ObjectiveTo investigate the effect of soluble β-amyloid protein (Aβ) oligomers on the expression levels of insulin signaling transduction cascades-associated proteins including insulin receptor ( InsR),insulin receptor substrate-Ⅰ( IRS-Ⅰ) and protein kinase B (PKB) of rat hippocampal neurons,and the pathogenesis of Alzheimer's disease (AD) in depth.MethodsSoluble Aβ oligomers (5 μl) were injected into the lateral ventriculus of the AD group by a microinjector under the stereotaxic apparatus.Normal saline solution ( NS,5 μl) was injected into the NS group in the same way,and the control group received the puncture without injection. It was repeated after 1 week and the behavior of all rats was evaluatedbyY-mazetestafter2weeks.Thenhippocampuswasremovedandunderwent immunohistochemical staining to detect the expression of proteins associated.ResultsCompared with the other groups,learning and memory ability of the Aβ-treated rats were impaired.To be specific,the times of learning were increased and the times of memory were decreased. However,there was no significant difference between the NS group and the control group.Besides,the expression levels of InsR,IRS-Ⅰ,and PKB were decreased in AD group showing that a mean optical density of staining on these proteins ( InsR:0.12 ± 0.0l ; IRS-Ⅰ:0.14 ± 0.02; PKB:0.12 ± 0.03 ) was reduced in contrast with that in the NS group and the control group.Whereas there was no significant difference between the NS group (0.40 ± 0.02,0.39 ± 0.06,0.38 ± 0.03,mean difference:- 0.13,- 0.13,- 0.17,all P ＜ 0.05 ) and the control group (0.38 ± 0.07,0.35 ± 0.03,0.35 ± 0.06,mean difference:- 0.15,- 0.07,- 0.73,all P ＜ 0.05 ).ConclusionsSoluble Aβ1-42 induced learning and memory disability of the rats.The mechanism might be that Aβ can lead to disorders of the insulin signaling transduction pathway of hippocampal neurons and decrease the expression levels of the proteins in the pathway.

Objective To investigate the change of adhesive properties of polymorphonuclear neutrophils(PMN) and endothelial cells (EC) in patients with cerebral infarction (CI), and define the effects of antibodies to intercellular adhesion molecular 1 (ICAM 1, anti CD54 antibodies) upon the adhesion.Methods We detected the adhesive rate between human umbilical vein endothelial cells (ECV 304) and PMN of patients with CI within 1 week and at 21 days.Results (1) The adhesive rate of ECV 304 to PMN of 30 patients with CI within 1 week increased significantly ( P

As the number and proportion of aging population increase,dementia has posed tremendous challenges to the sustainable social and economic development of many countries in the world.Thus,dementia has been identified as a global public health priority.Clinically,there is currently no cure for dementia.However,in the past decades epidemiological research has suggested that cardiovascular risk factors and psychosocial factors over the life-course could significantly affect the risk of dementia occurrence later in life.Of these factors,smoking,diabetes,and midlife hypertension,obesity,and high cholesterol might contribute to the clinical onset of late-life dementia by causing cerebral macro-and microvascular damage and neurodegeneration,whereas high educational attainments in early life and social engagement,physical and mentally-stimulating activities during adulthoods might help maintain late-life cognitive function by increasing cognitive reserve.Thus,theoretically clinical onset of dementia is likely to be postponed by implementing interventions targeting these factors over the lifespan.In recent years,evidence from research in Europe and North America has emerged that multimodal interventions that consist of intensive control of cardiovascular risk factors,balanced diets,physical activity,and cognitive training may help maintain cognitive function among individuals at risk for dementia.We call that population intervention research against dementia should be strengthened in China.Identifying the intervention programmes against dementia that are effective specifically among Chinese population is of high relevance for developing the national dementia action plan,and thus effectively dealing with the huge challenges by dementia.

BACKGROUND: Modern neuroradiological imaging techniques such as CT, MRI, and ultrasound help clinicians idenitify the location and volume of an infarct at present. At present, a widely available and easy laboratory examination for acute cerebral infarction is absent.OBJECTIVE: To investigate the relationship between the content S100-β in serum and infarct volume, and prognosis in patients with acute cerebral infarction.DESIGN: Case-control study.SETTING:Department of Neurology of Shandong Provincial Hospital of Shandong University.PARTICIPANTS: From September 2004 to August 2005, 58 patients with acute ischemic brain infarction less than 24 hours after symptom onset were hospitalized in the Department of Neurology of Shandong Provincial Hospital for evaluation and management and enrolled in case group. With the age of 36-86 years and a mean of (68±14) years. 21 were female and 37 were male. Included criteria: The diagnostic criteria was consistent with that of the Second China Cerebrovascular Disease Conference. Every patient who participated in the study underwent the examination of MRI or CT of the brain on admission, the patients were confirmed to be ones with cerebral infarction. Exclusion criteria: A history of a previous stroke and/or existing disability. 50 healthy participants in the control group were from Health Examination Center, including 32 male and 18 female aged 43-89 years and a mean of (68±9) years. Age means and gender were not significantly different between the case group and the control group (P＞0.05).METHODS:① Venous blood samples (2 mL) were drawn in case group at baseline, 1, 2, 3, 4, 6 and 10 days after symptom onset, and the same agent of samples were drawn in control group only at baseline. Enzymelinked immunosorbent assay was used for S100-β measurement. ② Infarct volume of patient was measured by Simes Somatom sensation cardiac wizard workstation volume for CT on day 7 after symptom onset. Neurological outcome was assessed at 3 months after the onset of symptom with modified Rankin scale (MRS) score.MAIN OUTCOME MEASURES: ① Level of S100-β in serum of the subject in the two groups. ② Final infarct volume of patients in case group on day 7 after symptom onset and functional outcome 3 months after symptom onset.RESULTS: 58 patients and 50 healthy control subjects were enrolled in the study. 6 patients in case group developed complete loss of brain stem reflexes and died within 2 months. The others entered the result analysis.①The level of S100-β protein: The level of S100-β protein increased gradually in the case group, peaked at day 3 [(0.61±0.13) μg/L], and decreased at day 10. The levels of S100-β in 6 days after symptom onset were significantly higher than that in control group. The level of S100-β at day 10 in the case group was similar with the control group. ② The level of serum S100-β content in patients of case group: The serum S100-β content were obviously correlated with the infarct volume at 1, 2, 3, 4, 6days after the symptom onset. S100-β value at day 3 provided the highest correlation coefficients (r=0.937, P ＜ 0.001) ③ The status of the cerebral infarction of patients after 3 months: S100-βmeasures and the MRS scores that were obtained 3 months after cerebral infarction revealed highly significant coefficients ranging by bivariate correlations (r=0.507, P ＜ 0.01).CONCLUSION: The content S100-β in serum and infarct volume of the patients with acute cerebral infarction revealed positive correlation. The content S100-β in serum can help to calculate neurological outcome of patients after acute cerebral infarction.

Objective To study the relationship between the prevalence of thyroid dysfunction and components of metabolic syndrome.Methods A total of 10 461 working and retired employees aged 20 to 90 years in a Petrochemical Corporation in Ningbo were included.Body mass index ( BMI),waist circumference,blood pressure,fasting blood glucose,blood lipid profile,serum thyroid-stimulating hormone (TSH),free thyroxine ( FT4 ),and free triiodothyronine (FT3 ) were measured in all subjects. Metabolic syndrome was diagnosed according to the International Diabetes Federation(IDF) criteria.Results ( 1 ) The prevalences of metabolic syndrome and overall thyroid dysfunction were 10.2％ and 4.6％,respectively. ( 2 ) 18.1％ petrochemical employees had abdominal obesity with at least one component of metabolic syndrome.( 3 ) There was no significant difference in the prevalence of metabolic syndrome among the groups with lowered,normal,and elevated TSH. (4) Logistic regression analysis revealed that lowered high density lipoprotein cholesterol ( HDL-C ) was associated with lowered TSH ( OR =0.313,95％ CI 0.184-0.530 ),and raised triglyceride was associated with elevated TSH ( OR =0.767,95％ CI 0.595-0.991 ). ( 5 ) There were significant associations between serum TSH levels and lipid parameters such as total cholesterol in males,triglyceride and low density lipoprotein cholesterol in females,and HDL-C in both genders.Conclusion The prevalence of thyroid dysfunction was not associated with central obesity,hypertension,and hyperglycemia.Lipid disorder was correlated with serum TSH levels.

Objective To compare the activation of microglia in vitro induced by oligomeric and fibrillar Aβ,and research the effects of Piper Kadsura Ohwi extracts on the microglial activation.Methods Microglia were divided randomly into 4 test groups,intervened by fibrillar Aβ25-35,fibrillar Aβ25-35 + Piper Kadsura Ohwi extracts,oligomeric Aβ25-35 and oligomeric Aβ25-35 + Piper Kadsura Ohwi extracts respectively.Also a blank contrast group was set without any intervention.48 hours later,activation of microglia was tested by immunocytochemistry,using the CD68 molecule as a specific marker of microglial activation and the incidences of active microglia in different groups were compared.Results Each of the 4 test groups had a higher positive incidence of CD68 expression than that of the blank contrast (5.1％ ) (P ＜ 0.05 ) ; positive incidence of fibrillar Aβ + Piper Kadsura Ohwi extracts group (52.1％) was lower than that of the fibrillar Aβ group (60.8％) (P＜0.05) ; positive incidence of oligomeric Aβ + Piper Kadsura Ohwi extracts group (67.0％) was not significantly different with that of the oligomeric Aβ group (71.2％),P=0.101.Conclusion Both fibrillar and oligomeric Aβ has the ability to activate the silent microglia.Piper Kadsura Ohwi extracts could inhibit the activation of microglia induced by fibrillar Aβ25-35,but didn't show significant effects on the activation induced by oligomeric Aβ25-35.

BACKGROUND: Learning and memory disorder exist in diabetic rats,which can be improved by APP 17-mer peptide. However, it is unclear whether learning and memory disorder in diabetes mellitus is caused by influencing neuronal mitochondrial transmembrane potentials and apoptosis in hippocampus or not and what is the related action mechanism of APP17-mer peptide.OBJECTIVE: To observe the effects of APP17-mer peptide on neuronal mitochondrial transmembrane potentials (△ψm) and apoptosis in hippocampal area of diabetic rats.DESIGN: A completely randomized, grouping and controlled trial.SETTING: Beijing Research Laboratory for Brain Aging, Beijing Xuanwu Hospital, Capital University of Medical Sciences; the Department of Endocrine, the First Central Hospital of Baoding.MATERIALS: The data measurement of the experiment was carried out in the Instrument Testing Center, the General Hospital of Chinese PLA between May 2002 and August 2002. The modeling and intervention of the experiment was carried out in the Animal Laboratory of Xuanwu Hospital, Capital University of Medical Sciences. Eighteen male Wistar rats were enrolled and randomized into control group, model group and APP17-mer peptide group with 6 rats in each group.METHODS: ① Diabetic models in the model and APP17-mer peptide groups were established by intraperitoneal injection of 60 mg/kg streptozotocin (pH=4.4) in fasted rats(fasting for 12 hours). Three days later, modeling was successful if blood sugar level in caudal vein was more than 15 mmol/L. Rats in the control group were not subjected to modeling.Then, the rats in the APP17-mer peptide group were subjected to the subcutaneous injection of APP17-mer peptide (3.4 μg for each rat once) three times a week and totally for ten weeks, whereas rats in the other groups were given saline of the same volume. ② After ten weeks, rats were anesthetized and decapitated to take out brain tissues, and then hippocampal tissues were isolated in ice bath for preparation of single cell suspension.JC-1 labeled mitochondrial transmembrane potentials and cell apoptosis in hippocampal area were measured by means of flow cytometry. ③ One-way analysis of variance was adopted in the comparison among groups.RESULTS: Eighteen rats were involved in the results analysis. ①Neuronal mitochondrial transmembrane potential was lower in the model group as compared with the control group [(551.91±53.36) vs (809.88±82.41) △ψm,P＜0.01] while it was higher in the APP17-mer peptide group as compared with the model group [(705.99±89.92) vs (551.91±53.36) △ψm, P ＜ 0.05].There was no difference between the APP17-mer peptide group and control group (P=0.146). ②) Apoptotic percentage of single cell in hippocampus was significantly higher in the model group than in the control and APP17-mer peptide groups [(5.32±1.37)%, (1.03±0.55)%, (2.80±0.92)%, P＜0.01, 0.05].CONCLUSION: Neuronal mitochondrial transmembrane potential and cell apoptosis in hippocampus may be involved in the occurrence and development of diabetes mellitus, and APP17-mer peptide plays an improved role in the process.

Through the excellent experiment of cardiovascular system in pathology, the prac-tice of the teaching reform was carried out such as combining flow model with real specimens, digital sections with light microscope slides, inserting the use of special staining experiments in combination with digital medical image analysis and the simulation of cardiovascular clinical pathological case dis-cussions. Linking theory with experiment teaching and experiment teaching with clinical practice was focused on, which not only stimulated students' interest in learning and their exploring thinking and hands-on ability, but also promoted them to obtain good learning effect, thus improving the teaching quality.

Objective To investigate the association of ERCC1 and BRCA1 gene expression with clinical features and sensitivity to platinum-containing chemotherapy in patients with ovarian epithelial carcinoma. Methods Primary ovarian epithelial carcinoma tissues were harvested from 48 patients receiving staging surgery or cytoreductive surgery. Expression of ERCC1 and BRCA1 in the tumor samples was detected by immunohistochemistry. Results ERCC1 expression was correlated with clinical stage(P﹤0. 05)but not with age,pathological type or degree of differentiation(P﹥0. 05). BRCA1 expression was not correlated with any of the clinicopathological features(P﹥0. 05);ERCC1 expression was significantly higher in drug-resistant tissues than in drug-sensitive samples(P﹤0. 05);The expression of ERCC1 and BRCA1 was positive in 89. 58%and 25. 00%of the samples,respectively. Conclusion ERCC1 gene expression is correlated with clinical stage but not with age,pathological type or degree of differentiation. BRCA1 gene expression is not correlated with clinicopathological features. ERCC1 has high positive expression in epithelial ovarian cancer and is correlated with sensitivity of platinum-containing adjuvant chemotherapy.

Objective To investigate the characteristics of cognitive impairment in patients with type 2 diabetes mellitus (T2DM),and to analyze the correlation of T2DM with its risk factors and serum insulin like growth factor-1 (IGF-1) levels Methods A total of 78 hospitalized patients with T2DM at our hospital from November 2011 to March 2012 were divided into the cognitive impairment group (n=39) and the non-cognitive impairment group (n=39) according to Montreal Cognitive Assessment (MoCA) scores,and general clinical data were collected.Levels of blood lipids,glycosylated hemoglobin (HbAlc),fasting blood glucose (FBG),fasting blood insulin (FBI) and other biochemical indicators were detected,insulin resistance index (HOMA-IR) scores were calculated,and serum IGF-1 levels were determined by the enzyme-linked immunosorbent assay (ELISA).Results The education levle was (8.94±4.13) years for the cognitive impairment group and (12.65[2.50) years for the non-cognitive impairment group,and there was a statistically significant difference between the two groups (P=0.004).HbAlc levels were (9.69 ± 1.25) and (7.96 ± 1.31) for the cognitive impairment group and the non-cognitive impairment group,respectively,and were statistically difference between the two groups (P =0.001).Serum IGF-1 levels were (122.60±11.56) mmol/L and (139.32±9.57) mmol/L in the cognitive impairment group and the non-cognitive impairment group,respectively,and had a statistically significant difference between the two groups (P =0.037).Additionally,compared with the non-cognitive impairment group,scores on visuospatial ability,naming,language,abstraction,delayed recall and orientation were lower in the cognitive impairment group (P＜[0.05 or 0.01).Moreover,MoCA scores were negatively correlated with TC,LDL-C,TG,HbAlc,FBI levels and HOMA IR (r=0.498,-0.411,0.414,-0.452,-0.449,-0.539,respectively,P＜0.05 for all),and positively correlated with education lcvcl and IGF 1 level (r=0.579 and 0.491,respectively,P＜0.05 for both) Conclusions Cognitive impairment caused by T2DM is prominent in visuospatial ability,language,memory and executive functions,and is closely related to poor education,poor glycemic control,dyslipidemia and insulin resistance.Furthermore,decreased serum IGF-1 levels might be a risk factor for diabetic cognitive impairment.