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Objective To investigate the mechanism and protective effect of Humanin(HN)on rotenone(Rot)-induced toxic damage for dopamine neurons.Methods The Rot-poisened PC12 cell model was constructed,and the control group,the Rot poisening group,the HN pretreated Rot poisening group,and the HN treatment group were set up.ELISA was used to detect the content of HN inside and outside of Rot-infected cells,CCK-8 assay was used to detect cell viability,and ATP detection kit was used to detect the intracellular ATP content.Dichloro-dihydro-fluorescein diacetate(DCFH-DA)assay was used to detect the level of reactive oxygen species(ROS)in cells.Western blotting was performed to detect the expression level of mitochondrial autophagy regulatory proteins Pink1,Parkin,p62,LC3,mitochondrial biogenesis regulatory protein PGC1α,division/fusion regulatory proteins OPA1,MFN2,DRP1,p-DRP1 and antioxidant stress regulatory proteins Keap1 and Nrf2.HBAD-mcherry-EGFP-LC3 adenovirus transfected cells was used to observed the number of autophagosomes and autophagolysosomes.Results The results showed that the intracellular concentration of HN in PC12 in the Rot poisening group was significantly higher than that in the control group(P＜0.05);Compared with the control group,the Rot poisening group had significantly decreased activity of PC12 cells,decreased ATP content and increased production of ROS.After the poisen of Rot in PC12 cells,the expression of Pink1 and p-Parkin,the ratio of LC3Ⅱ/LC3Ⅰ and the expression of p-DRP1 in mitochondrial fusion protein was increased,while the expression of p62,the expression of mitochondrial biogenesis protein PGC1 α,mitochondrial fusion proteins MFN2 and OPA1,and antioxidant stress proteins Keap1 and Nrf2 were decreased(all P＜0.05).The number of autophagosomes and autophagolysosomes in PC12 cells in the Rot poisening group was higher than that in the control group(P＜0.05),and HN pretreatment(20 μmol/L)could significantly improve the changes mentioned above caused by Rot poisening(P＜0.05).Conclusion HN ameliorates Rot-induced toxic damage for dopamine neurons by inhibiting mitophagy and mitochondrial division and promoting mitochondrial biogenesis and fusion,and anti-oxidative stress.
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Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients.Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region,were analyzed retrospectively.The first part,data of 106 patients with moderate,high-risk NMIBC were collected.A total of 83 patients were male,while the other 23 patients were female.The average age was 66.7 years old.The clinical staging were T1 in 86(81.1％) cases,Ta in 20(18.9％) cases and carcinoma in situ in 6 (5.7％) patients.Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor.The incidence rate of recurrence and progression during more than 6 months' follow-up time were observed.Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method.The second part,treatment compliance of 276 patients with bladder cancer,including moderate/high-risk NMIBC in 263 cases,moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries,were observed.Patients consisted of 211 males and 65 females with average age of 68.3 years.Results With a median follow-up of 12 months,9 (8.5％) patients experienced tumor recurrence and 2 (1.9％) patients were found progression in the first part.The one-year cancer free recurrence rate of the patients was 91.5％.Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR =3.214,95％CI0.804-12.845,P =0.099).In the second port,an incidence rate of adverse effects was 64.1％ (177/276).The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment.A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 ％),9 cases (3.3 ％) with economic reasons and 11 cases (4.0％) with serious complications.Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects.Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy.
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Objective To investigate the efficacy and toxicity of sorafenib in the treatment of advanced renal cell carcinoma. Methods From May 2007 to JUN 2009, 33 patients with advanced renal cell carcinoma were given oral sorafenib 400-600 mg twice daily. There were 23 males and 10 females in the study group. The pathological diagnosis of the primary tumors was clear cell carcinoma in 29 patients, papillary renal cell carcinoma in 2 patients, chromophobe renal cell carcinoma in 1 patient and chromophobe renal cell carcinoma mixed with clear renal cell carcinoma in 1 patient. Fifteen patients had multiple organ metastases and 18 patients had single organ metastasis. The median follow-up time was 29 weeks. Results Four (12%) patients achieved partial remission, 2 (6%) patients achieved progression disease, the remaining 27 (82%) patients achieved stable disease. Complete remission was not observed in the group. Two of the partial remission patients benefited on bone metastases. Common toxicities were skin reaction (85%), diarrhea (46%), erythra (42%), alopecia (36%), oral ulcer (18%) and hypertension (9%). Conclusions Sorafenib could be effective in controlling tumor growth. The overall effectiveness was 12%, the disease control proportion was 94% in this group and its toxicity was relatively minor and well tolerated.
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Objective To evaluate the tolerance and safety of sorafenib for elderly patients with advanced renal cell carcinoma.Methods Forty cases with advanced renal cell carcinoma were enrolled,26 were males and 14 were females,the average age was 70 years.Recurrence or metastasis was found in 32 patients who had received nephrectomy,22 of the 32 cases had received cytokine therapy before recurrence or metastasis.Primary renal lesions of 8 cases could not be resected,so patients get renal tumor biopsy.Pathological type of all patients was clear cell carcinoma.KPS of all the patients were ≥70 points.Sorafenib was used as first-line treatment,with 400 mg twice per day,until intolerance or disease progression occurred.Results The average treatment time was 7.5 months (3-18 months),CR 0 case,PR 6 cases,SD 29 cases,PD 5 cases.The overall objective response rate and disease control rate were 15.0% (6/40)and 87.5%(35/40),respectively.The median follow-up period was 11 months.The adverse reaction included hand-foot skin reaction(70.0%),alopecia (62.5%),rash(52.5%),diarrhea(37.5%),loss of appetite(32.5%),fatigue(27.5%).Most adverse reactions occurred around the second week after drug therapy initiation,their duration did not equal.And most of these adverse reactions could be released by symptomatic treatment,they did not affect the treatment.Conclusions The types of adverse reactions of sorafenib for elderly patients with advanced renal cell carcinoma are similar to those reported in the literature.Generally the degree of adverse reactions is minor,with good tolerance and safety.