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1.  Interaction of type 2 diabetes mellitus with Chromosome 9p21 rs10757274 polymorphism on the risk of myocardial infarction: a case–control study in Chinese population 
Myocardial infarction (MI) is a serious complication of Coronary Artery Disease (CAD). Previous studies have identified genetic variants on chromosome 9p21 and 6p24 that are associated with CAD, but further studies need to be conducted to investigate whether these genetic variants are associated with the pathogenesis of MI. We therefore performed this study to assess the association between the risk of MI and SNP rs10757274 on chromosome 9p21 and SNP rs6903956 on chromosome 6p24, and to explore the gene-environment interactions in a Chinese population.
A hospital-based case–control study, consisting of 502 MI patients and 308 controls, was conducted in a Chinese population. Demographic, behavioral information and clinical characteristics were collected, and genotyping of the two SNPs was performed using single base primer extension genotyping technology. The unconditional logistic regression (ULR) method was adopted to assess the association of the two SNPs with MI risk. Both generalized multifactor dimensionality reduction (GMDR) and ULR methods were applied to explore the effect of gene-environment interactions on the risk of MI.
After adjusting for covariates, it was observed that SNP rs10757274 on chromosome 9p21 was significantly associated with MI. Compared with subjects carrying the AA genotype, subjects carrying the GA or GG genotypes had a higher MI risk (ORa = 1.52, 95% CI:1.06–2.19, pa = 0.0227; ORa = 2.40, 95% CI:1.51–3.81, pa = 0.0002, respectively). Furthermore, a two-factor gene-environment interaction model of CDKN2A/B (rs10757274) and type 2 diabetes mellitus (T2DM) was identified to be the best model by GMDR (p = 0.0107), with a maximum prediction accuracy of 59.18%, and a maximum Cross-validation Consistency of 10/10. By using the ULR method, additive interaction analysis found that the combined effect resulted in T2DM-positive subjects with genotype GG/GA having an MI risk 4.38 times that of T2DM-negative subjects with genotype AA (ORadd = 4.38, 95% CI:2.56–7.47, padd < 0.0001).
These results show that gene polymorphism of CDKN2A/B (rs10757274) is associated with MI risk in a Chinese population. Furthermore, T2DM is likely to have an interaction with CDKN2A/B (rs10757274) that contributes to the risk of MI.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2261-14-170) contains supplementary material, which is available to authorized users.
PMCID: PMC4255939  PMID: 25430018
2.  Age Dependent Changes in Cartilage Matrix, Subchondral Bone Mass, and Estradiol Levels in Blood Serum, in Naturally Occurring Osteoarthritis in Guinea Pigs 
The Dunkin Hartley (DH) guinea pig is a widely used naturally occurring osteoarthritis model. The aim of this study was to provide detailed evidence of age-related changes in articular cartilage, subchondral bone mineral density, and estradiol levels. We studied the female Dunkin Hartley guinea pigs at 1, 3, 6, 9, and 12 months of age (eight animals in each group). Histological analysis were used to identify degenerative cartilage and electron microscopy was performed to further observe the ultrastructure. Estradiol expression levels in serum were assessed, and matrix metalloproteinase 3 and glycosaminoglycan expression in cartilage was performed by immunohistochemistry. Bone mineral density of the tibia subchondral bone was measured using dual X-ray absorptiometry. Histological analysis showed that the degeneration of articular cartilage grew more severe with increasing age starting at 3 months, coupled with the loss of normal cells and an increase in degenerated cells. Serum estradiol levels increased with age from 1 to 6 months and thereafter remained stable from 6 to 12 months. Matrix metalloproteinase 3 expression in cartilage increased with age, but no significant difference was found in glycosaminoglycan expression between 1- and 3-month old animals. The bone mineral density of the tibia subchondral bone increased with age before reaching a stable value at 9 months of age. Age-related articular cartilage degeneration occurred in Dunkin Hartley guinea pigs beginning at 3 months of age, while no directly positive or negative correlation between osteoarthritis progression and estradiol serum level or subchondral bone mineral density was discovered.
PMCID: PMC4159812  PMID: 25100170
osteoarthritis; cartilage; subchondral bone; estradiol; electron microscope
3.  A Comparison of Job Satisfaction of Community Health Workers before and after Local Comprehensive Medical Care Reform: A Typical Field Investigation in Central China 
PLoS ONE  2013;8(9):e73438.
The government of China promulgated new medical care reform policies in March 2009. After that, provincial-level governments launched new medical care reform which focusing on local comprehensive medical care reform (LCMR). Anhui Province is an example of an area affected by LCMR, in which the LCMR was started in October 2009 and implemented in June 2010. The objective of this study was to compare the job satisfaction (JS) of community health workers (CHWs) before and after the reform in Anhui Province.
A baseline survey was carried out among 813 community health workers (CHWs) of 57 community health centers (CHCs) (response rate: 94.1%) and an effect evaluation survey among 536 CHWs of 30 CHCs (response rate: 92.3%) in 2009 and 2012 respectively. A self-completion questionnaire was used to assess the JS of the CHWs (by the job satisfaction scale, JSS).
The average scores of total JS and satisfaction with pay, contingent rewards, operating procedures and communication in the effect evaluation survey were statistically significantly higher than those of the baseline survey (P<0.05). The average score of satisfaction with promotion (2.55±1.008) in the effect evaluation survey was statistically significantly lower than that in the baseline survey (2.71±0.730) (P=0.002). In both surveys, the average scores of satisfaction with pay, benefits and promotion were statistically significantly lower than the others (all P<0.05).
After two years’ implementation of the LCMR, CHWs’ total JS have a small improvement. However, CHWs have lower satisfaction in the dimensions of pay, promotion and benefits dimensions before and after the LCMR. Therefore, policy-makers should take corresponding measures to raise work reward of CHWs and pay more attention to CHWs’ professional development to further increase their JS.
PMCID: PMC3772794  PMID: 24058472
4.  Genome-Scale Screening of Drug-Target Associations Relevant to Ki Using a Chemogenomics Approach 
PLoS ONE  2013;8(4):e57680.
The identification of interactions between drugs and target proteins plays a key role in genomic drug discovery. In the present study, the quantitative binding affinities of drug-target pairs are differentiated as a measurement to define whether a drug interacts with a protein or not, and then a chemogenomics framework using an unbiased set of general integrated features and random forest (RF) is employed to construct a predictive model which can accurately classify drug-target pairs. The predictability of the model is further investigated and validated by several independent validation sets. The built model is used to predict drug-target associations, some of which were confirmed by comparing experimental data from public biological resources. A drug-target interaction network with high confidence drug-target pairs was also reconstructed. This network provides further insight for the action of drugs and targets. Finally, a web-based server called PreDPI-Ki was developed to predict drug-target interactions for drug discovery. In addition to providing a high-confidence list of drug-target associations for subsequent experimental investigation guidance, these results also contribute to the understanding of drug-target interactions. We can also see that quantitative information of drug-target associations could greatly promote the development of more accurate models. The PreDPI-Ki server is freely available via:
PMCID: PMC3618265  PMID: 23577055
5.  Atomic Force Microscopy Analysis of Progenitor Corneal Epithelial Cells Fractionated by a Rapid Centrifugation Isolation Technique 
PLoS ONE  2013;8(3):e59282.
To investigate the use of atomic force microscopy (AFM) to image the three groups of corneal epithelial cells fractionated by a novel rapid centrifugation isolation technique.
Epithelial cells harvested from primary cultures of rabbit limbal rings were centrifuged onto uncoated dishes, first at 1400 rpm and then at 1800 rpm. The adherent cells after centrifugation at 1400 rpm (ATC1), the adherent cells at 1800 rpm (ATC2) and the non-adherent cells at 1800 rpm (NAC) were investigated for BrdU retention and were subjected to contact mode AFM and Transmission Electron Microscopy (TEM).
Compared with unfractionated cells, the ATC1 group, accounting for about 10% of the whole population, was enriched in BrdU label-retaining cells. There were dramatic overall shape, surface membrane and intra-cellular ultrastructure differences noted among ATC1, ATC2 and NAC populations. The whole cell roughness measurements were 21.1±1.5 nm, 79.5±3.4 nm and 103±4.6 nm for the ATC1, ATC2 and NAC groups, respectively. The mero-nucleus roughness measurements were 34.2±1.7 nm, 13.0±0.8 nm and 8.5±0.5 nm in the ATC1, ATC2 and NAC populations, respectively.
AFM was found to be a good tool for distinguishing among the three groups of cells. BrdU label retention, the AFM parameters and TEM together suggest that the ATC1, ATC2 and NAC populations may be progenitor corneal epithelial cells, transit amplifying cells and terminal differentiation cells, respectively.
PMCID: PMC3608637  PMID: 23555648
6.  Methyl (R)-2-(2-chloro­phen­yl)-2-(3-nitro­phenyl­sulfon­yloxy)acetate 
The reaction between methyl (R)-2-(2-chloro­phen­yl)-2-hy­droxy­acetate and 3-nitro­benzene­sulfonyl chloride gave the title compound, C15H12ClNO7S, which is a promising inter­mediate for the synthesis of Clopidrogel, an anti­platelet drug used in the prevention of strokes and heart attacks. In the crystal, mol­ecules are linked through C—H⋯O interactions, and there is also a short Cl⋯O contact present [Cl⋯O = 3.018 (2) Å].
PMCID: PMC3379285  PMID: 22719483
7.  Genotypes and Characteristics of Clustering and Drug Susceptibility of Mycobacterium tuberculosis Isolates Collected in Heilongjiang Province, China▿ 
Journal of Clinical Microbiology  2011;49(4):1354-1362.
For the last decade China has occupied second place, after India, among the top five countries with high burdens of tuberculosis (TB). Heilongjiang Province is located in northeastern China. The prevalence of drug-resistant TB in Heilongjiang Province is higher than the average level in China. To determine the transmission characteristics of Mycobacterium tuberculosis strains isolated in this area and their genetic relationships, especially among the Beijing family strains, we investigated their genotypes. From May 2007 to October 2008, 200 M. tuberculosis isolates from patients presenting pulmonary TB were analyzed by molecular typing using PCR-based methods: spacer-oligonucleotide typing (spoligotyping), Beijing family-specific PCR (detection of the deletion of region of difference 105 [RD105]), and mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) analysis. Different combinations of MIRU-VNTR loci were evaluated to define the genotypes and clustering characteristics of the local strains. We found that Beijing family strains represented 89.5% of the isolates studied. However, the rates of multidrug-resistant (MDR) M. tuberculosis among Beijing and non-Beijing family strains were not statistically different. The 15-locus set is considered the optimal MIRU-VNTR locus combination for analyzing the M. tuberculosis strains epidemic in this area, while the 10-locus set is an ideal set for first-line molecular typing. We found that the clustering rate of all the M. tuberculosis isolates analyzed was 10.0% using the 15-locus set typing. We conclude that the Beijing family genotype is predominant and that highly epidemic TB and MDR TB are less likely associated with the active transmission of M. tuberculosis in the study area.
PMCID: PMC3122865  PMID: 21325562
8.  Effect of Vaccination on Bordetella pertussis Strains, China 
Emerging Infectious Diseases  2010;16(11):1695-1701.
Strains in China may differ from those in countries that have long histories of high vaccination coverage.
Whole-cell pertussis vaccine was introduced in China in the early 1960s. We used standard typing methods to compare 96 Bordetella pertussis isolates collected before and after introduction of vaccination, during 1953–2005. The following vaccine-type alleles of the pertussis toxin (ptx) gene were characteristic for all prevaccination strains: ptxA2, ptxA3, and ptxA4. The shift to ptxA1 occurred since 1963. All isolates collected since 1983 contained ptxA1. Pertactin (prn) allele 1, prn1, was predominant, although prn2 and prn3 have been detected since 2000. Serotypes fimbriae (Fim) 2 and Fim2,3 were found in all isolates collected before 1986. During 1997–2005, Fim3 became prevalent. Although changes in electrophoresis profiles over time were observed, the predominant profiles during 1997–2005 resembled those during the prevaccine era and those found in Europe before the 1990s. B. pertussis strains in China may differ from those in countries that have a long history of high vaccine coverage.
PMCID: PMC3294513  PMID: 21029526
China; Bordetella pertussis; whooping cough; pertussis; incidence; vaccination; genotyping; PFGE; bacteria; research

Results 1-9 (9)