Objective To study the preventive effects of nerve growth factor(NGF)on basal forebrain neurons to explore the therapy for Alzheimer disease.Methods Six aged Rhesus monkeys were divided into two groups(group A and group B)randomly.NGF transport from cerebral cortex were blocked in all the monkeys.Group A received homopleural intraventricular implants of polymer-encapsulated cells that were modified to secrete NGF.Group B received identical implants of empty capsules.Results Three to four weeks after operation,the monkeys in the group B displayed extensive reductions in the number of p75NGFr receptor immunoreactive neurons(53%)and choline acetyltransferase immunoreactive neurons (57%to 75%)within the septum.The monkeys in group A appeared to be normal size telative to the atrophic appearance of cholinergic neurons and p75NGFr receptor imrnunoreactive neurons in the monkeys receiving control implants.Conclusion NGF could prevent basal forebrain neuron degeneration in aged monkeys.

Ninety nine patients with trigeminal neuralgia (TN,n =59) or hemifacial spasm (HFS,n =40) underwent microvascular decompression (MVD) treatment in our hospital from January 2012 to December 2015,and were followed up for more than 1 year.Total 94 patients (94.9％) were cured after the surgery,including 55 TN cases (93.2％) and 39 HFS cases (97.5％).The 1-year follow up showed that total 98 patients (99.0％) were cured,including 58 TN cases (98.3％) and 40 HFS cases (100.0％).Among the HFS cases,1 patient got gentle spasm,1 patient got hearing deficit,1 patient got light facial palsy after the operation,and all recovered completely during the follow-up.Among the TN cases,4 patients got pain attack infrequently after the operation,3 of them recovered during the follow-up,and the symptoms were satisfactorily controlled by taking carbamazepine in rest 1 case.No cases had cerebrospinal fluid leakage or intracerebral infection.The results indicate that MVD is an effective treatment of HFS and TN with less surgical injury or complications.

The beta-secretase is one of prospective targets against Alzheimer's disease (AD). A three-dimensional quan titative structure-activity relationship (3D-QSAR) model of Hydroethylamines (HEAs) as beta-secretase inhibitors was established using Topomer CoMFA. The multiple correlation coefficient of fitting, cross validation and external validation were r2 = 0.928, q(loo)2 = 0.605 and r(pred)2 = 0.626, respectively. The 3D-QSAR model was used to search R groups from ZINC database as the source of structural fragments. As a result, a series of R groups with relatively high activity contribution was obtained to design a total of 15 new compounds, with higher activity than that of the template molecule. The molecular docking was employed to study the interaction mode between the new compounds as ligands and beta-secretase as receptors, displaying that hydrogen bond and hydrophobicity played important roles in the binding affinity between the new compounds and beta-secretase. The results showed that Topomer CoMFA and To pomer Search could be effectively used to screen and design new molecules of HEAs as beta-secretase inhibitors, and the designed compounds could provide new candidates for drug design targeting AD.
Amyloid Precursor Protein Secretases ; antagonists & inhibitors ; Drug Design ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Molecular Docking Simulation ; Quantitative Structure-Activity Relationship

Objective To investigate the relationship between expression of mucin1 (MUC1) and tumor invasion in pituitary adenomas.Methods The expression of MUC1 was detected by immunohistochemical analysis in 26 tissues of invasive pituitary adenoma and 29 of non-invasive pituitary adenoma.Results The expression of MUC1 in invasive pituitary adenomas tissues was 76.92 ％ (20/26).It was weakly positive or negative in non-invasive pituitary adenoma tissues,and the positive rate was 27.57 ％ (8/29).There was significant difference in two groups (x2 =13.35,P ＜ 0.01).The expression of MUC1 in functional pituitary adenomas was 44.82 ％ (13/35) and was 75.00 ％ (15/20) in non-functional pituitary adenomas.There were no significant difference in two groups (x2 =6.13,P ＞ 0.01).Conclusions Over-expression and aberrant localization of MUC1 in invasive pituitary adenoma may act as distinguishing diagnostic markers of invasive pituitary adenoma.MUC1 might be as the target of immunotherapy of invasive pituitary adenoma.

ObjectiveTo study the methods of how to protect facial nerve function following complete resection of acoustic neurinomas and the value of the techniques of F wave assisted electrophysiological monitoring intraoperatively.Methods Retrospectivelysummarizing theresultsof combining three electrophysiological monitoring techniques such as nasal muscle F wave recording,online EMG and triggered EMG to monitor 46 cases of microoperations for acoustic neurinomas intraoperatively during the period of Feb.2004 to Dec. 2008. Correlating every intraoperative monitoring index with their follow-up results of facial nerve function 1 day and 6 months after their operations.The tendency of the two continuous monitoring techniques between nasal F wave recording and online EMG of facial muscles has also been studied in this paper. Results Among 46 cases of acoustic neurinomas, 45(97.83 %) tumors have been totally resected, and 1 (2.17 %) tumor subtotally resected,lcase (2.17 %)died after operation,and 2ases occurred the leakage of cerebrospinal fluid(CSF) which have been cured through conservative treatment. The whole anatomic protection rate of facial nerve is 97.83 %,and their functional protection rates 6 months after operation are:HB Ⅰ - Ⅱ,75.56 %;Ⅲ-Ⅳ,22.22 % and Ⅴ-Ⅵ,2.22 %.The completely accordant rate between the intraoperative findings of nasal F wave recording and online EMG is 52.17 %, partially accordant rate is 45.65 %, and totally opposite rate is 2.17 % (x2 趋势= 6.113, P ＜0.05). The intraoperative monitoring indexes in nasal muscle F wave recording are correlated well with the facial nerve function in the 6th month' s follow-up (κ=0.429, P ＜0.001).In triggered EMG monitoring after tumors being resected,the stimulus threshold ratio and maximum amplitude ratio of facial nerve between leaving brain stem part and inner acoustic porus part are also correlated well with the facial nerve function 6 months after operation(κ=0.576, P ＜0.001; κ=0.595, P ＜0.001). ConclusionNasal muscle F wa recording cooperated well with online EMG and triggered EMG intraoperatively and correlates well with the postoperative facial nerve function, so they should be routinely applied together intraoperatively.

Objective To investigate the expression of FRAT1 and β-catenin in human brain glioma,analyze the correlation between the expression and clinical pathological grades and the correlation of the two genes.Methods FRAT1 and β-catenin were detected by immunohistochemistry in 84 human brain glioma tissues and 6 human normal brain tissues.Results 66.7 ％ (56/84) and 77.4 ％ (65/84) of human brain glioma tissues expressed FRAT1 and β-catenin protein,whereas no FRAT1 and β-catenin protein expression was detected in human normal brain tissues.The expression levels of FRAT1 and ββ-catenin increased markedly with the ascending of pathologic grade of tumor specimens (r =0.55,P ＜ 0.01,r =0.70,P ＜ 0.01),there was a positive correlation between FRAT1 and β-catenin (r =0.77,P ＜ 0.01).Conclusion FRAT1 and β-catenin over-expression maybe closely related with occurrence and development of human brain gliomas.The results provide important supplements for the research of Wnt/β-catenin pathway.Meanwhile,FRAT1 may act as a valuable biomarker for molecular diagnosis of glioma and a potential target for gene therapy of glioma.

Objective To evaluate clinical performance on dry chemistry method of Vitros 350 for the determination of serum bilirubin in order to ensure the quality of examination.Methods Evaluation protocols were employed to evaluate the precision,the trueness and the linearity of total bilirubin(TBIL),unconjugated bilirubin (Bu)and conjugated bilirubin (Bc)by dry chemistry method,to verify the reference ranges of TBIL,Bu and Bc simultaneously.Results The precision and trueness of TBIL,Bu and Bc were within the allowable ranges of Clinical and Laboratory Ltandards Institute (CLSI).The linear range of TBIL,Bu and Bc in our laboratory were 6.57-428.83 μmol/L,4.5-320.1 μmol/L and 4.5-364.9 μmol/L respectively.Conclusion Both technical per-formance evaluation and diagnostic performance verification of bilirubin by dry chemical detection system could meet the needs of the clinic.

Objective To explore the clinicopathological characteristics of hereditary ovarian cancer syndrome(HOCS). Methods From Jan. 2000 to Jan. 2007, among 580 cases of primary ovarian cancer, 42 cases(herediatary group),who had a positive family history of ovarian cancer and met the diagnostic criteria of HOCS, were analyzed retrospectively. One hundred cases without a family history of ovarian cancer were enrolled randomizely as control group (sporadic group). Results The incidence of HOCS was 7.2% (42/580). Forty-two cases associated tumors affected at least 2 successive generations in 31 families and affected 1 generation in 8 families. Eighty-seven percent (27/31)was from maternal lineage, while 13% (4/31)from paternal lineage. Earlier age of onset was significantly difference between two groups[(49±10) years vs. (55±10) years, P<0.05]. There were 90% belong to serous adenocarcinoma in the herediatary group, while 84% in the sporadic group. There was statistical difference in the proportion of mucinous adenocarcinoma (0 vs. 11%, P<0.05). The most common clinical manifestations were abdominal distention and anorexia (64% vs. 70%, P>0.05), International Federational of Gynecology Obstetrics(FIGO)stage Ⅲ (62% vs. 63%, P>0.05) between two groups. Fourteen cases (33%,14/42) were previously untreated in the herediatary group, while 40 cases (40%, 40/100) in the sporadic group. There were 15 cases (36%, 15/42) underwent secondary surgery and 15 cases (36%, 15/42) underwent third surgery or more in berediatary group, while 50 cases (50%, 50/100) and 27 cases(27%, 27/100) in the sporadic group. The mean number of ehemotberapy cycles received in two groups was 13.3 and 11.8 (P>0.05). The 3-year and 5-year survival rate in herediatary group were 73.6% and 54.9% respectively, compared with 47.4% and 21.2% (P<0.05) in sporadic group. Conclusion Hereditary ovarian cancer mostly from maternal lineage are featuring in early age of onset, serous adenocarcinoma, advanced stage (stage Ⅲ), and better prognosis after the comprehensive treated by cytoreductive surgery plus with chemotherapy.

Objective To discuss the association of allele polymorphisms SNP-rs1799724(C>T)in the TNF-αand SNP-rs11559013(G>A)in the ALCAM with HCV chronic infection in Han population in Yunnan province. Methods 434 HCV chronic infectious patients and 444 healthy individuals of Han Chinese population in Yunnan province were recruited. Two single nucleotide polymorphisms(SNPs)in the SNP-rs1799724(C>T) of TNF-αgene and SNP-rs11559013(G>A)of ALCAM gene were determined by real-time TaqMan polymerase chain reaction. We evaluated the associations of the two SNPs with HCV chronic infection. Results The distributions of allele and genotype of SNP-rs1799724(C>T)in the TNF-αand SNP-rs11559013(G>A)in the ALCAM between hepatitis C virus(HCV)chronic infectious patients and the healthy controls were not statistically significant(P > 0.05). Conclusion SNP-rs1799724(C>T)in the TNF-αand SNP-rs11559013(G>A) in the ALCAM have no association with HCV chronic infection in the Han population in Yunnan province.

Objective: To probe the incidence and risk factors for thrombosis in Chinese immune thrombocytopenia through a retrospective analysis of the inpatients referred to the Blood Disease Hospital, CAMS & PUMC. Methods: A retrospective survey of 3 225 patients with ITP from October 2005 to December 2017 was performed, the clinical data of the patients with thrombosis were collected to analyze the causes, diagnosis, treatment and prognosis. Results: A total of 46 patients experienced a thrombotic event with a prevalence of 1.43%(46/3 225 cases) with the median age of thrombosis as 54 years (26-83) years, the prevalence of thrombosis was 3.37% (40/1 187 cases) in>40 years old, which was significantly higher than 0.58% (6/1 030 cases) in those under 40 years old, in adults (P=0.00). There were 20 males and 26 females, there was no statistical difference in the incidence of thrombosis between males and females[1.53% (20/1 309) vs 1.36% (26/1 916), P=0.187]; The prevalence of arterial thrombosis was 1.12% (36/3 225) higher than venous thrombosis[0.22% (7/3 225), P=0.00]when 82.61%(38/46 cases) of patients with PLT<100×10⁹/L. Post-splenectomy are risk factors for thrombosis in ITP patients, P values was 0.022, There was no statistical difference in the presence or absence of thrombotic events whether received glucocorticoid or TPO/TPO-Ra treatment, the P values were 0.075 and 0.531, respectively. Conclusions In Chinese population, ITP disease maybe with a higher risk of thrombosis, there was no positive correlation between thrombosis and platelet level; and had obvious age distribution characteristics. The history of tobacco, hypertension, diabetes and post-splenectomy are risk factors for thrombosis in ITP patients.