Obesity is a prevalent metabolic disorder, which seriously affects human health and has become the world's public health problem. Kinase S6K1, an important downstream effector of mammalian target of rapamycin (mTOR), influences specific pathological responses, including obesity, type 2 diabetes and cancer. Presently, S6K1 has become an attractive therapeutic target in the treatment of these disorders. Here, the functions of kinase S6K1, its molecular regulation mechanisms, related pathogenesis of disease and relevant small molecular inhibitors are reviewed. Finally, the prospect of research toward S6K1 is expected as well.
Animals ; Diabetes Mellitus, Type 2 ; Humans ; Neoplasms ; Obesity ; Ribosomal Protein S6 Kinases, 70-kDa ; metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases ; metabolism

Aim To investigate the protection effect of icariin on isoproterenol induced neonatal rat cardiomyocytes injury.Methods Isolation of cardiomyocytes from Sprague-Dawley rats aging 1～3 d were performed.Cardiomyocytes were grown in DMEM culture medium containing 15% fetal bovine serum.The cell density was adjusted to 1?105～5?105 cells?L-1,and the suspension was pipetted into each well of culture plates.Cells were incubated at 37 ℃ in 5% CO_2 atmosphere for 72 h.Cultured rat cardiomyocytes were divided into different groups:control,0.5 mmol?L-1 isoproterenol(model),and therapeutic groups with 0.1,1 and 10 ?mol?L-1 icariin.Cell viability was analyzed using MTT assay.The potential of mitochondrial membrane was determined by laser scanning confocal microscope.Apoptotic cells were detected by using flow cytometric analysis.Results Compared with the control group,the cell activity was lower in model group(P

OBJECTIVE:To strength pharmacy management,improve pharmacy stocktaking efficiency and lower the error rate of the stocktaking in outpatient pharmacy.METHODS:Based on "Army No.1" inventory management system,the data were retrieved and adjusted using Excel spreadsheet,and the inter-district small-scale inventory table of the outpatient pharmacy was designed in which certain individuals should be responsible for certain drugs and the order of drugs in the inventory table were in line with the arrangement order of drugs.RESULTS:The new drug stocktaking model reduced the error rate of traditional monthly drug stocktaking by 3%.CONCLUSION:The established drug stocktaking method reduces human and material resources,facilitates a more flexible,convenient and rapid stocktaking,and greatly enhances the conformity rate between drugs and accounts.

Objective To study the relationship between tacrolimus blood level/dose and the genotype of CYP3A5 at 6th month after lung transplantation.Method Forty-six cases of lung transplant recipients who received the surgery between January 1st,2011 and January 1st,2013 served as the research subjects,and the genotypes of these patients were measured.These patients were divided into 3 groups (CYP 3A5 * 1 * 1,CYP 3A5 * 1 * 3,CYP 3A5 * 3 * 3) according to their different genotypes.The dose of tacrolimus and daily intake were detected at 6th month after surgery in each group,then the level/dose of tacrolimus was calculated.Result In all 46 recipients,5 of them were CYP 3A5 * 1 * 1 homozygous genotype,20 CYP 3A5 * 1 * 3 heterozygous genotype and 21 CYP 3A5 * 3 * 3 homozygous genotype.Under the condition of holding tacrolimus blood level between therapeutic range,there was significant difference in the dose of tacrolimus between the CYP3A5 * 1/ * 1 and * 1/* 3 versus * 3/* 3 genotypes (P＜0.01),but there was no significant difference between CYP3A5 * 1/* 1 genotype and * 1/* 3 genotype.Conclusion Tacrolimus dosing in lung transplant patients is associated with CYP 3A5 gene polymorphisms.

Objective To present the means of localizing the kidney with ectopic ureter in order to provide the reliable ground for surgical strategy. Methods Clinical manifestation study,IVU,SPECT imaging and cystoscopy were conducted.All the 58 patints are female with a mean age of 3.4 years.According to the creteria presented in reference,5 were type Ⅰ,42 type Ⅲ,1 type Ⅳ,8 type Ⅴ and 2 type Ⅵ. Results Operative finding revealed the accurate localization and diagnosis rate of IVU has been 95%(40/42) in type Ⅲ ectopic ureter,B-ultrasonograph 27%(12/53),SPECT 37%(6/16).With the combined consideration of imaging procedures and cystoscopy,the accurate localization and diagnosis rate has been 98%(57/58). Conclusions Combined use of imaging procedures and cystoscopy would improve the localization and diagnosis rate.Cystoscopy is the most reliable except in type Ⅲ ectopic ureter.

Objective To explore the value of apparent diffusion coefficient (ADC)in differentiating brain tuberculomas from me-tastases.Methods Conventional and enhanced MRI as well as diffusion weighted imaging (DWI)were performed in 24 cases of brain tuberculomas(immature in 18 cases and mature in 6 case)and 36 cases of metastases.The mean ADC values and relative ADC (rADC)values were calculated from the enhanced and non-enhanced regions of mass and the peripheral edema regions of brain le-sions.Results The mean ADC values and rADC values in the enhanced,non-enhanced and the peripheral edema regions were 796.90×10 -6 mm2/s and 1.1 6,864.85×10 -6 mm2/s and 1.27,1 531.60×10 -6 mm2/s and 2.24 for the immature brain tuberculo-mas;791.95×10 -6 mm2/s and 1.1 6,61 1.80×10 -6 mm2/s and 0.87,and 1 488.45×10 -6 mm2/s and 2.10 for the mature tubercu-lomas;421.95×10 -6 mm2/s and 0.61,961.00×10 -6 mm2/s and 1.36,1 545.00×10 -6 mm2/s and 2.18 for the brain metastases, respectively.There were significant differences in the mean ADC values (H =42.293,P ≤0.05)and rADC values (H =42.575, P ≤0.05)for the enhance regions in the three groups .There were also significant differences in the mean ADC values (H =33.100, P ≤0.05)and rADC values (H =1 7.867,P ≤0.05)for the non-enhance regions.No significant difference in the mean ADC values (H =1.550,P ≥0.05)and rADC values (H =5.511,P ≥0.05)were found for the peripheral edema regions.Conclusion The ADC values of DWI can help to differentiate brain tuberculomas from metastases,when combining with the conventional and enhanced MRI.

AIM: To estimate the antiasthmatic activity of new compounds: SDF-1, SDG-1 and SDG-3. F-1 is a furoxan derivative, G-1 and G-3 are hydroxylguanidine derivatives, SDF-1 is a novel seratrodast derivative connected with F-1, SDG-1 a seratrodast derivative connected with G-1, and SDG-3 a novel seratrodast derivative connected with G-3. METHODS: Firstly, the in vivo antiasthmatic activity was estimated in asthmatic guinea pigs induced by acetylcholine and histamine. Secondly, the in vitro NO releasement of these compounds was determined following the procedures of Griess. Finally, tracheal smooth muscle relexant potency of these compounds was evaluated on trachea of guinea pigs. RESULTS: The in vivo antiasthmatic activity of SDF-1 was more potent than seratrodast (P

Uncoupling protein 4 (UCP4) is a member of the multigenic uncoupling proteins (UCPs), specific expressing in the cerebral cortex and hippocampus. UCP4 plays an important role in Parkinson's disease, multiple sclerosis, epilepsy, stroke, brain trauma and other central nervous system diseases by uncoupling, decreasing mitochondrial membrane potential,regulating Ca2+ homeostasis and oxidative stress. This article reviews UCP4 and its roles in the central nervous system diseases in order to provide certain basis for the development of UCP4targeted medication.

Aim: To observe the effects of sarsasapogenin ( SAR) on osteoblasts and osteoclasts cultured in vitro. Methods: Colonal murine calvarial osteoblast-like cell line MC3T3-E1 cells were cultured in vitro. MTT,p-nitropheneye phosphate and tinctorial method of alizarin Bordeaux were used to investigate the effects of SAR on the proliferation, ALP expression, and mineralization tuberculation of MC3T3-E1 cells. Mature osteoclasts were i-solated from the long bone of one-day rat. Meanwhile, marrow cells of mouse bone were cultured with induction of 1,25( OH)_2VitD_3. During the culturing of osteoclasts or marrow cells, SAR of different concentrations was added into the medium. The number of osteoclasts was recognized as tartrate resistant acid phosphatase( TRAP) ( +) multinucleate cells and the resorption lacuna on bone slice were examined with toluidine blue staining. Results: Comparing with the control group, SAR (0.01, 0. 1, 1μg/mL) significanthy increased the proliferation of MC3T3-E1 cells (P <0. 05, P <0. 01). There was no significant difference in the expression of ALP in early pro-liferating MC3T3-E1 cells exposed to SAR of 0.01,0. 1, 1μg/mL, but in the differentiation phase MC3T3-E1 cells, SAR improved ALP activity very significantly if compared with the control group, of which SAR of 1 μg/mL had the most promotion effect(P <0. 01). In addition, compared to the control group, there were, to various ex-tents, increased in the number of mineral nodes in MC3T3-E1 cells after 15day incubation with SAR of different conentrations. Furthermore, no obvious effects of 0.01-1μg/mL SAR on mature osteoclast were observed. But typical osteoclasts were formed when marrow cells were cultured with the induction of 1,25(OH)_2D_3 in medium for 7 days while little or no osteoclasts were induced from marrow cells in the presence of SAR. Conclusion: The results suggest that SAR can effectively promote the proliferation, differentiation and mineralization of osteoblasts cultured in vitro. Besides, SAR can inhibit the generation of osteoclasts from marrow cells.

Aim: To study the therapeutic effects of ZK_(14), a novel nitric oxide donor, on hepatic fibrosis in rats. Methods: Rats were injected intraperitoneally with CCl_4 and induced to hepatic fibrosis, followed by intra-gasrtic administration with high dose of 20 mg/kg and low dose of 10 mg/kg of ZK_(14) for 4 weeks. The effects were evaluated in the content of nitric oxide of serum and nitric oxide synthases of liver, in serum levels of the hepatic functions indices and hepatic fibrotic index and in liver histopathology. Results: The biochemical indices and pathology grade were effectively improved in the group of ZK_(14) 20 mg/kg, and liver function was also effectively protected in this group. Conclusion: ZK_(14), a novel nitric oxide donating biphenyldicarboxylate derivative, showed preferable therapeutic effects on hepatic fibrosis of rats induced with CC14, and it may be of potential value in the treatment of hepatic fibrosis.