Objective: To observe the main pharmacodynamic effects of Yinaoning (YNN) on acute blood stasis rats and cerebral ischemia rats. Methods: Rats were prevented by the oral administration of YNN (0.4375～ 1.75g/kg once daily for 7 days. The acute blood stasis model and cerebral ischemaed model were used. Results: YNN could decrease the blood viscosity and plasma viscosity, shorten the length of in vitro thrombus, abate the wet and dry weights of thrombus in the acute blood stasis model group. It decreased the brain index significantly in the cerebral ischemia model group. The high dose of YNN could decrease the level of Evans blue obviously and reduce the degeneration of cranial nerve cells. These effects were similar to those of YNN Tablets and were dose dependent. Conclusion: YNN is effective for acute blood stasis rats and cerebral ischemaed rats.

Objective To investigate the influence of transforming growth factor ? 1 to expression of tumor necross factor ?(TNF ?) after cerebral ischemic reperfusion injury.Methods Using thread embolism method to develop the model of focal cerebral ischemic reperfusive injury in rats, different dose of TGF ? 1 or 0 9% NaCl was injected intracerebroventricularly.Neurological functional dificit scales in the different dose of TGF ? 1 groups and the expression of TNF ? were observed Results In both big and small dose of TGF ? 1 groups,the expression of TNF ? decreased after cerebral ischemic reperfusion,and the neurological functional dificit scales were significantly lower than those of the control.There was no significant difference between the group of big and small dose of TGF ? 1 Conclusion TGF ? 1 may have a protective effect on cerebral ischemic reperfusive injury by inhibiting expression of TNF ?,and it may be irrelative with the dose

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.

Ketoconazole(KET) is a new imi-dazole derivative with broad antimycotic spectrum. In order to verify the clinical toxic and side effect and its properties in animals, we made a long-term toxicity test for 30 days. Dosages of 70, 35 and 17. 5 mg?kg-1?d-1(e-quivalent to 21, 10. 5 and 5. 2 times of the clinical dosage) were given ig to dogs. The salivation , vomiting, anorexia, decrease in heart rate and loss of weight occurred in the large dosage group. Half of the dogs died from toxicosis within ig 15 days. Laboratory examination showed that the activities of ALT, LDH and ALP, the content of T-BIL, BUN in serum in-creased in this group. Pathological examination revealed that there were some pathological changes in the liver, kidneys, adrenal glands and sex gland in the group. There were no significant changes in other dosage groups compared with the normal control group. After withdrawal of KET, all toxic symptoms disappeared and the abnormal indexes were restored. The results indicated that toxic target organs of KET were liver, kidney, adrenal gland and sex glands. The safe dosage for dogs was about 17. 5 mg?kg-1?d-1.

Objective To investigate any changes in motor functional connectivity in the brains of acute ischemic stroke patients after low frequency electrical stimulation.Methods Twenty-five ischemic stroke patients were given low frequency electrical stimulation in addition to their conventional rehabilitation treatment.Another 20 patients received only conventional treatment as a control group.Resting-state functional magnetic resonance imaging (rs-fMRl)was employed to assess motor function connectivity in the brains of all 45 subjects before and after treatment.Any differences in functional impairment,extremity motor function or ability in the activities of daily living were also recorded before and after treatment.Results In both groups,average scores on the Canadian neurological scale (CNS)and the National Institutes of Health stroke scale (NIHSS) had been reduced significantly after treatment and FuglMeyer assessment (FMA) and modified Barthel index (MBI) scores had significantly increased.The average improvements in terms of FMA and MBI scores were significantly greater in the observation group.Compared with before treatment,the coefficient of functional connectivity of the bilateral motor cortex had decreased significantly after treatment in both groups.In the observation group the changes were significantly correlated with the improvements in FMA scores.Conclusion Neural functional impairment after ischemic stroke can be reduced significantly and extremity motor function and ability in the activities of daily living can be significantly improved by low frequency electrical stimulation.

Objective To investigate the clinical effect of botulinum toxin type A (BTX-A) injections guided by electromyography in combination with electrical stimulation in the treatment of upper limb spasticity poststroke.Methods Forty-five patients with upper limb spasticity following stroke were recruited.They received multiple intra-muscular BTX-A injections guided by electromyography and electrical stimulation.Rehabilitation training was administered after the BTX-A injections.The results were assessed using the modified Ashworth scale (MAS),the Fugl-Meyer upper limb assessment (FMA),active range of movement (AROM) and the modified Barthel index (MBI).All the assessments were performed at the baseline,and then 1 week,2 weeks,1 month,and 3 months after the injections.Results Compared with the baseline scores the MAS,FMA,AROM and MBI results had all obviously improved by 2 weeks after the BTX-A injections.Compared with 2 weeks after the injections,the FMA and AROM scores at 1 month were significantly higher and there were further significant improvements at 3 months.No patient demonstrated obvious side effects from the therapy.Conclusion BTX-A injection guided by electromyography and electrical stimulation is safe and has definite beneficial effects on upper limb spasticity after stroke.

Objective:To study the influence of silencing mesothelin(MSLN) gene on the proliferation of ovarian cancer cell line SKOV3 in vitro the growth of human ovarian xenograft in nude mice in vivo.Methods:MSLN-silenced cells (SKOV3-MSLN-shRNA ) and control cells (SKOV3-MSLN-neg) were established after being infected with RNA interference lentivirus and empty vector lentivirus, respectively. SKOV3 cells were used as blank control. Cell proliferation was assayed by clone formation test and cell counting assay. The xenografted model of the three cell lines were established in nude mice. After 2 weeks, the nude mice were sacrificed, and the tumor formation rate, tumor weight, tumor number, and tumor position were recorded. Results:The ability of proliferation of SKOV3-MSLN-shRNA cells was obviously decreased compared with SKOV3-MSLN-neg cells and SKOV3 cells in vitro. The difference was significant (P<0.05). In vivo, the tumor formation rate was 60% in xenografts of SKOV3-MSLN-shRNA cells and 100% in other two groups. The difference was not significant (P>0.05). The average tumor weight, tumor number, and number of tumor position were all decreased in SKOV3-MSLN-shRNA group compared with the two control groups (P<0.05). Conclusion:Silencing MSLN gene decreased the proliferation of ovarian cancer SKOV3 cells in vitro and inhibited the growth of xenografts of ovarian cancer cells in nude mice.

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.

Objective To investigate the etiological characteristics of diarrhea patients visiting enteric disease clinics in Beijing .Methods A total of 595 stool samples were collected among outpatients with diarrhea vistiting enteric disease clinics at two sentinel hospitals from July 2013 to June 2014 . Diarrheagenic Escherichia coli (E . coli) , Vibrio parahemolyticus , O1 or O139 Vibrio cholerae , Salmonella and Shigella were isolated according to standard methods . And rotavirus , norovirus , astrovirus and enteric adenovirus were identified by molecular techniques .The characteristics of population and temporal distribution , and serotypes of these pathogens were analyzed using descriptive epidemiological method .Chi‐square test was used for comparison between groups .Results Totally 128 bacterial strains were isolated from 595 samples ,and the detection rate was 21 .5% .Diarrheagenic E .coli was most common pathogenic bacteria (11 .4% ,68/595) ,followed by Vibrio parahemolyticus (6 .9% , 41/595) ,Salmonella (2 .4% ,14/595) and Shigella (2 .2% ,13/595) .No V ibrio cholerae was detected . One hundred and twelve viral strains were detected from all samples ,and the positive rate was 18 .8% . Norovirus was most common viral pathogen (9 .1% ,54/595) ,followed by rotavirus (8 .7% ,52/595) , astrovirus (1 .8% , 11/595 ) and enteric adenovirus (0 .7% , 4/595) . Enteropathogenic E .coli , enterotoxigenic E .coli and enteroadhesive E .coli were the most common types of diarrheagenic E .coli . The most common serotype of Vibrio parahaemolyticus was O4∶K8 .The detection rate of bacterial pathogens reached the peak from June to September ,while the highest detection rate of viral pathogens was found from November to the next March .Conclusion Norovirus and rotavirus are also the main pathogens of the diarnhea patients visiting enteric clinics ,which should be paid enough attention .

Objective To detect the impairment of response inhibition and working memory in patients with alcohol dependence.Methods A total of forty-eight alcohol dependent patients and fifty age,gender,IQ,education matched controls were recruited.Neuropsychological tests were applied to measure the differences of response inhibition and working memory between the two groups.Results In the response inhibition task,the patient group had more commission errors ((7.02± 3.48) vs (3.45± 1.52)) and longer reaction time ((605.45 ± 142.56)ms vs (435.72±51.18)ms) compared to the control group (t=6.534,P=0.000; t=7.781,P=0.000).In the spacial working memory task,the patient group also had more commission errors ((4.58± 3.45) vs (0.43± 0.88)) and longer reaction time((10566.16±2455.61) ms vs (9185.44±2677.52) ms) than control (t=8.085,P =0.000; t=2.657,P=0.009).Conclusion There are significant deficiencies in response inhibition and working memory in patients with alcohol dependence.