Objective To study the pharmacokinetics difference of levofloxacin polymorphs in rats, evaluate the advantageous medical polymorph,and explore the effects of different polymorphs on clinical medicine. Methods Four crystal forms of levofloxacin were administered intragastrically to rats,and high performance liquid chromatography( HPLC)was used to measure the contents of levofloxacin in rat plasma. The pharmacokinetic parameters were calculated and compared Results After a single oral dose,the peak plasma concentration(Cmax)of crystal forms ofⅠ,Ⅱ,ⅢandⅣof levofloxacin was 6. 984,9. 692,9. 405,6.424 mg·L-1;the time to peak(tmax)was 0.6,0.9,1.0,1.0 h;the half-life(t1/2)was 4.207,2.97,4.857,1.695 h;theareaunderthecurve(AUC0→12h)was31.478,42.385,32.406,31.636mg·h·L-1. Conclusion Thereisnostatistically significant difference in pharmacokinetic parameters. However,compared with other crystal forms,plasma concentration of crystal form II is higher and maintained longer. Therefore,crystal form II of levofloxacin is an advantageous polymorph for medicine.

Objective To study the relationship between the clinical imaging manifestations and the judgement of benign and malignant of solitary pulmonary nodules (SPN) .Methods A retrospective analysis of 146 patients with SPN which confirmed by pathological diagnosis .According to SPN diameter all SPN were divided into three groups ,the number of SPN which diameter smal-ler than 0 .8 cm were 16 case ,> 0 .8 - 1 .5 cm were 41 cases ,> 1 .5 - 3 .0 cm were 89 cases .Collect patients′ age ,sex ,smoking his-tory ,clinical symptoms and imaging data ,and analyze its relationship with pathological results .Results All the 146 patients were pathological diagnosis ,benign in 52 cases (35 .6% ) ,malignant in 94 cases (64 .4% ) .As the diameter increases ,the malignant rate increased .There was statistical significance in benign and malignant lesions with smoking history and clinical symptoms (P< 0 . 05) .Whether SPN boundary is clear ,have lobulation ,burr ,pleural indentation syndrome and vessel convergence in benign and ma-lignant lesions were statistically significant (P< 0 .05) .Conclusion The feature size and imaging performance of SPN has important reference value for the judgement of benign and malignant .The positive intervention to SPN have great significance on improve sur -vival rate of lung cancer .

OBJECTIVE To investigate the effect of bevacizumab ,an anti-human vascular endothelial growth factor monoclonal antibody,on pulmonary dissemination of colorectal cancer. METHODS A metastatic colorectal cancer mouse model was established. Mice were randomly divided into two groups(n=8). The mice in experimental group were administered ip with bevacizumab at the dosage of 5 mg · kg-1,and those in control group were given isotype IgG at the same dosage. The antibodies were administered on 2 d before initiation of model establishment and 2 d after that,then once every 5 d for 4 weeks,for a total of 7 times. Liver and lung metastases were determined by histopathological examination. The chemokine receptor C-X-C receptor 4(CXCR4)and its ligand C-X-C ligand 12(CXCL12)mRNA expression in the lung were detected by quantitative RT-PCR. Human colon cancer cells HCT116 were treated with bevacizumab(5 mg·L-1)for 24 h. The expression levels of vascular endothelial growth factor receptor 1(VEGFR1)and CXCR4/7 protein as well as CXCR3/4/7 mRNA were examined by Western blotting and quantitative RT-PCR respectively. RESULTS The number of mice(2/8) with liver metastases was reduced,while the number of mice(8/8) with lung metastases increased in experimental group compared with isotype IgG-treated group(6/8 and 2/8 respectively,P<0.05). The mRNA expression level of CXCR4 and CXCL12 in lung tissue was significantly up-regulated in bevacizumab-treated group com?pared with control group(P<0.05). The mRNA and protein expression level of CXCR4 and CXCR7 was dramatically increased in HCT116 cells treated with bevacizumab(P<0.05). CONCLUSION Bevacizumab can potentially promote lung metastases of colorectal cancer,which may be related to up-regulation of CXCR4 and CXCL12 expression.

Objective To observe the effects of Eldepryl on expressions of tyrosine hydroxylase (TH) and glial cell line-derived neurotrophic factor (GDNF) in substantia nigra and striatum in Parkinson’s disease (PD) and to explore the protective mechanism of Eldepryl on dopaminergic neuron . Methods Healthy male Sprague-Dawley (SD) rats (n=72) were randomly divided into control group, model group and Eldepryl group (n=24 in each group). Each group was divided random?ly into 2 subgroups as 4 day treatment group and 8 day treatment group (n=12 in each subgrop). Pakinson’s disease model was established by injecting rotenone subcutaneously back the neck, rats in the control group were injected with an equal vol?ume of sunflower oil subcutaneously at the same location. Rats in the Eldepryl group were then given Eldepryl 0.5 mg·kg-1 in?tragastrically every day for 4 or 8 consecutive days and rats in model group and control group were given an equal volume of saline instead. The expression of TH and GDNF in substantia nigra and striatum were detected by immunohistochemistry and Western blotting. Results Immunohistochemistry and Western blotting showed that strong expression of TH positive cells with little expression of GDNF positive cells were seen in substantia nigra and striatum in rats of control group, and there was no significant difference between subgroup of 8 day treatment and 4 day treatment within control group. The expression of TH cells and GDNF were both significantly reduced in model group compared with those in control group (both P<0.05), and there was no significant difference between subgroup of 8 day treatment and 4 day treatment within each group. The ex?pression of TH positive cells were significantly reduced in Eldepryl group compared with those in control group, and were sig?nificantly increased compared with those in model group. The expression of GDNF positive cells were significantly increased in Eldepryl group compared with those in control group and model group (all P<0.05). And there were significantly more ex?pression of TH positive cells and GDNF positive cells at subgroup of 8 day treatment compared with those at subgroup of 4 day treatment within Eldepryl group with (all P<0.05). Conclusion These data suggest that Eldepryl can protect the dam?age of dopaminergic neurons in substantia nigra and striatum of PD rats. And its therapeutic mechanism may be associated with increased expression of GDNF.

Objective To observe the effects of 1,25-dihydroxyvitamin D3 on the expressions of transforming growth factor-β1(TGF-β1), fibronectin(FN),and vascular endothelial growth factor(VEGF) in rats with diabetic nephropathy(DN), and to elucidate the protective mechanism played by 1,25-dihydroxyvitamin D3. Methods DN models were estabolished by injecting streptozotoein ( STZ ) into male SD rats, which were divided into TGF-β1 overexpression group, TGF-β1 overexpression plus vitamin D3 group, TGF-β1 low-expression group, TGF-β1 low-expression plus vitamin D3 group, TGF-β1 normal-expression group, and TGF-β1 normal-expression plus vitamin D3 group. After 1,25-dihydroxyvitamin D3 treatment for 37 days, renal function and blood biochemical parameters were evaluated. The morphology and fibrosis of kidney tissues were observed. The expressions of TGF-β1, FN, and VEGF in kidney cortex were measured by immunohistochemistry, realtime PCR, and Western blotting. Results The levels of cholesterol, triglyceride, creatinine,plasma glucose, HbA1C , and 24 h urinary protein were lower in vitamin D3treated groups than those in corresponding control groups(P<0. 05). The degree of renal fibrosis was raised with the increased level of TGF-β1. Vitamin D3 treatment decreased the fibrosis in diabetic kidney. There were significant differences in the mRNA and protein expressions of TGF-β1 in three control groups(P<0. 05). With the increased levels of TGF-β1, the expressions of FN and VEGF were increased. The expressions of TGF-β1, FN, and VEGF were lowered by vitamin D3compared with the corresponding control groups(P<0. 05). Conclusion 1,25-dihydroxy-vitamin D3 may protect the renal tissure in diabetic rats via inhibiting the expressions of TGF-β1, FN, and VEGF in the kidney.

Objective To explore clinical and muscular pathological features of statin-induced myopathy.Methods Nine patients were enrolled in this study,who were diagnosed as statin-induced myopathy by muscle biopsy in Peking University First Hospital from April,2012 to October,2014.The clinical data and pathological findings were analyzed.Results The exposure time to statins varied from 4 days to 4 years in the total of 9 patients,6 males and 3 females,with the average age of 63 ± 6 (55 to 74) years old.Three patients suffered from myalgia and 6 patients complained of weakness mainly at the proximal limbs,while no symptoms occured in 3 patients.Serum creatine kinase (CK) increased in all patients with the maximum value varied from 468 to 8 000 U/L.Serum myositis antibodies were tested in 7 patients and all were negative.Electromyogram was performed in six patients with myogenic damage found in 2 patients.MRI of bilateral thigh muscle was carried out in six patients with muscle edema and mild fatty infiltration found in 2 patients.All patients underwent skeletal muscle biopsy with histochemical and immunohistochemical staining.The main muscular pathological features were muscle fiber atrophy,necrosis,regeneration and increased lipid droplets.Ragged blue fiber,cytochrome C oxidase-negative muscle fibers and decreased NADH activity were observed in some patients.MHC-Ⅰ expressed in the sarcolemma of muscle fibers at various levels.Mild C5b-9 staining was found in the endomysium,capillary and cytoplasm.Symptoms and the level of CK were improved in 7 patients after discontinuing statins or changing to another statin,while the immunosuppressive therapy were used in 2 patients and shown to be effective.Conclusions Statin induced myopathy is self-limiting in most patients,with improvement after discontinuation of statins.Few patients with autoimmune necrotic myopathy need immunosuppressive therapy.

Objective To investigate the risk factors for hemorrhagic transformation (HT) and poor outcomes in patients with acute ischemic stroke after mechanical thrombectomy.Methods The patients with acute ischemic stroke received mechanical thrombectomy were enrolled retrospectively.The demography,vascular risk factors and other clinical data of the patents were collected.The modified Rankin scale (mRS) was used to evaluate the clinical outcomes at day 90.Good outcome was defined as mRS score 0-2.The patients were divided into either a HT group or a non-HT group according to their HT conditions.Multivariate logistic regression analysis was used to identify the independent risk factors for HT and poor outcomes.Results A total of 48 patients with acute ischemic stroke received mechanical thrombectomy were enrolled,including 25 males (52.1％).Their mean age was 64.77± 9.14 years.The mean National Institutes of Health Stroke Scale (NIHSS) score was 17.70 ± 3.77.Twenty-two patients (45.8％) occured HT,of which 9 were symptomatic HT;24 (50.0％) had good outcomes.The proportion of males in the HT group was significantly lower than that in the non-HT goup (30.4％vs.72.0％;x2 =8.293,P =0.004),while the proportions in patients with diabetes (65.2％ vs.36.0％;x2 =4.090,P =0.043) and atrial fibrillation (78.3％ vs.44.0％;x2 =5.880,P =0.015),as well as the baseline fasting blood glucose level (8.514 ± 4.400 mmol/L vs.6.354 ± 1.472 mmol/L;t =2.319,P =0.025) were significantly higher than those in the non-HT group.Multivariate logistic regression analysis showed that the atrial fibrillation (odds ratio [OR] 6.136,95％ confidence interval [CI] 1.617-23.291;P =0.042) was a risk factor for the occurrence of HT after mechanical thrombectomy.The proportion of diabetic patients (29.2％ vs.70.8％;x2 =8.333,P=0.04) and baseline NIHSS score (16.050±4.865 vs.19.210±4.423);t=2.310,P=0.026) of the good outcome group were significantly lower than those of the poor outcome group,while the proportions of patients in atrial fibrillation (75.0％ vs.45.8％;x2 =4.269,P =0.039),anterior circulation stroke (87.5％ vs.62.5％;x2 =4.000,P =0.046) middle cerebral artery (75.0％ vs.29.2％;x2 =10.113,P =0.006),vertebral basilar artery (37.5％ vs.12.5％;x2 =10.113,P =0.006) occlusion and parenchymal hematoma (33.3％ vs.4.1％;P=0.011) were significantly higher than the poor outcome group.Multivariate logistic regression analysis showed that diabetes (OR 5.898,95％ CI 1.699-20.479;P=0.005),baseline NIHSS score (OR 1.167,95％ CI 1.011-1.347;P =0.035),and parenchymal hematoma (OR 1.295,95％ CI 1.099-1.875;P=0.028) were the independent risk factors for poor outcomes.Conclusions Atrial fibrillation is an independent predictor of HT risk in patients with acute ischemic stroke after mechanical thrombectomy.Diabetes mellitus,higher baseline NIHSS score,and concurrent brain parenchymal hematoma are the independent predictors of poor outcomes.Therefore,the risk of HT and adverse outcomes should be fully assessed before mechanical thrombectomy in patients with acute ischemic stroke.

Objective To investigate the expression of 14-3-3ε protein in the bladder urothelial carcinoma (BUC) and to explore its association with the clinicopathologic features.Methods The bladder urothelial carcinoma samples were divided into three groups:normal control group of 10 cases,low-grade malignant BUC group of 25cases (includes 5 cases of papilloma,10 cases of PUNLMP and 10 cases of low grade non-invasive papillary urothelial carcinoma),high-grade malignant BUC group of 21 cases (includes 11 cases of high-grade non invasive papillary urothelial carcinoma and 10cases of infiltrating carcinoma).The expression and location of 14-3-3ε in three groups were detected by immunohistochemical EnVision and the relationship with clinicopathologic parameters was analyzed.Results 14-3-3ε expression was observed in the cytoplasm of the cell.The expression of 14-3-3ε in normal control group was 90 ％ (9/10),low-grade malignant BUC group was 72.0 ％ (18/25),high grade malignant BUC group was 14.3 ％ (3/21).It correlated with histological grading but had not showed correlation with other clinicopathologic parameters.There was significant difference in 14-3-3ε expression between the high grade malignant BUC group and the low-grade malignant BUC group,the high grade malignant BUC group and norml control group (all P ＜ 0.05).Conclusions 14-3-3ε plays an important role in carcinogenesis of BUC.It may be a biomarker for early diagnosis and classification of BUC and shows promise for clinic application.

Objective To evaluate the safety of endoscopic retrograde cholangiopancreatography (ERCP) for elder patients (age more than or equal to 80 years).Methods Data of 464 patients (age ≥ 80 years) who underwent ERCP procedures from June 2008 to June 2014 in the First Affiliated Hospital of Nanchang University were compared with those of patients less than or equal to 60 years old,randomly chosen at 1∶4,for comorbidity,feature of disease distribution,intraoperative situation and postoperative complications of ERCP.Results The comorbidity rates of coronary heart disease,hypertension,chronic pulmonary disease and type 2 diabetes in observation group were significantly higher than those in the control group(P＜0.05),but there was no significant difference between two groups regarding to the comorbidity rate of arrhythmia(P =0.111).The main feature of disease distribution in two groups was choledocholithiasis,but the rate of malignant tumor in observation group was higher than that in the control group(P＜0.05).The success rate of ERCP showed no significant difference in two groups (98.92％ VS 99.35％,P=0.358).There was no significant difference between the two groups in the complication rates of acute pancreatitis (4.96％ VS 3.18％,P =0.064),infection (0.43％ VS 0.54％,P =1.000) and hemorrhage (1.08％ VS 0.59％,P=0.259).However the rate of perforation in observation group was lower than that in the control group (0.43％ VS 0.05％,P =0.043).Conclusion ERCP is safe and effective for elder patients.

Objective To investigate the effect of overexpression of miR-218-5p and inhibition of TDP1 expression on rotenone-induced apoptosis of gastric cancer cells, and to elucidate its possible mechanism. Methods The expression levels of miR-218-5p and TDP1 in human normal gastric epithelial cells and four gastric cancer cells were detected by RT-PCR, and their correlation was analyzed. The targeting regulation of miR-218-5p on TDP1 was verified by dual luciferase reporter gene assay. Gastric cancer cell injury model was induced by 1.0 μmol/L rotenone. Cell cycle and apoptotic rate were detected by flow cytometry. TDP1 level in mitochondria and the expression of Bax and Cyt-c protein were detected by Western blot. Results The expression of miR-218-5p was low in gastric cancer cells (P < 0.05), and TDP1 was high (P < 0.01). There was a negative correlation between the expression of miR-218-5p and TDP1 (R²=0.9580, P=0.0212). Compared with the control group, SGC-7901 cells in the injured group developed G₁ phase arrest and the apoptotic rate increased (P < 0.01). After transfection of miR-218-5p-mimic, the cell arrest and apoptotic rate further increased (P < 0.01), the expression of Bax and Cyt-c increased (P < 0.01), while the level of TDP1 in mitochondria decreased (P < 0.01). The G₁ phase arrest of cells in TDP1 overexpression group was relieved, the apoptotic rate was decreased (P < 0.01), the level of TDP1 in mitochondria was increased (P < 0.01), and Bax and Cyt-c expression were decreased (P < 0.01). Conclusion MiR-218-5p can target TDP1 expression and induce apoptosis of gastric cancer cells. Its mechanism may be related to inhibiting mitochondrial DNA damage repair and function maintenance and activating mitochondrial endogenous apoptosis pathway.