Technology Support Project(2012BAI03B02)the Research Fund for the Doctoral Program of Higher Education of China(20120101110018)
文摘Background:Henoch-Schönlein purpura(HSP)is one of the most common vasculitides in children.It is manifested by skin purpura,arthritis,abdominal pain,renal involvement,etc.Typically,HSP is considered to be self-limiting,although renal involvement(HSP purpura nephritis,HSPN)is the principal cause of morbidity from this disease.For this reason,it is important to clarify the mechanism of onset and clinical manifestations of HSPN and to ascertain the most appropriate treatment for HSPN.In this article,we review the updated pathophysiology and treatment strategies for HSPN.Data sources:We searched databases including PubMed,Elsevier and Wanfang for the folowing key words:Henoch-Schönlein purpura,nephritis,mechanism and treatment,and we selected those publications written in English that we judged to be relevant to the topic of this review.Results:Based on the data present in the literature,we reviewed the following topics:1)the possible pathogenesis of HSPN:several studies suggest that immunoglobulin A immune complexes deposit in the mesangium and induce renal injury;2)multiple-drug treatment for HSPN:although there have been few evidence-based treatment strategies for HSPN,several studies have suggested that immunosuppressive drugs and multiple drug combination therapy were effective in ameliorating proteinuria and histological severity.Conclusions:HSPN is a severe disease of childhood.To better understand this disease,detailed investigations into the pathogenesis of HSPN and prospective randomized controlled treatment studies on children with severe HSPN are needed.
基金This study was supported by the National Natural Foundation of China(81770710)Key Research and Development Plan of Zhejiang Province(2019C03028)the Major projects jointly constructed by the Zhejiang Province,and National Health Commission(WKJ-ZJ-1908).
文摘Background Idiopathic nephrotic syndrome is a common form of glomerular nephropathy in children,with an incidence rate of 1.15-16.9/100,000 depending on different nationalities and ethnicities.The etiological factors and mechanisms of childhood idiopathic nephrotic syndrome have not yet been fully elucidated.This review summarizes the progress of the immunopathogenesis of idiopathic nephrotic syndrome in children.Data sources We review the literature on the immunopathogenesis of idiopathic nephrotic syndrome in children.Databases including Medline,Scopus,and Web of Science were searched for studies published in any language with the terms"chil-dren","idiopathic nephrotic syndrome","immunopathogenesis","T cells","circulating permeability factors",and"B cells".Results Dysfunction in T lymphocytes and pathogenic circulatory factors were indicated to play key roles in the pathogenesis of idiopathic nephrotic syndrome.Recently,some studies have shown that cellular immune dysfunction may also be involved in the pathogenesis of idiopathic nephrotic syndrome.Conclusions Both T-and B-cell dysfunction may play significant roles in the pathogenesis of idiopathic nephrotic syndrome,like two sides of one coin,but the role of B cell seems more important than T cells.
基金supported by National Natural Science Foundation of China(Grant Nos.81270792,81470939 and 81170664)Zhejiang Provincial Natural Science Foundation of China(LH14H050002)+1 种基金Research Fund for the Doctoral Program of Higher Education of China(20120101110018)Zhejiang Provincial Healthy Science Foundation of China(2012KYA119,2014KYA123)。
文摘Background:Congenital nephrotic syndrome(CNS),defined as heavy proteinuria,hypoalbuminemia,hyperlipidemia and edema presenting in the first 0-3 months of life,may be caused by congenital syphilis,toxoplasmosis,or congenital viral infections(such as cytomegalovirus).However,the majority of CNS cases are caused by monogenic defects of structural proteins that form the glomerular fi ltration barrier in the kidneys.Since 1998,an increasing number of genetic defects have been identifi ed for their involvements in the pathogenesis of CNS,including NPHS1,NPHS2,WT1,PLCE1,and LAMB2.Data sources:We searched databases such as PubMed,Elsevier and Wanfang with the following key words:congenital nephrotic syndrome,proteinuria,infants,neonate,congenital infection,mechanism and treatment;and we selected those publications written in English that we judged to be relevant to the topic of this review.Results:Based on the data present in the literature,we reviewed the following topics:1)Infection associated CNS including congenital syphilis,congenital toxoplasmosis,and congenital cytomegalovirus infection;2)genetic CNS including mutation of NPHS1(Nephrin),NPHS2(Podocin),WT1,LAMB2(Laminin-β2),PLCE1(NPHS3);3)Other forms of CNS including maternal systemic lupus erythematosus,mercury poisoning,renal vein thrombosis,neonatal alloimmunization against neutral endopeptidase.Conclusions:At present,the main challenge in CNS is to identify the cause of disease for individual patients.To make a definitive diagnosis,with the exclusion of infection-related CNS and maternal-associated disorders,pathology,family history,inheritance mode,and other accompanying congenital malformations are sometimes,but not always,useful indicators for diagnosing genetic CNS.Next-generation sequencing would be a more effective method for diagnosing genetic CNS in some patients,however,there are still some challenges with next-generation sequencing that need to be resolved in the future.
基金supported by the National Natural Foundation of China(81470939 and 81770710)the Natural Science Foundation of Zhejiang Province(LH14H050002,LY15H050001)the Zhejiang Medical and Health Science and Technology Project(2016KYB177).
文摘Background Huaiqihuang(HQH)granule is a traditional Chinese herbal complex that has been used as an adjuvant treatment in clinics for the primary nephrotic syndrome(PNS)for many years.However,the effectiveness and safety of HQH have not been systematically discussed.This review aimed to evaluate the effectiveness and safety of HQH in paediatric patients with PNS.Methods The following databases were searched from inception to Mar 2019:MEDLINE,Cochrane Library,EMBASE,CNKI,Wanfang Database,the Chinese Scientific Journal Database and the Chinese biomedical literature service system.All the randomized controlled trials(RCTs)eligible for inclusion were included.The primary outcomes were relapse,infection,remission and adverse events.The secondary outcomes included serum immunoglobulin levels(IgA,IgG or IgM),T-lymphocyte subtype(CD3+,CD4+,CD8+,CD4+/CD8+),IL-10,TNF-α,TNF-γ,total cholesterol and time of proteinuria turning negative.Results Fourteen RCTs(885 patients)were identified.Treatment with HQH reduced the chance of relapse[relative risk(RR):0.47;95%CI:0.34,0.66;P<0.001]and infections(RR:0.47;95%Cl:0.35,0.62;P<0.001).No significant difference was found in adverse events.HQH also increased the serum levels of IgA[weighted mean difference(WMD):0.40;95%Cl:0.20,0.60;P<0.001]and IgG(WMD:1.58;95%Cl:1.38-1.78;P<0.001),as well as CD4+[standard mean difference(SMD):0.90;95%Cl:0.12-1.68;P=0.02],CD3+(WMD:4.04;95% CI:3.27-4.82;P<0.001),and the CD4^(+)/CD8^(+)ratio(WMD:0.31;95% CI:0.21-0.41;P<0.001),but decreased the level of CD8+cells(WMD:-3.39;95% CI:-5.73-1.05;P=0.004).No statistically significant difference was found in IgM(WMD:0.05;95% CI:-0.13,0.24;P=0.57).Conclusions HQH could reduce the rate of relapse and the frequency of infection in children with PNS.No apparent adverse effects were found.Moreover,the beneficial influence of HQH may act through immunomodulation.Additional multi-center,large-sample,high-quality studies are needed to confirm the effectiveness and safety of HQH.
基金supported by National Natural Foundation of China(81470939&81770710)Natural Science Foundation of Zhejiang Province(LH14H050002,LY15H050001,LQ18H050001)Ai You Foundation.
文摘Background Dent disease is a rare tubulopathy characterized by manifestations of proximal tubular dysfunction,which occurs almost exclusively in males.It mainly presents symptoms in early childhood and may progress to end-stage renal failure between the 3rd and 5th decades of human life.According to its various genetic basis and to clinical signs and symp-toms,researchers define two forms of Dent disease(Dent diseases 1 and 2)and suggest that these forms are produced by mutations in the CLCN5 and OCRL genes,respectively.Dent diseases 1 and 2 account for 60% and 15% of all Dent disease cases,and their genetic cause is generally understood.However,the genetic cause of the remaining 25% of Dent disease cases remains unidentified.Data sources All relevant peer-reviewed original articles published thus far have been screened out from PubMed and have been referenced.Results Genetic testing has been used greatly to identify mutation types of CLCN5 and OCRL gene,and next-generation sequencing also has been used to identify an increasing number of unknown genotypes.Gene therapy may bring new hope to the treatment of Dent disease.The abuse of hormones and immunosuppressive agents for the treatment of Dent disease should be avoided to prevent unnecessary harm to children.Conclusions The current research progress in classification,genetic heterogeneity,diagnosis,and treatment of Dent disease reviewed in this paper enables doctors and researchers to better understand Dent disease and provides a basis for improved prevention and treatment.
基金supported by the National Natural Foundation of China(81470939 and 81770710)Natural Science Foundation of Zhejiang Province(LH14H050002,LY15H050001,Q18H050002).
文摘Introduction Idiopathic nephrotic syndrome(INS)is one of the most common renal diseases in the pediatric population,which is characterized by massive proteinuria,hypoalbuminemia,edema,and hyperlipidemia[1].
文摘Background Hereditary renal tubular disease can cause hypercalciuria,acid-base imbalance,hypokalemia,hypomagnesemia,rickets,kidney stones,etc.If these diseases are not diagnosed or treated in time,they can cause kidney damage and electrolyte disturbances,which can be detrimental to the maturation and development of the child.Glomerular involvement in renal tubular disease patients has only been considered recently.Methods We screened 71 papers(including experimental research,clinical research,etc.)about Dent's disease,Gitelman syndrome,and cystinosis from PubMed,and made reference.Results Glomerular disease was initially underestimated among the clinical signs of renal tubular disease or was treated merely as a consequence of the tubular damage.Renal tubular diseases affect glomerular podocytes through certain mechanisms resulting in functional damage,morphological changes,and glomerular lesions.Conclusions This article focuses on the progress of changes in glomerular podocyte function in Dent disease,Gitelman syndrome,and cystinosis for the purposes of facilitating clinically accurate diagnosis and scientific treatment and improving prognosis.
基金the National Natural Science Foundation of China(81470939,81270792 and 81170664)the Specialized Research Fund for the Doctoral Program of Higher Education(20120101110018)+1 种基金the Natural Science Foundation of Zhejiang Province(LH14H050002,LY15H050001)the Medicine&Health Technology Innovation Project of Zhejiang Province(2014KYA123)
文摘Background Calcineurin inhibitors(CNIs)are commonly given to transplant recipients of kidneys and other solid organs and to patients with immune disorders,such as steroid-resistant nephrotic syndrome,steroid-dependent nephrotic syndrome,and frequent relapse nephrotic syndrome.Although CNIs remain the most effective available immunosuppressant agent,there is clinical concern regarding possible long-term nephrotoxicity.This concern is especially significant in children who have a longer life expectancy and greater growth rate.Data sources In this review,we analyzed the literatures to identify original articles that examined use of CNIs in children who received organ transplantation and nephropathy to assess the available evidence of their nephrotoxicity.PubMed,Elsevier,and Tompson ISI Web of Knowledge were searched for identifying relevant papers.Results Clinical research supports the presence of CNI-related nephrotoxicity.However,some researchers have questioned the prevalence and seriousness of chronic CNIs nephrotoxicity,especially because the pathological lesions typically associ-ated with long-term CNI use are nonspecific.Many researchers have focused on early markers of CNI nephrotoxicity,and the methods that may help prevent and manage nephrotoxicity.Conclusions Future research should focus on investigating early markers of CNI nephrotoxicity and strategies for improved immunosuppressant therapy,and developing alternative treatments.CNI-mediated nephrotoxicity should always be taken seriously in clinic.
基金grants from National Natural Science Foundation of China(No.81770710,81470939 to Jian-Hua Mao)Natural Science Foundation of Zhejiang Province(No.LH14H050002,LY15H050001 to Jian-Hua Mao).
文摘Acute kidney injury (AKI) is a global public health concern with rapid decline in glomerular filtration rate and signifi-cant increase in serum creatinine and blood urea nitrogen, which is an independent risk factor for short-term and long-term mortality (1, 2)In addition to kidney disease, AKI can occur secondary to a variety of diseases, such as multi-organ dysfunction, respiratory distress syndrome, sepsis, losing of gastrointestinal fluids, cardiac surgery, using of nephrotoxic drugs and tumors. The most common causes for AKI of children include sepsis, ischemia and reperfusion injury and tubulointerstitial lesions (3)Additionally, morbidity and mortality were high in critically ill patients, especially for those who were admitted to pediatric intensive care unit (PICU) and underwent cardiac surgery (2–4)Although renal replacement therapies have greatly improved and can pro-vide relief for most patients, the mortality remained high for critically ill children as high as 10%, about six times higher than non-AKI patients (2)In the past few years, studies have reported that even mild elevation of serum creatinine levels may increase the risk of complications and mortality (5)In a prospective cohort study, 10.3% of survivors from AKI in the PICU eventually progress to chronic kidney disease [6].
基金This work was supported by a grant from National Institutes of Health Awards(F32GM125179).
文摘Despite tremendous efforts to fight cancer,it remains a major public health problem and a leading cause of death worldwide.With increased knowledge of cancer pathways and improved technological platforms,precision therapeutics that specifically target aberrant cancer pathways have improved patient outcomes.Nevertheless,a primary cause of unsuccessful cancer therapy remains cancer drug resistance.In this review,we summarize the broad classes of resistance to cancer therapy,particularly pharmacokinetics,the tumor microenvironment,and drug resistance mechanisms.Furthermore,we describe how bacterial-mediated cancer therapy,a bygone mode of treatment,has been revitalized by synthetic biology and is uniquely suited to address the primary resistance mechanisms that confound traditional therapies.Through genetic engineering,we discuss how bacteria can be potent anticancer agents given their tumor targeting potential,anti-tumor activity,safety,and coordinated delivery of anti-cancer drugs.
基金funding from the National Natural Foundation of China(81770710)Key Research and Development Plan of Zhejiang Province(2019C03028)+1 种基金the Major projects jointly constructed by the Zhejiang province and National Health Commission(WKJ-ZJ-1908)the Natural Science Foundation of Zhejiang Province(LQ18H050001).
文摘Introduction To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis(PMNE),a new modified 3-day weekend frequency-volume chart(FVC)was designed,and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society(ICCS)recommended voiding diary.Methods A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary.The primary outcome measure was the compliance,assessed by comparing the completing index and the quality score of diaries between two groups.The secondary outcome measure was the validity,evaluated by comparing the constituent of subtypes,micturition parameters and response rate to desmopressin.Results Among the 1200 participants enrolled in the study,447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary.The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group.In addition,there was no significant difference between these two groups in the subtype classification,or in the response rate to desmopressin.Conclusions The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.
文摘To the Editor:As the coronavirus disease 2019(COVID-19)pandemic continues to expand in many countries,and the more transmissible variants emerged,the second wave could be more severe and result in a greater peak of infection and mortality.There is an urgent need to develop effective vaccines,which remains a critical tool to control the pandemic.Vaccination is equally important in areas where outbreaks persist and in well-controlled countries.
基金This study was supported by National Natural Science Foundation of China(81270045 and 30771009)Zhejiang Provincial Natural Science Foundation of China(LY16H160024 and Y206058).
文摘Background:Hemolytic uremic syndrome (HUS) is a main cause of acute renal failure in children.This study aimed to analyze the clinical characteristics of HUS.Methods:A retrospective analysis was performed in 46 children with sporadic HUS.Results:Of the 46 HUS patients,20 (43.5%) were diarrhea-related HUS,and 26 (56.5%) were atypical HUS.Anemia,edema,oliguria,hemoglobinuria and hypertension were the most common manifestations.Thrombocytopenia,hyponatremia,hypocalcemia,hyperkalemia,metabolic acidosis,increased fibrinogen and hypocomplementemia were found in most patients.The age of onset (younger than 2 years or not,P=0.009),the duration of oliguria or anuria (more than one week or not,P=0.005),accompanied with extrarenal complications or not (P=0.005),dialysis and plasma exchange (P=0.04) were associated with the mortality rate.Conclusion:The age of onset younger than 2 years,oliguria/anuria more than 1 week,and associated with extrarenal complications were predictive factors of poor prognosis.
