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Biomedical subjects

Feng Zhao

Publications and source records attributed to Feng Zhao.

At least 55 records · Page 3Linked to original sources

Novel CYP2C9 genetic variants in Asian subjects and their influence on maintenance warfarin dose.

BACKGROUND: Commonly occurring genetic variants in CYP2C9 are known to reduce catalytic activity and are associated with enhanced patient sensitivity to warfarin. Interethnic differences in warfarin dose requirement have been described in the Asian population, and we postulate that this could be related to genetic variants of CYP2C9 that are unique to ethnic groups. METHODS: We prospectively genotyped 125 patients who were receiving a stable daily warfarin dose to maintain international normalized ratio values between 2 and 3 through comprehensive sequencing of the promoter and coding regions of the CYP2C9 gene. RESULTS: The mean weight-adjusted warfarin maintenance dose was significantly lower for Malay and Chinese subjects than Indian subjects ( P <.001 and.014, respectively). Warfarin dose negatively correlated with age (r = -0.4, P <.001) but not with sex. Multiple variants were detected in the promoter, exonic, intronic, and 3'-untranslated regions of CYP2C9, of which 16 were novel, including 7 nonsynonymous exonic variants ( 208G>C, 374G>A, 485C>A, 895A>G, 1144C>T, 1190A>C, and 1362G>C ). CYP2C9*3, but not CYP2C9*2, was found in Chinese and Malay patients, and carriers of the CYP2C9*3 variant in Chinese ( P <.01) and Indian ( P <.01) patients, but not Malay patients ( P =.77), required less warfarin. The influence of the novel exonic variants on warfarin dose requirement was unclear, because they were rare, but the lower warfarin dose requirement for Chinese and Malay patients existed despite omission of individuals with any coding region variants from analysis. CONCLUSIONS: Interethnic differences in warfarin dosing in Asian subjects may result from other genetic, dietary, or environmental influences; however, these novel variants in the gene warrant further characterization through functional studies.

Adult↗

Coercive sex in rural Uganda: prevalence and associated risk factors.

Despite growing recognition of the problem, relatively little is known about the issue of coercive sex in developing countries. This study presents findings from a community-based survey of 4279 reproductive-aged women in current partnerships in the Rakai District of Uganda carried out in 1998-99. One in four women in our study report having experienced coercive sex with their current male partner, with most women reporting its occasional occurrence. In a regression analysis of risk factors for coercive sex, conventional socio-demographic characteristics emerged as largely unpredictive of the risk of coercive sex. Behavioral risk factors-most notably, younger age of women at first intercourse and alcohol consumption before sex by the male partner-were strongly and positively related to the risk of coercive sex. Coercive sex was also strongly related to perceptions of the male partner's HIV risk, with women who perceived their partner to be at highest risk experiencing almost three times the risk of coercive sex relative to low risk partnerships. Supplemental analysis of 1-year longitudinal data provides additional support for the hypothesis that coercive sex may frequently be a consequence of women's perceptions of increased HIV risk for their male partner. The findings of this study are discussed in terms of the need for sexual violence prevention programs more generally in settings such as Uganda, and in terms of the possible importance of incorporating issues of sexual and physical violence within current HIV prevention programs.

Adolescent↗

Intermediates in the inactivation and unfolding of dimeric arginine kinase induced by GdnHCl.

Equilibrium studies of guanidine hydrochloride (GdnHCl)-induced unfolding of dimeric arginine kinase (AK) from sea cucumber have been performed by monitoring by enzyme activity, intrinsic protein fluorescence, circular dichroism (CD), 1-anilinonaphthalene-8sulfonate (ANS) binding, size-exclusion chromatography and glutaraldehyde cross-linking. The unfolding is a multiphasic process involving at least two dimeric intermediates. The first intermediate, I1, which exists at 0-0.4 M GdnHCl, is a compact inactive dimer lacking partial global structure, while the second dimeric intermediate, I2, formed at 0.5-2.0 M GdnHCl, possesses characteristics similar to the globular folding intermediates described in the literature. The whole unfolding process can be described as follows: (1) inactivation and the appearance of the dimeric intermediate I1; (2) sudden unwinding of I1 to another dimeric intermediate, I2; (3) dissociation of dimeric intermediate I2 to monomers U. The refolding processes initiated by rapid dilution in renaturation buffers indicate that denaturation at low GdnHCl concentrations (below 0.4 M GdnHCl) is reversible and that there seems to be an energy barrier between the two intermediates (0.4-0.5 M GdnHCl), which makes it difficult for AK denatured at high GdnHCl concentrations (above 0.5 M) to reconstitute and regain its catalytic activity completely.

Arginine Kinase↗

The cost-effectiveness of the use of clopidogrel in acute coronary syndromes in five countries based upon the CURE study.

BACKGROUND: The CURE study demonstrated that clopidogrel prevents a range of ischaemic cardiovascular events in patients with Acute Coronary Syndromes (unstable angina or non-ST-segment elevation MI). DESIGN: We undertook an economic analysis of the use of clopidogrel in the UK, USA, Sweden, France and Canada based on the CURE study. METHODS: The costs of hospitalization, study drug and other medications were calculated, based on resource utilization for all patients in CURE. Unit costs were obtained for all resource items for each country, and are reported in local currencies in 2001 prices. RESULTS: While hospitalization costs were lower in the clopidogrel group, when the acquisition cost of clopidogrel for 9 months is included, the average cost per patient is higher in the clopidogrel group than the placebo group in all countries [difference in costs (with 95% CI) 208 pounds sterling (119, 297), 451 US dollars (58, 845), SKr 2571 (728, 4412), 325 euros (85, 565), 161 Canadian dollars (-185, 506)]. The absolute reduction in the number of total primary events was 2.0%, resulting in an incremental cost-effectiveness ratio (ICER) of 10,366 pounds sterling in the UK, 22,484 US dollars in the USA, SKr 127,951 in Sweden, 16,186 euros in France, and 7973 Canadian dollars in Canada per primary event avoided with clopidogrel. CONCLUSIONS: Clopidogrel in CURE reduced hospitalization costs but the acquisition cost of clopidogrel creates an overall increase in direct health care costs over 9 months. Nevertheless, the cost-effectiveness is in a range comparable to other therapies currently utilized for acute coronary syndromes.

Angina, Unstable↗

[Measurement of uric acid of seminal plasma in fertile and infertile males].

OBJECTIVE: To measure uric acid of seminal plasma in fertile and infertile males. METHODS: One hundred and sixty-three infertile males were divided into an obstructive azoospermic group (15 cases), a non-obstructive azoospermic group (36 cases), an oligozoospermic group (43 cases), and an asthenozoospermic group (69 cases). Twenty fertile males were included in the control group. Uric acid concentrations of seminal plasma in the fertile and infertile men were assessed by spectrophotometer, and sperm parameters were analyzed by computer-assisted semen analysis (CASA) system. RESULTS: Uric acid concentration of seminal plasma in the control group was significantly higher than all the infertile groups (P < 0.01), and that of the obstructive azoospermic group significantly lower than the other infertile groups (P < 0.1), but no significant difference was observed among the other infertile groups (P > 0.05). CONCLUSION: Uric acid may play an important role in male reproduction because of its antioxidative property.

Adult↗

Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study.

BACKGROUND: We studied the benefits and risks of adding clopidogrel to different doses of aspirin in the treatment of patients with acute coronary syndrome (ACS). METHODS AND RESULTS: In the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial, 12 562 patients with ACS using aspirin, 75 to 325 mg daily, were randomized to clopidogrel or placebo for up to 1 year. In this analysis, patients were divided into the following 3 aspirin dose groups: < or =100 mg, 101 through 199 mg, and > or =200 mg. The combined incidence of cardiovascular death, myocardial infarction, or stroke was reduced by clopidogrel regardless of aspirin dose, as follows: < or =100 mg, 10.5% versus 8.6% (relative risk [RR], 0.81 [95% CI, 0.68 to 0.97]); 101 to 199 mg, 9.8% versus 9.5% (RR, 0.97 [95% CI 0.77 to 1.22]); and > or =200 mg, 13.6% versus 9.8% (RR, 0.71 [95% CI, 0.59 to 0.85]). The incidence of major bleeding increased with increasing aspirin dose both in the placebo group (1.9%, 2.8%, and 3.7%, respectively; P=0.0001) and the clopidogrel group (3.0%, 3.4%, and 4.9%, respectively; P=0.0009); thus, the excess risk with clopidogrel was 1.1%, 1.2%, and 1.2%, respectively. The adjusted hazard ratio for major bleeding for the highest versus the lowest dose of aspirin was 1.9 (95% CI 1.29 to 2.72) in the placebo group, 1.6 (95% CI 1.19 to 2.23) in the clopidogrel group, and 1.7 (95% CI 1.36 to 2.20) in the combined group. CONCLUSIONS: In patients with ACS, adding clopidogrel to aspirin is beneficial regardless of aspirin dose. Bleeding risks increase with increasing aspirin dose, with or without clopidogrel, without any increase in efficacy. Our findings suggest that the optimal daily dose of aspirin may be between 75 and 100 mg, with or without clopidogrel.

Acute Disease↗

Domestic violence in rural Uganda: evidence from a community-based study.

Although domestic violence is an increasing public health concern in developing countries, evidence from representative, community-based studies is limited. In a survey of 5109 women of reproductive age in the Rakai District of Uganda, 30% of women had experienced physical threats or physical abuse from their current partner--20% during the year before the survey. Three of five women who reported recent physical threats or abuse reported three or more specific acts of violence during the preceding year, and just under a half reported injuries as a result. Analysis of risk factors highlights the pivotal roles of the male partner's alcohol consumption and his perceived human immunodeficiency virus (HIV) risk in increasing the risk of male against female domestic violence. Most respondents--70% of men and 90% of women--viewed beating of the wife or female partner as justifiable in some circumstances, posing a central challenge to preventing violence in such settings.

Adult↗

Early and late effects of clopidogrel in patients with acute coronary syndromes.

BACKGROUND: The risk of ischemic events is high, both early and late after acute coronary syndromes (ACS). We examine the benefits and risks associated with the use of adding clopidogrel to aspirin within the first 30 days and later (31 days to 12 months) in 12 562 patients with ACS. METHODS AND RESULTS: A total of 12 562 ACS patients were randomized to receive clopidogrel (300 mg initially followed by 75 mg/d) or placebo for 3 to 12 months. The proportion of patients experiencing cardiovascular death, myocardial infarction, or strokes (primary outcome) at 30 days was 5.4% in the placebo group and 4.3% in the active group (relative risk 0.79, 95% CI 0.67 to 0.92). Beyond 30 days, the corresponding rates were 6.3% versus 5.2% (relative risk 0.82, 95% CI 0.70 to 0.95). There was no significant excess in life-threatening bleeds in each period (0.97% versus 1.28%, relative risk 1.32, 95% CI 0.95 to 1.84 for 0 to 30 days; 0.83% versus 0.91%, relative risk 1.09, 95% CI 0.75 to 1.59 for 31 days to 12 months). Further subdivision of the early data indicates benefits within 24 hours with consistently lower rates of the primary outcome in combination with refractory or severe ischemia. CONCLUSIONS: Clopidogrel reduces the risk of ischemic vascular events, with the benefits emerging within 24 hours of initiation of treatment and continuing throughout the 12 months (mean 9 months) of the study.

Acute Disease↗

An ab initio study of intermolecular interactions of nitromethane dimer and nitromethane trimer.

Different geometries of nitromethane dimer and nitromethane trimer have been fully optimized employing the density functional theory B3LYP method and the 6-31++G** basis set. Three-body interaction energy has been obtained with the ab initio supermolecular approach at the levels of MP2/6-31++G**//B3LYP/6-31++G** and MP2/aug-cc-pVDZ//B3LYP/6-31++G**. The internal rotation of methyl group induced by intermolecular interaction has been observed theoretically. For the optimized structures of nitromethane dimer, the strength of C--H...O--N H-bond ranges from -9.0 to -12.4 kJ mol(-1) at the MP2/aug-cc-pVDZ//B3LYP/6-31++G** level, and the B3LYP method underestimates the interaction strength compared with the MP2 method, while MP2/6-31++G**//B3LYP/6-31++G** calculated DeltaE(C) is within 2.5 kJ mol(-1) of the corresponding value at the MP4(SDTQ)/6-31G**//B3LYP/6-31++G** level. The analytic atom-atom intermolecular potential has been successfully regressed by using the MP2/6-31++G**//B3LYP/6-31++G** calculated interaction energies of nitromethane dimer. For the optimized structures of nitromethane trimer the three-body interaction energies occupy small percentage of corresponding total binding energies, but become important for the compressed nitromethane explosive. In addition, it has been discovered that the three-body interaction energy in the cyclic nitromethane trimer is more and more negative as intermolecular distances decrease from 2.2 to 1.7 A.

Journal Article↗

Expression of Tfap2d, the gene encoding the transcription factor Ap-2 delta, during mouse embryogenesis.

Tfap2d encodes a novel member of the AP-2 family of transcription factors, called Ap-2 delta. Ap-2 delta has a unique DNA sequence binding specificity and lacks a PY motif as well as several highly conserved residues in the transactivation domain that are essential for transcriptional activation for other AP-2 proteins. In this study, we characterized the expression pattern of Tfap2d in mouse embryos from E7.5 to E16.5 using in situ hybridization as a first step towards understanding the role of Ap-2 delta during development. Overall, Tfap2d is expressed with a more restricted temporal and spatial pattern than the other Tfap2 genes, with signals observed in the central nervous system, retina, and, uniquely, in the developing heart. Signals were not detected in tissues such as the neural crest, facial mesenchyme, and limbs where the other Tfap2 genes are expressed. The expression of Tfap2d was first noted at E9.5, later than other Tfap2 genes, with signals from the heart and brain. The expression in the developing myocardium persisted through E10.5. Expression of Tfap2d was diffuse in the developing brain at E10.5 to E11.0, but became restricted to the roof of the third vesicle with two narrow columns extending forward along the wall of the third vesicle and the roof of the heopallial cortex in the forebrain from E12.5 onwards. Tfap2d expression was also observed in the spinal cord at E10.5. From E13.5 to E16.5, Tfap2d was expressed in the retinal epithelium. Based on Tfap2d's unique expression pattern and functional features, we believe that Ap-2 delta plays a role during mammalian development that is non-overlapping with those of the other Ap-2 transcription factors.

Animals↗

Inhibitors of nitric oxide production from hops (Humulus lupulus L.).

Nitric oxide (NO) plays an important role in many inflammatory responses and is also involved in carcinogenesis. In the present study, we investigated the inhibitory effect of extracts from Humulus lupulus L. on both the production of NO and the expression of inducible NO synthase (iNOS) in mouse macrophage RAW 264.7 cells. The production of NO was induced by a combination of lipopolysaccharide (LPS) and IFN-gamma, and determined by Griess assay. The expression of iNOS was detected by Western blotting. The LPS/IFN-gamma-induced production of NO and expression of iNOS were significantly inhibited by the ethyl acetate soluble fraction of Humulus lupulus L. Through bioactivity guided fractionation, humulene, five chalcones, 2,2-di-(3-methyl-2-butyleyl)-4,5-dihydoxy-cyclopent-4-en-1,3-dione, lupulone and three of its derivatives were isolated from the ethyl acetate soluble fraction. The chalcones, including xanthohumol, significantly inhibited the production of NO by suppressing the expression of iNOS.

Animals↗

[Investigation on the gene expression pattern in cervical squamous cell carcinoma of uygur].

OBJECTIVE: To investigate the differentially expressed gene in cervical squamous cell carcinoma of uygur and normal cervical tissue using gene chip. METHOD: Gene chips containing 2,048 human genes were used to investigate the gene expression pattern of 3 samples of cervical cancer. RESULT: By applying this gene chip we identified 64 differentially expressed genes in all 3 clinical cervical cancer samples, and we further identified 53 upregulated and 11 downregulated genes for functional analysis. CONCLUSION: The analysis of gene expression pattern of tumor based on gene chip can realize high-throughput screening of the genes associated with the cervical cancer.

Carcinoma, Squamous Cell↗

Two-step K(+)-Na+ and Ag(+)-Na+ ion-exchanged glass waveguides for C-band applications.

A two-step K(+)-Na+ and Ag(+)-Na+ ion-exchange technique is introduced to fabricate single-mode channel waveguides in BK7 glass for the telecom-wavelength region. The dependencies of insertion loss, polarization-dependent loss (PDL), end bending loss of curved waveguides on channel width, diffusion time, and annealing time are investigated. Results show that postannealing is a required process for improving waveguide properties and an optimal annealing time exists. Although relatively narrow mask openings are used in most one-step ion-exchange processes, a wider channel width, to as wide as 10 microm, is preferred for this two-step method. The minimum coupling loss to/from single-mode fiber and the propagation loss is found to be 0.4 dB and 0.3 dB/cm, respectively. For 5-cm-long waveguides the PDL is less than 0.1 dB. For the S-bend structure the cosine curve exhibit apparently a lower bending loss than the double-arc curve.

Journal Article↗

Synthetic, structural, electrochemical, and theoretical studies of heterometallic aggregates with a [Pt(2)(mu-S)(2)M] core (M = Hg, Au).

Novel electroactive multimetallic compounds based on the [Pt(2)(mu(2)-S)(2)M] core, viz. [Pt(2)(PPh(3))(4)(mu(3)-S)(2)HgFc]PF(6) (1) [Fc = (eta(5)-C(5)H(4))Fe(eta(5)-C(5)H(5))] and [Pt(2)(PPh(3))(4)(mu(3)-S)(2)Hg(2)Fc'](PF(6))(2) (2) [Fc' = Fe(eta(5)-C(5)H(4))(2)], have been synthesized under the guide of electrospray mass spectrometry. The electrochemistry of these ferrocene funtionalized compounds together with the reported [Pt(2)(PPh(3))(4)(mu(3)-S)(2)HgPPh(3)](PF(6))(2) (3), [Pt(2)(PPh(3))(4)(mu(2)-S)(mu(3)-S)HgPh]PF(6) (4), and [Pt(2)(PPh(3))(4)(mu(2)-S)(mu(3)-S)AuPPh(3)]PF(6) (5) have been investigated using cyclic voltammetry and DFT calculations. These results point to a prominent ligand-based oxidation.

Journal Article↗

Athermalized low-loss echelle-grating-based multimode dense wavelength division demultiplexer.

A high-density wavelength division demultiplexer (DEMUX) capable of demultiplexing eight-channel 200-GHz optically spaced signals into a 62.5-microm multimode-fiber array is reported. The wavelength range of operation is from 1549.32 to 1560.61 nm within the International Telecommunication Union grid. The measured wavelength accuracy is within 0.04 nm. The mean insertion loss of this DEMUX is 1.95 dB. Thermal analysis and temperature testing results are reported. The temperature test cycling from 20 degrees C to 60 degrees C indicates that the wavelength thermal drift is less than 0.8 pm/degrees C. Adjacent cross talk is measured to be better than -45 dB. The measured data transmission bit rate of this device is higher than 3.5 Gb/s.

Journal Article↗

Benefit of clopidogrel in patients with acute coronary syndromes without ST-segment elevation in various risk groups.

BACKGROUND: The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial demonstrated that clopidogrel, given early and continued long term, was superior to placebo in patients with non-ST-elevation acute coronary syndromes receiving aspirin. The purpose of the present analysis was to estimate the treatment effect Zof clopidogrel in patients who were stratified according to their risk of future cardiovascular events. METHODS AND RESULTS: Patients (n=12 562) who presented within 24 hours after the onset of symptoms were randomized to receive clopidogrel (300 mg followed by 75 mg daily) or placebo in addition to aspirin for 3 to 12 months. Treatment effect was analyzed in various risk groups according to the Thrombolysis in Myocardial Infarction (TIMI) risk score. The TIMI risk model was validated in the CURE population (C statistic, 0.634). The primary composite outcome of cardiovascular death, myocardial infarction, or stroke increased proportionally with increasing risk according to the TIMI risk score. The impact of clopidogrel versus placebo on the rate of the primary outcome was as follows: low-risk group (TIMI score 0 to 2), 4.1% versus 5.7% (relative risk [RR], 0.71; 95% confidence interval [CI], 0.52 to 0.97; P< 0.04), intermediate-risk group (TIMI score 3 to 4), 9.8% versus 11.4% (RR, 0.85; 95% CI, 0.74 to 0.98; P<0.03), and high-risk group (TIMI score 5 to 7), 15.9% versus 20.7% (RR, 0.73; 95% CI, 0.60 to 0.90; P<0.004). There was no evidence of statistical heterogeneity among the groups. CONCLUSIONS: The benefit of clopidogrel demonstrated in the CURE trial is consistent in low-, intermediate-, and high-risk patients with acute coronary syndromes (as stratified by TIMI risk score), thus supporting its use in all patients with documented non-ST elevation acute coronary syndromes.

Acute Disease↗

Preparation and histological evaluation of biomimetic three-dimensional hydroxyapatite/chitosan-gelatin network composite scaffolds.

A novel biodegradable hydroxyapatite/chitosan-gelatin network (HA/CS-Gel) composite of similar composition to that of normal human bone was prepared as a three-dimensional biomimetic scaffold by phase separation method for bone tissue engineering. Changing the solid content and the compositional variables of the original mixtures allowed control of the porosities and densities of the scaffolds. The HA granules were dispersed uniformly in the organic network with intimate interface contact via pulverizing and ultrasonically treating commercial available HA particles. Scaffolds of 90.6% porosity were used to examine the proliferation and functions of the cells in this three-dimensional microenvironment by culturing neonatal rat caldaria osteoblasts. Histological and immunohistochemical staining and scanning electron microscopy observation indicated that the osteoblasts attached to and proliferated on the scaffolds. Extracellular matrices including collagen I and proteoglycan-like substrate were synthesized, while osteoid and bone-like tissue formed during the culture period. Furthermore, the cell/scaffold constructs had good biomineralization effect after 3 weeks in culture.

Animals↗

[Tissue engineering study on chitosan-gelatin/hydroxyapatite composite scaffolds--osteoblasts culture].

OBJECTIVE: To investigate the behavior of rat calvarial osteoblasts cultured on chitosan-gelatin/hydroxyapatite (CS-Gel/HA) composite scaffolds. METHODS: The rat calvarial osteoblasts (the 3rd passage) were seeded at a density of 1.01 x 10(6) cells/ml onto the CS-Gel/HA composite scaffolds having porosity 85.20%, 90.40% and 95.80%. Cell number was counted after cultured for 3 days, 1 week, 2 weeks and 3 weeks. Cell proliferation, bone-like tissue formation, and mineralization were separately detected by HE, von Kossa histological staining techniques. RESULTS: The CS-Gel/HA composite scaffolds supported the attachment of seeded rat calvarial osteoblasts. Cells proliferated faster in scaffold with higher porosity 90.40% and 95.80% than scaffold with lower porosity 85.20%. The osteoblasts/scaffold constructs were feasible for mineral deposition, and bone-like tissue formation in 3 weeks. CONCLUSION: This study suggests the feasibility of using CS-Gel/HA composite scaffolds for bone tissue engineering.

Animals↗