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 study the influence of different bed rest time on orthostatic hypotension,and explore a feasible and appropriate bed rest time for elderly patients after hemodialysis.Methods 58 elderly patients with regular hemodialysis were selected from January 2011 to May 2012.By self-control,they were divided into three groups according to different bed rest time:T0 group who got up immediately after the hemodialysis,T10 group who got up after 10-minute bed rest,T20 group who got up after 20-minute bed rest.The incidence of orthostatic hypotension was observed and compared between three groups.Results Compared to T0 group,the incidence of orthostatic hypotension in T10 and T20 groups was significantly reduced.However,no difference was seen between T10 and T20 groups.The acceptability rate in T10 group was 67.24％,higher than 17.24％ of the T20 group.Conclusions Elderly hemodialysis patients should continue to lie down for at least 10 minutes after hemodialysis,and then slowly get up,this measure can reduce the occurrence of orthostatic hypotension.

Objective To study a simple and manual contrast board in Double Contrast Examination,so as to decrease labor intensity and the X-ray influence to the work staff.Methods The integrated design consisted of two parts:filled gas and oppressive container.The gas and Barium was injected into the large intestine by manual control and its volume may be adjusted casually according to the requirement.Results It is proved in clinical application that the design is reasonable,the structure is simple and the operation is convenient.Conclusion The device makes the relationship between medical staff and patients more harmonious.It worth popularizing.

Objective To study the effect of IZL-2003Ⅱ Immune Therapy System on lymphocyte immuno-function induced by chemotherapy in advanced non-small-cell lung cancer(NSCLC)patients.Methods 112 cases of advanced NSCLC patients were randomly divided into the two groups .The treatment group ( n=56 ) was given IZL-2003ⅡImmune Therapy System after chemotherapy for 6d as a couse and the control group ( n=56) was given chem-otherapy only.The peripheral blood routine and T lymphocyte subgroup (CD3+,CD4+, CD8+and CD4+/CD8+)activity of patients in both group were measured by flow cytometry 1 day before chemotherapy and the 8th day after chemothera-py.ResultsThere was difference between the treatment group and control group on the increasing rate of Leucocyte (P<0.05)the 8th day after treatment;After the 8th day,the expression levels of CD8+T cells was lower,but has no significant(P<0.05);The expression levels of CD3+,CD4+and the ratio of CD4+/CD8+were higher in the treatment group(P<0.05).The expression levels of CD3+T cells was lower,but has no significant(P<0.05);The expression levels of CD4+T cells and the ratio of CD 4+/CD8+were significantly lower after treatment in control group ( P<0.05);the expression levels of CD8+T cell was higher significantly in the control group (P<0.05).Conclusion IZL-2003ⅡImmune Therapy System can antagonize myelosuppression and elevated the immunologyical function of advanced NSCLC patients significantly .

ObjectiveTo evaluate the efficacy of stereotactic body radiotherapy combined with coinstan taneous gemcitabine,and gemcitabine alone for advanced pancreatic cancer.Methods56 advanced pancreatic cancer patients were assigned into observation group,which accepted stereotactic body radiotherapy combined with coinstantaneous gemcitabine 500 mg/m2,d1,d8.Other 50 patients were assigned into the control group which only accepted gemcitabine 1 000 mg/m2,d1,d8,d15.Stereotactic body radiotherapy was delivered with a total dose of 4 000-4 500 cGy in 10 fractions.ResultsCT examinations were carried out 2 months after treatment.The response rate of the observation group and control group was 82％ and 16％ respectively,and the pain relief rate was 67％ and 17％ respectively.The time to progression of the observation group was 14 months,and was better than that of the control group(7.5 months,x2 =7.31,P =0.032).The median survival time of the observation group and control group was 15.8 months and 13.2 months,and the difference had no statistical significance(x2 =3.28,P =0.082).ConcolusionStereotactic body radiotherapy combined with gemcitabine has a better overall response rate and a pain relief rate.It can prolong the time to progression,but can't improve the overall survival.

Objective Multiple carboxylase deficiency(MCD) is an autosomal recessively inherited defect of organic acid metabolism.The underlying mechanism is biotinidase(BT) or holocarboxylase synthetase(HLCS) deficiency.The authors reported 15 cases of MCD(clinical characteristics,diagnosis and treatment) and outcomes of long-term follow-up.Methods The clinical data of 15 patients with MCD admitted to Guangzhou Women and Children's Medical Center between Aug.2001 and Feb.2013 were analyzed.The diagnosis was confirmed by urinary organic acid analysis with gas chromatography/mass spectrometry (GC/MS),blood enzymatic determination and gene analysis.The patients consisted of 12 male and 3 female.The onset age ranged from newborn infants to 16 months.Results 1.Remarkable elevations of urinary lactate,3-oxy-butyric acid,3-OH-isovalerate,methylcitrate,3-methylcrontonylglycine,3-OH-propionate were detected in all of 15 cases.Fourteen cases with HLCS deficiency and 1 case with BT deficiency were confirmed by gene analysis.2.Most of patients with HLCS deficiency presented in the neonatal period or early infancy.The main clinical manifestations were skin rash (14 cases),tachypnea (9 cases),developmental retardation (8 cases),vomiting(5 cases),poor feeding (3 cases),developmental regradation (1 case),convulsion (1 case).Laboratory evaluation showed persistent metabolic acidosis and varied degree of ketosis,lactic acidosis,hyperuricacidemia,ammoniemia and hypoglycemia.Biotin was given to 13 patients in 10 mg/d and their metabolic disorders were corrected within 48 h,except one who gave up treatment and died.Treatment with Biotin in 5 mg/d provided clinical stability and normal neurodevelopmental outcome on follow-up for 3-11 (6.47 ± 2.70) years.3.One patient with BT deficiency presented with severe neurological symptoms(impaired consciousness,limbs trembling,tachypnea with irregular respiratory rhythm) at 16 months old.Demyelination of corpus callosum was evident on magnetic resonance imaging.Biotin treatment was given to him on the second of onset,and 1-year follow-up indicated significant improvement of his clinical symptoms,but the right limb weakness did not completely recover.Conclusions The main clinical features of HLCS deficiency include frequent skin rash,tachypnea,and metabolic disorders.BT deficiency may produce variable neurologic manifestations including demyelination of corpus callosum.Urinary organic acid analysis with GC/MS is critical to the early diagnosis of MCD.Prompt biotin treatment is recommended to correct metabolic derangements and continued therapy is essential to the improvement of long-term prognosis.Delayed commencement of therapy in BT deficiency can result in irreversible neurological damage.

Objective To understand the clinical and molecular characteristics of children with Prader-Willi syndrome (PWS) in South China.Methods Clinical and molecular data of children diagnosed as PWS by Methylation-specific PCR(MS-PCR) and/or Array Comparative Genomic Hybridization(Array-CGH)in Guangzhou Women and Children's Medical Center from November 2012 to November 2014 were analyzed.Results A total of 27 children diagnosed as PWS were included in this study,including 21 cases diagnosed by Array Comparative Genomic Hybridization (Array-CGH) and 13 cases diagnosed by methylation-specific PC R (MS-PCR).Within the 27 cases,13 cases were male(48.1％) and 14 cases were female(51.9％).The age on diagnosis was from 16 days to 16 years old.MS-PCR was performed in 13 cases,7 cases of them also performed Array-CGH,both of them showed a 174 bp fragment from the methylated allele and a 100 bp fragment from the unmethylated allele.Array-CGH analysis was performed in 21 cases,paternal deletion in 18 cases and mean interstitial deletions measure (5.48 ± 0.51) Mb in size,paternal duplication in 2 cases,loss of heterozygosity measure approximately 79.58 Mb in 1 case.Eighteen simple chromosome deletion cases were divided into 6 Del Ⅰ and 12 Del Ⅱ according to the location of Array-CGH and query the database to DECIPHER(Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources).The major phenotype included central hypotonia and feeding difficulty in all cases (100.0％),hypogonadism in 25 cases (92.6％),weak crying in 22 cases(81.5％),and hypopigmentation in 22 cases(81.5％).Fourteen cases beyond 1 year old had varied degrees of development disability and behavioral and psychiatric disturbance:speech articulation defects in 13 cases(92.9％),hyperphagia and weight gain too fast in 13 cases(92.9％) when they were between 1 to 6 years old[(2.80 ± 1.32) years old],and obesity in 12 cases (85.7％).Conclusions For PWS children in South China,there is no statistically significant difference in the clinical manifestation between Del Ⅰ and Del Ⅱ.PWS children in South China have typical clinical characteristics,which can be used as a further screening indication to implement molecular diagnostics.

Objective To investigate the clinical efficacy and adverse events of methimazole ( MMI ) treatment for children with hyperthyroidism, and to identify the predictors of remission and relapse. Methods A total of379children(260girlsand119boys)diagnosedwithhyperthyroidismandtreatedbyMMIinGuangzhouWomenand Children's Medical Center from March, 2004 to July, 2014 were retrospectively analyzed. The average age at diagnosiswas(9.3±2.3)years(range2.0~15.9years). Results AftertreatmentwithMMIfor3and6months, the thyroid functions of 96. 3%(365/379) and 98. 9%(375/379) patients returned to normal, respectively. By the end of this study, 256(67. 5%) patients continued to use MMI treatment and 44 patients(11. 6%) dropped out. 79 patients(20. 8%) achieved remission, 35 patients (44. 3%) of whom experienced a later relapse. Children who achieved constant remission had significantly lower FT3 and FT4 levels at diagnosis compared with the relapsed children(P<0. 05 or P<0. 01). It was more likely to remain long-term remission for children turned to be euthyroid within 3 months after initiating MMI treatment(P<0. 05). The relieved patients with family history of thyroid diseases weremorelikelytoberelapsed(P<0.05). Therewerenosignificantdifferencesinage,gender,exophthalmos, initial goiter size, thyroid peroxidase autoantibody, and thyroglobulin antibody levels between the relieved and relapsed patients. The overall incidence of adverse events associated with MMI was 27. 7%, mainly elevated alanine aminotransferase, bilirubin, and neutropenia. Most(66. 7%) of adverse events occurred within the first three months of MMI treatment. Conclusion MMI has a good effect on pediatric hyperthyroidism, with low remission and high relapse rate. The low thyroid hormone concentrations at diagnosis and normalization of thyroid function within three months seem to be useful predictors of remission. Vigilance is needed concerning MMI-associated adverse events throughout the MMI treatment period, especially during the first trimester of MMI initiation.

BACKGROUND:Until now, it is stil unclear whether the stem cel transplantation triggersadverse effects on the myocardial electrical activity, resulting in the emergence of arrhythmia.
OBJECTIVE:To explore the effect of intracoronary transplantation of umbilical cord blood stem cels on arrhythmia score and incidence of ventricular arrhythmia.
METHODS:According to therapeutic strategies, 73patients with coronary heart disease were assigned to receive drug therapy in control group (n=38) and umbilical cord blood stem cel transplantation in observation group (n=35). Arrhythmia score, incidence of ventricular arrhythmia and adverse reactions were recorded and analyzed before and 1, 4, 8 weeks after transplantation.
RESULTS AND CONCLUSION:After treatment, arrhythmia scores were significantly reduced in the two groups, especialy in the observation group, to exhibit a continuous decline trend (P< 0.05). Compared with the control group, the incidence of ventricular arrhythmia was significantly lower in the observation (P< 0.05). However, there were no significant changes in the blood pressure, heart rate and blood oxygen saturation before and after transplantation, and no acute heart failure and death occurred in thetwo groups. These results suggest that the intracoronary transplantation of umbilical cord blood stem cels exhibits superiorities in the treatment of coronary artery disease, significantly reducing the arrhythmia score, reducing the incidence of ventricular arrhythmia, and resulting in less adverse reactions.

ObjectiveTo explore the clinical significance of heart-type fatty acid-binding protein (H-FABP) in acute myocardial infarction(AMI) patients. MethodsThe level of H-FABP was assayed within 30 min, 1 h, 2 h, 4 h,6 h and 12 h by enzyme linked immunosorbent assay (ELISA) in 46 AMI patients, and cardiac troponin Ⅰ(cTnⅠ) and creatinine kinase(CK-MB) also was assayed by routine method.The diagnostic accuracy was compared among different methods. ResultsThe diagnostic accuracy of H-FABP[95.7％ (44/46)] was significantly higher than cTnⅠ[65.2％(30/46)] and CK-MB[41.3％ (19/46)](P ＜0.05). The levels of H-FABP, cTnⅠ and CK-MB significantly increased after AMI onset 4,6,12 hrespectively. ConclusionThe diagnosticaccuracy of H-FABP is higher and can be used as a parameter for the early diagnosis of AMI.