Objective To investigate the expression of p38 mitogen actirated protein kinase (p38MAPK) in renal fibrosis in diabetic mice. Methods Male homozygous C57 BL/6 mice were divided at random into control group intraperitoneally(i. p.) injected with citrate buffer and diabetes group received 5 consecutive daily intraperitoneal inserum glucose level exceeding 16.7 mmol/L. Mice were killed at 0,4weeks ,8weeks, 12weeks and 16weeks respectively after STZ injected. The kidney tissues were obtained from diabetic and control mice. Serum glucose, extracellular matrix,and 24 h urinary albumin excretion rate(UAE)and the serum creatinine(Scr) were measured. The kidney tissue was used for histological and morphometric studies of glomerular matrix expansion (PAS), and the expression of phosphorylated p38MAPK and TGFβ1 were measured by immunohisteehemical staining. p38MAPK and TGFβ1mRNA were analyzed by reverse transeriptase-PCR. Results The serum level of glucose in diabetic mice increased significantly. Scr and 24 h UAE, and glomerular matrix expansion in diabetic mice were obviously higher than that in control mice. Phosphorylated p38MAPK and TGFβ1 levels were obviously increased in the kidney of diabetic mice compared with those in control mice(P ＜0. 01) ;TGFβ1 expression was positively related to the expression of phosphorylated p38MAPK. Conclusion The overexpression of phosphorylated p38MAPK in kidney shoud play an important role in the development of renal fibrosis associated with diabetic nephropathy in mice.

Objective To investigate the clinical features , diagnosis and key technique points of laparoscopic partial adrenalectomy for small adrenal pheochromocytoma . Methods From Oct.2006 to Jun. 2011, clinical data of 32 cases with small adrenal pheochromocytoma (≤3.0 cm) were collected and retro-spectively analyzed .Hypertension was observed in 12 patients, whereas 20 patients presented with adrenal incidentaloma .Thirteen patients had a left adrenal neoplasm , eighteen patients had a right adrenal tumor , while one patients had bilateral tumors .The positive rate of plasma-free metanephrines ( MNs) and 24-hours urinary catecholamine (CA) in diagnosing small renal pheochromocytomas was 92.6%(25/27) and 81.3%(26/32) respectively.The main localization diagnosis included ultrasonography , 131I-MIBG, and CT or MRI, with positive rates of 71.9%(23/32), 93.8%(15/16) and 96.9%(31/32) respectively.All the laparoscopic adrenalectomies were performed retroperitoneally .During the surgery , the internal part of the adrenal gland closing to the retroperitoneum was dissected first , and the whole adrenal gland was resected completely. Results Partial adrenalectomy was performed for 30 cases and radical adrenalectomy for 2 ca-ses.All operations were successful without perioperative or postoperative complications .The maximum diame-ter of tumor was 1.7±0.2 (1.0-3.0) cm.Histopathological results showed that all the cases were benign pheochromocytoma.The operative time was 82 (40-210) min.The estimated blood loss was 57 (20-180) ml.No patient required blood transfusion . Conclusions Plasma-free MNs, 24-hours urinary CA and VMA are important qualitative examinations in detection of adrenal pheochromocytoma .Ultrasonography , CT,MRI, and 131 I-MIBG are important in the localization of adrenal tumors .Retroperitoneal laparascopic partial adrenalectomy is the preferred choice in the management of small adrenal pheochromocytoma .Dissecting the internal part of the adrenal gland closing to the retroperitoneum first and exploring the whole adrenal tissue are the key technique points during the operations .

AIM: To investigate the functional role of TGF-?_1 signal protein Smad2/3 in tubulointerstitial fibrosis associated with unilateral ureteral obstruction in rats. METHODS: The unilateral ureteral obstruction (UUO) model was induced by the ligation of left ureter. Rats were sacrificed at 1, 3, 7, 14, 21, and 28 days after UUO was initiated. TGF?_1 protein, phosphorylated Smad2/3 and interstitial ?-smooth muscle actin (?-SMA) expression were assayed by immunohistochemical staining. TGF-?_1 mRNA in the obstructed kidney was analyzed with in situ hybridration. HE and Masson staining were used for histological and morphometric studies of the pathological change in obstructed kidney. RESULTS: The results showed that upregulation of TGF-?_1 in tubulointerstitium of both cortex and medulla at day 3 (a 3.1 fold increase vs control, P

Objective To study the prognostic factors of survival in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib.Methods From May 2008 to Dec 2012,the clinical data of 82 cases with mRCC adminstered by sunitinib were reviewed retrospectively.The study included 60 male patients and 22 female patients,whose age ranged from 29 to 82 years [mean (56.1±11.3) years].Among them,52 cases presented hematuria,flank pain and palpable mass.The size of renal tumor ranged from 2.0 to 18.0 cm [mean (8.0±3.0) cm].The location of tumor included 41 in left kidney,37 in right kidney and 4 in bilateral kidney.The pathological tissue obtained from the operation in 69 cases and from biopsy in 13 cases.The pathological results demonstrated renal cell carcinoma in 75 cases,papillary cell carcinoma in 2 cases,chromophobe cell carcinoma in 2 cases,sarcomatoid carcinoma in 2 cases,collecting duct carcinoma in one case.The site of metastasis included lung in 50 cases,liver in 11 cases,bone in 14 cases,pancrease in 3 cases,retroperitoneal lymph node in 31 cases.In 52 cases,the ECOG scores ranged from 1 to 2.The others scores were more than 3.The average level of hemoglobin,AKP,LDH and leukocyte were (132±24)g/L,(90±65) U/L,(168±114) U/L and (6.4±2.0)×109/L,respectively.Before treatment,the abnormal cases in those parameters were 59,9,6 and 2,respectively.According to the MSKCC risk model,14 cases were classified into the high risk group and 68 cases into medium risk group.74 cases were accepted the sunitinb therapy within one year after diagnosis and 8 cases were accepted same therapy until one year after diagnosis.The overall survival (OS) rates were calculated by Kaplan-Meier method and Cox regression model was used to analyze the relationship between the influencing factors and the prognosis.Results The average OS was (21.6± 14.1) months (ranged 2.8 to 64.1 months).The survival rate at 1 st,2nd and 3rd year were 71％,64％ and 58％,respectively.Single factor analysis showed that significant prognostic factors were as follows:ECOG performance status ≥ 2 (P =0.005),clinical symptom during first clinic visiting (P =0.031),without nephrectomy (P =0.012),the number of metastatic sites ≥ 2 (P =0.015),hemoglobin before treatment (P=0.005),serum AKP level before treatment (＞126 U/L) (P=0.007),MSKCC score≥ 3 (P =0.000),the presence of liver metastases (P =0.000) and bone metastases (P =0.000) and relative dose intensity in the first month (1M-RDI) of sunitinib ≥ 50％ (P=0.000).Cox regression model showed that the beneficial predictive factors were ECOG performance status＜2 (P=0.136),no symptom during the first clinic visiting (P=0.801),serum AKP ＜126 U/L (P=0.618) before treatment,the absence of bone (P =0.068) and pancreas metastases (P =0.265).Sunitinib 1M-RDI ≥ 50％ was the independent predictive factor (P=0.000).Conclusions In targeted therapy era,there is some change in the prognostic factors for mRCC and target drug play an important role in the prognosis of mRCC.Sunitinib 1M-RDI ≥50％ is the independent predictive factor for the prognosis of renal carcinoma.

AIM:To investigate the expression and probable role of extracellular signal-regulated protein kinase(ERK1/2)in renal fibrosis associated with diabetic in mice.METHODS:Male homozygous C57BL/6 mice were divided at random into control group(intraperitoneally injected with citrate buffer)and diabetes group(received 5 consecutive daily intraperitoneal injections of streptozotocin at dose of 50 mg?kg-1?d-1).All mice were followed up for 16 weeks.Diabetes was confirmed by serum glucose levels exceeding 16.7 mmol/L.Mice were killed at 0,4,8,12 and 16 weeks respectively after streptozotocin injection.The kidney tissues were obtained from diabetic and control mice.Serum glucose,kidney weight/body weight(KW/BW),24 h albumin excretion rate(UAE)and the serum creatinine(Scr)were measured.The kidney tissue was used for histological and morphometric studies of glomerular size,glomerular matrix expansion(PAS),and the expression of TGF-?1,phosphorylated ERK1/2 and collagen Ⅲ by immunohistochemical staining.RESULTS:The serum level of glucose in streptozotocin-induced diabetic mice increased significantly.The kidney weight/body weight ratio,glomerular volume and glomerular matrix expansion in diabetic mice were obviously higher than those in control mice.Serum creatinine and 24 h albumin excretion rate in diabetic mice increased significantly compared with control mice.TGF-?1,phosphorylated ERK1/2 and collagen Ⅲ levels were obviously increased in the kidney of diabetic mice compared with those in control mice(P

Objective To understand the various HPV types and the factors influencing their distribution among women with normal cervical cytology in the Shanghai area, to provide basic data for cervical cancer prevention and vaccine use.Methods A questionnaire-based survey was conducted among 3 372 married women in the Shanghai area. A PCR reverse dot blot (PCR-RDB) method was adopted for HPV genotyping of cervical exfoliated cell samples from 3 206 women. Odds ratio (OR) for HPV infection were analyzed using logistic regression. Results Of the 3 206 women investigated, 669 (20.87%) were positive for HPV infection. The highest incidence of HPV infections was seen in the age groups of 55-59 years, 50-54 years and 45-49 years, with the rates of positive detection being 27.67%, 21.65%, and 21.55%, respectively. While 70.4% of the positive cases had a single infection, 29.6% showed multiple infections. In cases with multiple infections, double infection was predominant (20.63%). The top five high-risk gene types were HPV52(3.65%),HPV53(2.71%),HPV51(2.03%),HPV58(1.87%),and HPV16 (1.40%). The top three low-risk gene types were HPV81 (2.03%), HPV42 (1.43%), and HPV55 (1.31%). Among the women with HPV infections,there were 483 having medium-high-risk HPV infection.There were significant differences in the age,the age at first sexual activity,sexual activities per week,education,and alcohol consumption between HPV positive and HPV negative patients. Age stratification showed that the infection rates in the 55-59 years old group were significantly higher than that in the other age groups(χ2=15.349, P=0.000). Both single factor and multivariate non-conditional logistic regression analyses showed that higher education and the start of sexual activity at a later age were protective factors for medium-high-risk HPV infection,with regression coefficients of-0.165 and-0.08,respectively (P<0.01) in the multivariate analysis. The risk factors included age between 55- 59 years, menstrual status (menopause), sexual activity (≥3 times per week) and alcohol consumption. High-risk HPV infections also had the same risk factors,and the odds ratios were 1.558,1.275,and 1.678,respectively(P<0.01).However, 55-59 years of age and alcohol consumption are independent risk factors for medium-high risk HPV infection. Conclusions High-risk HPV in women of Shanghai is commonly caused by HPV52, HPV53, HPV51,HPV58,and HPV16.The high-risk group includes women who are 55-59 years old.While drinking is an independent risk factor for medium-high risk HPV infection, a moderate sex life and delayed age at first sex can reduce the risk of high-risk HPV infections.

Objective To observe the synergistic effect of metformin and anti-vascular endothelial growth factor (VEGF) in the treatment of diabetic retinopathy.Methods This study was composed of clinical data review and in vitro cell experiment.Ten patients (12 eyes) with diabetic macular edema treated with antiVEGF drugs were included in the study.Patients were randomly divided into the VEGF group (anti-VEGF drug therapy) and the combined treatment group (anti-VEGF drug combined with metformin).The changes of visual acuity and central retinal thickness (CRT) were compared between the two groups.As far as the in vitro experiment was concerned,vascular endothelial cells were divided into the control group (normal cells),the VEGF group (50 ng/ml VEGF),the anti-VEGF group (50 ng/ml VEGF+2.5 μg/ml of conbercept),and the combined group (50 ng/ml VEGF +2.5 μg/ml of conbercept +2.0 mmol/L of metforrnin).And then MTT cell viability assay,scratch assay and real-time quantitative polymerase chain reaction assay were performed to analyze the cell viability,cell migration and mRNA level of VEGFR2,protein kinase C (PKC)-α and PKC-β successively.Results Review of clinical trial shows that the CRT recovery rates in the combined treatment group were much higher than that in the VEGF group at 3 month after the operation,while the difference was statistically significant (t=-2.462,P＜0.05).In vitro cell experiment results showed that VEGF induction upregulated the viability and mobility of vascular endothelial cells obviously compared with control group,at the same time,the use of anti VEGF drugs can effectively reverse the trend,in contrast,combination of metformin and anti-VEGF showed a more superior effect to some extent (P＜0.05).In the VEGF group,the mRNA expression of VEGFR2,PKC-αand PKC-[β were significantly increased compared with the control group (P＜ 0.01);while the mRNA expression of VEGFR2,PKC-αand PKC-β in the combination group decreased significantly compared with the VEGF group and the control group (P＜0.05).However,in the anti-VEGF group,the mRNA expression of VEGFR2,PKC-αand PKC-β were decreased,but has failed to reach the level of statistical learn the difference.Conclusions The combination ofmetformin and anti-VEGF drugs can reduce the CRT of diabetic retinopathy patients and inhibit the proliferation and migration of retinal vascular endothelial cells which induced by VEGF.The synergistic mechanism may be related to the inhibitory effect of metformin on the expression of VEGFR and PKC.