1?cm group as compared with cm group compared with CDFI group (74.4% vs. 44.2%, P

To explore new agents of quinolone derivatives with high antibacterial activity, 7-(4-alkoxyimino-3-methyl-3-methylaminopiperidin-1-yl)quinolones were designed and synthesized, and their activity against gram-positive and gram-negative strains was tested in vitro. Sixteen target compounds were obtained. Their structures were established by 1H NMR, HRMS and X-ray crystallographic analysis. Compounds 14k and 14m-14o show good antibacterial activity against the tested five gram-positive strains and five gram-negative strains (MIC: 0.25-16 micromg x mL(-1)), of which the most active compound 14o is 8-fold more potent than levofloxacin against S. pneumoniae (MIC: 4 microg x mL(-1)), and comparable to levofloxacin against S. aureus, S. epidermidis, E. faecalis and E. coli (MIC: 0.25-1 microg x mL(-1)), but generally less potent than gemifloxacin.

Objective To evaluate the clinical effects and adverse reactions of concurrent radiotherapy combined with S-1 for elderly patients with locally advanced esophageal cancer.Methods From January 2011 to April 2013,a total number of 50 elderly patients with locally advanced esophageal carcinoma were randomly divided into concurrent chemo-radiotherapy combined with S-1 group (treatment group) (25 cases) and radiotherapy alone group (control group) (25 cases).Intensity modulated radiation therapy (IMRT) was administered in all cases,with a total dose of (58-60) Gy/(29-30) fx,conventional fractionation.Patients in the treatment group received S-1 of 80 mg/m2 orally bid on day 1-14,with 21 days as a cycle.All the patients should take it until the end of the radiotherapy treatment.Results The efficacy of the 47 cases could be evaluated.In treatment group,5 cases achieved CR,14 cases PR,3 cases SD,1 case PD.The response rate (RR) was 82.6 ％ (19/23).In control group,3 cases achieved CR,12 cases PR,6 cases SD,3 cases PD.The RR was 62.5 ％ (15/24).There was a statistical significant difference between the two groups.The one-year local control rates of treatment group and control group were 63.6 ％ and 43.5 ％,respectively,and the one-year overall survival rates were 68.2 ％ and 39.1％,respectively.The main toxicities included bone-marrow suppression,gastrointestinal reactions,radiation esophagitis and radiation pneumonitis.The incidences of bone-marrow suppression and gastrointestinal reactions were higher in treatment group than those in control group,but the toxic reaction was mild and tolerable.There were no significant differences in terms of bone-marrow suppression,gastrointestinal reactions,radiation esophagitis and radiation pneumonitis between both groups.Conclusion Concurrent chemotherapy combined with S-1 is more effective in the treatment of the elderly patients with locally advanced esophageal cancer and the toxicity is tolerable,which is worth studying furtherly.

0.05). ConclusionsConventional radiotherapy plus three dimensional conformal radiotherapy combined with chemotherapy may significantly improve the survival rate and reduce the distant metastasis rate of locally advanced or recurrent rectal cancer.

Objective To evaluate the effect of angiotensin Ⅱ (Ang Ⅱ ) on the change of nephrin phosphorylation both in Ang Ⅱ-infused rat model and cultured podocytes.Methods Thirty Wistar rats were subcutaneously embedded with osmotic minipumps and randomly divided into 3 groups according to receiving either Ang Ⅱ at a dose of 400 ng· kg-1· min-1 or Ang Ⅱ +telmisartan at a dose of 3 mg·kg-1 ·d-1,or normal saline as a control group.Blood pressure and 24-hour urinary albumin were measured at 0 d,7 d,14 d,21 d and 28 d of the experiment.Renal histomorphology was evaluated through electron microscopy.The concentrations of Ang Ⅱ both in blood plasma and kidney were detected by radioimmunoassay.In vitro,cultured murine podocytes were exposed to Ang Ⅱ (10-6 mol/L) pretreated with or without losartan (10-5 mol/L) for different time periods.Nephrin and its phosphorylation expression were analyzed by Western blotting.The distribution of F-actin was presented by FITC-phallodin labeling.The change in phenomenon of F-actin was evaluated by cortical F-actin score index (CFS).Results (1)Ang Ⅱ-infused rats exhibited increased Ang Ⅱ concentration,significant hypertension and marked albuminuria.(2)In Ang Ⅱ-infusion group,nephrin expression was decreased (P＜0.05).Ang Ⅱ-receiving rats displayed diminished phosphorylation of nephrin.(3)In vitro,the phosphorylation of nephrin was significantly reduced after Ang Ⅱ stimulation for 3-6 hours (P＜0.05).(4)Ang Ⅱ stimulatation resulted in irregularly arrangement of F-actin followed by the redistribution of F-actin to podocyte periphery and formation of F-actin ring,in which the CFS obviously increased compared to control (P＜0.05).Conclusions Phosphorylation of nephrin is important for the survival status of podocytes.Ang Ⅱ-induced nephrin dephosphorylation may be an important molecular mechanism for Ang Ⅱ-induced podocyte cytoskeleton rearrangement and foot process effacement.