Fengcheng, China
Fengcheng, China

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Wang Y.,No1 Hospital Of Xian | Wang Y.,Ophthalmological Institute of Shaanxi Province | Jin T.,Northwest University, China | Jin T.,System Detection | And 18 more authors.
Ophthalmic Genetics | Year: 2013

Objective: To investigate whether the tag single nucleotide polymorphisms (tSNPs) in VSX1, COL4A3, COL4A4, IL1A and IL1B genes were associated with keratoconus (KTCN) in the Han Chinese population. Methods: Ninety-seven KTCN patients and 101 healthy controls were enrolled in this study. All cases were diagnosed on the basis of clinical examination. Twenty-one tSNPs were selected for association study in five genes. SNP genotyping was performed by Sequenom MassARRAY RS1000. Sequenom Typer 4.0 Software, PLINK, Haploview and SHEsis software platform were used to perform data management and analyses. Results: Three tSNPs in the VSX1 gene were observed to be associated with KTCN risk at a 5% level by χ2 test (rs56157240 and rs12480307, p = 0.0499, OR: 6.42, 95% CI: 0.77-53.78; rs6050307, p = 1.22 × 10-7, OR: 0.05, 95% CI: 0.01-0.23). Rs2071376 in the IL1A gene was also associated with KTCN (p = 0.0487, OR: 1.51, 95% CI: 1.00-2.26). Three haplotypes in the VSX1 gene were found to be associated with risk of KTCN (p < 0.05). Conclusions: Our findings confirmed previous reports that polymorphisms of VSX1 and IL1A genes were associated with risk of KTCN in the Chinese population, suggesting an important determinant of KTCN development by VSX1 and IL1A genes. Copyright © Informa Healthcare USA, Inc.

Zi J.,Life Detection Systems | Zi J.,Microbiology Institute of Shaanxi Province | Liu D.,Life Detection Systems | Ma P.,Life Detection Systems | And 5 more authors.
Drug Metabolism and Pharmacokinetics | Year: 2010

Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the metabolism of many important drugs, including diclofenac. CYP2C9*3 and CYP2C9*13 are the principal variant alleles found in the Chinese population. CYP2C9*3 has been reported to reduce the metabolism of diclofenac and alter the extent of drug-drug interactions (DDIs). The effects of CYP2C9*13 on diclofenac metabolism are not well studied, and the influences of CYP2C9*13 on DDIs between diclofenac and clinical drugs are still unknown. In this study, CYP2C9.1 (the wildtype enzyme), CYP2C9.3 and CYP2C9.13 were expressed in yeast, and their metabolic kinetics for diclofenac 4′-hydroxylation were examined. From the in vitro data, we predicted a decrease in the ratio of diclofenac oral clearance (the ratio of oral clearance in subjects with variant CYP2C9 alleles to that in wildtype subjects (CLoralR)) in subjects carrying CYP2C9*3 or CYP2C9*13 alleles. Furthermore, we investigated the effects of these two alleles on diclofenac-drug interactions. The potentials of nine clinically used drugs to inhibit diclofenac 4′-hydroxylation catalyzed by the alleles were compared. Our results indicated that CYP2C9.3 and CYP2C9.13 can alter the CYP-inhibitory potencies of some tested drugs. In particular, CYP2C9.13 significantly weakened the inhibitory potencies of sulfaphenazole, fluvasta-tin, fluvoxamine and tranylcypromine. These data provide helpful guidelines for co-administration of diclofenac with other drugs in individuals carrying CYP2C9*3 and CYP2C9*13 alleles.

Zhu H.,Northwest University, China | Yan K.,Northwest University, China | Dang X.,Shaanxi Cancer Hospital | Huang H.,Northwest University, China | And 6 more authors.
Artificial Cells, Blood Substitutes, and Biotechnology | Year: 2011

Polymerized Porcine Hemoglobin (pPolyHb), a hemoglobin-based oxygen carrier (HBOC), was developed as a potential red blood substitute for clinical applications. Assessment of its effects on the immune system is an important component of the overall safety evaluation of HBOC. For this purpose, we assessed three inflammation indicators, including complement C3a, IL-6, and TNF-α in cultured cells and in a rat model when pPolyHb was incubated or administrated with the cells/animals. Our results suggested that the levels of these three indicators were not statistically changed upon pPolyHb stimulation, indicating that pPolyHb is not immunotoxic to cells and animals in this aspect. © 2011 Informa Healthcare USA, Inc.

Zhu H.,Northwest University, China | Dang X.,Shaanxi Cancer Hospital | Yan K.,Northwest University, China | Dai P.,Northwest University, China | And 5 more authors.
Artificial Cells, Blood Substitutes, and Biotechnology | Year: 2011

The objective of the present study is to evaluate the pharmacodynamic properties of polymerized porcine hemoglobin (pPolyHb) in an exchange transfusion model. Each of two groups of rats received a volume of pPolyHb or hetastarch that equalled 120-140% of estimated total blood volume (70 ml/kg) exchange transfusion. The results showed pPolyHb retained hemodynamic stability and exhibited superior volume expansion capability. Furthermore, pPolyHb effectively reverse anaerobic metabolism caused by a large amount of volume exchange. In comparison with hetastarch, pPolyHb increased blood oxygen content and tissue oxygenation. All these properties contribute to a higher effectiveness in sustaining the lives of rats in pPolyHb group. Copyright © 2011 Informa Healthcare USA, Inc.

Jin T.-B.,Tibet University | Jin T.-B.,Life Detection Systems | Jin T.-B.,Shaanxi Lifegen Co. | Ma L.-F.,Tibet University | And 8 more authors.
Gene | Year: 2013

The cytochrome P450 2D6 enzyme (CYP2D6) metabolizes about 25% of prescribed drugs in the endoplasmic reticulum, and genetic polymorphisms in CYP2D6 can greatly affect its activity and lead to differences among individuals in drug efficacy and adverse drug reactions. To investigate genetic polymorphisms in CYP2D6 among Tibetan Chinese, we directly sequenced the whole gene in 96 unrelated, healthy Tibetans from The Tibet Autonomous Region of China and screened for genetic variants in the promoter, exons, introns, and 3'UTR. We detected fifty-one genetic polymorphisms in CYP2D6, and 16 of them are novel. The allele frequencies of CYP2D6*1, *2, *5, *10, *41, and *49 were 0.25, 0.43, 0.02, 0.29, 0.02, and 0.01, respectively. The frequency of CYP2D6*10, a putative poor-metabolizer allele, was lower in our sample population compared with that in the Han Chinese population (p < 0.001). In addition, haplotype analysis allowed 15 CYP2D6 haplotypes to be classified into three groups. In conclusion, our results provide basic information about CPY2D6 alleles in Tibetans and suggest that the enzymatic activities of CYP2D6 may differ among the diverse ethnic populations of China. Our results provide a basis for safer drug administration and better therapeutic treatment among Tibetans. © 2013.

Wang H.,Life Detection Systems | Bian T.,Life Detection Systems | Liu D.,Life Detection Systems | Liu D.,Shaanxi Lifegen Co. | And 5 more authors.
Pharmacogenomics | Year: 2011

Aim: Tegafur is primarily converted to 5-fluorouracil (5-FU) by CYP2A6 in the human liver to exert its antitumor effect. Our objective was to comprehensively investigate the effects of CYP2A6 genetic polymorphisms on tegafur bioactivation activity. Materials & methods: Using a set of over 45 Chinese livers, the association between CYP2A6 genetic variations and 5-FU formation rates from tegafur, as well as CYP2A6 mRNA and protein levels, was determined. Results: A total of 20 polymorphic variants and 20 haplotypes of CYP2A6 were identified. From genotype/haplotype-phenotype association tests, we demonstrated that CYP2A6*4 was the main allele responsible for the decreased 5-FU formation from tegafur and CYP2A6 expression in this population. By contrast, haplotype 14 (a novel CYP2A6*1B allele) was associated with increased microsomal 5-FU formation activity and CYP2A6 expression, and this may be attributed to the combined effects of three single variants (g.22C>T, g.1620T>C and a gene conversion in the 3′-UTR) included in this haplotype. Conclusion: We concluded that CYP2A6*4 and the novel CYP2A6*1B variant were the major genetic determinants of interindividual variability in 5-FU formation from tegafur in Chinese livers. © 2011 Future Medicine Ltd.

Li G.,PLA Fourth Military Medical University | Jin T.,Life Detection Systems | Liang H.,PLA Fourth Military Medical University | Zhang Z.,PLA Fourth Military Medical University | And 7 more authors.
Diagnostic Pathology | Year: 2013

As glioma ranks as the first most prevalent solid tumors in primary central nervous system, certain single-nucleotide polymorphisms (SNPs) may be related to increased glioma risk, and have implications in carcinogenesis. The present case-control study was carried out to elucidate how common variants contribute to glioma susceptibility. Ten candidate tagging SNPs (tSNPs) were selected from seven genes whose polymorphisms have been proven by classical literatures and reliable databases to be tended to relate with gliomas, and with the minor allele frequency (MAF) > 5% in the HapMap Asian population. The selected tSNPs were genotyped in 629 glioma patients and 645 controls from a Han Chinese population using the multiplexed SNP MassEXTEND assay calibrated. Two significant tSNPs in RTEL1 gene were observed to be associated with glioma risk (rs6010620, P = 0.0016, OR: 1.32, 95% CI: 1.11-1.56; rs2297440, P = 0.001, OR: 1.33, 95% CI: 1.12-1.58) by χ2 test. It was identified the genotype "GG" of rs6010620 acted as the protective genotype for glioma (OR, 0.46; 95% CI, 0.31-0.7; P = 0.0002), while the genotype "CC" of rs2297440 as the protective genotype in glioma (OR, 0.47; 95% CI, 0.31-0.71; P = 0.0003). Furthermore, haplotype "GCT" in RTEL1 gene was found to be associated with risk of glioma (OR, 0.7; 95% CI, 0.57-0.86; Fisher's P = 0.0005; Pearson's P = 0.0005), and haplotype "ATT" was detected to be associated with risk of glioma (OR, 1.32; 95% CI, 1.12-1.57; Fisher's P = 0.0013; Pearson's P = 0.0013). Two single variants, the genotypes of "GG" of rs6010620 and "CC" of rs2297440 (rs6010620 and rs2297440) in the RTEL1 gene, together with two haplotypes of GCT and ATT, were identified to be associated with glioma development. And it might be used to evaluate the glioma development risks to screen the above RTEL1 tagging SNPs and haplotypes. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1993021136961998. © 2013 Li et al.; licensee BioMed Central Ltd.

Wang H.,Life Detection Systems | Kim R.A.,GenePrism Inc. | Sun D.,Xuzhou Normal University | Gao Y.,Life Detection Systems | And 2 more authors.
Xenobiotica | Year: 2011

To comprehensively understand the effects of CYP2C19 genetic polymorphisms on inhibition-based drugdrug interactions (DDIs), 18 human CYP2C19 non-synonymous single-nucleotide polymorphic variants and the wild-type isoform (CYP2C19.1A) were expressed in yeast cells. Using a fluorescence-based high-throughput method, the kinetic constants of these variants, as well as the inhibition constants for 10 drugs, were determined. CYP2C19.5B and CYP2C19.6 showed no activity towards CEC (3-cyano-7-ethoxycoumarin) O-deethylation. CYP2C19.8, CYP2C19.9, CYP2C19.10, CYP2C19.16, CYP2C19.19, E122A and A161P* (an allele containing both A161P and I331V) exhibited significantly reduced catalytic activities compared with CYP2C19.1A. The inhibition assay showed that the CYP2C19 genotype significantly affected the in vitro drug inhibition potential. Although the effect on drug inhibition potential is genotype- and inhibitor-dependent, there was an obvious trend: drugs tended to exhibit higher IC50 values (i.e. decreased inhibition potential) towards variants with reduced activity compared with variants with normal activity. This indicated that patients with reduced-function alleles may be less susceptible to CYP2C19-related DDIs. In this study, we provided the first in vitro evidence of CYP2C19 genotype-dependent effects on drug inhibition potential. This work greatly extends our understanding of the functional consequences of CYP2C19 genetic polymorphisms, and thus should prove valuable for CYP2C19 genotype-based therapy. © 2011 Informa UK, Ltd.

Yan K.-P.,Northwest University, China | Zhu H.-L.,Northwest University, China | Zhu H.-L.,Shaanxi Lifegen Co. | Dan N.,Northwest University, China | And 3 more authors.
Chromatographia | Year: 2010

An improved HPLC procedure for the separation of phospholipids is described. The method described utilizes a solvent mixture of acetonitrile-methanol-water-trifluoroacetic acid (100:25:1.7:2.5, v/v) as the mobile phase, which is more compatible with the pump than mobile phases containing inorganic acids. Separation was by isocratic elution on a Hypersil silica column coupled to an evaporative light scattering detector. Complete separation of phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylcholine (PC) and sphingomyelin (SM) was achieved in less than 20 min. The detection limits for PS, PE, PC and SM were 50, 50, 80 and 150 ng (S/N = 3), respectively. Human, bovine and porcine erythrocyte ghost membranes and animal tissues have been successfully analyzed for their phospholipid contents. © 2010 Vieweg+Teubner Verlag | Springer Fachmedien Wiesbaden GmbH.

Zhang W.,Northwest University, China | Zhang W.,Jilin Medical College | Yan K.,Northwest University, China | Yan K.,Shaanxi Lifegen Co. | And 4 more authors.
Artificial Organs | Year: 2012

Hemoglobin-based oxygen carriers (HBOCs), with their capacity for delivering oxygen, could potentially function as red blood cell substitutes or primary resuscitation solutions. However, there has been some concern regarding redox-related safety issues of HBOCs. The present study describes a novel function of polymerized porcine hemoglobin (pPolyHb) in protecting a human umbilical vein endothelial cell line from H 2O 2-induced cytotoxicity. Through the examination of H 2O 2 consumption and ferrylhemoglobin formation, we found that pPolyHb exhibits antioxidant activity, suggesting that pPolyHb may protect cells from free radical-induced cell damage. Additionally, we investigated the effect of pPolyHb on H 2O 2-induced cell cytotoxicity, and found that pPolyHb significantly inhibits H 2O 2-mediated endothelial cell damage as well as apoptosis. Thus, pPolyHb may be developed as a new HBOC in the future. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

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