Cell Adhesion ; drug effects ; Cytokines ; blood ; drug effects ; Humans ; Paraquat ; toxicity

Objective To study the clinical application value of advanced breast cancer which resistence CAF regimen,treated with semimonthly regimen for paclitaxel combined with 5-fluorouracil/leucovorin 48-hour continuouse infusion.Methods 80 paients with CAF-regimen-resistant ABC were treated with paclitaxel combined with 5-fluorouracil/leucovorin continuouse infusion,paclitaxel 95mg/m2,d_1,LV 200mg,d_1,5-fluorouracil 3g/m2,continuouse infusion for 48 hours with infusion pump.every cycle lasted 2 weeks,at least 4 cycles.Results Of 80 patients,there were 9 complete and 26 partial responses,32 cases remained stable and 13 progressive.The overall response rate of 43.8%.The median time to progression was 8 months.The median survival time was 16.7 months,the patients with soft tissue,lung,pleura,bone,liver obtained response rat was 46.7%(21/45),38.5%(5/13),31.3%(5/16),40%(4/10),20%(2/10).Conclusions semimonthly regimen for paclitaxel combined with 5-fluorouracil/leucovorin 48-hour continuouse infusion is effective and acceptable toxicity,it could be considered as one of the standard chemotherapy for advanced breast cancer which resistence CAF regimen.

OBJECTIVE To explore the absorption mechanism of thiophenorphine, and its effect on P-glycoprotein (P-gp) expression by using Caco-2 cell monolayer model. METHODSThe LC-MS-MS method was applied to determine thiophenorphine concentration in millicell system. The bi-directional permeability studies were performed to investigate the potential involvement of efflux carriers in the intestinal absorption. P-gp inhibition was studied by flow cytometry using calcein-AM as P-gp substrate.The expression of P-gp was evaluated using Western blotting. RESULTSThiophenorphine transport in Caco-2 cells was in time-dependent manner. Its average apparent permeability coefficient (P_(app)) was 2.338×10~(-6) cm·s~(-1). P_(app) was increased 2.8 folds by P-gp inhibitor ciclosporin A, and 2.3 folds by mulitdrug resistance-associated protein2 (MRP2) inhibitor MK571. The accumulation of calcein-AM and the expression of P-gp in Caco-2 cell line wasn't changed noticeably by thiophenorphine. CONCLUSION Thiophenorphine is a common substrate of P-gp and MRP2 and it shows normal transport in millicell system. The expression of P-gp doesn't induce by thiophenorphine.

Objective To investigate the effects of arsenic trioxide(As2O3) on the cell proliferation and apoptosis of C6 glioma cells in vitro.Methods The C6 glioma cells were treated by 1,3,5 μ mol/L of As2O3 with different duration and observed under the microscope and electromicroscope.The viability of C6 glioma cells was examined by methyl thiazolyl tetrazolium (MTT) assay,and cell cycle and apoptosis were examined by flow cytometry.Results After treatment of 1,3,5 μ mol/L As2O3,C6 glioma cells were inhibited obviously with a dose- and time-dependent manner (P ＜0.05) by MTT.During flow cytometry,more increasing apoptotic cells were found in different concentration As2O3.Characteristic morphological changes were observed in As2O3 intervention by transmission election microscopy including cell shrinkage,physaliphore,nuclear condensation and apoptosis and so on.Conclusion As2O3 can inhibit the cell proliferation and induce the apoptosis of C6 glioma cells.

Objective To investigate the correlative factors influencing long-term efficacy of patients with liver neoplasms after interventional therapy. Methods A total of 495 patients underwent transcatheter arterial chemoembolization (TACE), and the data were retrospectively analyzed. The patients were divided into two groups according to the survival time after interventional therapy: ≥5 years and ＜5 years. Correlative factors were compared in both two groups. Results In 31 patients survived longer than 5 years, 18 patients with Lipiodol filling type Ⅰ tumor, and 13 with type Ⅱ tumor. The 5, 7, 10 years survival rate in all 495 patients was 6.26% (31/495), 1.41% (7/495) and 0.40% (2/495), respectively. Factors including tumor pattern, clinical classification, the features of angiography, with or without heptic arteriovenous fistula, the pattern of Lipiodol filling, with or without invasion and metastasis, hepatic function, patient's age, tumor diameter, AFP value before and after TACE, the variety of AFP value after TACE influenced the long-term survival rate after interventional therapies (P＜0.05). Conclusion The characteristics of tumor, patient's status, the quality of TACE, whether combined with PEI, and/(or) anti-virus treatment have significant influence on long-term efficacy after interventional therapy in patients with liver neoplasms.

Objective To establish an LC-MS/MS method for determination of S-071031 B, a novel antidepressant , in rat plasma and to study its pharmacokinetic profiles .Methods An LC-MS/MS method was established to determine S-071031B in rat plasma, and L-8021 was employed as the internal standard .The analytes were separated on a C18 column with a mobile phase consisting of water-acetonitrile containing 0.1%(v/v) formic acid at a flow rate of 0.3 ml/min.The mass spectrometer was operated in a selected reaction monitoring ( SRM ) mode with a positive electrospray ionization (ESI) interface.The plasma concentration-time curve was drawn and pharmacokinetic parameters were calculated by DAS 2.0.Results The linear range was from 2 to 1000 ng/ml with a sensitivity of 2 ng/ml as the lower limit of quantification . The intra-day and inter-day precisions , recoveries and matrix effects at three spiked levels were all suited to the determina-tion of biological samples.After oral administration of S-071031B, the Cmax of S-071031B was (287.2 ±50.8) μg/L and the Tmax was (0.8 ±0.3) h, with a t1/2of (2.9 ±0.6) h and an AUC(0-∞)of (1372.6 ±255.3) μg/L· h.Conclusion This method is sensitive and specific enough for determination of S-071031 B in rat plasma to facilitate the study of its phar-macokinetics .

Objective To study the effects of the clinical pathway on hip arthroplasty. Methods Fifty patients with hip arthroplasty were selected. Twenty-three cases in the control group were treated with traditional methods, and 27 cases in the experimental group were applied with the clinical pathway for standardized treatment. Any differences in Harris scores, hospital costs and days in postoperative care at 1 week and 3 months were compared statistically between the two groups. Results Complications, hospital costs and average length of stay in postoperative care were significantly lower in the experimental group than among the controls. The Harris scores in postoperative week 1 were significantly higher in the experimental group than among the controls. Conclusion The clinical pathway using standard diagnosis and treatment can not only decrease hospital costs and average length of stay, it can also limit postoperative complications and quickly improve joint function, giving better quality medical care.

Objective To explore the clinical results and complications of the traditional skeletal traction through olecranon on treating the irreducible humeral supracondylar fracture in children with of ulna.Methods Ninety-eight children patients of humeral supracondylar fracture with failure of reduction manipulation were selected as our subjects.The towel clamp-skeletal traction through olecranon of ulna was applied as the additional treatment methods.Meanwhile 5-24 months' follow-up were performed.Results According to Flynn elbow joint function evaluation standard.The curative effect was as followed.71 patients (74.7％) got the excellent outcome,17 patients (17.9％) for good outcome and 7 patients for improved utcome(7.3％).Therefore,the ratio of excellent operation reached to 92.6％.Conclusion The towel clampskeletal traction through olecranon of ulna might be an effective method to treat reliable fixation regarding of its high curing rate and simple process of performance.

BACKGROUND: Diabetes causes abnormal insulin like growth factor-1 (IGF-1) gene expression, which contributes to initiation and development of peripheral neuropathy.OBJECTIVE: To investigate the efficacy of a single dose of methylcabalamin on prevention of experimental diabetic neuropathy and the possible molecular mechanism of its involvement in IGF-1 gene expression.DESIGN: Completely randomized and controlled experiment.SETTING: Endocrinology Department of the First Affiliated Hospital of Nanjing Medical University.MATERIALS: The study was carried out in an Animal Center of Nanjing Medical University. Totally 80 male Sprague Dawley rats (sanitary degree)were randomly selected.METHODS: ① Totally 64 rats were chosen to be induced diabetic. They were injected intravenously with alloxan dissolved in saline solutions, at the dose of 240 mg/kg. ② Of 16 rats were chosen as normal control group who were injected intravenously with equivalent volume of saline solution. ③ Of 64 established diabetic rats were treated with daily subcutaneous injection of pork regular insulin in combination of protamine zinc insulin (2:1) then further divided into 2 groups as insulin-treatment diabetic control groups based on different blood glucose levels: group 1 with relatively better control of diabetes, group 2 with relatively worse control of diabetes, with 32 rats in each group. Totally 16 rats of each group were treated with methylcobalamin injection intramuscularly with 500 μg/kg body weight, thus correspondingly divided into insulin +methylcobalamin group 1 and insulin+methylcobalamin group 2. The remaining 16 rats of each group as respective insulin-treatment diabetic control groups were treated with equivalent volume of saline. ④ Initiate weight and end weight were measured at beginning of the experiment and after diabetic model was established. Glucose oxidase was used to detect glucose level. 1-deoxy-1-malin was used to detect fructose level. ⑤ Parameters were measured as follows: Sensory/motor nerve conduction velocity (SNCV, MNCV) and evoked potential amplitude (EPA) of sciatic nerves detected by evoked electromyogram; IGF-I mRNA by reverse-transcriptase polymerase chain reaction (RT-PCR); IGF-1 peptide by enzyme-linked immunosorbent assay (ELISA). ⑥ One-way analysis of variance was used to analyze the Significance of differences among groups.MAIN OUTCOME MEASURES: ① Tissue IGF-1 mRNA/ IGF-1 peptide, electrophysiological data of individual groups at different points of the experiment. ② Comparison between individual groups in glucose metabolic parameters and body weights at different points of the experiment.RESULTS: Three rats died for diabetic infection or other acute complications and only 77 rats were included in the final statistical analysis.① Body weight and glucose metabolic parameter changes: After diabetic model, glucose, fructose level and body weight change between methylcobalamin+insulin treated groups and insulin treated groups were not significant. ② IGF-1 mRNA/peptide changes: Tissue IGF-1 mRNA increased significantly in methylcobalamin + insulin treated groups than that in insulin treated groups, respectively (P ＜ 0.05-0.01). Two weeks after diabetic model was established, the sciatic tissue IGF-1 mRNA contents were obviously higher in methylcobalamin + insulin treated group 1 than that in insulin treated group 1 (P ＜ 0.05), but not significantly different from that in NC group; Similarly, tissue IGF-1 mRNA contents were obviously higher in methylcobalamin + insulin treated group 2 than that in insulin treated group 2 (P ＜ 0.05), but lower than that in NC group (P ＜ 0.01); Month 2, tissue IGF-1 contents in methylcobalamin+ insulin treated groups were lower signiiicantly than NC groups, but higher than insulin treated groups (P ＜ 0.05-0.01). By month 3, IGF-1 mRNA level in methylcobalamin+ insulin treated group 2 was not significantly different from that in insulin treated group 2. The IGF-1 peptide levels in nerve tissue changed approximately parallel to IGF-1 mRNA level over time course. ③ Nerve electrophysiological data changes: Month 2 and 3, SNCV, MNCV and EPA were significantly higher in methylcobal-amin+ insulin treated group 1 than in insulin treated group 1 (P ＜ 0.05);Month 2, SNCV and EPA were higher in methylcobalamin+ insulin treated group 2 than in insulin treated group 2 (P ＜ 0.05); Month 3, SNCV, MNCV and EPA were significantly lower in methylcobalamin + insulin treated group 2 than in control group (P ＜ 0.05-0.01), whereas no difference was observed between methylcobalamin + insulin treated group 2 and insulin treated group 2.CONCLUSION: ① Methylcobal has not effect on blood glucose. ②Methylcobal could prevent occurrence of experimental neuropathy through its effect on nerve IGF-1 gene expression of diabetic rats. ③ A better efficacy could be achieved by Methylcobal with a good control of blood glucose level in prevention of diabetic peripheral neuropathy.

OBJECTIVE To investigate the effect of ketoconazole on the pharmacokinetic (PK) behaviors of midazolam and its metabolite through intranasal and intragastric(ig) routes in rats. METHODS Twenty-four rats were evenly divided into 4 groups. Two groups of rats were administrated singly with midazolam (1 mg?kg-1) through intranasal or ig route. The other two groups were concomitant with CYP3A inhibitor,ketoconazole(30 mg?kg-1),midazolam(1 mg?kg-1)through the same two routes. Blood samples were collected from different time points. Plasma concentration of midazolam and 1′-hydroxymidazolam was determined. Major pharmacokinetic parameters were calculated and statistical tests were performed by using t test. RESULTS Tmax was about 2 and 25 min for rats administered singly with midazolam via intranasal or ig routes,respectively and AUC was 296 and 179 μg?L-1?h, respectively. When concomitant with ketoconazole,AUC increased to 2.1 and 3.3 folds the original value for intranasal and ig routes,respectively. However,the Tmax value of midazolam via intranasally didn′t change after being coadministrated with ketoconazole,but Tmax increased to 1.14 h via ig. CONCLUSION Compared with administration via ig,intranasal route administrated midazolam displays significant advantages of faster absorption and higher exposure,which are vital for the first aid. Concomitant with CYP3A inhibitor and midazolam via intranasal route,the absorption speed is not affected,but with the metabolism blocked,the systemic exposure is greatly elevated. While via ig,both absorption speed and metabolism are inhibited. The dose should be cut down or the dosing interval increased in clinic practice in this concomitant situation.