[Objective] To investigate the therapeutic effect of Honghua injection plus prednisone and cyclophosphamine on refractory nephrotic syndrom.[Methods] 38 patients with refractory nephrotic syndrom were given intravenous Honghua and cyclophosphamine plus oral prednisone.Serum total cholesterol,triglyceride,liver and renal function,blood routine test,24h protennuria were observed.[Results] Total effective ratio was 92.1%.Cure ratio was 73.68%.Partly cure ratio was 18.42% and ineffective ratio was 7.89%.[Conclusions] Patients with refractory nephrotic syndrom were treated by Honghua injection plus prednisone and cyclophosphamine,which could reduce the application of prednisone,its side effects and enforce its therapeutic effect.What is more,this treatment could lessen therapeutic process,prevent relapse and recoil,protect effectively the retreat syndrom of prednisone as well.

Objective To investigate the effects of the combination of tripterygium wilfordii Hook F (TwHF) and irbesartan on urinary podocyte in diabetic kidney disease (DKD) patients,and to discuss the mechanism of protective effect of TwHF on DKD.Methods A total of 45 type 2 diabetic kidney disease patients were enrolled into this prospective study,and were randomly divided into 3 groups:TwHF treatment group (DT,n =15),irbesartan treatment group (DI,n =15),and TwHF combined with irbesartan treatment group (DTI,n =15).After 6 weeks washout,the 3 groups were given TwHF (1-2 mg · kg-1 ·d-1),irbesartan (150-300 mg/d),and TwHF (1-2 mg · kg-1 · d-1) combined with irbesartan (150-300 mg/d) for 12 weeks respectively.Fifteen healthy volunteers served as controls.Urinary podocytes were identified and quantitated by immunofluorescence staining of urinary sediments labeled by monoclonal antibody podocalyxin.In addition,we studied urinary connective tissue growth factor (CTGF),osteopontin (OPN) and transforming growth factor β1 (TGFβ1) concentrations in DKD patients by enzyme-linked immunosorbent assay.Results Urinary detached podocytes were obviously higher in the urine of DKD patients than in healthy controls (P ＜0.01).Podocyte detection rate was 86.6％ in the urine of DKD patients.The protein expressions of CTGF,OPN and TGFβ1 in patients with urinary podocyte were significantly increased than those without urinary podocyte (P ＜ 0.05 or 0.01).Correlation analysis showed that there was positive correlation between urinary protein excretion and urinary podocytes (r =0.79,P ＜ 0.01) and there were positive correlations between the number of urinary podocytes and urinary protein expressions of CTGF,OPN and TGFβ1 (r =0.56,0.41,0.44,respectively,all P values ＜ 0.01).Urinary albumin excretion and urinary podocytes were significantly decreased in all treatment groups (P ＜ 0.01),simultaneously,urinary concentrations of CTGF,OPN and TGFβ1 were reduced in all groups at week 12 after intervention of TwHF,irbesartan and TwHF combined with irbesartan (P ＜ 0.01),and these changes were more distinguished in combined treatment group (P ＜ 0.05).Conclusion Urinary podocyte in the urine may be suggested to be an early effective marker of disease activity in DKD.TwHF may be effective to prevent podocyte injury in DKD,which may be mediated,at least partly,by down-regulating the expression of CTGF,OPN and TGFβ1.There is a synergistic protective effect of TwHF combined with irbesartan on podocyte injury in DKD patients.

Objective:To explore the role of osteopotin in lupus nephritis (LN).Methods:Sera osteopotin( OPN )levels were measured by enzyme linked immunosorbent assay in 90 patients with systemic lupus erythematosus (SLE),15 non-SLE patients with renal impairment,and 30 healthy volunteers.OPN mRNA expression in peripheral blood mononuclear cells (PBMCs) was also investigated with reverse transcription-polymerase chain reaction semi-quantitative method.Results:The expression of OPN was significantly higher in active LN groups than in all other groups(P0.05).Conclusion:The expression of PBMCs OPN mRNA is up regulation in active SLE.Meanwhile,its expression levels are correlated with the activity of LN.

Objective To detect the effect and mechanism of Cyr61 on the apoptosis of renal tissue caused by early stage of ischemic acute kidney injury (AKI). Methods 30 SD rats were randomized into 5 groups, including control group, AKI group, AKI+bicarbonate group, AKI+blank virus group, and AKI+over?expression Cyr61 virus group. After animal models were created for 2h, serum and renal tissue were collected from sacrificed animals. Expression level of TNF?α was determined by ELISA. HE staining was used to observe the histologic changes of renal tissues. The levels of NF?κB p65 and TNFR1 were measured by immunohistochemical method. RT?PCR and Western blotting assay were adopted to detect the mRNA and protein expression levels of NF?κB p65, TNFR1 and Caspase3. Results Compared with control group, AKI group, AKI+bicarbonate group, AKI+blank virus group, AKI+over?expression Cyr61 virus group had obvious kidney injury. The levels of TNF?α, the mRNA and protein expression levels of NF?κB p65, TNFR1 and caspase3 were markedly up?regulated. Over?expression of Cyr61 significantly attenuated the degree of pathological injury, numbers of apoptotic renal tubular epithelial cells and increased the degree of Scr. Although compared with other groups, the level of TNF?α in kidney tissue had no difference, there was obvious decreased protein level of NF?κB p65, while the increase of TNFR1 and Caspase3 protein was moderate. Conclusions During the early stage of AKI, over expression of Cyr61 could inhibit apoptosis, which may be related to the suppression of TNFR1 transcriptional expression and interference of TNF?αpathway. Its underlying mechanism therefore deserves further research.

ObjectiveTo investigate the protective effect of combination of triptolide and irbesartan on the podocytes in a type 2 diabetic(T2DM) rat model,and evaluate its mechanism.Methods T2DM rats were induced by fed with high-sucrose-high-fat diet combined with a low dose of streptozocin.The rats were randomly divided into 5 groups:normal control group ( NC,n =10),diabetes group ( DM,n =11),triptolide treatment group (DT,n =12),irbesartan treatment group (DI,n =12) and triptolide combined with irbesartan treatment group (DTI,n =13). Ultrastructure of podocytes was observed by electronic microscopy and urinary albumin (UAL) excretion by ELISA was determined after 8 weeks.The expression of nephrin and bone morphogenetic protein-7(BMP-7), connective tissue growth factor (CTGF),transforming growth factor (TGF)β1 mRNA and proteins were detected by immunohistochemistry,real-time PCR and Western blot. Results Increased UAL was significantly attenuated in all treatment groups.Compared to NC group,UAL in DM group was increased significantly (0.45 ± 0.09 vs 6.36 ± 0.87,P ＜ 0.01 ),while decreased in triptolide or irbesartan alone treatment group (2.48 ± 0.37 and 2.68 ±0.42,both P ＜ 0.01 ).Compared with those in control groups,kidney expression of nephrin,BMP-7 mRNA and proteins were downregulated while CTGF, TGFβ1 mRNA and proteins were significantly upregulated in T2DM rats. Triptolide or irbesartan each alone moderately ameliorated albuminuria and podocyte damage.However,their combined usage showed a dramatic therapeutic synergism,manifested by prevention of progressive albuminuria,restoration of the glomerular filtration barrier,reversal of the decline in slit diaphragm proteins,reduction expression of CTGF,TGFβ1,and upregulation of BMP-7.Conclusion Our findings show that triptolide can increase the efficacy of irbesartan,leading to a more effective prevention of kidney disease in T2DM rat model,which may through upregulation of BMP-7 and inhibition the overexpression of CTGF and TGFβ1.

Objective To analyze the clinical features and prognostic factors of patients with malignant tumor complicated by acute kidney injury (AKI),and provide the basis for preventing AKI and improving the prognosis.Methods Malignant tumor patients complicated by AKI were screened with the electronic medical records system from January 2001 to December 2012 at the Affiliated Hospital of Qingdao University.The clinical characteristics in the 12 years were analyzed by statistical analysis and compared.The risk factors of the hospital mortality in malignancies tumor complicated by AKI were analyzed by Logistic regression analysis.Results A total of 100 patients with malignant tumor complicated by AKI were collected,accounting for 24.94％ of AKI patients and 1.66‰ of malignant tumor patients at the same period.Malignancies were consist of hematologic malignancies (11％),non-metastatic solid tumor (47％),metastatic solid tumor (42％).The most common factor leading to AKI for malignancies was post-renal obstruction (64％),followed by nephrotoxic drugs or contrast agents (24％),hypovolemia (18％).There was no significant change of the etiologies for AKI between the first six-year and the second six-year (P ＞ 0.05).The hospital mortality of patients with malignant tumor complicated by AKI was 25％,and multivariate Logistic regression analysis showed that multiple etiologies (OR=13.356),multiple organ failure (OR=222.256),and metastatic solid tumors (OR=8.497) were the independent risk factors for hospital mortality.Conclusions AKI is a common complication in patients with malignant tumors,and the most common factor leading to AKI is postrenal obstruction.The hospital mortality in malignancies with AKI is high,which should get the attention of clinicians.

Objective To observe the expression of cysteine rich-protein 61 (Cyr61) on renal tubular cells,to explore its effects against hypoxic induced kidney injury and the underlying mechanisms.Methods A stably Cyr61 expressed tubular cell line Cyr61-HK2 was established based on HK2 cells and recombinant Cyr61-lentivirus.BrdU incorporation assay was used for cell proliferation.The apoptosis of cells was analyzed by flow cytometry with Annexin V and propidiumiodide staining.Western bloting was used to detect the protein expression of BAD,Akt and ERK.Results (1) Cyr61-HK2 cells displayed more proliferation ability than HK2 cells.(2) Under hypoxia condition,the apoptosis of both HK2 and Cyr61-HK2 cells increased,but the apoptosis of Cyr61-HK2 cells was lesser than HK2 cells.(3) The expression of Cyr61 led to the phosphorylation of BAD,Akt and ERK on 0 h,0.5 h,1 h (all P ＜ 0.05).Conclusion The expression of Cyr61 can promote cell proliferation and dampen cell apoptosis induced by hypoxia,which may be involved in the Akt/ERK signal pathway.

HBx gene is a multifunctional regulator,which has extensive trans-activating effects,and can activate transcription factors,inhibit DNA repair and regulate cell proliferation,differentiation and apoptosis.In recent years,the role of HBx gene in pathogenesis of hepatitis B virus-associated glomemlonephritis (HBV-GN) has been extensively studied,and the results show that HBx can promote glomerular mesangial cell proliferation,and induce damage or apoptosis of podocytes and renal tubular epithelial cells.This paper reviews the research progress on biological characteristics of HBx and its role in pathogenesis of HBV-GN.

BACKGROUND:Transient receptor potential channel C6 (TRPC6) is a new and important slit diaphragm-associated protein in podocytes involved in regulating glomerular filter function. Glomerular TRPC6 expression is closely associated with proteinuria in diabetic kidney disease. OBJECTIVE: To investigate the expression of canonical TRPC6 in mouse podocytes induced by high glucose, and to explore the possible mechanism of diabetic kidney disease. METHODS:Mouse podocyte cels were cultured and divided into normal glucose group (5.6 mmol/L D-glucose), normal control group (5.6 mmol/L D-glucose+25 mmol/L mannitol) and experimental groups which were in the environment of high glucose (30 mmol/L). The experimental groups included high glucose group, valsartan treatment groups (10-5 mol/L) and U73122 control group (10μmol/L U73122). After 48 hours, the expressions of mRNA and proteins of TRPC6, nephrin and angiotensin II (AngII) were detected respectively by real-time quantitative PCR and western blot analysis. RESULTS AND CONCLUSION:Compared with the normal control group, the expressions of mRNA and proteins of TRPC6 and angiotensin II were markedly elevated in the high glucose group (P < 0.01), while the expressions of mRNA and proteins of nephrin were decreased (P < 0.01). The mRNA and proteins of TRPC6 and angiotensin II expressions were significantly down-regulated by valsartan (P < 0.05,P < 0.01), while the mRNA and protein expressions of nephrin were effectively up-regulated (P < 0.05). Compared with the high glucose group, the expressions of mRNA and proteins of TRPC6 and angiotensin II were ameliorated in the U73122 control group. The expressions of mRNA and proteins of TRPC6, nephrin and angiotensin II had no statistical significance between the normal control group and normal glucose group (P > 0.05). Angiotensin II-TRPC6 signaling pathway may mediate high glucose-induced podocyte injury, meanwhile it provides a new theoretical basis for the treatment of diabetic kidney disease, by which the angiotensin receptor blockers can protect podocytes in diabetic kidney disease.

Objective To investigate the relationship between urine neutrophil gelatinase-associated lipocalin (uNGAL) level and activity and pathological types of lupus nephritis (LN).Methods Thirty cases of biopsy proven LN patients as the initial onset were enrolled into the study.Ten healthy persons were selected as controls.The clinical and pathological data and blood, urine specimen were collected.The uNGAL was measured by enzyme linked immunosorbent assay.The relationship between uNGAL and clinical and pathological features of LN was analyzed.One-way analysis of variance (ANOVA) and Pearson's correlation analysis were used for statistical analysis.Results Nineteen cases were in the LN active group and 11 cases were in the inactive group.The level of plasma NGAL had no significant difference between the active LN group [(64±6) ng/ml] and the inactive LN group [(58±20) ng/ml] and the healthy control group [(57±20) ng/ml] (P＞0.05).The level of urine NGAL in the active LN group [(69±3) ng/ml] and inactive LN group [(66±5) ng/ml] was higher than that in the healthy control group [(64±5) ng/ml, P=0.009, 0.016, respectively].Urine NGAL level in active LN group was higher than that in the inactive group (P=0.012).Urine NGAL level was positively correlated with SLEDAI, R-SLEDAI, GAI, TLAI, AI (r=0.472, 0.521, 0.502, 0.516, 0.597, respectively, P=0.042, 0.036,0.042, 0.021, 0.007, respectively).The urine NGAL concentration after comparing to different pathological conditions were: urine NGAL's level [(69.7±2.4) ng/ml] of type Ⅳ LN was higher than type ⅢN [(65.3±3.2)ng/ml] and type Ⅴ [(64.6±5.0) ng/ml] (P=0.031, 0.028, respectively).Receiver operating characteristic (ROC) indicated that uNGAL was more sensitive(86.7％) and specific (73.3％) for the diagnose of type Ⅳ LN than type Ⅲ or type Ⅴ LN.Conclusion uNGAL is closely related with disease activity and pathological activity in LN.uNGAL enables clinician to assess the activity of LN and could be a sensitive marker for the diagnosis of type Ⅳ adult LN.