According to the actual situation that neurosurgery professional postgraduate is un-even and the ability of operation is low and combined with new requirements of medical development, the author discusses concretely the neurosurgery master graduate students' clinical ability cultivation from the necessity and teaching measures of adding neurosurgery microscopy techniques course, neural micro dissection course, neuroimaging curriculum course. The specific course orienta-tion andproject drive-independent inquiry teaching mode are the characteristics of cultivation measures. The key point for the implementation of measures lies in the teachers' effective guidance of students' intrinsic motivation according to the discipline direction, on the basis of grasping curriculum positioning.

Objective To observe cerebral apoplexy patients complicated with carotid atherosclerosis plaque given aggressive lipid lowering treatment on the prognosis of stroke and reduce the recurrence rate through the large sample study on neurological department of internal medicine.Methods 300 cases of cerebral infarction complicated with different degree of neck lesions were selected and randomly divided into 3 groups,each group had 100 cases.Intensive lipid-lowering group received fluvastatin,80mg/d + 100mg aspirin,conventional dose group received fluvastatin,40mg/d + 100mg aspirin,aspirin group was given aspirin 100mg.After 4 weeks,8 weeks,12 weeks,16 weeks,20 weeks,24 weeks,blood lipid level,changes in internal carotid artery plaque (CIMT),plaque area,and the incidence rate of cerebral vascular events after 24 weeks were observed.Results The results of intensive lipid-lowering treatment group IMT (1.06 ± 0.36) mm,plaque area (8.09 ± 0.47) mm3,the incidence rate of cerebral vascular events after 24 weeks (12％),serum lipid levels and regular dose group after treatment with IMT (1.19 ±0.39) mm,plaque area (9.91 ± 0.78) mm3,the incidence rate of cerebral vascular events after 24 weeks (18 ％),serum lipid levels after aspirin group were significantly reduced(P ＜ 0.05).Aspirin group before and after treatment,IMF,plaque area and lipid levels had no significant differences(P ＞ 0.05).Intensive lipid-lowering treatment group compared with the conventional dose group,IMT,plaque area and lipid levels improved obviously(P ＜ 0.05),the recurrence rate of ischemic cerebral vascular disease had significant difference compared with the other two groups (P ＜ 0.05).Conclusion Intensive lipid-lowering treatment on blood lipid levels,delay and reverse the carotid atherosclerosis is superior to conventional dose using fluvastatin group and simply antiplatelet group,and can prevent the recurrence of ischemic cerebrovascular disease.

Objective To observe the effect of intravenous low intensity laser radiation (ILLLI) combined with traditional Chinese medicine on TXB2, 6-Keto-PGF1? and Ang II of the rabbits of experimental diabetic stroke. Method 35 successfully modeled rabbits, after alloxian injection for diabetes and photochemical radiation for stroke, were randomized into four treatment group-control group (B), ILIB group (C), a group with compound treatment of ILIB and TCH (D), TCM treatment group (E), and 7 unmodeled rabbits were made as the normal group (A). TXB2, 6-Keto-PGF1? and Ang II level were observed and compared. Result Compared with group B, group C and E can significantly rectify the disorderly TXB2, 6-Keto-PGF1? and Ang II, Group D was better than C and E. Conclusion ILLLI combined with TCM can effectively rectify the TXB2, 6-Keto-PGF1? and Ang II level, reduce nervous injury, cure diabetes cerebral infarction.

Objective To investigate the principle and its clinical initial application of the dual-energy imaging with the dual-source CT and increase the realization of it. Methods According to the research results of the dual-energy imaging with the dual-source CT and the course of development of the dual-energy imaging to analyze and summarize the basis radiological physics, the principles, the correlation parameters and the clinical initial application of the dual -energy imaging with the dual -source CT. Results The dual -energy imaging with the dual -source CT is different from other common dual-energy imaging, it has its own special feature. Conclusion According to the analysis of the dual-energy imaging with the dual-source CT, greatly increase the realization of the dual-energy imaging with the dual-source CT.

The methyl group plays an important role in the rational drug design. Introducing methyl into small molecules has become an important strategy of lead compound optimization. The application of methyl in drug design is reviewed in this paper. Methyl can modulate the physicochemical, pharmacodynamic, and pharmacokinetic properties by ortho effect, inductive effect, and conformational effect. It also improves the metabolic stability as a soft metabolic point. In addition, introducing methyl into drug molecules can also be applied as a strategy in new uses of old drugs and generate me-too drugs.

BACKGROUND: Chinese herb tuber fleeceflower root can enhance learning and memory ability and anti-cerebral ischemia ability in rats,while 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside,the main effective component of tuber fleeceflower root,has very strong brain-protecting ef fects such as anti-oxidation and anti-aging.OBJECTIVE: To observe the amelioration of learning and memory dis order after administration of 2,3,5,4'-tetrahydroxystilbene-2-O-3-D-glucoside in mice with learning and memory disorder caused by scopolamine.DESIGN: Randomized controlled trial.SETTING: Institute of Pharmacology, Xuanwu Hospital of Capital University of Medical Sciences.MATERIALS: The experiment was conducted in the Institute of Pharmacology,Xuanwu Hospital of Capital University of Medical Sciences,be tween February 2000 and May 2000.Totally 50 male Kunming mice were recruited and randomized into 5 groups: normal control group, model group,positive control group, 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside 0.03 g/kg group (low-dose group), and 2,3,5,4 '-tetrahydroxystilbene-2-O-β- D-glucoside 0.1 g/kg group(high-dose group).2,3,5,4'-tetrahydroxystil bene-2-O-β-D-glucoside was an effective component extracted from Chinese herb tuber fleeceflower root in the Department of Pharmacology, Xuanwu Hospital of Capital University of Medical Sciences.Piracetam was the positive control drug.Morris water maze and passive avoidance reflex box were made in the Institute of Materia Medica, the Chinese Academy of Medical Sciences.METHODS:Administration was given 5 days before experiment.Tap water was intragastrically grven into the mice in normal group and model group. Piracetam of 0.7 g/(kg.d) was given to the mice in positive control group and 0.03 g/kg of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside was given to small-dose group and 0.1 g/kg to large-dose group for 5 consecutive days.Model establishment started 30 minutes after adminis tration in each group on day 6. The same volume of normal saline was in traperitoneally injected into the mice in normal control group and 1 mg/kg of scopolamine was intraperitoneally injected into mice in the other groups.Morris water maze and passive avoidance tests were carried out 20 minters later.Injection dose of model establishment of Morris water maze was 1 mg/kg and that of passive avoidance test was 10 mg/kg.MAIN OUTCOME MEASURES:① Searching distance and time of mice in Morris water maze in each group.② Latency and entry-times of mice in passive avoidance test in each group.RESULTS:All the 50 mice were recruited in the experiment,and 49 of them entered the result analysis,1 mouse in model group died because of intraperitoneal hemorrhage when scopolamine was injected.① Results of Morris water maze test: Searching time and distance were significantly shortened in large-dose group as compared to those in model group[(77.814± 46.492), (99.319± 38.104)s; (1 370.914± 917.40), (1 808.77± 869.36)cm; P all ＜ 0.05]. ② Results of passive avoidance test: The number of en try times in small-dose group and large-dose group was significantly de creased compared with that in model group [(0.00± 0.00), (0.00± 0.00),(0.8571± 2.267) times, P ＜ 0.01], and the latency had an extended tenden cy [(300± 0.00), (300± 0.00), (269.71± 80.128) s ].CONCLUSION: 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside given to mice with learning and memory disorder induced by scopolamine can shorten the searching time and distance in Morris water maze and reduce the number of mistake-making times in passive avoidance test. It suggests that it has ameliorative effects on learning and memory disorder.

To construct a lentiviral shRNA vector targeting human protein phosphatase 1D magnesium-dependent (PPM1D) gene and detect its effectiveness of gene silencing in human gliomas, specific siRNA targets with short hairpin frame were designed and synthesized. DNA oligo was cloned into the pFU-GW-iRNA lentiviral expression vector, and then PCR and sequencing analyses were conducted to verify the constructs. After the verified plasmids were transfected into 293T cells, the lentivirus was produced and the titer of virus was determined. Real-time quantitative PCR and Western blot were performed to detect the PPM1D expression level in the infected glioma cells. PCR and Western blot analyses revealed the optimal interfering target, and the virus with a titer of 6×10(8) TU/mL was successfully packaged. The PPM1D expression in human glioma cells was knocked down at both mRNA and protein levels by virus infection. The expression of PPM1D mRNA and protein was decreased by 76.3% and 87.0% respectively as compared with control group. The multiple functions of human glioma cells after PPM1D RNA interference were detected by flow cytometry and cell counting kit-8 (CCK-8). Efficient down-regulation of PPM1D resulted in significantly increased cell apoptosis and reduced cell proliferation and invasion potential in U87-MG cells. We have successfully constructed the lentiviral shRNA expression vector capable of stable PPM1D gene silencing at both mRNA and protein levels in glioma cells. And our data gave evidence that the reduced cell growth observed after PPM1D silencing in glioma cells was at least partly due to increased apoptotic cell death.

Background Hypoxia is the main factor of retinal neovascularization and is closely associated with retinal ganglial cells (RGCs) degeneration.However, the study of retinal neural tissue lesions is rare.Objective This study was to investigate the influence of hypoxia environment on the expression of annexin A2 (ANXA2) in mouse RGC-5 cells and explore the mechanism of RGCs damage induced by hypoxia.Methods Immortalized mouse RGC-5 cells were cultured in high glucose DMEM with 10％ fetal bovine serum.The cells were identified by detecting the expression of Thy-1 ,a specific biomarker of RGCs.CoCl2 was added into the medium at the final concentrations of 50,100,200 and 300 μmol/L, and the cells without CoCl2 served as the control group.Cell viability (absorbance) was assayed by cell counting kit-8 (CCK-8) method in 12,24 and 48 hours after addition of CoCl2.The hypoxic cell models were established in DMEM with 100 μmol/L CoCl2 and divided into the hypoxic 3-hour group, hypoxic 6-hour group, hypoxic 12-hour group and hypoxic 24-hour group,with the normal cultured cells as the normal control group.Apoptotic cells were determined by using hoechst 33342 stain.The expression levels of ANXA2 mRNA and protein in the cells were detected by real-time quantification PCR and Western blot,respectively.The expression and location of ANXA2 in the cells were examined by using immunofluorescence technique.Results The cultured cells grew well and showed the fusiform and polygonal shape,with positive expression of Thy-1 protein.Compared with the normal control group, the viabilities of the cells were insignificantly changed in the 50 μ mol/L CoCl2 group and 100 μmol/L CoCl2 group (all at P＞0.05) ,but the cell viabilities were significantly reduced in the 200 μμmol/L CoCl2 group and 300 μmol/L CoCl2 group in various time points (all at P＜0.05).Hoechst 33342 staining showed that the apoptotic cells with nuclear condensation and high green fluorescence intensity were obtained in the hypoxia groups.The relative expression levels of ANXA2 mRNA were significantly lower in the hypoxic groups than those in the normal control group (all at P ＜ 0.05).The relative expression levels of ANXA2 protein were significantly lower in the hypoxia 3-,6-, 12-and 24-hour group than those in the normal control group (all at P＜ 0.05).Apoptotic cells were seen in the hypoxic 3-hour group, hypoxic 6-hour group, hypoxic 12-hour group and hypoxic 24-hour group compared with the normal control group, showing the bright blue fluorescence in cellular nucleus for hoechst 33342.The relative expressing levels of ANXA2 mRNA in the cells were 0.80±0.14,0.67±0.33, 0.49±0.17 and 0.39±0.02 in the hypoxic 3-hour group,hypoxic 6-hour group, hypoxic 12-hour group and hypoxic 24-hour group, which were significantly declined in comparison with the normal control group, with a statistically difference among the groups (F=434.354, P =0.000).The relative expression values of ANXA2 protein were 0.552 6±0.012 3,0.425 9± 0.033 4,0.344 9 ± 0.017 8 and 0.382 7 ± 0.022 1 in the hypoxic 3-hour group, hypoxic 6-hour group, hypoxic 12-hour group and hypoxic 24-hour group,which were remarkably lower than 0.602 1 ±0.001 4 in the normal control group, showing considerably difference among the groups (F =3.057, P =0.000).ANXA2 proteins were highly expressed in the cellular nucleus and less expressed in the cell membrane and cytoplasm in the normal cells.Compared with the normal control group, the ANXA2 protein showed weak expression in the hypoxia group and primarily in the cytoplasm.Conclusions The expression of ANXA2 down-regulates in hypoxic mouse RGC-5 cells,which may participate in the apoptosis process of RGCs in high glucose environment.

Objective To study on the relationship between plasminogen and brain-derived neurotrophic factor(BDNF),and explain the molecular mechanism of depression ,then provide new clew for diagnosis and treatment of depression .Methods The chronic unpredictable mild depression rat mode was established ,then depression symptoms including absence of delight ,the decline of actions and activities ,and weight reduction of rat were tested .The levels of individual plasminogen and BDNF in hippocampus were determined by Western blot .Results The expression of BDNF and plasminogen in depression rat mode and control group was significantly different(P<0 .01) ,and there was a positive correlation between BDNF and plasminogen(r=0 .65 ,P<0 .01) .Accord-ing to the linear-regression analysis ,there was a dependence relationship between them(r2 =0 .423) .The equation of regression was YBDNF=0 .750XPlasminogen +0 .201 .Conclusion Stress could affect the growth and survival of nerve cell ,which lead to the depression behavior of rats ,meanwhile ,the decline of plasminogen and BDNF levels ,the positive correlation between them illustrate that plas-minogen and BDNF take part in the mechanism of depression .

Objective To investigate the regulatory networks of DNA methylation profiles in STEMI by methylation microarrays.Methods A total often male patients with STEMI and ten male healthy controls were recruited.Methyl-DNA immunoprecipitation and Nimblegen HG18 Meth 385K promoter plus CpG island microarrays were used to identify differentially methylated regions.And several bioinformatics analysis tools which included chromosomal assignment, gene ontology analysis and pathway analysis with SignalMap and The Database for Annotation, Visualization and Integrated Discovery were used to high-throughput analysis.Results Compared with healthy controls, DMRs of STEMI is 1 634, There are 1 480 (90.57％), 131 (8.02％) and23 (1.41％) methylated sites were separately located on High CpG-containing promoter, Intermediate CpG-containing promoter and Low CpG-containing promoter;Gene Ontology and Pathway analysis expressed DNA methylated genes of signaling pathway in MI identified glycerophespholipid metabolism, cysteine and methionine metabolism, Dilated cardiomyopathy, Arrhythmogenic right ventricular cardiomyopathy, regulation of actin cyteskeleton, calcium signaling pathway.However, the signal pathway about lipid metabolism is shown no significant difference.Conclusions Bioinformatics tools could provide the quick and high-throughput analysis of data from methylation microarray and enable the function classification of differentially expressed genes of STEMI.