OBJECTIVE: To compare the pharmacokinetic parameters between matrine tablets and matrine capsules in healthy volunteers and evaluate the bioequivalence of the two formulations.METHODS: 18 healthy volunteers were assigned to receive matrine tablets(test formulation,600mg) and matrine capsule(reference formulation) respectively q.d on empty stomach.The plasma concentrations of oxymatrine before and after medication were determined by HPLC and the pharmacokinetic parameters(calculated by oxymatrine) were calculated.RESULTS:The pharmacokinetic parameters of matrine tablets vs.matrine capsules in healthy volunteers were as follows:t1/2:(1.51?0.62)h vs.(1.53?0.54)h;Tmax:(1.35?0.13) hvs.(1.29?0.13)h;Cmax:(730.86?101.13)ng?mL-1 vs.(729.58?74.35)ng?mL-1;AUC0～8:(2 579.1?244.4)ng?h? mL-1 vs.(2 505.7?223.5)ng?h?mL-1;AUC0～∞:(2 754.1?331.8)ng?h?mL-1 vs.(2 659.4?253.5)ng?h?mL-1.The relative bioavailability of matrine tablets(calculated by oxymatrine) was(103.7?13.3)%.CONCLUSION: There are no significant differences between matrine tablets and matrine capsule in main pharmacokinetic parameters,which were in conformity with the presumption of bioequivalence between different individuals,different periods or different dosage forms.The two formulations are bioequivalent.

Objective To investigate the features of renal lesions in von Hippel-Lindau (VHL) disease and the surgical intervention. Methods The clinical and pathological data from 6 patients with renal lesions in a large Chinese VHL disease kindred were reviewed individually.One patient had multifocal renal cysts,and 5 patients had bilateral renal cell carcinomas and multifocal renal cysts. Results Among 10 kidneys in the 5 cases of bilateral renal cell carcinomas, nephron-sparing surgery (NSS) was performed in 5,radical nephrectomy (RN) in 3 and observation in 2.After operation,the pathological findings indicated that all solid lesions were renal clear cell carcinoma, with one malignant cyst being detected.The Fuhrman's nuclear grade of the RCC was grade Ⅰ in 14 tumors,grade Ⅱ in 6 tumors.The TNM stage was T 1N 0M 0 in 4 cases and T 2N 0M 0 in 1 case.During a mean follow-up of 47 months (range,9 to 113 months),all patients were alive without evidence of RCC recurrence and metastasis.Five patients had normal renal function and 1 patient experienced an increase in serum creatinine but without dialysis. Conclusions The renal lesions in VHL disease include both cysts and carcinomas,which are often multifocal and bilateral.Almost all the tumors are of clear cell type with a low stage and grade.Nephron-sparing surgery may be justified and effective in the management of VHL patients.

Objective To study the effects of community-based rehabilitation on cerebral apoplexy patients with cognitive disorders.Methods 30 cases of cerebral apoplexy patients were enrolled according to relevant standards,who were given standard rehabihtation care in Community Health Service Center(training group) ,while another 30 similar cases from subordinate health service stations (control group) given only rehabilitation guidance once a week.Two groups were not do professional cognitive training.All patients were assessed with Mini Mental State Examination( MMSE), Fugl-Meyer Assessment(FMA) and modified Bathel index rating scale(MBI) to evaluate their cognition ,movement function and activity of daily living(ADL) before training as well as after 4-week and 8-week training.Results There was no signficant difference in cognition,movement functions and ADL between training group and control group before treatment(P>0.05).The differences in the assessment of Brounnstrom scale and MBI between two groups after 4-week training were not significant( P > 0.05 ).The scores of Fugl-Meyer scale, MMSE and Barthel index of the training group after 8-week training were significantly higher than those of control group( all P < 0.05 ).Conclusion Community-based rehabilitation training could improve the movement functions and ADL,and cognitive functions of cerebral apoplexy patients.

Background: Hypoalbuminemia adversely affects the clinical outcomes of various cancers. The purpose of this study was to estimate the prognostic value of hypoalbuminemia 3–5 weeks after treatment in patients with metastatic renal cell carcinoma (mRCC) who received sorafenib or sunitinib as first-line treatment. Methods: In this single-center, retrospective study, we assessed the progression-free survival (PFS) and overall sur-vival (OS) of 184 mRCC patients who received first-line sorafenib or sunitinib treatment. PFS and OS were compared between patients with post-treatment hypoalbuminemia (post-treatment albumin level <36.4 g/L) and those with normal post-treatment albumin level (albumin level ≥36.4 g/L). The Memorial Sloan Kettering Cancer Center (MSKCC)risk model stratified mRCC patients into three risk categories. Prognostic values of all patient characteristics including MSKCC risk category were determined by using univariate and multivariate Cox regression models. Prognostic value was further determined using the Harrell concordance index and receiver operating characteristic curve analysis. Results: The median PFS and OS of the 184 patients were 11 months (95% confidence interval [CI] 9–12 months) and 23 months (95% CI 19–33 months), respectively. Patients with post-treatment hypoalbuminemia had significantly shorter median PFS (6 months [95% CI 5–7 months]) and OS (11 months [95% CI 9–15 months]) than patients who had normal post-treatment albumin levels (PFS: 12 months [95% CI 11–16 months], P < 0.001; OS: 31 months [95% CI 24–42 months], P < 0.001), respectively. Multivariate analysis showed that post-treatment hypoalbuminemia was an independent predictor of PFS (hazard ratio [HR], 2.113; 95% CI 1.390–3.212; P < 0.001) and OS (HR, 2.388; 95% CI 1.591–3.585; P < 0.001). Post-treatment hypoalbuminemia could also be combined with the MSKCC risk category for better prediction about OS. The model that included post-treatment hypoalbuminemia and MSKCC risk category improved the predictive accuracy for PFS and OS (c-index: 0.68 and 0.73, respectively) compared with the basic MSKCC risk model (c-index: 0.67 and 0.70, respectively). The prognostic values for PFS and OS of the integrated MSKCC risk model involving post-treatment hypoalbuminemia were significantly more accurate than the basic MSKCC risk model using likelihood ratio analysis (both P < 0.001). Conclusions: Post-treatment hypoalbuminemia can be considered an independent prognostic factor for patients with mRCC who undergo first-line treatment with tyrosine kinase inhibitors. Additionally, integrating post-treatment serum albumin level into the basic MSKCC risk model can improve the accuracy of this model in predicting patient overall survival and progression-free survival.

Objective To study the natural history of renal cell carcinomas associated with von Hippel-Lindau disease (VHL). Methods An active surveillance strategy was carried out on 11 VHL cases(5 males and 6 females with average age of 45 years)with 32 renal masses. The mean maximum diameter of these masses at initial diagnosis was 2. 5 cm ranging from 0. 5 to 6.2 cm. Clinical materials, radiographic, and pathologic records were reviewed to determine tumor growth rate, subsequent interventions and outcome of follow-up. Results During a median follow-up of 70 months (range 32 to 258 months), bilateral solid renal tumors developed in 6 patients;13 surgical interventions were performed in 8 cases;tumor local recurrence occurred in 4 cases;3 cases died (2 of metastasis diseases and 1 of an unrelated disease) ;8 cases survived with 1 case taking regular hemodialysis.The median follow-up duration for 32 renal masses was 51 months (range 19 to 106 months). The mean tumor growth rate observed were 0. 55 cm/year (range 0. 04 to 1.75 em/year). Three tumors grew faster (1.13-1.75 cm/year), and the other 29 tumors grew slower (0. 17-0.88 cm/year).Among the 3 tumors, 1 was found to be grade Ⅱ at pathologic examination and another developed metastasis. Progression to metastatic disease was found in 2 patients. At the last follow-up, 27 (84 %)tumors were larger than 3 cm and no metastasis disease developed among tumors less than 4 cm.Conclusions The majority of enhanced renal masses with VHL disease may still be indolent and do not metastasize during long period of follow-up even in tumors larger than 3 cm. Active surveillance appears to be a reasonable option for VHL patients with enhanced renal masses less than 4 cm.

Objective To discuss the management of renal cell carcinoma(RCC) associated with von Hippel-Lindau(VHL) disease. Methods Clinical data were analyzed retrospectively from 28 ca-ses ( 16 males and 12 females, with a mean age of 45 years), of whom 15 had bilateral RCC and 13 had unilateral RCC. VHL germline mutation was analyzed in 25 cases. Nephron sparing surgery (NSS) or radical nephrectomy was performed in 24 cases. Results VHL germline mutations were detected in 25 cases including 14 asymptomatic patients. Among 29 solid renal tumors in 9 cases observed for a mean time of 44 months (range 12 to 86), the mean increase in tumor size was 0. 531 cm/year. There were 19(65.5%) tumors>3 cm at the end of follow-up but only 1 developed retroperitoneum lymph nodes metastasis. A total of 87 solid tumors were removed and 62 (71.3%) solid tumors were man-aged by NSS. Pathological results showed 86 clear cell carcinomas (73 Fuhrman Ⅰ and 12 Fuhrman Ⅱ ) and 1 calcified lesion. During mean follow-up of 50(5-237) months, local recurrence occurred in 4 cases treated with NSS; 26 patients were alive at the end of follow-up. Conclusions DNA testing might be helpful in the earlier detection of asymptomatic VHL patients. Most solid renal tumors in VHL disease grow slowly. The majority of the tumors >3 cm may still be indolent and do not metas-tasize during longer follow-up and can be observed. NSS is effective and safe for RCC in VHL disease.

Objective To discuss the necessity of closing the peritoneum during the operation of ileal conduit after the radical cystectomy.Methods We retrospectively analyzed the clinical data of 395 patients with bladder cancer who received radical cystectomy from Jan.2014 to Sep.2016.The amount of male was 327,female was 68.The mean age was (65.8 ± 9.7) years old.Patients were divided into four groups according to the surgical method of cystectomy and urinary diversion.In group A,patients,including 78 males and 9 females,were received open radical cysectomy (ORC) with extraperitoneal ileal conduit.The mean age was (67.8 ± 9.2) years old.In the preoperative clinical staging,66 cases were less than T2 and 21 cases were more than T2.Preoperative pathological grade in 83 cases and low grade in 4 cases.In group B,patients,including 31 males and 2 females,were accepted ORC with ileal conduit without peritoneum closure.The mean age was (67.3 ± 8.7) years old.Preoperative clinical staging showed less than T2 in 25 cases,more than T2 in 8 cases,The preoperative pathological grade showed high grade in 33 cases.In group C,patients,including 112 males and 27 females,were accpeted LRC with ileal conduit without peritoneum closure.The mean age was (64.3 ± 10.5)years old.The preoperative clinical staging showed less than T2 in 107 cases and more than T2 in 32 cases.The preoperative pathological grade showed high grade in 135 cases and low grade in 4 cases.In group D,patients,including 106 males and 30 females,were accepted RARC with ileal conduit without peritoneum closure.The mean age was (65.9 ±10.0)years old.Preoperative clinical staging showed less than T2 in 103 cases and more than T2 in 33 cases.The preoperative pathological grade showed high grade in 132 cases and low grade in 4 cases.Ileal conduit without peritoneum closure means completely open the peritoneum after anastomosis of the ureter and intestine in the urinary diversion surgery without shutting down the peritoneum,which is different from the extraperitoneal ileal conduit.The operating time,blood loss,blood transfusion rate,recovery time of intestinal function and perioperative complications and rate of hydronephrosis were analyzed.Results The 395 cases completed operation successfully,no LRC or RARC had been converted to ORC.The operative time was (280.1 ± 92.3) min,(233.6 ± 99.4) min,(304.8 ± 108.9) min,(364.6 ± 86.4) min in four groups,respectively (P ＜ 0.05).The blood loss in four groups were (489.1 ± 285.6) ml,(431.8 ± 233.1) ml,(373.0 ±213.7) ml,(205.6 ± 137.8) ml,respectively (P ＜0.05).The transfusion rate in four groups were 18 (20.7％),16 (48.0％),15 (10.8％),14 (10.3％),respectively (P ＜ 0.05).The mean time to flatus in four groups were (3.7 ±1.8)d,(3.6±1.0)d,(3.5±1.2)d,(2.2±1.7)d,respectively (P ＜ 0.05).While ileal obstruction rate had no statistical difference in four groups [group A 17 cases(19.5％),group B 6 cases(18.2％),group C 27 cases(19.4％),group D 19 cases(14.0％),P =0.678].Urine leakage,intestinal leakage,lymphocyst were only occurred in group A [7 cases (8.0％),2 cases (2.3％),2 cases (2.3％)].Pyelonephritis was noticed in each group,including 14 cases(16.1％)in group A,2 cases(6.1％)in group B,9 cases (6.5％)in group C,6 cases(4.4％)in group D (P ＜ 0.05).Hydronephrosis 6 months after surgery was observed in four groups,including 15 cases(17.2％)in group A,3 cases(9.1％)in group B,7 cases(5.0％)in group C,5 cases(3.7％)in group D (P ＜ 0.05).Conclusions Ileal conduit without peritoneum closure would not increase the incidence of complications,on the contrary,it would relieve the tension of anastomosis,and reduce the occurrence of complications such as urine leakage.

Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma (mRCC) in China. This study aimed to compare the efficacy, safety, and quality of life (QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy. Methods: Clinical data of patients with mRCC who received sorafenib (400 mg twice daily; 4 weeks) or sunitinib (50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved. Primary outcomes were overall survival (OS), progression-free survival (PFS), adverse events (AEs), and QoL (SF-36 scores), and secondary outcomes were associations of clinical characteristics with QoL. Results: Medical records of 184 patients (110 in the sorafenib group and 74 in the sunitinib group) were reviewed. PFS and OS were comparable between the sorafenib and sunitinib groups (bothP > 0.05). The occurrence rates of leukocytopenia, thrombocytopenia, and hypothyroidism were higher in the sunitinib group (36.5％ vs. 10.9％, P < 0.001; 40.5％ vs. 10.9％,P < 0.001; 17.6％ vs. 3.6％,P= 0.001), and that of diarrhea was higher in the sorafenib group (62.7％ vs. 35.2％,P < 0.001). There was no significant difference in SF-36 scores between the two groups. Multivariate analysis indicated that role-physical and bodily pain scores were associated with the occurrence rate of grade 3 or 4 AEs (P= 0.017 and 0.005). Conclusions: Sorafenib has comparable efficacy and lower toxicity profile than sunitinib as first-line therapy for mRCC. Both agents showed no significant impact on QoL of patients.

Objective To study the histological classification,clinical stage,histological grade and prognosis of renal cell carcinoma by analyzing the records of the patients in Shanghai Renji hospital. Methods A consecutive series of 435 patients with renal cell carcinoma between 2003 and 2005derived from the renal cancer database were reviewed clinically and pathologically.The 1997 version of WHO histological classification for renal epithelial tumor,the 2002 version of AJCC clinical TNM staging system and the 1982 version of Fuhrmaffs system for nuclear grade were used.By survival analysis of 57 cases with advanced renal cell carcinoma using Kaplan-Meier method prognostic factors were confirmed using logrank test. Results Of a total 435 patients,cases were classified into 10(accounting for 2.4%of renal cell tumors)hereditary renal cancer in VHL disease,372(85.5%)clear cell renal cell carcinoma(CCRCC),13(3.0%)papillary renal cell carcinoma(PRCC),18(4.1%)chromophobe renal cell carcinoma(CRCC),4(0.9%)oncocytoma,4(0.9%)carcinoma of the collecting ducts of Bellini(CCDB),and 14(3.2%)renal cell carcinoma unclassified.There were 335(77%)patients undergone radical nephrectomy,74(17%)nephron sparing surgery and 26(6%)others,such as palliative nephrectomy.The patients with VHL disease come from 5 Chinese kindred and all had bilateral clear cell renal cell carcinomas and multifocal renal cysts.There were 7 paients of stage Ⅰ and 3 cases of stage Ⅱ and 6 cases of grade Ⅰ and 4 cases of grade Ⅱ.Genetic test revealed that all patients had VHL gene mutation.4 patients had recurrence while no evidence of local advance and distant metastasis were found during a mean of 28.6 months.Patients with chromophobe RCC are all of stage Ⅰ and 5 cases of grade Ⅰ and 13 cases of gradeⅡ.All patients are alive without recurrence or metastasis during a mean of 19.8 months.Collecting ducts RCC all presented with stage Ⅰ but grade Ⅲand with the median survival only 11.3 Months.Of clear cell and papillary RCC,260(67.6%),64(16.6%),32(8.3 %),29(7.5%)were stage Ⅰ,Ⅱ,Ⅲand Ⅳ,and of stage Ⅰ patients 147(38.2%),113(29.4%)were T1a and T1b respectively.124(32.2%),219(56.9%),40(10.4)and 2(0.5%)were grade Ⅰ,Ⅱ,Ⅲ,Ⅳ,respectively.Median survival of 57 advanced RCC is 16.0±1.3months,1-year survival is 55%,and 2-year survival is 31%,respectively.By using logrank test,clinical stage(＜0.01),tumor size(＜0.01),lymphadenopathy(＜0.01),metastasis(＜0.01)and tumor grade(＜0.01)were anatomical and histological prognostic factors for advanced RCC. Coneluslons Different RCC subtypes have different clinical course.The RCC patients in VHL disease have VHL gene mutation and the tumors are often multifocal,bilateral,clear cell type with a low stage and grade which often recurrence but without metastasis.Chromophobe RCC may have a favorable prognosis but collecting duct RCC poor prognosis.In anatomical and histological level,clinical stage,tumor size,lymphadenopathy,metastasis and tumor grade are prognostic factors of survival for advanced RCC.

ObjectiveTo analyze the incidence of benign lesions in patients undergoing surgery for presumed renal cell carcinoma (RCC) and investigate the correlation of tumor size and histopathological characteristics.MethodsFrom Jan 2003 to Sep 2010,1531 patients (1042 males,489 females with average age of 55.1 years (15 -89 years) underwent nephrectomy.There were 1123 radical nephrectomies and 408 partial nephrectomies for solitary renal cortical neoplasms presumed to be RCC in preoperative imaging study.The pathological tumor size,the percentage of benign lesions and histologic subtypes were analyzed retrospectively.The correlation of Fuhrman grading and tumor size in clear cell type RCC and papillary RCC was investigated as well.Results Pathological examinations revealed that there were 81 (5.3％)benign lesions of 1531 patients.The incidence of benign lesions was 7.8％ in renal masses smaller than 4.0cm,3.8％ in masses with 4.1 - 7.0 cm,and 1.1％ in masses larger than 7.0 cm ( P ＜ 0.01 ).Angiomyolipoma was the most predominant histologic subtype in benign renal lesions with a frequency of 69.5％,52.6％ and 33.3％ in ≤4.0 cm,4.1 - 7.0 cm and ＞ 7.0 cm subgroups,respectively.Oncocytoma was present in 13.6％,15.8％ and 33.3％ of the benign lesions in the above 3 subgroups (P =0.47).One thousand four hundred and fifty cases of malignancies (94.7％) were identified.The frequency of clear cell type RCC was 91.7％ in malignant tumors smaller than 4.0 cm,88.1％ in 4.1 - 7.0 cm malignancies,and 77.6％ in tumors ＞7.0 cm； the frequency of papillary RCC was 4.0％,4.2％ and 7.7％ in the above 3 subgroups,and the frequency of chromophobe cell RCC was 3.6％,5.2％ and 6.3％ accordingly ( P ＜0.01 ).One thousand three hundred and seventeen cases of clear cell type RCC and papillary RCC with definite Fuhrman grading were identified.The probability of high grade tumors increased with size,while the probability of low-grade lesions decreased (r =0.94,P ＜ 0.01 ),especially for tumors smaller than 11.0cm.ConclusionsPatients in the present study population show a low incidence of benign renal lesions.Benign lesions are less common in larger tumors than in smaller ones.The proportion of clear cell type RCC decreases in larger tumors,however papillary RCC and chromophobe cell RCC are increasing.The probability of high-grade tumors increases with size.The correlation between tumor size and histopathological characteristics may be helpful in patients counseling and decision-making.