Objective To examine the expression of TGF-?1/Smads signaling pathway in renal tubulointerstitial fibrosis.Methods Male SD rats were divided into control,sham operation and tubulointerstitial fibrosis groups.They were sacrificed at day 3,7,14,28 after operation.Use masson coloration to examine the area of pathological changes.The level of TGF?1,p-Smad2/3 and smad7 protein was examined by immunohistochemistry staining and Western blot.The level of TGF-?1 mRNA and smad7 mRNA was analyzed by RTPCR.Results Compared with sham operation group,TGF-?1 and p-Smad2/3 were significantly increased in UUO rats,while smad7 protein reduced in it.The mRNA of TGF-?1 and smad 7 increased from day 3 to day 28.Smads protein plays an important role in the synthesis and accumulation of extracellular matrix in tubulointerstitial area.The reduction of smad 7 protein may be a major cause of the interstitial fibrosis in this model.Conclusion TGF-? /Smads protein pathway perhaps is essential in the development of tubulointerstitial fibrosis.

Objective To study the expression and significance of the p38 mitogen-activated protein kinase (MAPK) and cAMP-responsive element binding protein (CREB 1) in experimental diabetic mellitus rats, and their relationship with extracllular matrix (ECM) restructuration. Methods Sixty male Wistar rats, with their kidneys removed surgically, were divided in two groups: control group (n=30) and diabetic group (n=30). Diabetic model was reproduced by intraperitoneal injection of Streptozocin (STZ, 65mg/kg). Six rats of each group were sacrificed at 1, 2, 4, 8 and 12weeks after STZ injection. Immunohistochemistry was used to assess the expression of p-p38 MAPK and p-CREB 1 in both control and diabetic groups. Western blot was performed to determine the activity of p-p38 MAPK and p-CREB 1 in both groups. Semiquantitative competitive reverse transcription polymerase chain reaction (PCR) was performed to detect the expression of mRNA of p38 MAPK, CREB 1 and fibronectin (FN). Results Compared with the control group, expression of p-p38 MAPK in diabetic glomeruli was significantly enhanced at 1, 2, 4, and 8 weeks, then it lowered at 12 weeks. P-CREB 1 was increased at 2, 4, 8 weeks, also decreased at 12 weeks. Elevation of FN mRNA began after 4 weeks in diabetic rats. Conclusions Glomerular p38 MAPK activity was increased in early stage of diabetes. This activated p38 MAPK pathway in diabetic glomeruli may in part play a role in the pathogenesis of extracellular matrix restructuring.

Objective To investigate the effects of angiotensin II type I receptor antagonist losartan on apoptosis and the expression of Fas and Fas-L in the kidney of diabetic rats. Methods Uninephrectomized, STZ(65 mg/kg) -induced diabetic male SD rats were used. Losartan(40 mg/kg) was delivered daily by gavage from the next day of the induction to diabetes for 12 weeks. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling(TUNEL) . Flow cytometry and immunohistochemistry were used to detect the expression of Fas and Fas-L. Results Compared with those in the kidneys of control group, apoptotic cells were more in number and the expression of Fas and Fas-L was higher in the diabetic kidneys( P

AIM: To investigate the effect of activation of JAK/STAT signaling pathway on the transdifferentiation induced by high concentration of glucose in renal proximal tubular epithelial cells(HKCs).METHODS: Cultured HKCs cells were divided into four groups: low glucose group(LG),high glucose group(HG),high mannitol group(LG+M),and HG+AG490 group(AG).Immunoprecipitation and Western blotting analysis were used to determine the expression of tryosine phosphorylated Janus kinase 2(p-JAK2).The protein expressions of STAT1,STAT3,p-STAT1 and p-STAT3 and expressions of ?-SMA,E-cadherin were observed by Western blotting.The contents of TGF-?1 and type I collagen in the supernatants of the cultured HKCs were detected by enzyme-linked immunoadsorbent assay(ELISA).TGF-?1 mRNA were measured by reverse transcription and polymerase chain reaction(RT-PCR).RESULTS: Compared with low glucose control group,the expression of JAK2,p-STAT1,p-STAT3 and TGF-?1 mRNA was significantly increased in HG group at different stimulated time from 6 h to 72 h.Meanwhile,the contents of TGF-?1 and collagen I in the supernatants and the expression of ?-SMA were increased,the expression of E-cadherin were decreased.The expression of JAK2,p-STAT1,p-STAT3 and TGF-?1 mRNA and the levels of TGF-?1,collagen I in the supernatants in HG+AG490 group were obviously lower than those in HG group.The expressions of ?-SMA and E-cadherin were also decreased in HG+AG490 group.CONCLUSION: Activation of JAK/STAT signaling pathway may be involved in the high glucose-induced transdifferentiation and overproduction of TGF?1 and ECM proteins in HKCs.

Objective To investigate the effect of high glucose on the expression of transforming growth factor-?1(TGF-?1),?-SMA,E-Cadherin in renal proximal tubular epithelial cells(HKCs)and role of AG490,an antagonist of Janus kinase.Methods Cultured HKCs cells were divided into four groups:low glucose group(LG),high glucose group(HG),high mannitol group(LG+M),and HG+AG490 group(AG).Immunoprecipitation and Western blot analysis were used to measure the expressions of tryosine phosphorylated Janus kinase 2(p-JAK2),STAT1,STAT3,p-STAT1,p-STAT3 and ?-SMA,E-Cadherin.The contents of TGF-?1 and type I collagen in the supernatants of the cultured HKCs were detected by ELISA.TGF-?1 mRNA were measured by RT-PCR.ResultsCompared with low glucose control group,the expressions of JAK2,p-STAT1,p-STAT3 and TGF-?1 mRNA were significantly increased in HG group from 6 to 72 h.Meanwhile,the contents of TGF-?1 and collagen I in the supernatants and the expression of ?-SMA were increased,the expression of E-Cadherin was decreased.The expression of JAK2,p-STAT1,p-STAT3 and TGF-?1 mRNA and the level of TGF-?1,collagen I in the supernatant s in HG+AG490 group were obviously lower than those of the HG group.The expression of ?-SMA and E-Cadherinwas also decreased in HG+AG490 group.Conclusion Activation of JAK/STAT signaling pathway seems to be involved in the high glucos induced overproduction of TGF-?1 and ECM proteins in HKCs.

ObjectiveTo investigate and analyze the clinical and pathological features of surgical treatment for primary bronchogenic carcinoma in adolescent patients.MethodsA retrospective review is presented of patients less than 30 years with surgical treatment of bronchogenic carcinoma between 1969 and 2008.There were59 patients (36 male and 23 female).Mean age was 23 years ( range 8-29 ) .The ratio of men to women patients was 1.7∶1.Forty-nine cases ( 83.0% ) were symptomatic at presentation and 18 cases(30.5% )were misdiagnosed as other diseases.Surgical procedures included radical resection in 46 cases,palliative resection in 3 cases,thoracotomy only for unresectable disease in 7 cases and VATS biopsy in 3 cases.The histological types were 18 adenocarcinomas,13 carcinoids,9 mucoepidermoid carcinoma,5 squamous cell carcimomas,4 small cell lung cancer,3 adenosquamous carcinoma and 4 others.On TNM staging,8 cases in stage Ⅰa,3 cases in stage Ⅰb,9 cases in stage Ⅱ a,12 cases in stage Ⅱb,15 cases in stage Ⅲa,8 cases in stage Ⅲb,4 cases in stageⅣ.ResultsThere were no operative death in radical group.Post-operative atelectasis in 3 cases.One case died from postoperative respiratory failure in explosive group,the postoperative five year survival rate was 27.0%.radical resection group 5-year survival was 35%.Univariate analysis identified TNM stage and surgical procedures as predictors of survival( P <0.05).factors that had no significant effect on overall survival included gender,histologic sbutype and postoperative chemotherapy (P > 0.05).The 5 year survival in stage Ⅰ,Ⅱ,Ⅲa,Ⅲb + Ⅳ were 75.0%,33.3%,14.3% and 0,respectively.The 5 year survival in lobectomy,pneumonectomy and exporsive were 43.0%,18.2% and O,respectively.On multivariate analysis,TNM stage of disease was the only independent predictor of survival ( P =0.000) .ConclusionWe should pay attention to adolescent lung cancer and improve the diagnosis rate avoiding of delaying surgical treatment.The five year survival rate of radical resection for adolescent lung cancer was good.They should be treated with aggressive multimodality therapy and surgical resection is the first-line treatment for them.

OBJECTIVE: Using simultaneous multi-gene mutation screening to survey the molecular epidemiological basis of 355 patients with nonsyndromic hearing loss of Inner Mongolia Autonomous region, we can identify the causes of their deafness,and verify the new method for simultaneous multi-gene mutation screening. METHOD: Three hundred and fifty-five patients with severe non-syndromic deafness from Inner Mongolia Autonomous regior were included in the study. The SNPscan technology was used for screening the 115 spots mutations in three common deafness-related genes(GJB2, SLC26A4, MT-12S rRNA) of patients with nonsyndromic hearing loss of Inner Mongolia Autonomous region. RESULT: In 355 patients, there were 89 cases of deafness caused by mutatior (25.07%). 53 patients with the GJB2 mutations were found(14.93%), including 24 cases of homozygous mutations (6.76%), 29 patients (8.17%) of compound heterozygous mutations, and 3 cases (0.85%) of single heterozygous mutations. 33 patients with the SLC26A4 mutations were found (9.30%), including 15 cases of homozygous mutations (4.23%),18 patients (5.07%) of compound heterozygous mutations, and 5 cases (1.41%) of single heterozygous mutations. mtDNA12S rRNA A1555G mutation was found in 6 patients (1.69%). mtDNA12S rRNA 1494C>T mutation was not found. CONCLUSION SNPscan technology allows accurate, rapid and cost-effective diagnostic screening in patients with hearing loss for etiology investigation. The SNPscan technology can serve as a good diagnostic tool for large-scale genetic testing for hereditary deafness and should be widely applied.
China ; Connexins ; DNA Mutational Analysis ; methods ; Deafness ; genetics ; Genetic Testing ; methods ; Heterozygote ; Homozygote ; Humans ; Mutation ; Polymorphism, Single Nucleotide ; RNA, Ribosomal

Aim To investigate the effects of valsartan on activation of signal transducers and activators of transcription 1,3 in glomerular mesangial cells(GMCs) under high concentration of glucose.Methods we used high concentration glucose and valsartan to stimulate the cultured rat GMCs in vitro.The protein expressions of signal transducer and activatior of transcription 1,3(STAT1,STAT3),p-STAT1 and p-STAT3 were observed by Western blot.The protein synthesis of TGF-?_1,fibronectin and type IV collagen in the supernatants of the GMCs were detected by enzyme-linked immunoadsorbent assay(ELISA) and radioimmunoassay.TGF-?_1 mRNA was measured by reverse transcription and polymerase chain reaction(RT-PCR).Results Compared with low glucose control group,the expressions of p-STAT1,p-STAT3 and TGF?_1 mRNA were significantly increased in GMCs under high concentration glucose medium and there observed the high concentration of TGF-?_1,fibronectin and type IV collagen in the supernatants.The expression levels of p-STAT1,p-STAT3 and TGF-?_1 mRNA were significantly lower in the valsartan group than in those the high concentration glucose group.The concentration of TGF-?_1,fibronectin and type IV collagen in the supernatants in the valsartan group were lower than that in the high concentration glucose control group.Conclusion Valsartan can inhibit overproduction of TGF-?_1 and ECM proteins in GMCs under high concentration of glucose,partly by regulating the phosphorylation of STAT1 and STAT3.

Objective To investigate the effects of rapamycin on p-JAK2,STAT3,p-STAT3 and PCNA in ranal tissue of IgAN rats.Methods The animal models of IgA nephropathy were devided into control group,IgAN model group,losartan group and rapamycin group.The clinical efficacy of rapamycin,and its influences on the protein and mRNA expressions of STAT3,p-STAT3,p-JAK2 and PCNA were determined by western blot,RT-PCR and immunohistochemical techniques respectively.Results The protein and mRNA expressions of p-STAT3,STAT3,p-JAK2 and PCNA were significantly increased in kidney of IgAN rats(P