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.

From both doctors and patients′different perspectives , this paper analyses the causes of conflict of doctor-patient communication , and from the subjective and the objective , the history and reality , individual and social aspects of light on the restricting factors for good doctor -patient communication , and puts forward strengthe-ning the consciousness of active , rule execution , achieving full coverage , explore ways to standard mode , rich di-verse ways and other countermeasures .

AIM To examine the effects of the APP17-mer peptide against A? 25-35 -induced apoptosis and gain some insight into the neuroprotective mechanism of the APP17-mer peptide. METHODS Protective effects of APP17-mer peptide against A? 25-35 -induced apoptosis in SH-SY5Y cell was proved by cell morphology, LM-PCR DNA ladder assay and FCM assay. The antiapoptotic mechanism of APP17-mer peptide was investigated using the MTT assay to measure mitochondrial energy redox state, using the fluorescent probe DCF-DA?Rhodamine 123 to measure relative levels of cellular peroxides and mitochondrial membrane potential and using Western blot for AIF and NF-?B to detect the expression of AIF and NF-?B. RESULTS Damage of cell morphology was ameliorated by pretreating with APP17-mer peptide. The apoptotic rate of the SH-SY5Y cells exposed to A? 25-35 in the presence of APP17-mer peptide decreased from 63.75% to 28.25%. Exposure of SH-SY5Y to A? 25-35 for 48 h resulted in an increase in DCF-DA fluorescence,a decrease in Rhodamine 123 fluorescence and MTT reduction, the results were weakened by pre-incubating with APP17-mer peptide for 30 minutes. Treatment of cells with APP17-mer peptide resulted in a significant attenuation in the expression of AIF and a strong increase in the expression of NF-?B. CONCLUSION APP17-mer is protective against cell apoptosis induced by A? 25-35 by provoking and sustaining upregulation of a key antiapoptotic transcription factor NF-?B, by suppressing oxyradical production and by preserving mitochondrial function and inhibiting the release of apoptotic protein from mitochondria.

AIM: To observe the expression of apoptosis-related proteins in hippocampal neurons of (ovariectomized) (OVX) rats and explore the neuroprotective mechanism of the App17-mer peptide. METHODS: Female Wistar rats were randomly divided into three groups. Bilaterally ovariectomized rats with injection of App 17P peptide (3.5 ?g in 0.1 mL/per rat, three times a week) formed the experimental group (17P+ OVX group). Anti-AIF, Bcl-2 and Bax antibodies were applied in the immunohistochemistry experiment. TUNEL was employed to detect apoptosis. RESULTS: The number of apoptotic neurons was clearly higher in hippocampal and cortex in OVX group than that in OVX+17P group. Immunohistochemistry demonstrated the increased expression of AIF, Bax in hippocampal neurons of OVX group. OVX group showed a significantly reduced expression of Bcl-2 in hippocampal neurons. Hippocampal tissue from OVX group showed the increased expression of AIF, Bax, and showed diminished expression of Bcl-2, treating with App17-mer peptide normalized the expression of these proteins. CONCLUSIONS: The expression of apoptosis-related proteins were abnormal in the OVX rats, App17-mer peptide normalized these changes. Estrogen deficiency induced neuronal apoptosis, and App17-mer peptide diminished apoptosis.

AIM:To observe the influence of beta-amyloid precursor protein (APP17) on the study ability, memory and the expression of neurotrophin-3 (NT-3), nerve growth factor(NGF)in the hippocampus neuron of the model mice. METHODS: Mice brain aging model were produced with D-galactose(D-gal), the model mice were given hypodermic injection of APP17 peptide. APP17 peptide is the 319-335 peptide sequence of beta-amyloid precursor protein. Eight weeks later, the animals were observed by water labyrinth test and immunohistochemistry assay. RESULT:(1) The whole time needed and total times of wrong response for the D-gal group mice to complete the whole course of the water labyrinth test is significantly higher than the normal control group. (2) The expression of NT-3, NGF in the hippocampus neurons of the mice in APP17 peptide group is significantly higher than that of the normal control group and D-gal mice group, P

BACKGROUND: Overexpression of phosphorylated Tau protein is a factor of dementia, and scholars abroad find that APP17 peptide may have effect on it.OBJECTIVE: To observe changes of phosphorylated Tau protein Ser202/Thr205 of mice with diabetes mellitus (DM) after injection of APP17 peptide.DESIGN: Randomized control study.SETTING: Department of Pathology, Capital University of Medical Sciences; Department of Brain Aging, Xuanwu Hospital, Capital University of Medical Sciences.MATERIALS: The experiment was carried out in the Pathological Department of Capital University of Medical Sciences and Brain Aging Department of Beijing Xuanwu Hospital. A total of 18 male Kunming mice of 8 weeks old and weighing 28-32 g were randomly divided into control group, DM group and APP17 peptide group with 6 in each group.METHODS: DM models were induced by streptozotocin (STZ) through selectively destroying β-islet cells; meanwhile, APP17 peptide was intraperitoneally injected into mice. Four weeks later, brain tissue underwentimmunohistochemical staining with AT-8 (Ser202/Thr205, a special monoclonal antibody).MAIN OUTCOME MEASURES: ① Morphological observation; ② AT-8 distribution; ③ quantitative analysis of immunohistochemical staining.RESULTS: Positive AT-8 cells in DM group were distributed in retrosplenial cortex, hippocampus, thalamus, hypothalamus, etc.; however, those incontrol and APP17 peptide groups were only distributed in retrosplenial cortex and hippocampus, and poorly stained.CONCLUSION: Positive AT-8 cells may be widely distributed in neurons of brains of DM mice; however, APP17 peptide may normalize the expression of positive AT-8 cells.

Objective To investigate the predictive value of early prognosis of the 40 Hz auditory steady-state response (40 Hz ASSR) in patients with coma following cardiopulmonary resuscitation (CPR). Methods Thirty patients with coma following CPR admitted in the Neurological Intensive Care Unit (NICU) were examined with the 40 Hz ASSR and shortlatency somatosensory evoked potential (SLSEP), and both were graded. Using transferred out of NICU as the short-term outcome end point, the patients with coma following CPR were divided into a survival group (n =21) and a death group (n =9; including brain death). The correlation between the 40 Hz ASSR and SLSEP grading and prognosis was analyzed. Results The grades of the 40 Hz ASSR (r = 0. 722, P = 0.000) or SLSEP (r = 0. 430, P = 0.018) was significantly correlated with the short-term prognosis. The sensitivity, specificity and accuracy of the 40 Hz ASSR for predicting the short-term prognosis were 77. 8%, 100% and 93.3%, respectively; and those of SLSEP were 88. 9%, 61. 9% and 70. 0%, respectively. Conclusions The 40 Hz ASSR has a certain prognostic value in patients with coma following CPR. The higher the grade of the 40 Hz ASSR is, the greater the likelihood of the recent death.

Objective To investigate the predictive value of prognosis of the 95% spectral edge frequency (SEF95) and total power (TP) in quantitative electroencephalography (qEEG) in patients with disturbance of consciousness. Methods The patients with disturbance of consciousness admitted in the neurointensive care unit (NICU) in Nanfang Hospital from January 2008 to June 2010 were included. Glasgow Coma Scale (GCS) scores were performed on admission and EEG monitoring was performed simultaneously. The patients were divided into either a survival group or a death group according to the survival status of the patients at the time of leaving NICU. The age, sex, hypertension, diabetes, GCS scores, SEF95, and TP were compared between the two groups. A multivariate logistic regression analysis was performed for the above factors. The prognostic indicators were analyzed with the receiver operating characteristic (ROC) curves and the of qEEG predictive ability of death in patients with disturbance of consciousness were determined. Results A total of 109 patients with supratentorial lesions were enrolled in the study, 79 of them were in the survival group and 30 of them were in the death group. The GCS scores (5 ±3vs. 9 ±3, P =0. 000) and SEF95 (7. 0 ±4.0 vs. 10. 0 ±4. 0, P = 0. 002) in the death group were significantly lower than those in the survival group. Multivariate logistic regression analysis showed that GCS scores (odds ratio 0. 100, 95% confidence interval 0. 029-0. 353) and SEF95 (odds ratio 0. 853, 95% confidence interval 0. 740-0. 983) were the independent predictors of recent prognosis. ROC curve analysis showed that the lower the GCS scores and SEF95 were, the greater the likelihood of death in patients. When SEF95 was ＜7. 75, the sensitivity to determine the death was 60. 0%, the specificity was 72. 2%, the positive predictive value was 82. 6%, and the negative predictive value was 45. 0%; when the GCS score was ＜8, the sensitivity to determine the death was 83. 3%, the specificity was 73. 4%,the positive predictive value was 82. 6%, and the negative predictive value was 45. 0%. Conclusions SEF95 helps determine the prognosis of patients with disturbance of consciousness, and it is expected to become an important means of bedside assessment of prognosis in patients with disturbance of consciousness in NICU.

at model is an ideal MS model for clinical MRI study.

Objective:To analyze a novel epitope of Homo sapiens synapse associated protein and synthesize polyclonal antibody.Methods:FRG4 full-length sequence was obtained by PCR from human fetal liver library;by bioinformatics to detect the second structure of amino acids encoded by FRG4 and its epitope and motifs;by solid-phase peptide synthesis method to synthesize FRG4 peptides,then peptides were immunized to rabbits;by immunohistory to detect the expression of FRG4 in HepG_2 cells.Results:Select 13-peptides PKLVKEEVFWRNY by bioinformatics to synthesize rabbit anti-human FRG4 polyclonal antibody.Antibody purity was 82.79% and antibody dilution was 1∶16 000 detected by ELISA.The antibody had a good reaction and speciality in Western blot,it was mainly expressed in cytoplasm of HepG_2 cells.Conclusion:A novel Homo sapiens synapse associated protein(FRG4) antibody was synthesized successfully.