The human immunodeficiency virus type 1(HIV-1)can interact with and exploit the host cellular machinery to replicate and propagate itself.Numerous studies have shown that the Mitogen-activated protein kinase(MAPK)signal pathway can positively regulate the replication of HIV-1,but exactly how each MAPK pathway affects HIV-1 infection and replication is not understood.In this study,we used the Extracellular signal-regulated kinase(ERK)pathway inhibitor,PD98059,the Jun N-terminal kinase(JNK)pathway inhibitor,SP600125,and the p38 pathway inhibitor,SB203580,to investigate the roles of these pathways in HIV-1replication.We found that application of PD98059 results in a strong VSV-G pseudotyped HIV-1NL4-3 luciferase reporter virus and HIV-1NL4-3 virus inhibition activity.In addition,SB203580 and SP600125 also elicited marked VSV-G pseudotyped HIV-1NL4-3 luciferase reporter virus inhibition activity but no HIV-1NL4-3 virus inhibition activity.We also found that SB203580 and SP600125 can enhance the HIV-1 inhibition activity of PD98059when cells were treated with all three MAPK pathway inhibitors in combination.Finally,we show that HIV-1virus inhibition activity of the MAPK pathway inhibitors was the result of the negative regulation of HIV-1 LTR promoter activity.

Bacteremia ; etiology ; Catheterization ; adverse effects ; Child ; Coagulase ; metabolism ; Cross Infection ; etiology ; Drug Resistance, Bacterial ; drug effects ; Endocarditis, Bacterial ; etiology ; Humans ; Methicillin ; pharmacology ; Quinolones ; pharmacology ; Staphylococcal Infections ; complications ; drug therapy ; microbiology ; Staphylococcus ; classification ; drug effects ; pathogenicity ; Urinary Tract Infections ; etiology ; Vancomycin ; pharmacology

In 2012,Beijing Children’s Hospital established the Beijing Children’s Hospital Group to explore the new model of public hospital reform.This study covered the target setting,management framework,network system,and sharing mechanism of the group,and discussed the merits and setbacks of such a practice,for insights of public hospital reform.

Adolescent ; Adult ; Dust ; Female ; Humans ; Male ; Mental Health ; statistics & numerical data ; Middle Aged ; Occupational Exposure ; Steel ; Surveys and Questionnaires

Background Congenital heart disease (CHD) is a diverse group of diseases determined by genetic and environmental factors.Considerable research has been done on genes associated with the development of the heart.Recently,focus is on the role of transcription factor NFATc1 in the development of proper valve and septa.As part of a larger study,high density single nucleotide polymorphism (SNP) scanning was used to explore the relationship between NFATc1 gene polymorphism and susceptibility to ventricular septal defect (VSD) in the Chinese Han population.Methods One hundred and ninety-two pediatric patients with congenital VSD and 192 matching healthy control subjects were studied.The haplotype reconstructions were calculated by PHASE2.0 software.Haploview software was used to perform linkage disequilibrium assessment and define haplotype blocks.The algorithm used for defining the blocks was the confidence interval method.Results The NFATc1 gene region can be divided into 11 haplotype blocks.Strong linkage disequilibrium existed within blocks 6,8,9,and 11.Three SNPs (rs7240256,rs11665469,and rs754505) within the NFATc1 gene had significant correlation with VSD by single marker association analysis.In addition,two haplotypes correlated with VSD.Conclusions NFATc1 is associated with the occurrence of VSD and it may be a predisposing gene to CHD in Han Chinese.This finding has set a direction for further genetic and functional studies.

Introduction: Tuberculosis (TB) in internal migrants is one of three threats for TB control in China. To address this threat, a project was launched in eight of the 19 districts of Shanghai in 2007 to provide transportation subsidies and living allowances for all migrant TB cases. This study aims to determine if this project contributed to improved TB control outcomes among migrants in urban Shanghai. Methods: This was a community intervention study. The data were derived from the TB Management Information System in three project districts and three non-project districts in Shanghai between 2006 and 2010. The impact of the project was estimated in a difference-in–difference (DID) analysis framework, and a multivariable binary logistic regression analysis. Results: A total of 1872 pulmonary TB (PTB) cases in internal migrants were included in the study. The treatment success rate (TSR) for migrant smear-positive cases in project districts increased from 59.9% in 2006 to 87.6% in 2010 (P < 0.001). The crude DID improvement of TSR was 18.9%. There was an increased probability of TSR in the project group before and after the project intervention period (coefficient = 1.156, odds ratio = 3.178, 95% confidence interval: 1.305–7.736, P = 0.011). Conclusion: The study showed the project could improve treatment success in migrant PTB cases. This was a short-term programme using special financial subsidies for all migrant PTB cases. It is recommended that project funds be continuously invested by governments with particular focus on the more vulnerable PTB cases among migrants.

A series of isoindoline derivatives were designed, synthesized, and evaluated for their double inhibitory activities. All of them were new compounds, and their structures were confirmed by 1H NMR and HR-MS. Preliminary in vitro pharmacological tests showed that all compounds exhibited 5-HT or NE reuptake inhibition activity. Among the tested compounds, compound I-3 exhibited potent inhibitory activity against 5-HT and NE reuptake in vitro, and exhibited potent antidepressant activity in vivo. These compounds designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.
Antidepressive Agents ; chemical synthesis ; chemistry ; Biological Transport ; Drug Design ; Isoindoles ; chemical synthesis ; chemistry ; Serotonin Uptake Inhibitors ; chemical synthesis ; chemistry ; Structure-Activity Relationship

OBJECTIVETo investigate the effect of Buyang Huanwu Decoction (BYHWD) and the different combinations of its ingredients on neurogenesis following ischemic stroke in rats.

METHODSThe model rats of ischemic stroke was established by blocking cerebral media artery with electrocoagulation through craniectomy, and electric stimulation, given from 24 h after blocking, 2 h daily for 15 successive days. They were divided into four groups, Group A treated with saline, Group B treated with BYHWD, Group C treated with BYHWD but earthworm subtracted, and Group D treated with Danggui Buxue Decoction (DGBXD). The expression of 5-bromodeoxyuridine (BrdU) in cerebral tissue was determined by immunohistochemical method.

RESULTSLarge amount of BrdU immunoreactive cells presented in the hippocampal region of rats in Group B and C, densely arranged, partial in cluster, with the figure significantly different to that in Group A (P < 0.01), and the amount in the ischemic side was significantly more than that in the opposite side (P < 0.05). While comparing between Group A and D, the amount of BrdU immunoreactive cells in the hippocampal region showed insignificant difference (P > 0.05).

CONCLUSIONBYHWD has a effect in promoting neurogenesis better than DGBXD.

Animals ; Bromodeoxyuridine ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hippocampus ; drug effects ; metabolism ; pathology ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; drug therapy ; Male ; Neurons ; drug effects ; metabolism ; pathology ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Phytotherapy ; Random Allocation ; Rats ; Rats, Wistar

Objective To study effects of early non-invasive ventilation (NIV) application in treating elderly patients with acute left ventricular failure induced respiratory failure. Method Totally 32 elderly patients with acute left ventrieular failure induced respiratory failure, admitted from August 1997 to February 2007, received NIV treatment, and were retrospectively studied. There were 22 male and 10 female, aged (81.5?8.6) yearsdd. The changes of rahs, respiration rate, heart rate, arterial blood gas, cardiac function before and after NIV application were compared. According to the application time of NIV, 32 patients were divided into two groups: group A (early NIV application group, n=17) and group B (non-early NIV application group, n= 15). The time to improve the symptoms, the application time of NIV, cure rates, tracheal intubation rates and mortality were compared between the two groups. Results Thirty of the 32 patients survived, cardiac function was improved from New York classⅣtoⅠ～Ⅱ, respiratory rate, heart rate and blood pressure significantly decreased, PaO_2 and SaO_2 significantly increased and PaCO_2 significantly decreased. The tracheal intubation was performed in 4 patients. The time needed to improve the symptoms and the application time of NIV were significantly different between group A and group B (P

A strain of yeast capable of hydrolyzing ethyl ester of racemic Ketoprofen with high enantioselectivity has been isolated from soil after two-step enrichment. The yeast was identified as Trichosporon brassicae. The process of growth and enzyme production was investigated. The catalytic performance of the resting cell of KET4 in kinetic resolution of Ketoprofen was also investigated. When the conversion of substrate reached 41% , enantiomeric excess of the (S) - Ketoprofen produced was 91 % , indicating a high enantiomeric ratio of 45.