Objective To investigate the effect of suppressor of cytokine signaling 3 (SOCS3)on the proliferation of human mesangial cells stimulated by aggregated IgA1 (aIgA1) from patients with IgA nephropathy(IgAN),and explore its possible mechanism.Methods Serum monomeric IgA1 was isolated with jacalin affinity and Sephacryl S-200 HR chromatography from IgAN patients,and then heated to aggregated form (aIgA1).Human glomerular mesangial cells(HMC) were transfected with AdvSOCS3-IRES2-EGFP for 48 hours,and incubated with aIgA1 for 12-48 h.The cells were divided into blank control group,IgA1 group,IgA1 +Adv-EGFP group and IgA 1 +Adv-SOCS3-IRES2-EGFP group.The mesangial cell proliferation was observed through MTT,and the levels of SOCS3,TLR4,TGF-β1 protein and mRNA were detected through Western blotting and real-time PCR.Results HMC proliferation was promoted significantly after IgA1 stimulated at 24 h.Compared with control group,the protein and mRNA expression of SOCS3,TLR4,TGF-β1 were significantly increased in IgA1 group (P ＜ 0.05).Compared with IgA1 group and IgA1 +Adv-EGFP group,MTT absorbency was obviously reduced after incubation with aIgA1 for 24 h and 48 h in IgA+Adv-SOCS3-IRES2-EGFP group,and the protein and mRNA expression of TLR4 and TGF-β1 were significantly decreased in IgA1 +AdvSOCS3-EGFP group (P＜ 0.05).Conclusion Over-expression of SOCS3 may inhibit the proliferation of HMC stimulated by aIgA1,partly through down-regulating the expression of TLR4 and TGF-β1.

Objective To investigate the effect and mechanism of Src kinase in renal interstitial fibrosis of unilateral ureteral obstruction (UUO) mice.Methods Male C57BL/6J mice were randomly divided into 4 groups,including sham operation group (n=8),sham operation+PP2 group (n=8),UUO operation group (n=8) and UUO operation+PP2 group (n=8).The mice were injected 2 mg/kg PP2 by intraperitoneal everyday after surgery in sham+PP2 group and UUO+PP2 group.PP2 dissolved in 1％ DMSO (formulated with normal saline).Sham and UUO group were given equal 1％ DMSO.The mice were sacrificed at 7th day.Renal collagen was observed with Sirius red stain.The activities of Src,protein kinase B (PKB,AKT),p38 mitogen-activated protein kinase (p38 MAPK),extracellular signal-regulated kinase (ERK) and the protein expressions of α-smooth muscle actin (α-SMA) and fibronectin (FN) were detected by Western blotting.The expression of collagen I (COL [) was detected by immunohistochemistry and the expressions of matrix metalloprotein 9 (MMP-9),tissue inhibitor of metalloproteinase 1 (TIMP-1),transforming growth factor-β31 (TGF-β31),monocyte chemotactic protein-1(MCP-1),interleukin-6 (IL-6) were measured by ELISA.Resuts Compared with sham mice,UUO mice on 7th day displayed obvious renal fibrosis.Meanwhile,UUO mice had increased expressions of COL Ⅰ and FN,and activities of AKT,ERK and p38 MAPK (all P ＜ 0.05).Their renal expressions of α-SMA,TGF-β1,MMP-9,TIMP-1,MCP-1 and IL-6 were also raised (all P ＜ 0.05).Compared with those in UUO group,in UUO + PP2 group the activities of Src,AKT,p38 MAPK and ERK,and expressions of TGF-β1,MCP-1 and IL-6 decreased (all P ＜ 0.05).Additionally,expressions of COL Ⅰ,FN and α-SMA,collagen deposition and renal fibrosis receded in UUO + PP2 group (all P ＜ 0.05).However,the expressions of MMP-9 and TIMP-1 were not influenced by PP2 treatment.Conclusions Src kinase promotes myofibroblasts accumulation and inflammatory reaction through activating its downstream signaling pathway in the progressing of renal interstitial fibrosis.

Objective To investigate the microbiological trends and antibiotic susceptibility of peritoneal dialysis(PD)-related peritonitis (PDAP).Methods All patients who developed PDAP between 2004 and 2015 in Renji Hospital,Shanghai Jiao Tong University School of Medicine were enrolled.Demographic data,results of dialysate pathogen culture and drug susceptibility test were recorded.The trend of peritonitis incidence was measured by Poisson regression and the chi-square test or Fisher exact test method was used to compare the composition of causative organisms and their antimicrobial susceptibilities over time.Results During the study period,a total of 711 episodes of PDAP were occurred in 386 patients.The culture positive rate of pathogens rose from 52.0％ in 2004 to 77.0％ in 2015 (P ＜ 0.001).The distribution of causative organisms of the culture positive peritonitis was gram-positive bacteria (270,59.5％),followed by gram-negative bacteria (129,28.4％),polymicrobial(39,8.6％),fungi (15,3.3％) and mycobacteria (1,0.2％).From 2004 to 2015,the incidence of peritonitis decreased from 0.214 to 0.160 episodes/patient·year (P=0.034).The incidence of coagulase-negative staphylococcus peritonitis decreased from 0.049 to 0.027 episodes/patient · year (P=0.025),while others had no significant change;A significant decline was observed in the sensitivity of Gram-positive strains to the first generation cephalosporin and ampicillin/sulbactam in 2010-2015 group compared with those in 2001-2009 group (61.3％ vs 88.2％,P ＜ 0.001;61.7％ vs 85.5％,P=0,001),whereas the sensitivity to vancomycin remained the same.The sensitivity of Gram-negative strains to ceftazidime and amikacin showed no significant change.As for the gram-positive peritonitis treated with cefradine as empirical treatment,compared with those in 2004-2009 group,in 2010-2015group the proportion of patients requiring to change their treatment regime was significantly higher,and the treatment course was longer.Conclusions A gradual decline is observed in the incidence of PDAP and the culture positive rate of pathogens improves.Peritonitis caused by coagulase-negative staphylococcus decreases overtime.The present empirical treatment protocols may need re-evaluation considering the decreased rate of the first generation cephalosporin sensitivity in recent years.

Objective To investigate the prevalence,missed diagnosis rate and causes of acute kidney injury (AKI) in hospitalized children,and its impact on hospitalization cost,length of stay and outcome.Methods The data of children admitted in Children's Hospital Affiliated to Capital Institute of Pediatrics from December 1st to 31st 2014 were collected,and those whose serum creatinine (Scr) were measured at least two times were selected.Patients were diagnosed as AKI according to the diagnostic criteria of 2012 Kidney Disease:Improving Global Outcomes,then divided into AKI group and non-AKI group,the former of which was further divided into AKI1 group (Scr peak value in normal range) and AKI2 group (Scr peak value above normal range).The causes and impact of AKI on hospitalization cost,length of stay and outcome in different groups were compared and analyzed.Results (1) Among 921 patients with at least two Scr results,170 patients met with the diagnostic criteria of AKI,including 100 males and 70 females.There were 112(65.9％) in AKI stage 1,43(25.3％) in stage 2,and 15(8.8％) in stage 3.The overall prevalence of AKI was 18.5％.With only 7cases getting diagnosed,the diagnostic rate was 4.1％,while 95.9％ of patients missed diagnosis.(2)Among AKI patients,67 cases had pre-renal causes,103 cases had intra-renal causes and mixed factors.100(58.8％) cases got complete recovery,34(20.0％) cases recovered partially and 36(21.2％)cases did not improve,including 4 cases of death.(3) The prevalence of AKI among those below 1-year old was higher than children elder than 1-year (23.0％ vs 15.5％,P=0.004).The prevalence of AKI in surgical ward was higher than medical ward (30.7％ vs 15.8％,P ＜ 0.001).(4) Compared with those in non-AKI group,there was lower age [1.1(0.2,3.5) year vs 2.0(0.3,4.9) year] and higher hospitalization time[12.5(8.0,20.0) d vs 8.0(6.0,11.0) d],hospitalization costs [25 279.2(13 822.8,48 856.7) yuan vs 12 616.9(8680.1,19 345.1) yuan] and mortality (2.4％ vs 0.3％) in AKI group (all P ＜ 0.05).(5) There were 126 cases in AKL group and 44 cases in AKI2 group.The costs of hospitalization,outcome and mortality showed no difference between two groups (all P ＞ 0.05).The hospitalization time in AKI2 group was shorter than that in AKL group (P=0.038).Conclusions Among hospitalized children the missed diagnosis rate of AKI is high.Pre-renal factor is the main cause of AKI.Children younger than 1-year old are more susceptible to AKI.AKI children have lower age and higher hospitalization time,hospitalization costs and mortality than non-AKI children.The effect of Scr fluctuation within normal levels needs to be further studied.

Objective To analyze the mutations of causal genes in sixteen Chinese patients with suspicious Bartter syndrome,and follow up their treatment results.Methods Mutations were identified by the next generation sequencing and the multiplex ligation-dependent probe amplification (MLPA).Clinical and biochemical features at the first presentation as well as follow-up results were reviewed.Results 15 different CLCNKB gene mutations were identified in sixteen patients with BS,including 11 novel ones.A novel missense mutation and a novel small deletion were found from SLC12A1 gene.A novel gross deletion was found in CLCNKA gene.A recurrent missense mutation was identified from BSND gene.The whole gene deletion mutation of CLCNKB gene was the most frequent mutation (32％),and the rate of gross deletion was up to 50 percent in this group of Chinese patients.The most common clinical manifestations were development retardation (15/16),polydipsia and polyuria (15/16).All of the patients were detected with hypokalemia,hypochloremia and metabolic alkalosis.Indomethacin treatment had significant improvement to the stature and weight restoration.Conclusion The present study has found 19 mutations,including 14 novel ones,which enriches the human gene mutation database (HGMD) and provides valuable references to the genetic counseling and diagnosis of Chinese population.

Objective To investigate the clinicopathological characteristics of IgAN patients with massive proteinuria,as well as their treatment response to glucocorticoids and long-term prognosis.Methods Clinical and pathological parameters were collected in patients diagnosed with IgA nephropathy in our hospital from Jan 2003 to Oct 2015.Patients were followed up for at least six months under the treatment with full dosage of glucocorticoids.Responses of patients with and without nephrotic syndrome were compared.Results A total of 156 patients were enrolled for the analysis (86 patients in the nephropathic proteinuria group,and 70 patients in the nephrotic syndrome group).Patients presented with nephrotic syndrome showed higher proportion of IgM deposition in renal slides.There exited no difference in treatment response to glucocorticoids between the two groups.Patients with full or partial remission showed a better prognosis by Kaplan-Meier analysis than no remission group (P ＜ 0.001).The ratio of segmental sclerosis was negatively correlated with treatment response to glucocorticoids by multiple linear regression (3 value=-0.330,P ＜ 0.001).Multivariate Cox regression model showed that glomerular density (HR=0.45,P=0.02) and eGFR (HR=0.95,P=0.001)were independent influential factors for renal survival.Conclusions Patients presented with nephrotic syndrome show higher proportion of IgM deposition in renal slides.Patients in remission after treatment with 6-month glucocorticoids present a better prognosis than no remission patients,and glomerular density as well as eGFR are independent influential factors for renal survival.

Objective To evaluate the diagnostic value of clinical laboratory indexes on judgment of hypovolemia in the patients with nephrotic syndrome (NS).Methods The blood volume of each 50 cases of healthy adult men and women was assessed with indocyanine green-pulse dye densitometry (ICG-PDD).The normal range of blood volume and the cut-off value of hypovolemia were determined.The blood volume of 81 patients with NS was also measured with ICG-PDD and then these patients were divided into the hypovolemic group (21 cases) and the non-hypovolemic group (60 cases) according to the cut-off value of hypovolemia.The test data of clinical laboratory indexes of the patients in the two groups were compared,and the indexes with statistic difference were screened out.Their diagnostic values on judgment of hypovolemia were evaluated by receiver operating characteristic (ROC) curve analysis,and finally the indexes with high judgment accuracy were selected.Results ①The cut-off values of hypovolemia are ＜ 52.9 ml/kg for the male and ＜ 52.5 ml/kg for the women,which were determined with ICG-PDD.②The five clinical laboratory indexes,including orthostatic heart rate (OHR) increase ＞ 10 bit per minute,fractional excretion of sodium (FENa) ＜ 1,transtubular potassium gradient (TTKG) ＞ 60％,blood urea nitrogen/serum creatinine ratio (BUN/Scr) ＞ 20,and urine specific gravity (SG) ＞ 1.020,were used to judge the hypovolemia in NS patients in this study.ROC curve analysis showed that the diagnostic accuracy in judgment of hypovolemia by one index or two indexes combination only belonged to medium level.However,the diagnostic accuracy in judgment of hypovolemia by the following three indexes combination,i.e.OHR increase+FeNa+BUN/Scr,FeNa+ BUN/Scr+SG,OHR increase+TFKG+BUN/Scr,or ORG increase+FeNa+TTTKG,reached high level.Conclusion This study obtained the cutoff value of Chinese adults hypovolemia are ＜ 52.9 ml/kg for the male and ＜ 52.5 ml/kg for the women,which are determined with ICG-PDD,through evaluation we recommend applying the above four specific combinations of three indexes for diagnosis of hypovolemia in NS patients.

Objective To investigate the effects of nephroblastoma over-expressed protein (CCN3) on the formation of extracellular matrix (ECM) induced by transforming growth factor-β1 (TGF-β1) in human mesangial cells (HMCs) and its underlying signal transduction mechanism related with microRNA-29(miRNA-29).Methods HMCs were pretreated with different doses of exogenous CCN3 (5 μg/L,50 μg/L and 500 μg/L) or transfected with pcDNA3.1(+)-CCN3 before exposed to TGF-β1(2 μg/L),to observe the expression of fibronectin (FN),type I collagen (COL I) and miRNA-29a,b and c.The mimics or inhibitor of the miRNA-29a were transfected into HMCs to analyze whether miRNA-29a affect CCN3.The expressions of FN mRNA,COL I mRNA and miRNA-29 family were detected by real time PCR.The protein expressions of FN and COL I were detected by Western blotting and cell immunofluorescence.Results (1) Compared with the normal control group,the expressions of FN and COL I were up-regulated in TGF-β1 group,while the expressions of miRNA-29a,b,c were down-regulated in TGF-β1 group (all P ＜ 0.05).(2) Compared with the TGF-β1 group,the expressions of FN and COL I were decreased when pretreated with the different doses of exogenous of CCN3 or transfected with pcDNA3.1(+)-CCN3 (all P ＜ 0.05).Meanwhile,the expression of miRNA-29a was significantly increased when pretreated with 50 μg/L and 500 μg/L CCN3 or transfected with pcDNA3.1(+)-CCN3 (all P ＜ 0.05);whereas miRNA-29b and c had no statistical difference (all P ＞ 0.05).(3) Compared with TGF-β1+CCN3 group,the expressions of FN and COL I were decreased in CCN3+TGF-β1+miRNA-29a mimics group (all P ＜ 0.05),whereas the expressions of FN and COL I in CCN3+TGF-β1+miRNA-29a inhibitors group were increased (all P ＜ 0.05).Conclusions CCN3 reduces the TGF-β1-induced production of ECM by the up-regulation of miRNA-29a.

Objective To investigate the relationship between dyslipidemia and nephrolithiasis in a population-based study.Methods All participants were investigated by questionnaires,physical examinations and laboratory tests including liver and renal function,lipid profile,serum fasting glucose,glycosylated hemoglobin.Nephrolithiasis was diagnosed by kidney Bultrasonography.Subjects with estimated glomerular filtration rate (eGFR) ＜ 60 ml · min-1 · (1.73 m2)-1were excluded.Results 10 316 individuals were enrolled with an average age of (54.88 ± 10.27) years (range 17-88 years) and the ratio of male to female 1:1.12.The prevalence of nephrolithiasis was 5.6％,3.7％ and 7.8％ for whole population,women and men,respectively.In women,only eGFR in stone group was significantly lower than that in non-stone group (P ＜ 0.05).However,participants in stone group were significantly older (P ＜ 0.05),of higher blood pressure (P ＜ 0.01),higher serum uric acid (P ＜ 0.01),worse renal function (serum creatinine,P ＜ 0.05;eGFR,P ＜ 0.01),and higher low-density lipoprotein (LDL) (P ＜ 0.05),compared with those in non-stone group in men.Logistic regression analysis showed that only eGFR (P ＜ 0.05) was the independent influential factor for kidney stones in women;In men,LDL was an independent influential factor for nephrolithiasis with a hazard ratio of 1.149 (95％CI 1.003-1.317,P ＜ 0.05),except for mean blood pressure and eGFR.After being divided into normal group,borderline high group and high LDL group according to the LDL level,with the increase of LDL,the prevalence of nephrolithiasis was significantly increased by 7.3％,8.3％ and 10.6％ in men respectively.There was no significant relationship between total cholesterol,triglyceride,high-density lipoprotein and nephrolithiasis.Conclusions Dyslipidemia is associated with nephrolithiasis in men,and high LDL cholesterol is an independent risk factor for nephrolithiasis.Clinical lipid testing not only helps to reduce the risk of atherosclerotic disease,but also reduces the risk of kidney stones.

Objective To investigate the prevalence and correlation factors of cardiovascular damage in patients with diabetic nephropathy (DN) and non-diabetic nephropathy (NDN).Methods A total of 278 chronic kidney disease (CKD) patients admitted to the First Affiliated Hospital of Jinan University from January 2014 to May 2016 were enrolled,including 78 case of DN and 200 case of NDN.Patients had cardiac and carotid ultrasonography test by colour doppler ultrasonography,and their clinical and biochemical data were collected.Multiple linear regression analysis and multivariable logistic regression analysis were applied to study the correlation factors of cardiovascular damage in CKD patients.Results Mean age was 48.22 years in the 278-patient cohort,which included 178(64.03％) men.Compared with NDN group,DN patients had higher left atrial dimension,interventricular septal thickness,left ventricular end-diastolic dimension,left ventricular posterior wall thickness,left ventricular mass index (LVMI),carotid intima-media thickness (cIMT) and carotid plaques ratio.Their estimated glomerular filtration rate (eGFR) and the ratio between the peak speed of the early filling wave and that of the atrial contraction wave (E/A ratio) were however lower (all P ＜ 0.05).Prevalence of left ventricular hypertrophy (LVH),left ventricular relaxant function reduction and cIMT thickening in DN group were 67.95％,70.27％ and 57.14％,higher than those in NDN group (40.00％,42.31％ and 17.39％,respectively) (all P＜ 0.05).Along with the progress of CKD,LVMI and LVH proportion in patients with DN and NDN increased gradually.LVMI and LVH proportion in DN patients in CKD 1-2 phase and CKD 3-4 phase were higher than those in NDN patients (all P ＜ 0.05).In all CKD phases,cIMT and cIMT thickening proportion in DN group were higher than those in NDN group (all P ＜ 0.05).Just in CKD 1-2 phase,DN group had lower E/A ratio and higher proportion of left ventricular relaxant function reduction than NDN group (all P ＜ 0.05).After multiple linear regression analysis,gender,BMI,hemoglobin,eGFR and DN were related with LVMI;age,serum calcium and DN were related with E/A ratio;age and DN were related with cIMT (all P ＜ 0.05).In multivariate logistic regression,DN,hemoglobin and eGFR decrease were independently associated with LVH;age and BMI were independently associated with reduction of left ventricular relaxant function;age and DN were independently associated with cIMT thickening in all CKD patients (all P ＜ 0.05).Conclusions DN patients have more severe cardiovascular damage than NDN patients,and DN may be associated with LVMI,E/A ratio,cIMT,LVH and cIMT thickening in all CKD patients.