How does brain select and adjust the distributed neural activities to achieve its function? To address this problem,researchers introduce Granger causality analysis method to brain functional study,which deals with the estimation of causal influences among multi-variables.First,basic principles of Granger Causality and its improved algorithm structural vector autoregression (SVAR) are introduced.Then several technical problems are reviewed which should be noted when analyzing brain functional signals by Granger Causality Methods.In the end,the application foreground of Granger Causality in epilepsy localization is introduced by taking idiopathic generalized epilepsy as the example.

BACKGROUND: Besides being a basic growth factor crucial to maintain and promote the development, differentiation and survival of the central nervous system, nerve growth factor(NGF) also plays an important role in the repair of injured peripheral nerves.OBJECTIVE: To investigate the effect of the muscular injection of NGF on the regeneration and functional recovery of rat sciatic nerve after crush injury.DESIGN: A randomized controlled pilot study in rats with repeated observation and measurement.SETTING: Center for new drug evaluation in a military medical university.MATERIALS: This study was performed in the Center for New Drug Evaluation, Department of Basic Medicine, Second Military Medical University during the period from July 1999 to March 2000, using 40 SD rats weighing 200 to 250 g(of either sex of half number) provided by the Sino-British SIPPR/BK Lab Aninal Ltd (Shanghai).METHODS: Forty rats were randomized into high-, mid- and low-dose NGF treatment groups, normal control group and model control group. The sciatic nerves were clamped at 6 nm distal to the sciatic notch to induce a 4-mm-wide area of crush injury. In the high-, mid-; and low-dose NGF groups, the rats were given NGF at 8, 4 and 2 μg/kg per day(corresponding to 1.6 × 10 3, 8 × 10 2 and 4 × 10 2 IU/kg per day) respectively via the muscular injection for 56 consecutive days.(NCVs) and sciatic function index(SFI) at different time points after the RESULTS: Compared with that of the model control group, the NCVs significantly increased in the high-dose NGF group 35 and 56 days after the injury,and in the mid-dose NGFgroup at 35 days(t=2.32-5.14, P ＜0.05-0.01 ). The SFIs significantly increased in all NGF-treated groups at 14 days ( t = 2. 29-6.28, P ＜ 0.05-0.01 ), with the recovery most conspicuous in high-dose NGF group; No significant difference in the SFIs was found between the NGF-treated groups on the 56th day. Morphological examination of the tissues identified no significant difference in the nerve myelin sheaths and axons in NGF-treated groups as compared with the normal control group,while in the model control group, myelin sheath dislocation with unclear microstructure was observed, accompanied by Schwann cell degeneration and necrosis.CONCLUSION: NGF promotes the repair of the damaged nerve myelin sheath and axon and stimulates nerve fiber regeneration and function recovery of the crushed rat sciatic nerves.

Objective To study the methods and outcome of 71 patients with Parkinson's disease treated with microelectrode-guided stereotactic pallidotomy and thalamotomy. Method Pallidal and thalamal target sites are chosen by supervision of microelectrode recording technique in 71 patients with Parkinson's disease. The UPDRS motor score was used to evaluate the outcomes 12 weeks before and after operation Result After 12 months follow-up, tremor disappeared completely or nearly completely in 12 patients who underwent unilateral and l bilateral ventrolateral thalamotomy. Dramatic improvement of tremor, rigidity, bradykinesia were observed in 57 patients underwent posteroventral pallidotomy,including 6 underwent bilateral posteroventral pallidotomy. Intracerebral hemorrhage was observed in l patient. Conclusion Microelectrode-guided stereotactic pallidotomy and thalamotomy are effective in treatmenting Parkinson's disease, but with serious complications

AIM: Site-specific functional neurons of brains were with different cellular morphology. It has not been fully understood whether the grafted neural stem cells could differentiate into the site-specific neurons. This experiment is to investigate the neuronal differentiation of the neural stem cells derived from a human fetal brain after transplanted into young rats' brains, to study the possibility of cell-replacement therapy for children's brain disorders with neural stem cells. METHODS: Experiments were performed at the Cell Laboratory of Naval General Hospital from April to July 2007. ①Human fetal brain tissues of 16 week gestation were provided by Department of Gynaecology and Obstetrics of Naval Hospital. Pregnant woman and family members signed an informed consent. Experimental intervention was approved by Hospital Ethical Committee. Fourteen clean brood young SD rats aged 10 days, irrespective of gender, were provided by Experimental Animal Center of Medical College of Peking University. Animal intervention met the animal ethical standards. ②The neural stem cell spheres were derived from the fetal brain tissues of 16 week gestation. The differentiation multipotency of the neurosphere was identified when cultured in a child's cerebrospinal fluid (CSF). The neurospheres cultured in vitro for 14 days were injected into the lateral ventricles of young rats of 10 days old. The rats were respectively killed at days 4, 7 and 14 after transplantation. The special immuno-fluorescent assays were performed using anti-human neurofilament (anti-hNF) to show the location and morphology of graft neurons. RESULTS: ①The typical floating neurospheres were obtained, with the potency to differentiate into neurons, astrocytes and oligodendrocytes. ②The neuronal differentiation of grafts was detected with the mixture of three monoclonal antibodies against human neurofilament. Four days after transplantation, the immune response positive cells lied within the granule cell layer of cerebral cortex were shown in the shape of granule cells, or within the pyramid cell layer in the shape of pyramid cells with long processes, and the interneuron-like cells also were seen. The Purkinje cells arranging in a monolayer were detected in the cerebellum. Compared the results at different time points, the location of grafts were the same. The graft cells were less and the processes were longer over time. CONCLUSION: The in vitro cultured neurosphere cells can migrate into brain tissues and differentiate into site-specific neurons in shape after transplanting into the lateral ventricles of young rats. It is suggested that the host brain tissue microenvironment played an important role in guiding the graft differentiation into neurons. The results have an important significance for understanding cell replacement of developing brain disorders.

Objective To evaluate the value of fMRI guided brain surgery for the lesions in or around Broca's area.Methods Forty-three patients with lesions in or adjacent to the Broca's area were studied.fMRI imaging was obtained by BOLD technique with the tasks of reciting.Fiber tract imaging of white matter was obtained by DTI technique.All functional imaging and anatomic imaging were transferred to neuronavigation system.The technique of direct cortical stimulation was used to validate the language cortex in fMRI.The lesions were resected in microscope.Results Broca's area activation was detected in 38 cases..The distance between the fMRI peak and direct cortical stimulation was rated as overlapping (<1 cm diatance) in 25 cases and neighbouring (<2 cm diatance) in 11 cases.Total lesion resection was achieved in 17 cases, subtotal resection in 14 cases, and partial resection in 12 cases.Postoperative neurological functions were improved in 8 cases, unchanged in 31 cases, and temporary worsen in 4 cases.Conclusions The identification of the Broca's area by reciting task in fMRI is sensitive and precise.The fMRI is helpful to decrease the side effect injury in the brain surgery for the lesions in or around the Broca's area.

Objective To lateralize epileptic foci in interictal electroencephalography (EEG) signal by using causal analysis method.Methods On the basis of frequency domain causal analysis,the adapted directed transfer function (ADTF),power spectrum weighted ADTF(psADTF) method was proposed by applying the power spectrum information in defined frequency band with normalized ADTF,to fit the frequency information features of different epileptic wave.EEG signals of two groups of 30 epilepsy patients were analyzed by psADTF.Group Ⅰ included 15 presurgical patients and 104 epilepsy spikes were picked from EEG signals.Group Ⅱ included 15 outpatient patients and 98 epilepsy spikes were picked from EEG signals.Results 96 of 104 spikes of group Ⅰ were lateralized properly by psADTF according to surgery sites,and the accuracy rate was 92％.94 of 98 spikes of group Ⅱ were lateralized properly by psADTF according to three technicians' judgments,with the accuracy rate of 96％.Conclusion Our results proves that the psADTF method over interictal EEG spikes can be a great help to clinical epileptic foci lateralization.

ObjectiveTo investigate the expression of CXCR4 and CD133mRNA in primary lesion of primary gastric adenocarcinoma and the relation with clinicopathological features,and to explore the correlation of CXCR4 and CD133.MethodsThe primary lesion of primary gastric adenocarcinoma and normal tissues adjacent to gastric cancer were obtained from 50 patients.The diction of CXCR4 and CD133 protein expression was detected by the immunohistochemical staining,and the relative gray scale values of CXCR4 and CD133mRNA by semi-quantitative RT-PCR (Fisher' s exact probability method).Their relationship with clinicopathological features was also investigated ( Spearman relation analysis).ResultsThe positive rates of CXCR4 and CD133 protein in gastric cancers were 76.0％ and 66.0％ respectively,which were significantly higher than that in normal tissues adjacent to gastric cancer ( 16.0％ and 10％ ; P =0.000,P =0.000).The increment of relative gray scale values of CXCR4mRNA was associated with the larger tumor diameter,the later TNM stage and the occurrence of lymphatic metastasis( P ＜ 0.05 ).And the larger diameter of tumor,the later TNM stage were associated with the higher relative gray scale values of CD133mRNA (P ＜0.05).The levels of the relative gray scale values of CXCR4 mRNA and CD133mRNA were positively related(r =0.453,P ＜ 0.01 ).ConclusionsThe higher expression of CXCR4 and CD133mRNA correlateswith tumour diameter,TNM stage and lymphatic vessel invasion. The relative gray scale values of CD133mRNA increase with the increment of the relative gray scale values of CXCR4.

OBJECTIVE: To investigate the effects of human cerebrospinal fluid (CSF) during development phase on migration and differentiation of fetal brain neural stem cells (NSCs).METHODS: Fetal brain cells of gestational age of 16 weeks that were frozen in liquid nitrogen were obtained, resuscitated and incubated in DMEM/F12 medium containing epithium growth factor (EGF), basic fibroblast growth factor (bFGF), B27 and N2. The neurospheres cultured for 14 days were obtained. CSF was absorbed from the subarachnoid cavity and brain ventricle in the embryonic group. CSF was collected by lumbar puncture or ventricular puncture in the child group. The neurospheres cultured for 14 days were transplanted into the pure CSF in an incubator containing 5% CO_2 at 37 ℃. Cellular migration and growth of neurospheres in CSF were observed. Effects of CSF on neural cell differentiation were identified by immunofluorescence. RESULTS: Neural stem cells in the form of neurospheres derived from fetal brain were inoculated into the pure CSF, and cell migration were commonly observed besides few of neurospheres in child CSF culture at 6 hours following culture. Surrounding cells of neurospheres extended processes, forming cell cord that became cell webs after extension. Compared with the embryonic group, positive rate of glial fibrillary acidic protein was significantly increased in the children group (P < 0.01), but positive rates of nerve fiber and nestin were significantly decreased (P < 0.01). In addition, galactocerebroside-positive cells were only found in 3 baby CSF cultures. CONCLUSION: There existed significant affections on both migration and differentiation of human neural stem cells when cultured in pure CSF with different developmental phase, suggesting that CSF is one of major niche factors for central neural system development.

Objective To analyze CD127 expression on the memory CD8+ lymphocytes from hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients treated with peginterferon α-2a (Pegasys). Methods Thirty HBeAg positive CHB patients were treated with peginterferon α-2a 180 μg once a week for 48 weeks and followed up for 24 weeks. The memory CD8+ lymphocytes were characterized by expressing CD45RA and CD27 markers. CD127 expression on cell surface was measured by four-colour flow cytometry. The difference of mean values between groups was evaluated by Mann-Whitney test. Results The CD127 expression on CD8+ T lymphocytes was significantly lower in HBeAg positive CHB patients compared to healthy controls (Z=2.889, P＜0.05), which was negatively correlated with serum hepatitis B virus (HBV) DNA level and HBeAg titers. The CD127 expression increased along with the decrease of HBV DNA and HBeAg after 24-week, 48-week and 72-week treatment in patients showing good response to peginterferon α-2a, while CD127 expression didn't change markedly in non responders (Z24w = 1.954, Z48w = 2.789, Z72w = 2. 989; all P＜0. 05). Conclusion CD127 expression on memory CD8+ lymphocytes increases along with effective anti-HBV treatment in CHB patients, which can be used as a marker for evaluating the effectiveness of anti-viral treatment.

Objective:To investigate the long-term toxicity of recombinant human interleukin-11(rhIL-11) in cynomolgus. Methods: Eighteen cynomolgus were randomized into 4 groups: control group(2/sex), low dose group(2/sex), medium dose group(2/sex)， and high dose group(3/sex). The drug groups were sc adminstered 0.1, 0.3 and 1.0 mg/kg of rhIL-11 for 90 days with a 30-day recovery period. The clinical signs were observed, electrocardiogram, hematological, biochemical, urinary and immunological parameters were measured, organ masses were weighed, bone marrow and pathological histology were observed. Results: The food consumption, body mass of the drug groups were decreased, the body temperature was increased transiently. One of the low dose group showed restricted movements and tremors. One of the high dose group vomited and another died. Reduced red blood cell(RBC) count, hemoglobin(Hb) concentration, hematocrit(Hct), mean corpuscular volume(MCV), mean corpuscular hemoglobin(MCH), and mean corpuscular hemoglobin concentration(MCHC), dose-related increase of platelet(Plat) counts were present in drug groups. Biochemical examinations revealed dose-related decreases in serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactate dehydrogenase(LDH), total proteins(TP) and albumin(Alb) increases in serum alkaline phosphatase(ALP) levels. Positive antibody responses were seen and circulatory immune complex(CIC) was significantly increased in all drug groups. Hypertropy of marrow megakaryocyocytes was noted in the medium and high dose groups. The heart and liver masses were slightly increased in all treatment groups. Treatment-related microscopic findings included dose-related degeneration in the liver and the kidney. The adverse effects were reversed by the end of the recovery period. Conclusion: The target organs and systems are blood, liver, kidney, immmue system and bone marrow. The toxicity injuries were reversible and the no-toxic-effect level is 0.1 mg/kg.