Autophagy can be activated after cerebral ischemia and involved in the occurrence and development of ischemic brain injury. Therefore, the study of autophagy related signal transduction pathways may provide a new therapeutic target for ischemic brain injury. This article reviews the signal transduction pathways of autophagy after cerebral ischemia.

Background and purpose:Chemotherapy is the important way of breast cancer treatment, but the drug-resistance has attracted special attention. The emergence of drug resistance is closely related to the abnormal enhancement of DNA-damage repair. Both Kif4A and PARP-1 are important molecules of DNA repair. The research investigated the function of Kif4A in epirubicin up-regulating the activity of PARP-1 in breast cancer cells and possible significance. Methods:Western blot was used to detect the expression of Kif4A and PARP-1 after treatment with epirubicin in MDA-MB-231 and MCF-7 cells; the expression of PARP-1 and its activity were detected after high expression of Kif4A and treatment with epirubicin;FCM was used to detect cell apoptosis after treatment with epirubicin combined with PARP-1 inhibitor 3-ABA. Results:Epirubicin up-regulated PARP-1 activity and induced low expression of Kif4A in breast cancer cells, both of them showed dose-dependent and time-dependent. After high expression of Kif4A, the activity of PARP-1 was inhibited and the apoptosis of cells increased, epirubicin partially reversed the activity of PARP-1 inhibited by high Kif4A expression. Both of epirubicin and 3-ABA induced cell apoptosis, combination of them further increased cell apoptosis compared with alone used (P<0.05). The results also showed the apoptosis rate of MDA-MB-231 cells induced by epirubicin, PARP-1 inhibitor 3-ABA and high expression Kif4A was higher than that of MCF-7 cells (P<0.05). Conclusion:Epirubicin increases the activity of PARP-1 dependent on the low expression of Kif4A in breast cancer cells. Kif4A might become a novel target for overcoming resistance of epirubicin.

Objective To evaluate the relationship between aberrant crypt foci(ACF) and colon cancer by observing the sequential development of ACF in cancer models of rats. Methods The colon cancer models in 60 Wistar rats were established by subcutaneously injection of dimethylhydrasine (DMH) once a week for 18 weeks. The rats were sacrificed and the colon tissues stained by methylene blue were observed with a stereomicroscope. Results There were two types of ACF, named cACF and dACF. The microscopic findings in dACF were similar with that in early colon cancer, while those in cACF were not. The expression of β-catenin in cACF and dACF were 4. 84% and 100% (P =0. 000) , respectively, and the expression of MMP-7 were 7. 87% and 81.82% (P =0. 000), respectively. There was no significant difference in expression of β-catenin and MMP-7 between dACF and colon cancer ( P ＞ 0. 05 ). Conclusion The microscopic and molecular changes in dACF is similar with that in colon cancer, and dACF may progress to cancer through Wnt pathway.

Background and purpose. Chemotherapy is a standard treatment for patients with advanced stage non-small cell lung cancer (NSCLC) However, platinum based chemotherapeutic regimen haves high toxicity profile to normal tissues. Lobaplatin (LBP) is a new third-generation antitumour platinum drug. Studies abroad have shown that Iobaplatin has an anticancer activity similar to cisplatin with better tolerance and is more effective for those who are resistant to cisplatin. This study was aimed to observe the effectiveness and toxicities of lobaplatin combined with vinorelbine (NVB) for the treatment of advanced NSCLC. Methods: Sixty-four patients pathologically diagnosed as clinical stage Ⅲ_B-Ⅳ NSCLC who did not receive treatment before, were randomly assigned to two groups. NL group (NVB+LBP): LBP at a dose of 30 mg/m~2 intravenous infusion on day 1, and NVB at a dose of 25 mg/m~2 intravenous infusion on days 1 and 8. NP group (NVB+DDP): Cisplatin (DDP) at a dose of 30 mg/m~2 intravenous infusion on day 1, 2 and 3 and NVB at a dose of 25 mg/m~2 intravenous infusion on days 1 and 8. Treatments were repeated every 21-28 days for 3 cycles. Results: For 34 patients of NL group, there were CR (1 cases), PR(13 cases), NC(15 cases), and PD(5 cases). The overall response rate (RR) was 41.2%, disease control rate (DCR) was 85.3%. In NP group: RR was 43.3%, DCR was 83.3% (X~2=0.05, P>0.05). Median overall survival time was 8.6 months and 8.9 months for NL group and NP group, respectively. The main toxicities in NL group were myelosuppression. Digestive toxicity such as anorexia, nausea,vomiting were less than those in the NP group (X~2=7.43, P<0.05), Peripheral hour,toxicity, serious liver and renal toxicity were not observed in NL group. Conclusion: Compared with cisplatin plus vinorelbine, domestic lobaplatin with vinorelbine yielded similar efficacies for NSCLC, but had less toxicity and well tolerate.

Objective To study the effect of chitosan-pCrmA nanoparticles on the apoptosis of chondrocytes induced by interleukin-1 beta (IL-1β).Methods Chitosan-pDNA nanoparticles were prepared and characterized.The transfection efficiency of chitosan-mediated pIRES2-EGFP was evaluated using fluorescence microscope.The cytotoxicity of chitosan-pIRES2-EGFP nanoparticles in primary rabbit chondrocytes was analyzed by MTT assay.The expression of chitosan-mediated pCrmA in primary rabbit chondrocytes was verified by Western blotting.The effect of chitosan-mediated CrmA on chondrocytes apoptosis induced by IL-1β were analyzed by TUNEL assay.One-way ANOVA was used to analysis.Results The size of chitosan-pDNA nanoparticles was 50 nm.The pDNA release of chitosan-pDNA nanoparticles appeared as biphasic release at pH 2.0 and pH 7.4 buffer.The expression of CrmA in rabbit primary chondrocytes mediated by chitosan could be detected.The chitosan-pIRES2-EGFP nanoparticles had no cytotoxicity.The apoptosis rate of chondrocytes in the chitosan-pCrmA nanoparticles treated group was significantly lower than that of the chitosan treated group (P＜0.05) and PBS group (P＜0.01).Conclsion Chitosan is an effective non-viral gene transfer vector.The CrmA mediated by chitosan can significantly inhibit chondrocytes apoptosis induced by IL-1β,suggesting that chitosan-pCrmA nanoparticles may be the treatment of osteoarthrifis.

Objective To measure left atrial appendage (LAA)in patients with atrial fibrillation using Flexi Slice imaging by real time 3D transesophageal echocardiography (TEE),and compare with common multiplane TEE.Methods Forty-six patients with atrial fibrillation were performed 2D and real time 3D TEE.Zero degree,45°,90° and 135° plane were acquired by 2D TEE and Flexi Slice remolding. Maximum and minimum values of ostium of left atrial appendage were acquired in the short axis view of LAA by Flexi Slice remolding.Results Compared with 2D TEE,values acquire by Flexi Slice in measurement of LAA ostium showed no significant difference(P >0.05).The depth measurement by Flexi Slicein 45° and 90° plane showed significant difference with 2D TEE (P-values were successively 0.045, 0.002),and in 0 and 135° plane showed no difference.All values measured by 2D TEE and Flexi Slices showed significant correlation.Bland-Altman plot showed that 94.29% of plots were among limits of agreement,which was (-2.5 mm,2.9 mm).The maximum values of LAA ostium values ranged from 30° to 160°,among which 87% (40/46 cases)distributed between 90° and 1 50°,and minimum values ranged from 0°to 160°,among which 85%(39/46 cases)distributed between 0°and 60°.Conclusions Measurement of LAA can be well achieved by Flexi Slice imaging,which showed significant advantage compared with 2D TEE.

Objective To assess the left ventricular dyssynchrony in coronary artery disease(CAD) without visual segmental wall motion abnormalities using strain delay index (SDI).Methods A total of 135 patients under suspicion of CAD were recruited in this study.Two-dimensional cchocardiography was performed to collect dynamic images of left ventricular apical long axis views,tow-chamber views,four chamber views and parasternal short axis mitral views,papillary views and apical views.The time to minimal systolic longitudinal,radial,circumferential strain (Tssl,Tssr and Tssc) were measured from the start point of QRS wave in electrocardiogram.The left ventricular segmental standard deviation (Tssl-SD,Tssr-SD,Tssc-SD),maximal difference (Tssl-Dif,Tssr-Dif,Tssc-Dif) and longitudinal,radial,circumferential SDI (LSDI,RSDI,CSDI) of 18 left ventricular segments were calculated.Results According to coronary angiography results,patients were divided into three groups:severe stenosis group,mild stenosis group and control group.Compared with the other two groups,SDI and Tssl-SD,Tssl-Dif were decreased in severe stenosis group (P ＜0.001 or P ＜0.05).However,there were not significant differences between the mild stenosis group and the control group except Tssr-SD.The receiver operating characteristic (ROC) curves analysis demonstrated that LSDI had the highest accuracy and Tssl-SD had the lowest accuracy for detecting severe CAD (areas under the curve were 0.891,0.797,0.666,0.580 and 0.556 respectively).High sensitivity and specificity (80.6％ and 86.7％,respectively) were shown when using-12.67％ as a cutoff point of LSDI to diagnose severe CAD.Conclusions SDI can be helpful for assessing the left ventricular dyssynchrony in patients without visual segmental wall motion abnormalities,and LSDI is the most effective parameter to detecting severe CAD.

Objective To assess left ventricular function early and late improvement of patients with acute myocardial infarction (AMI) treated by percutaneous coronary intervention (PCI) by speckle tracking imaging (STI).The clinical values of the assessment of STI for the prognosis and heart function improvement of AMI patients treated by PCI were discussed.Methods 73 AMI patients who had AMI for the first time and had been treated by primary PCI from September 2010 to July 2011 and were examined in the follow-ups from December 2010 to February 2012 in our hospital were enrolled.Dynamic images were acquired before PCI,at 3 months and 6 months after PCI and analyzed by STI.Dynamic images were analyzed for longitudinal peak systolic strain (LPSS),radial peak systolic strain (RPSS) and circumferential peak systolic strain (CPSS) values by STI.According to the comparison of left ventricular ejection fraction (LVEF) before PCI and 6 months after PCI,patients were divided into left ventricular function improved group (ΔLVEF6＞5％) and not-improved group.According to the comparison of LVEF before PCI and 3 months after PCI,improved group were divided into left ventricular function early-improved group (ΔLVEF3 ＞5％) and late-improved group.Results The values of all STI parameters before PCI,3 months and 6 months after PCI in improved group were higher than those in not-improved group (P ＜0.001,all).LPSS before PCI and at the follow-ups and RPSS at 3 months after PCI in early-improved group were higher than those in late-improved group (LPSS at 3 months after PCI:P＜0.001;Other parameters:P ＜0.05).There were significant correlations between all STI parameters and both ΔLVEF3 and ΔLVEF6.LPSS before PCI was more closely related to ΔLVEF3 (r =-0.781,P ＜0.001).CPSS at 6 months after PCI was more closely related to ΔLVEF6 (r =-0.834,P ＜ 0.001).Conclusions Early and late function improvement of left ventricle in AMI patients who is treated by PCI are accurately assessed by STI.The precise analyses of longitudinal and circumferential movements in STI are important for clinical diagnosis.

Objective To assess the left ventricular function of patients with acute myocardial infarction (AMI) treated by percutaneous coronary intervention (PCI) by speckle tracking imaging (STI).Methods 75 AMI patients who had AMI for the first time and have been treated by primary PCI were enrolled.Dynamic images were acquired before PCI,at 6 months after PCI and analyzed by STI.Dynamic images were analyzed for longitudinal peak systolic strain (LPSS),radial peak systolic strain (RPSS) and circumferential peak systolic strain (CPSS) values by STI.According to the comparison of left ventricular ejection fraction (LVEF) before PCI and 6 months after PCI,patients were divided into left ventricular function improved group (△LVEF≥5％) and not-improved group.Results Compared to non-improved group,LPSS (P ＜0.001),RPSS (P ＜0.05,P ＜0.001) and CPSS (P ＜0.001) of improved group were all higher before and 6 months after PCI.LPSS (r =-0.578,P ＜0.001) and CPSS (r =-0.817,P ＜0.001) before PCI were both closely related to △LVEF.In single parameter mode of ROC curve analysis,the area under the ROC curve (AUC) (0.867),sensitivity (94.7％) and specificity (74.4％) of CPSS are relatively higher than other STI parameters.In multiple parameters united mode of ROC curve analysis,AUC (0.897),sensitivity (94.7％) and specificity (74.4％) of LPSS,RPSS and CPSS united were the highest among all the combinations of all STI parameters.Conclusions Left ventricular function improvement of patients with AMI 6 months after PCI is accurately assessed and predicted by STI.CPSS is a strong predictor for left ventricular function improvement 6 months after PCI of AMI patients among all the STI parameters and is an effective indicator for the assessment of left ventricular function improvement of AMI patients.

Objective To assess left ventricular(LV) longitudinal strain in patients with coronary heart disease by two-dimensional speckle tracking imaging (2DSTI),and to explore the clinical value of 2D longitudinal strain in detecting myocardial ischemia. Methods Forty-four patients with coronary heart disease (CHD group) and 28 age-matched subjects (control group) were enrolled into this study. The two-dimensional data were obtained in apical 4-chamble, 2-chamber and long axis view. And the longitudinal strains of every segments, the average longitudinal strain of LV 18 segments (SL18), the average longitudinal strain of 12 segments (SL12,excluded the 6 apical segments) were analyzed. Results In the patients with CHD, the longitudinal strain of ischemia segments and the global LV longitudinal strain were significantly decreased than that of the control subjects. Both in patients with CHD and in control subjects,the longitudinal strains in apical segments were higher than that of middle and basal segments. There was significant difference between SL18 and SL12 ( P=0.027 in CHD group and P =0.003 in control group).Receiver operating curve (ROC) analysis demonstrated that the cutoff point of SL18 to detect myocardial ischemia was - 18.8％ (sensitivity 80.2％ and specificity 74.1％ ) ,and the cutoff point of SL12 to detect myocardial ischemia was - 17.8％ ( sensitivity 81.7％ and specificity 85.6％ ). Conclusions 2D longitudinal strain was sensitive to detect myocardial ischemia, SL12 was better than SL18 in detecting myocardial ischemia. 2DSTI might be useful for identifying patients with severe CHD.