Usage of the fruit and bark of a Melia-family plant as a digestive tract-parasiticide and agricultural insecticide was recorded about two thousant years ago in ancient China. Toosendanin (TSN), a triterpenoid, is an effectual ingredient extracted from the plant. Studies have demonstrated that TSN selectively affects neurotransmitter release, effectively antagonizes botulism, induces cell differentiation and apoptosis and inhibits proliferation of various human cancer cells, inhibits feeding and dovelopment in insects and modifies K+- and Ca2+-channel activity. The research data to demonstrate that TSN inhibits K+-channel and facilitates L-type Ca2+-channel are summarized, and the mechanism of action of TSN is discussed.

Botulinum neurotoxin(BoNT) is the most lethal biotoxin known to mankind. It inhibits acetylcholinerelease from the cholinergic nerve ending by cleavage of SNARE proteins, followed by neuromuscular blockadeand paralysis. Gangliosides are considered to act as a first receptor of BoNT with low affinity.Then the membranebound gangliosides-BoNT complex moves laterally to reach and bind the toxin specific protein receptor,synaptotagmin, with a high affinity constant. At last the gangliosides-BoNT-synaptotagmin complex undergoesreceptor-mediated endocytosis. This double-receptors theory is widely accepted. The research data are summarizedand reviewed.

Objective:To investigate if the combined use of CDAⅡ and sodium butyrate can induce demethylation and re-expression of retinoic acid receptor?2(RAR?2)gene in cultured human breast cancer cells MCF7.To explore if the two drugs can inhibit cell growth and induce cell apoptosis synergetically.Methods:MCF7 cell line was treated with CDAⅡ,sodium butyrate,combination of the two drugs respectively.Methylation was assessed by methylation-specific polymerase chain reaction(MSP)for RAR?2 gene.Gene expression was evaluated by reverse transcription polymerase chain reaction(RT-PCR).Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling(TUNEL)and Hoechst33342/propidiumiodide(PI)staining.Cell growth inhibition was measured by MTT assay.Results:Neither CDAⅡ nor sodium butyrate induced demethylation and re-expression of RAR?2 gene,Combination of the two drugs partially demethylated gene promoter accompanied by re-expression of RAR?2.The apoptotic cells in the double-drug group were obvious following Hoechst33342/PI staining.The percentage of apoptotic cells in the double-drug group was significantly higher than that of the two single-drug group(39.5% vs 5.2%,8.1%)(P

Objective To evaluate and compare the curative effect between the microinvasive craniopuncture therapy and the clearance of hematoma by craniotomy with small bone flap in treating patients with moderate cerebral hemorrhage (30-60 ml)in the basal ganglion part of the brain. Methods Ninety-five patients with intracerebral hemorrhage were randomly divided into treatment group (microinvasive craniopuncture therapy) and control group (the clearance of hematoma by craniotomy with small bone flap). The main indexes of evaluation were the neurological impairment degree (NID) on the 14th day after treatment, activities of daily living (ADL) by the end of the third month, the incidence rate of complications, and the case fatality during 3 months. Results On the 14th day after treatment, there was no significant difference between the two groups in the NID and the ADL of patients. The incidence rate of respiratory tract infection, gastrointestinal hemorrhage, electrolyte disorder in treatment group [16.33% (8/49), 6.12% (3/49), 6.12% (3/49), respectively] was significantly reduced than those of control group [56.52% (26/46), 21.74%(10/46), 21.74% (10/46),respectively] during hospitalization (P < 0.05). By the end of the third month, there was significant difference in favorable outcomes (Barthel index 95-100) (χ~2 = 18.7524,P =0.0009) and in improving the ADL (MRS)(t =5.2723,P =0.0001) between the two groups [39.13% (18/46), 4.65% (2/43),respectively]. In ease fatality, there was no significant difference between the two groups [6.12% (3/49),6.52% (3/46),respectively]. Conclusion As compared with the clearance of hematoma by craniotomy with small bone flap, the microinvasive craniopuncture therapy can remarkably reduce the incidence of complications, and improve the ADL of patients with moderate cerebral hemorrhage (30-60 ml) in the basal ganglion, and decrease disability without increasing fatality.

Objective To evaluate the value of MRI performance for the differential diagnosis of atypical solitary metastatic malignant melanoma from spinal hemangioma.Methods Thirteen patients of atypical solitary metastatic malignant melanoma and 40 patients of spinal solitary hemangioma were retrospectively analyzed.Conventional MR imaging (T1WI,T2WI,and fat suppressed T2WI) and enhanced imaging were performed at 1.5T MRI.The signal intensities (SIs) of spinal lesions were qualitatively evaluated on conventional imaging and were described as hypointense,isointense,or hyperintense.The spinal lesions were qualitatively categorized into minimal enhancement,iso-enhancement,slightly hyper-enhancement,or strong enhancement on contrast-enhanced imaging.The lesions' maximum diameter was also measured and the mean value was obtained.Results The qualitative assessment of SIs on T1WI showed that 76.92％ (10/13),15.38％ (2/13) and 7.69 ％ (1/13) of atypical solitary metastatic malignant melanoma were hypointensity,isointensity and hyperintensity respectively.The qualitative evaluation of SIs on T2WI were found that 61.54％ (8/13) of atypical solitary metastatic malignant melanoma with hypointense,30.77％ (4/13) with isointensity and 7.69％ (1/13) with hyperintensity,respectively.About 92.31％ (12/13) of atypical solitary metastatic malignant melanoma displayed strong enhancement on contrast-enhanced imaging.There were significant differences in SIs on T1WI,T2WI and contrast-enhanced imaging between atypical solitary metastatic malignant melanoma and hemangioma (all P＜0.05).The maximum diameter of atypical solitary metastatic malignant melanoma was significantly higher than that of spinal hemangioma (P＜0.001).Conclusion MR imaging would be practicable for differentiation between atypical solitary metastatic malignant melanoma and hemangioma in spine.

Objective To investigate the immunomodulatory effects and the mechanism of interferon (IFN)-γ-pretreated adult autologous adipose tissue-derived mesenchymal stem cells (ADSCs) on peripheral blood lymphocytes. Methods ADSCs were obtained from adult subcutaneous adipose tissues. IFN-γ with and without pretreated ADSCs were used as IFN-γ-pretreated group and IFN-γ-unpretreated group, which were cultured with autologous peripheral blood mononuclear cells (PBMCs) at different concentrations of ADSCs-to-PBMCs ratios in presence of concomitant phytohemagglutinin (PHA)/interleukin (IL)-2 stimulation. After 5 days of culture, the proliferatory inhibitory rate of activated T cells, the percentage of CD4+CD25+ regulatory T cells (Treg), and the expression of indoleamine 2,3-dioxygenase (IDO) mRNA were assessed. Results ADSCs were isolated from autologous adipose tissue, which strongly expressed CD73, CD90, and CD105, as well as displayed adipogenic and osteogenic differentiation. The percentage of CD4+CD25+Treg was significantly higher in IFN-γ-pretreated group than that of IFN-γ-unpretreated group. The expression level of IDO mRNA in ADSCs was significantly increased in IFN-γ-pretreated group than that of IFN-γ-unpretreated group. The proliferation inhibition of activated T cells was significantly decreased in IDO-blocker group than that of IFN-γ-pretreated group (P < 0.01). Conclusion These results suggest that IFN-γ can promote immunosuppressive effects of ADSCs on activated T cells through increased expression of IDO.

Objective To assess the clinical efffects off Ipratropium bromide combined with atomization inhalation of budesonide via a ventilator with a Y-shaped connector on acute exacerbation off chronic obstructive pulmonary disease (AECOPD).Methods A total off 62 AECOPD patients treated at our hospital from June 2013 to September 2014 were randomly divided into the experimental group (n=31,treated with ipratropium bromide combined with atomization inhalation of budesonide) and the control group (n =31,treated with the same amount of saline).Results The airway pressure of mechanical ventilation,the time of mechanical ventilation and the time of staying in the intensive care unit all showed significant differences between the experimental and control groups [(25.4±5.2) cmH2O vs.(38.1±3.4) cmH2O,(6.5±1.3) d vs.(6.8±1.4) d,(8.9±2.1) d vs.(9.5±1.5) d,t=10.934,0.960,1.108,respectively,P＜0.05 for all].The rate of tracheotomy was lower in the experimental group than in the control group (17/31 or 54.8％ vs.20/31 or 64.5％,x2 =0.603,P＜0.05).Conclusions Ipratropium bromide combined with budesonide inhalation under mechanical ventilation via a Y-shaped connector has ffavorable clinical effects on AECOPD.

Objective To investigate the effect of bortezomib with arsenic trioxide different concentration on the cell cycle and apoptosis of Raji cells. Methods Flow cytometry analysis showed that the relative number of cells in different phases and the percentages of cells calculated in G1 and S phase of the cell cycle and apoptosis were assessed after treatment with As2O3 and BOR or in combination with BOR in different concentration at indicated time (24 h, 48 h, 72 h). Results Flow cytometric analysis showed that the cell cycle was arrested at G1 phase, the number of cells G1 period increased significantly, and S phase decreased on Raji cells after As2O3 treatment. The relationship between the cellular DNA contents and the concentration of As2O3 showed a dose-and time-dependent manner (P ＜0.0001). But it was found that BOR had no effect on Raji cell cycle, but, in two drugs combination, cell apoptosis rate significantly increased from 16.98 % to 45.84 %. Conclusion The results show that As2O3 exerted variable and definite effects on lymphoma Raji cells, which indicated that As2O3 might induce apoptosis and arrest cell cycle. The combination of two drugs had a effective and synergistic effect on apoptosis.

Objective To evaluate the efficacy of high resolution MR T2WI combined with DWI in evaluation of pathological complete response after neoadjuvant therapy in rectal cancer.Methods Totally 364 patients with locally advanced rectal cancer who recieved neoadjuvant therapy and radical surgery,underwent MR scanning before and after neoadjuvant therapy,were enrolled in this study.The diagnostic efficacy of high resolution MR T2WI and high resolution MR T2WI combined with DWI in evaluation on pathological complete response after neoadjuvant therapy in rectal cancer were compared.Results Finally 49 cases were demonstrated pathologic complete response.Accuracy,sensitivity,specificity,positive predictive value and negative predictive value of high resolution MR T2WI and high resolution MR T2WI combined with DWI in predicting on pathological complete response after neoadjuvant therapy were 82.69％ (301/364),40.82％ (20/49),89.21％ (281/315),37.04％ (20/54),90.65％ (281/310)and 87.36％ (318/364),65.31％ (32/49),90.79％ (286/315),52.46％ (32/61),94.39％ (286/303),respectively.Sensitivity had statiatical significant difference between two methods (x2 =4.96,P=0.03).Conclusion Compared with high-resolution T2WI,the combination of DWI and high-resolution T2WI can improve the diagnostic efficacy in evaluation of pathologic complete response of locally advanced rectal cancer.

Objective:To investigate the pahtogengesis and pathology of delayed xenograft rejection (DXR) after pig to rhesus monkey heart xenotransplantation.Methods:Heterotopic xenogeneic heart transplantation in the abdominal cavity was performed using piglet as donors.4 monkeys were used as recipients.Complete complement depletion was achieve in the recipients treated with repetitive doses of a high activity cobra venom factor (Y CVF).The recipients were immunosuppressed with a combination of cyclosporine A,cyclophosphamide and steroids.Sera were analyzed for C3,C4 levels and complement activity and anti pig endotheliocyte xenoantibody.The graft were examined histopathologically and immunohistochemically for C3,C4,C5b 9,IgM,IgG,necrosis factor alpha (TNF alpha),intercellular adhesion molecule 1 (ICAM 1),CD57 (NK cells),CD68 (macrophages),CD4 and CD8.Results:The xenografts survived 8,10,13,13 days respectively and all grafts occoured DXR.Venular thrombosis was outstanding feature within DXR xenografts,complicated with interstitial edma,local hemorrhage and myocardial necrosis,with mild to moderate cellular infiltration.The serum C3 levels and complement activity almost decreased to 0 from the day of transplantation due to Y CVF,the C4 level began to decrease 2 4 days before the cardic xenografts losing their function.The anti pig endotheliocyte xenoantibody also decreased after transplantation,and slightly increased during DXR,all rejected xenografts showed C3,C4,C5b 9,IgG and IgM deposits in different degree.Large numbers of macrophages (50% of total leukocytes) were found infiltrating the entire xenograft,a few natural killer cells (8%～10%),some of CD4+T cells (15%) and CD8+T cells (25%) were detcted also,up regulation of ICAM 1 on the graft endothelial cells and TNF alpha in the interstitial were demonstrated in the rejected heart.Conclusion:Both Humor and cell mediated immunologic reaction may play an important role in pahtogengesis of DXR. [