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 retrospectively analyze the clinical epidemiology features of adult idiopathic membranous nephropathy (IMN) in Zhongshan Hospital,and to investigate their therapeutic effect and its possible influence factors.Methods A total of 183 patients admitted to the Zhongshan Hospital of Fudan University and diagnosed as IMN by renal biopsy from January 2013 to December 2015 were involved.Their baseline information including demographics and pathologic was collected.Patients were followed up for at least 12 months.Serum albumin ＜ 30 g/L and 24 h urine protein ＞ 3.5g were defined as nephrotic syndrome (NS).IMN patients were divided into NS and non-NS groups and compared.Furthermore,the baseline data of remission and no remission patients were compared,and the correlations of their baseline data with conservative and immunosuppressive therapy were assessed by logistic regression analysis.Results (1) IMN accounted for 11.1％ of renal biopsy cases in our hospital,with an average age of 57 years and 59.6％ male patients.(2) Compared with patients without NS,IMN patients with NS were older,had a shorter time from the onset to receive renal biopsy,lower estimated glomerular filtration rate,and higher total cholesterol,low density lipoprotein cholesterol,triglyceride and serum creatinine (all P ＜ 0.05).(3) The effective rate of conservative treatment in IMN patients without NS was 65.7％,and the ineffective group had higher triglyceride compared with the effective group (P=0.019).(4) The effective rate of immunosuppressive therapy in IMN patients with NS was 81.2％,and low serum albumin was an independent risk factor for the poor efficacy of immunosuppressive therapy (OR=1.202,95％ CI 1.003-1.440,P=0.046).(5) The effective rate of conservative treatment in IMN patients with NS was 55.5％,and low serum albumin was an independent risk factor for the poor efficacy of conservative treatment (OR=1.629,95％CI 1.047-2.536,P=0.023).Conclusions The detection rate of IMN is increasing year by year,but the remission rate of conservative treatment is still not low in mild and moderate patients.For the patients without NS,high triglyceride may predict a poor effect of conservative treatment.Hypoproteinemia is a predictor of poor effect,no matter what a NS patient takes immunosuppressive therapy or conservative treatment.

Objective To explore prognosis and remission-related factors in lupus nephritis (LN) patients.Methods Patients diagnosed as LN by renal biopsy in Tongji Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology between Jan 1,2011 and July 31,2016 were enrolled.All related baseline clinical data was recorded and regular follow-up was performed.Kaplan-Meier curves was used to analyze partial remission and complete remission rates.Log-rank test was performed to compare remission rates of patients with nephrotic-range proteinuria (24-hour proteinuria≥3.5 g) and without nephrotic-range proteinuria (24-hour proteinuria＜3.5 g).Univariate and muhivariate Cox regression analyses were performed to evaluate the remission-related factors in different periods.Results A total of 115 patients,with 88.7％ female and (31.5±9.5)years mean age,were followed up for up to 5 years.During follow-up period 2 patients died and 1 dialyzed.The 6-,12-,24-and 36-and 48-month renal partial remission and complete remission rates were 33.3％,58.2％,71.5％,84.0％,89.6％,and 18.9％,40.5％,67.3％,79.4％,87.0％,respectively.Patients without nephrotic-range proteinuria had higher complete remission than patients with nephrotic -range proteinuria (HR=2.01,95％CI 1.15-3.34,P=0.014),but there was no difference in their partial remission (HR=1.33,95％ CI 0.74-2.43,P=0.341).Multivariate Cox regression model indicated that every 1 g/L increase in baseline level of serum albumin was associated with increased 8％ and 9％ risk,respectively,in partial remission (HR=1.08,95％CI 1.01-1.15,P=0.024) and complete remission (HR=1.09,95％CI 1.01-1.07,P=0.038).Conclusions Around half of LN patients reach remission during 1 year.Patients without nephrotic-range proteinuria have higher complete remission,and serum albumin is a remission-related factors.

Objective To compare the influence of hemodialysis (HD) and peritoneal dialysis (PD) on early outcome of patients underwent kidney transplantation from donation after cardiac death (DCD).Methods Patients admitted in the First People's Hospital of Foshan with DCD kidney transplant from January 1st,2011 to June 30th,2016 were analyzed retrospectively.Recipients were grouped into HD group (n=61) and PD group (n=28) according to their pre-transplant dialysis modality.Their short-term outcomes after DCD kidney transplant were compared,including recovery of renal function,short-term complications and laboratory data.Results Patients had longer dialysis duration and lower hemoglobin,serum albumin and phosphorus in PD group than those in HD group (all P ＜ 0.05),but no significant difference shown in age,gender,body mass index,primary disease,blood pressure,and hepatitis B infection (all P ＞ 0.05).HD patients with 6.00(4.00,11.00) d recovery time of renal function,18.00(17.00,21.50) d hospital time,had 24.59％ the delayed graft function (DGF),3.28％ acute rejection and 16.39％ infection during hospitalization.While for PD patients the recovery time of renal function was 4.00(3.75,7.00) d;hospital time was 19.00(15.00,21.75) d;the incidence rate of DGF was 14.29％;acute rejection was 3.57％;and infection during hospitalization reached 17.86％.Above indexes were not significantly different between HD and PD groups (all P ＞0.05).Repeated measure ments showed that,compared with those before transplant surgery,after 1 month,3 months and 6 months HD and PD groups had decreased creatinine and phosphorus,and increased hemoglobinserum albumin and calcium;Serum albumin and calcium were different between the two groups (P ＜ 0.001,P=0.040),whereas creatinine,hemoglobin and phosphorus did not show difference (all P ＜ 0.05).After transplantation the trends of creatinine,hemoglobin,calcium and phosphorus were not different between the two groups (P values were 0.295,0.310,0.501 and 0.063,respectively).Conclusions No significant difference of the recovery regarding renal function,anemia,nutrition status and mineral metabolites was found between pre-transplant HD and PD modality in patients who underwent DCD kidney transplantations.

Objective To analyze the validity of Caprini venous thrombosis risk assessment model (Caprini RAM) in the tunneled cuffed dialysis catheters (TCCs) dysfunction patients with central venous thrombosis (CVT).Methods A total of 187 maintenance hemodialysis patients with TCCs dysfunction admitted to West China Hospital of Sichuan University from January 2013 to September 2016 were analyzed retrospectively.According to the chest computed tomography venography results,patients were divided into CVT group and non CVT group.Their general clinical data (age,gender,primary diseases,history of dialysis access,etc.),blood biochemical data (hemoglobin,serum albumin,blood lipid,etc.) and 40 risk factors of Caprini RAM were collected.Caprini RAM scores were computed for risk stratification of thrombosis.Two groups were compared to analyze the value of Caprini RAM in these patients by statistics.Results One hundred and twenty CVT patients and sixty-seven non CVT patients were enrolled.In CVT group the duration of dialysis,hemoglobin and hematocrit were higher than those in non CVT group (all P ＜ 0.05).There was no significant difference between the two groups in gender,age,primary diseases,duration of catheter dependence,catheter tip position,usage of urokinase (all P ＞ 0.05).The average score of Caprini RAM in CVT group and non CVT group did not show statistical difference (6.23+ 1.81 vs 6.19+ 1.95,P=0.913).All patients were stratified into higher risk level and highest risk level according to Caprini RAM.Higher risk level patients accounted for 18.18％ and highest risk level patients accounted for 81.82％.As patients with inequable Caprini RAM scores,their incidence of CVT did not differ statistically (x2=0.105,P=0.746).CVT incidence rate of higher risk level patients was 61.76％,and of highest risk level patients was 64.70％.Conclusions Caprini RAM verifies that maintenance hemodialysis patients with TCCs dysfunction have high risk of venous thrombosis,but this model fails to distinguish patients between CVT group and non CVT group.Its clinical diagnosis is relatively limited and needs to be further explored.