The body is equipped with kinds of transporters which generally exist in liver,kidney,and intestine.Multidrug and toxin extrusion proteins(MATEs;SLC47A)are predominantly expressed in the brush-border membrane of proximal tubule epi-thelial cells in the kidney and the canalicular membrane of hepa-tocytes.Functionally,MATEs act as efflux transporters for or-ganic compounds.The article discusses type,structure,poly-morphism and function of MATE1and MATE2-K,and also dis-cusses the effect of single nucleotide polymorphisms (SNPs)in the SLC47A1 gene and SLC47A2 on the pharmacokinetics and pharmacodynamics of metformin and platinum-based chemothera-peutic agents.

Objective To evaluate the clinical efficacy and safety of gemcitabine combined with cisplatin in the treatment of bladder cancer.MethodsFrom October 2012 to August 2015, 92 patients with bladder cancer were enrolled in our hospital.Patients were divided into observation group and control group by random number table method.On the basis of routine nutrition support and symptomatic treatment, cisplatin was administered by intravenous infusion of cisplatin 70mg/m2 in the first 3d in control group.On the 1d and 8d, gemcitabine 1000mg/m2 was intravenously infused in observation group and 21 days treatment was taken continuous for 2 courses.Curative effect, IL-17, IL-18, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF) and urinary TGF-β1 levels and adverse reactions of two groups were comparatively studied.ResultsThe total effective rate in the control group (63.05%) was significantly lower than that in the observation group (76.09%) (P<0.05).After treatment, the levels of serum IL-17, IL-18, TGF-β1 and VEGF in the two groups were significantly decreased and with significant difference between two groups (P<0.05).The levels of urinary TGF-β1 were significantly increased and with significant difference between two groups (P<0.05).The incidence of adverse reactions in the control and observation groups was 15.22% and 6.52%, respectively.There was no significant difference between the two groups.ConclusionGemcitabine combined with cisplatin has a significant clinical efficacy and safety in the treatment of bladder cancer.

Objective To evaluate the efficacy of partial cystectomy in treatment of localized muscle invasive bladder cancer.Methods From 1999 to 2005,data from 71 patients with muscle invasive bladder cancer(MIBC) were reviewed.There were 47 patients underwent partial cystectomy (PC) and 24 underwent total cystectomy (TC).The overall survival and disease-free survival in patients with MIBC with PC or TC were compared.All patients had pathologic T2-T3.Matched Kaplan-Meier survival analyses compared the effect of PC vs.TC on overall survival and disease-free survival.Univariate (log rank) and multivariate (Cox' proportional hazard model) analyses were used to test the statistical significance of several potential prognostic factors for survival rate.Results In the entire cohort,the overall survival rate and disease-free survival rate estimated at 5 years were 57％ and 50％ for PC patients,53％ and 46％ for TC patients,respectively (P＞0.05).On univariate analysis,T stage (include vessel tumor embolus) and whether the tumor was pedunculated were the significant predictors of tumor recurrence.Age,gender,tumor quantity,tumor size and histology category were not associated with prognosis.Cox proportional hazard regression model confirmed that the independent prognosis factors of tumor was T stage (EXP(B)=1.64,P＜0.05).Conclusions PC might not undermine cancer control in appropriately selected patients with MIBC.

Objective To evaluate the predictive value of tumor metabolic indexes measured by 18F-FDG PET/CT in recurrence of stage Ⅰ NSCLC after surgery.Methods A total of 85 patients (44 males,41 females,age (62.46± 10.38) years) in Shanghai Renji Hospital with stage Ⅰ NSCLC,who underwent 18F-FDG PET/CT and subsequent surgical resection,were retrospectively enrolled from April 2006 to December 2011.Gender,age,tumor size,pathology,SUVmax,MTV and TLG of the primary tumor were selected as variables.ROC curve analysis was used to analyze the cut off value.The prognostic significance of parameters for recurrence-free survival (RFS) was evaluated by univariate and multivariate analyses.Survival analysis was analyzed by Kaplan-Meier method.Results During follow-up period,tumor recurrence occurred in 21 patients (24.7％,21/85) and 11 patients (12.9％,11/85) died.The median follow-up period was 44 months.The median values of SUVmax,MTV and TLG were 4.100,3.048 cm3 and 7.970,respectively.Cut off values of SUVmax,MTV and TLG were 7.115,4.701 cm3 and 12.015 according to ROC curve analysis.Univariate Cox analysis showed that SUVmax(x2 =22.091),MTV (x2 =4.941) and TLG(x2 =10.488) were associated with RFS(all P＜0.05).But gender,age,tumor size,and pathology were not independent risk factors of recurrence (x2=0.248-3.888,all P＞0.05).Multivariate Cox analysis revealed that SUVmax(=16.902,HR=15.426,P＜0.05) and TLG (x2=6.029,HR=4.054,P＜0.05) were independent prognostic factors for recurrence.Kaplan-Meier survival analysis showed that the period of RFS in high SUVmax (＞ 7.115) group (x2=32.545,P＜0.05) and in high TLG (＞12.015) group (x2=12.665,P＜0.05) were lower than those in low SUVmax group and low TLG group.Conclusion The SUVmax and TLG measured by 18F-FDG PET/CT have significant value for predicting the recurrence of stage Ⅰ NSCLC.

Objective: To investigate the effects of simvastatin and non-POU-dormain-containing, octamer-binding protein (NONO): on the proliferation of breast cancer MCF-7 cells, and to explore its possible mechanism. Methods: The expression levels of NONO mRNA and protein and the proliferation of breast cancer MCF-7 cells after transfection with NONO gene-targeted small interfering RNA (siRNA): (siRNA-NONO): and the NONO over-expression recombination vector pcDNA4/TONONO were detected by real-time fluorescence quantitative PCR, Western blotting, and cell counting, respectively. The proliferation and expression levels of NONO mRNA and protein of breast cancer MCF-7 cells after treatment with simvastatin (20 μmol/L): were detected by cell counting, real-time fluorescence quantitative PCR, and Western blotting, respectively. The proliferation of MCF-7 cells after treatment with simvastatin in pcDNA4/TO-NONO transfection group was determined by cell counting. The expression level of 3-hydroxy-3-methylglutaryl-CoA reductase (HMCCR): mRNA and the concentration of cholesterol were examined by real-time fluorescence quantitative PCR and tissue total cholesterol assay, respectively. Results: The expression levels of NONO mRNA and protein of MCF-7 cells in siRNA-NONO transfection group were lower than those in siRNA negative control (siRNA-NC): transfection group (P < 0.01, P < 0.05). The expression levels of NONO mRNA and protein of MCF-7 cells in pcDNA4/TO-NONO transfection group were higher than those in the empty vector pcDNA4/TO transfection group (both P < 0.01). The ability of proliferation of MCF-7 cells in siRNA-NONO transfection group was lower than that in siRNA-NC group (P < 0.05), while the ability of proliferation of MCF-7 cells in pcDNA4/TO-NONO transfection group was higher than that in the empty vector pcDNA4/TO transfection group (P < 0.05). The ability of proliferation and the expression levels of NONO mRNA and protein of MCF-7 cells in simvastatin (20 μmol/L): treatment group were lower than those in the control group (MCF-7 cells without simvastatin treatment): (P < 0.05, P < 0.01, P < 0.05). The ability of proliferation of MCF-7 cells after treatment with simvastatin in pcDNA4/TO-NONO transfection group was lower than that in the group without simvastatin treatment (P < 0.01). The expression levels of HMCCR mRNA and cholesterol of MCF-7 cells in siRNA-NONO transfection group were lower than those in the siRNA-NC transfection group (all P < 0.01): Conclusion: Simvastatin can suppress the proliferation of breast cancer MCF-7 cells, and this effect may be related to the inhibition of NONO expression.

Cadmium (Cd) is a well-known hepatotoxic environmental pollutant. We used rat hepatocytes as a model to study oxidative damage induced by Cd, effects on the antioxidant systems, and the role of N-acetylcysteine (NAC) in protecting cells against Cd toxicity. Hepatocytes were incubated for 12 and 24 h with Cd (2.5, 5, 10 microM). Results showed that Cd can induce cytotoxicity: 10 microM resulted in 36.2% mortality after 12 h and 47.8% after 24 h. Lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase activities increased. Additionally, reactive oxygen species (ROS) generation increased in Cd-treated hepatocytes along with malondialdehyde levels. Glutathione concentrations significantly decreased after treatment with Cd for 12 h but increased after 24 h of Cd exposure. In contrast, glutathione peroxidase activity significantly increased after treatment with Cd for 12 h but decreased after 24 h. superoxide dismutase and catalase activities increased at 12 h and 24 h. glutathione S-transferase and glutathione reductase activities decreased, but not significantly. Rat hepatocytes incubated with NAC and Cd simultaneously had significantly increased viability and decreased Cd-induced ROS generation. Our results suggested that Cd induces ROS generation that leads to oxidative stress. Moreover, NAC protects rat hepatocytes from cytotoxicity associated with Cd.
Acetylcysteine/*metabolism ; Animals ; Antioxidants/*metabolism ; Cadmium/*toxicity ; Cell Survival/drug effects ; Cells, Cultured ; Environmental Pollutants/*toxicity ; Hepatocytes/drug effects/metabolism ; *Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/*metabolism

Nasal preparations have unique advantages in drug delivery and are widely used in the treatment of local and systemic diseases. Nasal administration of traditional Chinese medicine （TCM） has a long history in China. In recent years， nasal preparations of TCM have attracted wide attention. Based on the information about nasal preparations of TCM from the database of National Medical Products Administration （NMPA）， Yaozh.com and China National Knowledge Internet （CNKI） in the recent 30 years， the formulation， the listed products， commonly used TCM， pharmaceutical excipients， clinical application and safety research of modern nasal preparations of TCM were summarized and expounded. Focusing on many problems in the development of modern nasal preparations of TCM， such as inaccurate dosage of some products， incomplete quality standard system of pharmaceutical excipients， imperfect safety evaluation， lack of research and development of nasal drug delivery devices and so on， the possible solutions and prospects were put forward from the aspects of optimizing the extraction and separation process of TCM， the quality control and application method of pharmaceutical excipients， the development of new dosage forms， the safety evaluation of nasal administration of TCM， and the design and development of nasal administration devices. The aim is to provide ideas for the development of nasal preparations of TCM and provide scientific basis for its sustainable utilization.