Proteasomes is a multienzyme complex.It can degradate cyclin,which control the process of cell cycle and cell apoptosis.Proteasome inhibitor regulate cell cycle and promote cell apoptosis through suppressing UP pathway.Proteasome inhibitor can stimulate apoptosis of various hematological systemetic malignant tumor and cause cell apoptosis through different mechanism in vivo and vitro.Therefore,proteasome inhibitor is a new-style tumor targeted therapy drug.

Objeetive To observe NB4 cells that is treated with both ATO and BOR.Methods MTT assay demonstrated that NB4 cell lines,growth inhibiting effect after interfered with BOR alone or BOR plus ATO.Flow cytometry detect cell cycle and apoptosis.RT-PCR method detect the expression of survivin mRNA.Results MTT assay showed depressant effect by BOR.BOR can strengthen cells,lethal effect by ATO.Flow cytometry investigate obvious apoptosis and cycle blockage of G2/M stage.RT-PCR discover that ATO or BOR can downregulate the expression of survivin mRNA alone,there is an additional effect if used them at the same time.Conclusion Combination of BOR and ATO have stronger inflictive and apoptosisinducing activity.The blockage of G2/M stage and degression of survivin mRNA is a possible mechanism that leads to cell apoptosis treated with BOR and ATO.

Macrophages have been identified to play an important role in acute and chronic renal injury through exerting multiple biological effects.This review focus on the origin of macrophages in kidney, mechanism of renal injury and strategy of inhibiting macrophage infiltration. [

Objective In this study, the best domestic digestive departments' websites are evaluated, adopting the meth-od of cross-sectional descriptive research, to evaluate the quality of such sites, and describe their characteristics. Methods Using a pre-defined evaluation standard, two well-trained evaluators independently explore and analyze 10 websites of domestic best departments of digestive diseases. Selection of departments is based on a domestic au-thoritative released rank of the best departments which has high credibility. Results These sites perform well in the content, perform in function and design, but perform not well in management & maintenance. Conclusion As the public use the websites of professional websites more and more to obtain information and services, domestic best di-gestive departments should better their sites' quality to meet the growing demands of consumers.

Objective To evaluate the usage situation and the trend of traditional Chinese medicine injection for activating blood circulation in our hospital. Methods The sales amount and drug use frequency (DDDs) and drug utilization index (DUI) of traditional Chinese medicine injection for activating blood circulation were sorted and analyzed in our hospital from the fourth quarter of 2011 to the third quarter of 2012. Results The total sales amount of traditional Chinese medicine injection for activating blood circulation gradually increased in our hospital during that time. The proportion of varieties with the ratio DUI sum/DDDs sort of closed to 1 (0.75≤order ratio≤1.25) in the three quarters of 2012 accounted for 53.33%, 53.33%, and 66.67%, respectively. This indicated that the usage of traditional Chinese medicine injection for activating blood circulation was more unreasonable, but tended to be reasonable. Conclusion The usage of traditional Chinese medicine injection for activating blood circulation was basically rational in our hospital, and efficacy of clinical pharmacist intervention was obvious. Effective and safe evaluation of traditional Chinese medicine injection can be further strengthened, in order to improve the efficacy and reduce the adverse reaction.

Objective To construct a scientific,valid evaluation system for excellent clinical nurses.Methods Based on the framework of competency theory,systematic literature reviewing,nursing experts discussion and the Delphi method were used to determine the primary indexes for the evaluation system.The evaluation system was determined from three perspectives,doctors',nurses' and patients'.Analytic Hierarchy Process (AHP) was then used to determine the weight of each index.Results The weight of doctors',nurses' and patients' perspective was 0.2,0.4,0.4 respectively.Doctors' and nurses' perspective(hereinafter referred to as staff's perspective) had the same evaluating indexes,which both consisted of 5first-dimensions,22 second-dimensions.The patients' perspective contained 3 first-dimensions,14 seconddimensions.In two-round Delphi technique,the rates of questionnaire retrieve were 91.2％ (31/34),100.0％(31/31),respectively;the colleagues' coordination coefficients were 0.784,0.858,respectively,and the patients' coordination coefficients were 0.05,0.216,respectively.Conclusions A evaluation system of high reliability and validity for excellent clinical nurseshas been successfully constructed.It may be utilized as a tool to for nursing administrator selection,training,assessment of excellent clinical nurses.

Objective To evaluate the relationship between carotid plaque instability and coronary heart disease by contrast-enhanced ultrasound. Methods Thirty-five patients with acute coronary syndrome (ACS) and 32 patients with stable coronary artery disease(sCAD) were included. Inclusion criteria were at least 1 carotid atherosclerotic plaque with thickness larger than 2.0 mm. Contrast-agent enhancement in the plaque was evaluated by visual interpretation and quantitative analysis. Results The percentage of soft plaque in ACS group was significantly higher than that in sCAD group ( P ＜0.001 ). The proportion of contrast-agent enhancement in patients with ACS was significantly than that in patients with sCAD( P =0. 037). The enhanced intensity in the plaque and the ratio of enhanced intensity in the plaque to that in the carotid artery lumen in patients with ACS were significantly larger than those in patients with sCAD ( P ＜0.001, P = 0.026, respectively). Sensitivity and specificity of prediction ACS were 74% and 60%,respectively,for enhanced intensity in the plaque and 86% and 67%, respectively, for ratio of enhanced intensity in the plaque to that in the lumen of the carotid artery. Conclusions The subjects with ACS had more intense contrast-agent enhancement than the subjects with sCAD. Contrast-enhanced ultrasound can be used to evaluate the relationship between carotid plaque instability and coronary heart disease.

OBJECTIVE: To compare the acute toxicity of common injection and sustained-release preparation of norcantharidin for mice so as to identify the attenuation of the sustained-release preparation of norcantharidin. METHODS: The poloxamer 407 was used as a sustained-release vehicle for topical administration of norcantharidin, and the acute toxicity of mice treated with common injection and sustained-release preparation of norcantharidin was observed. The median lethal dose (LD(50)) was calculated by Bliss software. RESULTS: The symptoms of mice were similar between the two groups, but the appearance of symptoms in norcantharidin/poloxamer 407 group was 4 hours later than that in norcantharidin group. The LD(50) of norcantharidin administered through vein injection was 12.6 mg/kg. The LD(50) of norcantharidin/poloxamer 407 administered through intraperitoneal injection, intrahepatic injection and intramuscular injection were 19.9, 19.1 and 20.9 mg/kg, respectively, and the LD(50) of the common preparation were 13.0, 13.1 and 15.1 mg/kg, respectively. CONCLUSION: The norcantharidin/poloxamer 407 is less toxic than the equivalent dose of norcantharidin, mainly because norcantharidin/poloxamer 407 may release norcantharidin sustainedly, thus reducing norcantharidin concentration in blood.

AIM: To investigate the role of HGF/c-Met signaling pathway in crizotinib-induced apoptosis of different lung carcinoma cell lines and to analyze its potential regulatory mechanisms .METHODS: EML4-ALK positive cell line H2228, c-Met proliferation cell line H1993 and control cell line A549 were treated with crizotinib at different doses for different time periods .The viability of the cell lines was measured by MTT assay .The apoptosis was analyzed by flow cytometry with PI staining.The protein levels of MET and phosphorylated MET (p-MET) of HGF/c-Met signaling pathway as well as its down-stream key proteins AKT , ERK, p-AKT and p-ERK in the cell lines before and after crizotinib treatment were examined by Western blot .RESULTS:The growth of H1993, H2228 and A549 cell lines was inhibited after crizoti-nib treatment for 72 h in a dose-dependent manner .Apoptotic rates of H1993 cells and H2228 cells were increased with the crizotinib concentration and exposure time .Down-regulation of p-MET, p-AKT and p-ERK at protein levels in H1993 cells and H2228 cells after exposure to crizotinib for 72 h was confirmed by Western blot .No obvious change of the related-pro-teins of HGF/c-Met signaling pathway was found in A 549 cell line.CONCLUSION: HGF/c-Met signaling pathway may contribute to crizotinib-induced apoptosis of H1993 cells and H2228 cells, which provides the experimental basis for MET-targeting treatment of lung cancer .

AIM:To detect the changes of active status of bypass signaling pathways in EML4-ALK positive lung cancer cell line H3122 treated with alectinib, hepatocyte growth factor (HGF), epidermal growth factor (EGF) and transforming growth factor-α (TGF-α), and to explore the potential mechanisms.METHODS:EML4-ALK positive cell line H3122 was treated with increasing concentrations of alectinib or/and induced by HGF, EGF and TGF-α.The cell viability was measured by CCK-8 assay.The cell apoptosis was analyzed by flow cytometry.The protein levels and phosphorylation status of ALK, c-Met and EGFR, and the downstream molecules AKT, ERK, p-AKT and p-ERK were examined by Western blot.RESULTS:The viability of the H3122 cells was inhibited by alectinib in a dose-dependent manner after administrated for 72 h, and the IC50 value was 0.042 μmol/L.The concentration-growth curves of the H3122 cells shifted to the right after induced by HGF, EGF and TGF-α.After treatment with alectinib at 0.05 μmol/L for 48 h, the apoptotic rate of H3122 cells was (20.12±1.36)%, while the apoptotic rates of the cells in the groups of alectinib combined with HGF, EGF or TGF-α were (7.85±1.03)%, (5.60±0.79)% and (4.58±1.00)%, respectively.Those values were remarkably lower than those in alectinib single treatment group (P<0.05).Alectinib inhibited the protein levels of p-ALK and its downstream signaling pathway molecules, while HGF significantly up-regulated the protein levels of p-Met and its downstream p-AKT and p-ERK.Besides, EGF and TGF-α remarkablely up-regulated the protein levels of p-EGFR and its downstream p-AKT and p-ERK.Combined treatment with crizotinib and 17-DMAG successfully inhibited the viability of the H3122 cells even in the presence of the HGF and EGFR ligands, respectively.CONCLUSION:Bypass signaling pathways are activated by HGF, EGF and TGF-α in EML4-ALK positive lung cancer cell line H3122, which may be linked to alectinib resistance.