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1.  The Tripartite Virions of the Brome Mosaic Virus Have Distinct Physical Properties That Affect the Timing of the Infection Process 
Journal of Virology  2014;88(11):6483-6491.
The three subsets of virions that comprise the Brome mosaic virus (BMV) were previously thought to be indistinguishable. This work tested the hypothesis that distinct capsid-RNA interactions in the BMV virions allow different rates of viral RNA release. Several results support distinct interactions between the capsid and the BMV genomic RNAs. First, the deletion of the first eight residues of the BMV coat protein (CP) resulted in the RNA1-containing particles having altered morphologies, while those containing RNA2 were unaffected. Second, subsets of the BMV particles separated by density gradients into a pool enriched for RNA1 (B1) and for RNA2 and RNA3/4 (B2.3/4) were found to have different physiochemical properties. Compared to the B2.3/4 particles, the B1 particles were more sensitive to protease digestion and had greater resistivity to nanoindentation by atomic force microscopy and increased susceptibility to nuclease digestion. Mapping studies showed that portions of the arginine-rich N-terminal tail of the CP could interact with RNA1. Mutational analysis in the putative RNA1-contacting residues severely reduced encapsidation of BMV RNA1 without affecting the encapsidation of RNA2. Finally, during infection of plants, the more easily released RNA1 accumulated to higher levels early in the infection.
IMPORTANCE Viruses with genomes packaged in distinct virions could theoretically release the genomes at different times to regulate the timing of gene expression. Using an RNA virus composed of three particles, we demonstrated that the RNA in one of the virions is released more easily than the other two in vitro. The differential RNA release is due to distinct interactions between the viral capsid protein and the RNAs. The ease of RNA release is also correlated with the more rapid accumulation of that RNA in infected plants. Our study identified a novel role for capsid-RNA interactions in the regulation of a viral infection.
PMCID: PMC4093861  PMID: 24672042
2.  Fusion of mApple and Venus fluorescent proteins to the Sindbis virus E2 protein leads to different cell-binding properties 
Virus research  2013;177(2):138-146.
Fluorescent proteins (FPs) are widely used in real-time single virus particle studies to visualize, track and quantify the spatial and temporal parameters of viral pathways. However, potential functional differences between the wild type and the FP-tagged virus may specifically affect particular stages in the virus life-cycle. In this work, we genetically modified the E2 spike protein of Sindbis virus (SINV) with two FPs. We inserted mApple, a red FP, or Venus, a yellow FP, at the N-terminus of the E2 protein of SINV to make SINV-Apple and SINV-Venus. Our results indicate that SINV-Apple and SINV-Venus have similar levels of infectivity and are morphologically similar to SINV-wild-type by negative stain transmission electron microscop. Both mutants are highly fluorescent and have excellent single-particle tracking properties. However, despite these similarities, when measuring cell entry at the single-particle level, we found that SINV-Apple and SINV-Venus are different in their interaction with the cell surface and FPs are not always interchangeable. We went on to determine that the FP changes the net surface charge on the virus particles, the folding of the spike proteins, and the conformation of the spikes on the virus particle surface, ultimately leading to different cell-binding properties between SINV-Apple and SINV-Venus. Our results are consistent with recent findings that FPs may alter the biological and cellular localization properties of bacterial proteins to which they are fused.
PMCID: PMC3797254  PMID: 23916968
Alphaviruses; fluorescent proteins; surface properties
3.  The development and evaluation of individualized templates to assist transoral C2 articular mass or transpedicular screw placement in TARP-IV procedures: adult cadaver specimen study 
Clinics  2014;69(11):750-757.
The transoral atlantoaxial reduction plate system treats irreducible atlantoaxial dislocation from transoral atlantoaxial reduction plate-I to transoral atlantoaxial reduction plate-III. However, this system has demonstrated problems associated with screw loosening, atlantoaxial fixation and concealed or manifest neurovascular injuries. This study sought to design a set of individualized templates to improve the accuracy of anterior C2 screw placement in the transoral atlantoaxial reduction plate-IV procedure.
A set of individualized templates was designed according to thin-slice computed tomography data obtained from 10 human cadavers. The templates contained cubic modules and drill guides to facilitate transoral atlantoaxial reduction plate positioning and anterior C2 screw placement. We performed 2 stages of cadaveric experiments with 2 cadavers in stage one and 8 in stage two. Finally, guided C2 screw placement was evaluated by reading postoperative computed tomography images and comparing the planned and inserted screw trajectories.
There were two cortical breaching screws in stage one and three in stage two, but only the cortical breaching screws in stage one were ranked critical. In stage two, the planned entry points and the transverse angles of the anterior C2 screws could be simulated, whereas the declination angles could not be simulated due to intraoperative blockage of the drill bit and screwdriver by the upper teeth.
It was feasible to use individualized templates to guide transoral C2 screw placement. Thus, these drill templates combined with transoral atlantoaxial reduction plate-IV, may improve the accuracy of transoral C2 screw placement and reduce related neurovascular complications.
PMCID: PMC4255074  PMID: 25518033
Transoral Atlantoaxial Reduction Plate; Accuracy; Atlantoaxial Dislocation; Transoral Transpedicular Screw
4.  The sociocultural health behavioral model and disparities in colorectal cancer screening among Chinese Americans 
The purpose of this study was to validate a Sociocultural Health Behavior Model using a structural equation analysis to determine the direction and magnitude of the interdependence of model components in relation to health behavior associated with colorectal cancer (CRC) screening among Chinese Americans.
A cross-sectional design included a sample of 311 Chinese American men and women age 50 and older. The initial step involved use of confirmatory factor analysis which included the following variables: access/satisfaction with health care, enabling, predisposing, cultural, and health belief factors. Structural equation modeling analyses were conducted on factors for CRC screening.
Education and health insurance status were significantly related to CRC screening. Those with less than a high school education and without health insurance were more likely to be “never screened” for CRC than those having more education and health insurance. The path analysis findings also lend support for components of the Sociocultural Health Belief Model and indicated that there was a positive and significant relationship between CRC screening and the enabling factors, between cultural factors and predisposing, enabling, and access/satisfaction with health care factors and between enabling factors and access/satisfaction with health care.
The model highlights the significance that sociocultural factors play in relation to CRC screening and reinforced the need to assist Chinese with poor English proficiency in translation and awareness of the importance of CRC screening. The use of community organizations may play a role in assisting Chinese to enhance colorectal cancer screening rates.
PMCID: PMC4214268  PMID: 25364475
Colorectal cancer; Cancer screening; Chinese Americans; Sociocultural health behavior model; Structural equation modeling
5.  Physiochemical Properties of Caulobacter crescentus Holdfast: a Localized Bacterial Adhesive 
The journal of physical chemistry. B  2013;117(36):10492-10503.
To colonize surfaces, the bacterium Caulobacter crescentus employs a polar polysaccharide, the holdfast, located at the end of a thin, long stalk protruding from the cell body. Unlike many other bacteria which adhere through an extended extracellular polymeric network, the holdfast footprint area is tens of thousands times smaller than that of the total bacterium cross-sectional surface, making for some very demanding adhesion requirements. At present, the mechanism of holdfast adhesion remains poorly understood. We explore it here along three lines of investigation: a) the impact of environmental conditions on holdfast binding affinity, b) adhesion kinetics by dynamic force spectroscopy, and c) kinetic modeling of the attachment process to interpret the observed time-dependence of the adhesion force at short and long time scales. A picture emerged in which discrete molecular units called adhesins are responsible for initial holdfast adhesion, by acting in a cooperative manner.
PMCID: PMC3926197  PMID: 23924278
Caulobacter crescentus; bacterial bioadhesive; atomic force microscopy; dynamic force spectrometry; adhesion kinetics
6.  Identification and Genetic Analysis of a Factor IX Gene Intron 3 Mutation in a Hemophilia B Pedigree in China 
Turkish Journal of Hematology  2014;31(3):226-230.
Objective: Hemophilia B is caused by coagulation defects in the factor IX gene located in Xq27.1 on the X chromosome. A wide range of mutations, showing extensive molecular heterogeneity, have been described in hemophilia B patients. Our study was aimed at genetic analysis and prenatal diagnosis of hemophilia B in order to further elucidate the pathogenesis of the hemophilia B pedigree in China.
Materials and Methods: Polymerase chain reaction amplification and direct sequencing of all the coding regions was conducted in hemophilia B patients and carriers. Prenatal diagnosis of the proband was conducted at 20 weeks.
Results: We identified the novel point mutation 10.389 A>G, located upstream of the intron 3 acceptor site in hemophilia B patients. The fetus of the proband’s cousin was identified as a carrier.
Conclusion: Our identification of a novel mutation in the F9 gene associated with hemophilia B provides novel insight into the pathogenesis of this genetically inherited disorder and also represents the basis of prenatal diagnosis.
PMCID: PMC4287022  PMID: 25330515
Hemophilia B; Factor IX; mutation; Intron 3; mRNA splice site
7.  Association of the histone-lysine N-methyltransferase MLL5 gene with coronary artery disease in Chinese Han people 
Meta Gene  2014;2:514-524.
MLL5, a member of the histone-lysine N-methyltransferase family, has been implicated in the control of the cell cycle progression and survival. The aim of this study was to explore the relationship between the interaction of histone-lysine N-methyltransferase MLL5 gene polymorphism and CAD in a Chinese Han population.
Using a case–control study of Chinese CAD patients (n = 565) and healthy controls (n = 694), we investigated the MLL5 gene polymorphism by the use of polymerase chain reaction fragment length polymorphism (PCR–RFLP) analysis.
For total, the distribution of SNP1 (rs12671368) and SNP2 (rs2192932) genotypes showed a significant difference between CAD and control participants (P1 = 0.03, P2 = 0.02). For total the distribution of SNP1 (rs12671368) and SNP2 (rs2192932) alleles in the dominant model (GG vs. AA + AG) and the recessive model (AA vs. AG + GG) showed a significant difference between CAD and control participants (for allele: P1 < 0.01 and P2 = 0.05, for dominant model: P1 > 0.05 and P2 = 0.02, for recessive model: P1 = 0.03 and P2 = 0.78, respectively). For total the significant difference of the distribution of SNP1 and SNP2 in the dominant model and recessive model was retained after adjusting for covariates (for dominant model: SNP1 OR: 1.68, 95% confidence interval [CI]: 1.08–2.64, P = 0.02; SNP2 OR: 0.51, 95% CI: 0.36–0.72, P = 0.01; for recessive model: SNP1 OR: 1.84, 95% confidence interval [CI]: 1.28–2.64, P < 0.01; SNP2 OR: 0.65, 95% CI: 0.35–1.22, P = 0.18).
The GG genotype of rs12671368 and the AA genotype of rs2192932 in the MLL5 gene could be protective genetic markers of CAD.
PMCID: PMC4287819  PMID: 25606435
MLL5; Single nucleotide polymorphism; Coronary artery disease; Case–control study
8.  Optimal cutoff of the waist-to-hip ratio for detecting cardiovascular risk factors among Han adults in Xinjiang 
The optimal cutoff of the waist-to-hip ratio (WHR) among Han adults in Xinjiang, which is located in the center of Asia, is unknown. We aimed to examine the relationship between different WHRs and cardiovascular risk factors among Han adults in Xinjiang, and determine the optimal cutoff of the WHR.
The Cardiovascular Risk Survey was conducted from October 2007 to March 2010. A total of 14618 representative participants were selected using a four-stage stratified sampling method. A total of 5757 Han participants were included in the study. The present statistical analysis was restricted to the 5595 Han subjects who had complete anthropometric data. The sensitivity, specificity, and distance on the receiver operating characteristic (ROC) curve in each WHR level were calculated. The shortest distance in the ROC curves was used to determine the optimal cutoff of the WHR for detecting cardiovascular risk factors.
In women, the WHR was positively associated with systolic blood pressure, diastolic blood pressure, and serum concentrations of serum total cholesterol. The prevalence of hypertension and hypertriglyceridemia increased as the WHR increased. The same results were not observed among men. The optimal WHR cutoffs for predicting hypertension, diabetes, dyslipidemia and ≥ two of these risk factors for Han adults in Xinjiang were 0.92, 0.92, 0.91, 0.92 in men and 0.88, 0.89, 0.88, 0.89 in women, respectively.
Higher cutoffs for the WHR are required in the identification of Han adults aged ≥ 35 years with a high risk of cardiovascular diseases in Xinjiang.
PMCID: PMC4122671  PMID: 25074400
Cutoff; Waist-to-hip ratio; Cardiovascular risk factors; Han adults; Xinjiang
9.  Association of Egr3 genetic polymorphisms and coronary artery disease in the Uygur and Han of China 
Endothelial cell activation and dysfunction are the foundation of atherosclerosis, including coronary artery disease (CAD). Endothelial cell activation is mediated by the level of gene transcription. Early growth response 3 (Egr3) is a critical determinant of vascular endothelial growth factor (VEGF) signalling in activated endothelial cells. If endothelial cells are excessively activated, it may lead to vasculopathic diseases, such as pathologic angiogenesis, inflammation, and atherosclerosis. The aim of the present study was to assess the association between the Egr3 gene polymorphisms and CAD.
Two independent case–control studies that involved the Han group (409 CAD patients and 351 control subjects) and the Uygur group (299 CAD patients and 303 control subjects) analysed the relationship between Egr3 SNPs (rs1996147 and rs1008949) and CAD. Genotyping was undertaken using the TaqMan SNP genotyping assay.
The entire Uygur group and the males in the Uygur group showed a higher frequency of the A allele (rs1996147) in CAD patients than in the control subjects (P = 0.003 and P = 0.005, respectively). Additionally, the distribution of the recessive model of rs1996147 (AA vs GG + AG) for the total sample and the males was significantly different between CAD patients and control participants (P = 0.002 and P = 0.003, respectively), and the difference remained statistically significant following multivariate adjustment (Total: OR = 1.705; 95% CI: 1.166-2.494, P = 0.006; males: OR = 1.908, 95% CI: 1.189-3.062, P = 0.007). However, for Uygur females, we did not observe a difference in the allele frequency or genotypic distribution of rs1996147 between CAD patients and control participants. Similarly, the distribution of the rs1996147 allele frequency or genotypes showed no significant difference between patients with CAD and control participants in the Han group. The distribution of rs1008949 genotypes, dominant model, recessive model, and allele frequency did not show a significant difference between patients with CAD and the control subjects in the Han and Uygur groups.
rs1996147 may be a novel polymorphism of the Egr3 gene associated with CAD in males of the Chinese Uygur population.
PMCID: PMC4040484  PMID: 24886494
Egr3; Coronary artery disease; Polymorphism
10.  Folate receptor-targeted liposomes enhanced the antitumor potency of imatinib through the combination of active targeting and molecular targeting 
Imatinib inhibits platelet-derived growth factor receptor (PDGFR), and evidence shows that PDGFR participates in the development and progression of cervical cancer. Although imatinib has exhibited preclinical activity against cervical cancer, only minimal clinical therapeutic efficacy was observed. This poor therapeutic efficacy may be due to insufficient drug delivery to the tumor cells and plasma protein binding. Therefore, the purpose of this study was to explore a novel folate receptor (FR)-targeted delivery system via imatinib-loaded liposomes to enhance drug delivery to tumor cells and to reduce plasma protein binding.
Imatinib was remote-loaded into FR-targeted liposomes which were prepared by thin film hydration followed by polycarbonate membrane extrusion. Encapsulation efficiency, mean size diameter, and drug retention were characterized and cellular uptake, cell cytotoxicity, and cell apoptosis on cervical cancer HeLa cells were evaluated. Comparative pharmacokinetic studies were also carried out with FR-targeted imatinib liposomes, simple imatinib liposomes, and free imatinib.
High encapsulation efficiency (>90%), appropriate mean particle size (143.5 nm), and zeta potential (−15.97 mV) were obtained for FR-targeted imatinib liposomes. The drug release profile showed minimal imatinib leakage (<5%) in phosphate-buffered saline (PBS) at pH =7.4 within 72 hours of incubation, while more leakage (>25%) was observed in PBS at pH =5.5. This indicates that these liposomes possess a certain degree of pH sensitivity. Cytotoxicity assays demonstrated that the FR-targeted imatinib liposomes promoted a six-fold IC50 reduction on the non-targeted imatinib liposomes from 910 to 150 μM. In addition, FR-targeted imatinib liposomes enhanced HeLa cell apoptosis in vitro compared to the non-targeted imatinib liposomes. Pharmacokinetic parameters indicated that both targeted and non-targeted liposomes exhibited long circulation properties in Kunming mice.
These findings indicate that the nano-sized FR-targeted PDGFR antagonist imatinib liposomes may constitute a promising strategy in cervical cancer therapy through the combination of active targeting and molecular targeting.
PMCID: PMC4019625  PMID: 24855354
liposomes; imatinib; folate receptor; tumor targeting; PDGFR
11.  Association between the APC gene D1822V variant and the genetic susceptibility of colorectal cancer 
Oncology Letters  2014;8(1):139-144.
Adenomatous polyposis coli (APC) gene polymorphisms are believed to contribute to tumor susceptibility. However, the association between genetic variants (A/T) in the APC gene D1822V polymorphism and colorectal cancer (CRC) susceptibility remains unknown. To determine this association, a case-control study was performed. The genotype of the APC gene D1822V variants was analyzed by DNA sequencing in blood samples collected from 196 patients with CRC and 279 healthy subjects. There were no significant associations between the case and control groups in the distribution of AT [odds ratio (OR), 0.604; 95% confidence interval (CI), 0.355–1.029) and TT genotypes (OR, 0.438; 95% CI, 0.045–4.247) relative to the AA genotype. The ratio of the T allele was significantly lower (P=0.047) in the case group compared with the control group (OR, 0.611; 95% CI, 0.374–0.997), indicating that the T allele conferred a protective effect in CRC. The frequency of the AT genotype among the subjects diagnosed at >45 years of age was lower than those diagnosed at a younger age (P<0.05). The present study demonstrates that the T allele of the D1822V polymorphism may exert a protective effect against CRC, however, these findings require further validation in a larger sample size.
PMCID: PMC4063591  PMID: 24959234
colorectal cancer; APC gene; single nucleotide polymorphism; genetic susceptibility
12.  Hacking on decoy-state quantum key distribution system with partial phase randomization 
Scientific Reports  2014;4:4759.
Quantum key distribution (QKD) provides means for unconditional secure key transmission between two distant parties. However, in practical implementations, it suffers from quantum hacking due to device imperfections. Here we propose a hybrid measurement attack, with only linear optics, homodyne detection, and single photon detection, to the widely used vacuum + weak decoy state QKD system when the phase of source is partially randomized. Our analysis shows that, in some parameter regimes, the proposed attack would result in an entanglement breaking channel but still be able to trick the legitimate users to believe they have transmitted secure keys. That is, the eavesdropper is able to steal all the key information without discovered by the users. Thus, our proposal reveals that partial phase randomization is not sufficient to guarantee the security of phase-encoding QKD systems with weak coherent states.
PMCID: PMC3996487  PMID: 24755767
13.  Repair of Segmental Bone Defect Using Totally Vitalized Tissue Engineered Bone Graft by a Combined Perfusion Seeding and Culture System 
PLoS ONE  2014;9(4):e94276.
The basic strategy to construct tissue engineered bone graft (TEBG) is to combine osteoblastic cells with three dimensional (3D) scaffold. Based on this strategy, we proposed the “Totally Vitalized TEBG” (TV-TEBG) which was characterized by abundant and homogenously distributed cells with enhanced cell proliferation and differentiation and further investigated its biological performance in repairing segmental bone defect.
In this study, we constructed the TV-TEBG with the combination of customized flow perfusion seeding/culture system and β-tricalcium phosphate (β-TCP) scaffold fabricated by Rapid Prototyping (RP) technique. We systemically compared three kinds of TEBG constructed by perfusion seeding and perfusion culture (PSPC) method, static seeding and perfusion culture (SSPC) method, and static seeding and static culture (SSSC) method for their in vitro performance and bone defect healing efficacy with a rabbit model.
Our study has demonstrated that TEBG constructed by PSPC method exhibited better biological properties with higher daily D-glucose consumption, increased cell proliferation and differentiation, and better cell distribution, indicating the successful construction of TV-TEBG. After implanted into rabbit radius defects for 12 weeks, PSPC group exerted higher X-ray score close to autograft, much greater mechanical property evidenced by the biomechanical testing and significantly higher new bone formation as shown by histological analysis compared with the other two groups, and eventually obtained favorable healing efficacy of the segmental bone defect that was the closest to autograft transplantation.
This study demonstrated the feasibility of TV-TEBG construction with combination of perfusion seeding, perfusion culture and RP technique which exerted excellent biological properties. The application of TV-TEBG may become a preferred candidate for segmental bone defect repair in orthopedic and maxillofacial fields.
PMCID: PMC3984127  PMID: 24728277
14.  C-kit induces epithelial-mesenchymal transition and contributes to salivary adenoid cystic cancer progression 
Oncotarget  2014;5(6):1491-1501.
Epithelial–mesenchymal transition (EMT) is associated with salivary adenoid cystic cancer (ACC) progression and metastasis. Here, we report that ectopic overexpression of c-kit in ACC cell lines is sufficient for acquisition of mesenchymal traits, enhanced cell invasion, along with stem cell properties defined by the presence of a CD133 + /CD44 + cell subpopulation. c-kit positively regulated expression of known EMT inducers, also activating TGF-β to contribute to EMT. c-kit itself was induced by TGF-β in ACC cell lines and required for TGF-β–induced EMT. Xenograft experiments showed that c-kit cooperated with oncogenic Ras to promote tumorigenesis in vivo. Finally, in human specimens of ACC, we found that c-kit was abnormally overexpressed and correlated with the prognosis of ACC. Our findings define an important function for c-kit in ACC progression by orchestrating EMT, and they implicate this gene product as a marker of poor prognosis in this disease.
PMCID: PMC4039226  PMID: 24721839
salivary adenoid cystic cancer; epithelial–mesenchymal transition (EMT); c-kit; cancer stem cell; metastasis
15.  Social influences on Cigarette Smoking Among Mainland Chinese and Chinese Americans: A Comparative Study 
The purpose of this cross-national study was to determine the leading social influences on smoking among Chinese Americans and mainland Chinese adults with the aim of improving prevention and intervention strategies to reduce smoking rates. A comparative cross-sectional design was used and a stratified-cluster sampling technique was employed in identifying the study sample. An 80-item questionnaire was administered in Chinese to 1222 participants, 812 in China and 410 in the U.S. Data were analyzed using descriptive and inferential statistical tests. Results contain comparative data on social influences of smoking among Chinese Americans and mainland Chinese, as well as factors influencing smoking behavior which include cultural beliefs, gender roles, and family relationship dynamics. Grandparents were influential and significantly correlated with current smokers in China. Findings indicate differential effects of social influences on smoking behavior. Similarities and differences provide a basis for improving and/or developing smoking intervention programs of mutual benefit to China and the U.S..
PMCID: PMC3914219  PMID: 24511220
16.  Prevalence, awareness, treatment and control of dyslipidemia among adults in Northwestern China: the cardiovascular risk survey 
The aim of this study was to estimate the prevalence, awareness, treatment, and control of dyslipidemia in Xinjiang, China.
Stratified sampling method was used to select a representative sample of the general population including Chinese Han, Uygur, and Kazak in this geographic area. Seven cities were chosen. Based on the government records of registered residences, one participant was randomly selected from each household. The eligibility criterion for the study was ≥ 35 years of age.
A total of 14,618 participants (5,757 Han, 4,767 Uygur, and 4,094 Kazak), were randomly selected from 26 villages in 7 cities. The prevalence of dyslipidemia was 52.72% in the all participants. The prevalence of dyslipidemia was higher in Han than that in the other two ethnic (58.58% in Han, 48.27% in Uygur, and 49.60% in Kazak, P < 0.000). The prevalence of dyslipidemia was higher in men than that in women (56.4% vs. 49.3%, P < 0.000). Among the participants with dyslipidemia, the proportion of those who aware, treat, control of dyslipidemia were 53.67%, 22.51%, 17.09% in Han, 42.19%, 27.78%, 16.20% in Uygur, 37.02%, 21.11%, 17.77% in Kazak.
Dyslipidemia is highly prevalent in Xinjiang. The proportion of participants with dyslipidemia who were aware, treated, and controlled is unacceptably low. These results underscore the urgent need to develop national strategies to improve the prevention, detection, and treatment of dyslipidemia in Xinjiang.
PMCID: PMC3895843  PMID: 24393232
Dyslipidemia; Prevalence; Awareness; Treatment; Control
17.  Effects of Upregulation of Hsp27 Expression on Oocyte Development and Maturation Derived from Polycystic Ovary Syndrome 
PLoS ONE  2013;8(12):e83402.
Heat shock protein 27 (Hsp27) is a heat shock protein family member which can inhibit apoptosis. Our previous studies reported down-regulated Hsp27 in ovarian tissue derived from women with polycystic ovary syndrome (PCOS) however, the exact effect of Hsp27 on oocyte maturation and developmental competence in PCOS is unclear. The effect of Hsp27 over-expression was studied in vitro using oocytes derived from PCOS patients. An artificial GFP-plasmid was injected into human oocyte to increase Hsp27 protein level. Oocyte maturation was evaluated by morphological observation. Mature oocytes were fertilized by intracytoplasmic sperm injection (ICSI) and embryonic developmental competence was evaluated. Critical apoptotic factors and cytokines were measured at both the mRNA and protein level. Our results revealed that Overexpression of HSP27 lowered the maturation rate of oocytes derived from PCOS patients. Meanwhile, fertilization rate and high quality embryo rate were similar between the Hsp27 overexpressing group and controls; however, the blastocyst formation rate in this group was significantly higher than control. Expression analysis revealed that the oocyte-secreted factors, BMP15 and GDF9, and the apoptotic-related regulators, Caspase 3, 8 and 9, were all significantly decreased in Hsp27 overexpressing oocytes. In conclusion, upregulation of Hsp27 inhibits oocyte maturation from PCOS patients, but improves embryonic developmental potential.
PMCID: PMC3877038  PMID: 24391762
18.  Prevalence of major cardiovascular risk factors and adverse risk profiles among three ethnic groups in the Xinjiang Uygur Autonomous Region, China 
Prevalence of cardiovascular disease (CVD) risk factors have been scarcely studied in Xinjiang, a multi-ethnic region.
Multi-ethnic, cross-sectional cardiovascular risk survey study in Xinjiang, including individuals of Uygur (n = 4695), Han (n = 3717) and Kazakh (n = 3196) ethnicities, aged 35-74 years. Analyses involved 11,608 participants with complete data enrolled between October 2007 and March 2010.
There were differences in age-standardized prevalence of CVD risk factors between the three groups (all P < 0.001). Hypertension, obesity and smoking rates were higher among Kazakh (54.6%, 24.5%, and 35.8%, respectively). Dyslipidemia prevalence was higher among Uygur (54.3%), and diabetes prevalence was higher among Hans (7.1%). Age-standardized prevalence of adverse CVD risk profiles was different across different ethnicities. Compared with the Han participants, the Uygur and Kazakh had more CVD risk factors (P < 0.001). Compared with the Han participants, the adjusted odds ratios of 1, 2, and ≥3 risk factors profiles for Kazakh and Uygur participants were higher (all P < 0.001).
The present study showed the pervasive burden of CVD risk factors in all participant groups in the Xinjiang region. Three major ethnic groups living in Xinjiang had striking differences in the prevalence of major CVD risk factors and adverse risk profiles. Ethnic-specific strategies should be developed to prevent CVD in different ethnic groups, as well as to develop strategies to prevent future development of adverse CVD risk factors at a younger age.
PMCID: PMC3866600  PMID: 24341701
Cardiovascular disease; Risk factors; Disparities; Ethnicity; Epidemiology
19.  Modified Uterine Allotransplantation and Immunosuppression Procedure in the Sheep Model 
PLoS ONE  2013;8(11):e81300.
To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model.
In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively.
Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe) revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis.
We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus) is similar to the human anatomy, making the ovine model excellent for human uterine transplant research.
PMCID: PMC3838404  PMID: 24278415
20.  Appropriate Body Mass Index and Waist Circumference Cutoffs for Categorization of Overweight and Central Adiposity among Uighur Adults in Xinjiang 
PLoS ONE  2013;8(11):e80185.
The current overweight and central adiposity guidelines based on Western populations were not consistent with many studied based on the Asian populations. Uighur people live in Xinjiang Uighur Autonomous Region which is located in the center of Asia. Their overweight and central cutoffs were largely unknown. We aimed to identify cutoffs for body mass index (BMI; in kg/m2) and waist circumference (WC; in cm) for categorization of overweight and central adiposity among Uighur adults in Xinjiang.
4767 Uighur participants were selected from the Cardiovascular Risk Survey (CRS) which was carried out from October 2007 to March 2010. The age of the participants were from 35 to 101 years old with the mean age of 50.09 years. Anthropometric data, blood pressure, serum concentration of serum total cholesterol, triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL) and fasting glucose were documented. The prevalence, sensitivity, specificity and distance on the receiver operating characteristic (ROC) curve of each BMI and waist circumference values were calculated.
The prevalence of hypertension, hypercholesterolemia and hypertriglyceridemia were higher with higher BMI for both men and women. The prevalence of hypertension and hypercholesterolemia were higher with higher waist circumference for both men and women. In women, the prevalence of hypertriglyceridemia was noticed to increase as the waist circumference increased. The shortest distance in the receiver operating characteristic curves for hypertension, dyslipidemia, diabetes, or ≥ 2 of these risk factors suggested a BMI cutoff of 26 and a waist circumference cutoff of 90 cm for both men and women.
Higher cutoffs for BMI and waist circumference are needed in the identification of Uighur patients at high risk of cardiovascular disease.
PMCID: PMC3820640  PMID: 24244645
21.  A novel polymorphism (901G > a) of C5L2 gene is associated with coronary artery disease in Chinese Han and Uyghur population 
C5L2, a G protein-coupled receptor (GPCR), has been demonstrated to be a ligand for acylation-stimulating protein (ASP). The aim of the present study is to evaluate the association of a novel variation (901A > G) of C5L2 gene with coronary artery disease (CAD).
We identified a novel single nucleotide polymorphism (SNP), (901G > A), in exon 2 using a polymerase chain reaction direct-sequencing method. This nucleotide change causes the amino-acid order from Arginine to glutaminate at codon 300. We analyzed the relationship between this SNP and CAD in two independent case–control studies: one was in a Han population (492 CAD patients and 577 control subjects) and the other was in a Uygur population (319 CAD patients and 554 control subjects).
The frequency of AG genotype in CAD subjects was less than that in the control subjects not only in Han (1.8% vs 8.6%, P < 0.001, OR = 0.143, 95% CI: 0.068 ~ 0.302) but also in Uygur population (0.9% vs 5.2%, P = 0.001, OR = 0.246, 95% CI: 0.072 ~ 0.837). After adjustment for known CAD risk factors such as hypertension, diabetes, smoking, age and gender, the difference remained significant.
The 901G > A polymorphism of C5L2 may be a genetic maker of CAD in the Han and Uygur population in western China.
PMCID: PMC3850511  PMID: 24073849
Acylation stimulating protein; C5L2; Triglyceride synthesis; Coronary artery disease
22.  Pathways of Breast Cancer Screening Among Chinese American Women 
The purpose of this community-based study was to develop a structural equation model for factors contributing to breast cancer screening among Chinese American women.
A cross-sectional design included a sample of 440 Chinese American women aged 40 years and older. The initial step involved use of confirmatory factor analysis, which included the following variables: access/satisfaction with health care, enabling, predisposing, and cultural and health belief factors. Structural equation model analyses were conducted to evaluate factors related to breast cancer screening in Chinese American women.
Initial univariate analyses indicated that women without health insurance were significantly more likely to report being never-screened compared to women with health insurance. Structural equation modeling techniques were used to evaluate the utility of the Sociocultural Health Behavior model in understanding breast cancer screening among Chinese American women. Results indicated that enabling and predisposing factors were significantly and positively related to breast cancer screening. Cultural factors were significantly associated with enabling factors and satisfaction with healthcare. Overall, the proposed model explained 34% of the variance in breast cancer screening among Chinese American women.
The model highlights the significance of enabling and predisposing factors in understanding breast cancer screening behaviors among Chinese American women. In addition, cultural factors were associated with enabling factors, reinforcing the importance of providing translation assistance to Chinese women with poor English fluency and increasing awareness of the critical role of breast cancer screening. Partnering with community organizations may help to facilitate and enhance the screening rates.
PMCID: PMC3762685  PMID: 24013711
Mammograms; Breast cancer screening; Chinese women
23.  Genetic variation in Tanis was associated with elevating plasma triglyceride level in Chinese nondiabetic subjects 
The association of genetic polymorphisms of Tanis with triglyceride concentration in human has not been thoroughly examined. We aimed to investigate the relationship between triglyceride concentrations and Tanis genetic polymorphisms.
All participants (n=1497) selected from subjects participating in the Cardiovascular Risk Survey (CRS) study were divided into two groups according to ethnicity (Han: n=1059; Uygur: n= 438). Four tagging SNPs (rs12910524, rs1384565, rs2101171, rs4965814) of Tanis gene were genotyped using TaqMan® assays from Applied Biosystems following the manufacturer’s suggestions and analyzed in an ABI 7900HT Fast Real-Time PCR System.
We found that the SNP rs12910524 was associated with triglyceride levels by analyses of a dominant model (P<0.001), recessive model (P <0.001) and additive model (P < 0.001) not only in Han ethnic but also in Uygur ethnic group, and the difference remained significant after the adjustment of sex, age, alcohol intake, smoking, BMI and plasma glucose (GLU) level (All P < 0.001). However, this relationship was not observed in rs1384565, rs2101171, and rs4965814 before and after multivariate adjustment (All P > 0.05). Furthermore, there were significant interactions between rs12910524 and GLU on TG both in Han (P=0.001) and Uygur population (P=2.60×10-4).
Our results indicated that the rs12910524 in the Tanis gene was associated with triglyceride concentrations in subjects without diabetes in China.
PMCID: PMC3706366  PMID: 23829426
Genetics; Tanis; Triglyceride; Diabetes; Polymorphisms
24.  Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Isolates Causing Invasive Diseases from Shenzhen Children’s Hospital 
PLoS ONE  2013;8(6):e67507.
To provide guidance for clinical disease prevention and treatment, this study examined the epidemiology, antibiotic susceptibility, and serotype distribution of Streptococcus pneumoniae (S. pneumoniae) associated with invasive pneumococcal diseases (IPDs) among children less than 14 years of age in Shenzhen, China.
Materials and Methods
All the clinical strains were isolated from children less than 14 years old from January 2009 to August 2012. The serotypes and antibiotic resistance of strains of S. pneumoniae were determined using the capsular swelling method and the E-test.
A total of 89 strains were isolated and 87 isolates were included. The five prevailing serotypes were 19F (28.7%), 14 (16.1%), 23F (11.5%), 19A (9.2%) and 6B (6.9%). The most common sequence types (ST) were ST271 (21.8%), ST876 (18.4%), ST320 (8.0%) and ST81 (6.9%) which were mainly related to 19F, 14, 19A and 23F, respectively. The potential coverage by 7-, 10-, and 13-valent pneumococcal conjugate vaccine were 77.0%, 77.0%, and 89.7%, respectively. Among the 87 isolates investigated, 11.5% were resistant to penicillin, and for meningitis isolates, the resistance rate was 100%. Multi-drug resistance (MDR) was exhibited by 49 (56.3%) isolates. Eighty-four isolates were resistance to erythromycin, among which, 56 (66.7%) carried the ermB gene alone and 28 (33.3%) expressed both the ermB and mefA/E genes.
The potential coverage of PCV13 is higher than PCV7 and PCV10 because high rates of serotypes 19A and 6A in Shenzhen. The clinical treatment of IPD needs a higher drug concentration of antibiotics. Continued surveillance of the antimicrobial susceptibility and serotypes distribution of IPD isolates may be necessary.
PMCID: PMC3696094  PMID: 23840728
25.  Pathways of cervical cancer screening among Chinese women 
The purpose of this community-based study was to develop a structural equation model for factors contributing to cervical cancer screening among Chinese American women.
A cross-sectional design included a sample of 573 Chinese American women aged 18 years and older. The initial step involved use of confirmatory factor analysis, that included the following variables: access to and satisfaction with health care, and enabling and predisposing cultural and health beliefs. Structural equation model analyses were conducted on factors related to cervical cancer screening.
Age, marital status, employment, household income, and having health insurance, but not educational level, were significantly related to cervical screening status. Predisposing and enabling factors were positively associated with cervical cancer screening. The cultural factor was significantly related to the enabling factor or the satisfaction with health care factor.
This model highlights the significance of sociocultural factors in relation to cervical cancer screening. These factors were significant, with cultural, predisposing, enabling, and health belief factors and access to and satisfaction with health care reinforcing the need to assist Chinese American women with poor English fluency in translation and awareness of the importance of cervical cancer screening. Community organizations may play a role in assisting Chinese American women, which could enhance cervical cancer screening rates.
PMCID: PMC3702238  PMID: 23843708
Papanicolaou test; cervical cancer screening; Chinese women

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