Objective: Using receiver operating characteristics (ROC) curve to evaluate the value of pulse wave velocity (PWV) in the diagnosis of coronary heart disease (CHD). Methods: By using coronary angiography as golden dia...Objective: Using receiver operating characteristics (ROC) curve to evaluate the value of pulse wave velocity (PWV) in the diagnosis of coronary heart disease (CHD). Methods: By using coronary angiography as golden diagnostic standard of CHD, 218 patients were divided into both CHD group (n=121) and non-CHD group (n = 97). All these patients received PWV test. The efficacy of PWV of each artery segments in the diagnosis of CHD was evaluated by ROC curve. The sensitivity and specificity were calculated with the golden diagnostic standard of CHD. Results:The PWV of right carotid to femoral artery (Rc-f), left carotid to femoral artery (Lc-f), right radial to carotid artery (Rc-r), left radial to carotid artery (Lc-r) in CHD group were significantly higher than that of non-CHD group (9. 31±1. 75 vs 7.60±1.59, P<0. 01; 9. 02±1.71 vs 7. 52±1.50, P<0. 01; 8. 69±1. 37 vs 8. 00±1. 27, P<0. 01; 8.52±1. 03 vs 8. 03±1. 2, P<0. 01 respectively). However, the PWV of both right and left femoral to ankle artery (Rf-a and Lf-a) had no significant differences between the two groups. We then compared the area under curve (AUC) of each ROC(AUCROC) of PWV of Rc-f, Lc-f Rc-r and Lc-r to evaluate their diagnostic efficacy for CHD. We found that AUCROC of Rc-f PWV was the biggest (AUCROC = 0. 818), at the peak point of its ROC curve, the PWV was 8. 32 m/s. PWV>8. 32 m/s of Rc-f could predict the presence of CHD with a sensitivity of 79% and specificity of 77%. Conclusion: The PWV of Rc-f, Lc-f, Rc-r, Lc-r are significantly higher in CHD group than that in non-CHD group, and PWV of Rc-f is the most accurate in the detection of CHD. The PWV>8. 32 m/s of RC-F is a valuable predictor of CHD.展开更多
Objective The study aimed to synthesize and characterize pyrimidine-linked benzimidazole hybrids,define their antimicrobial and antifungal activities in vitro,and determine their ability to inhibit the main protease a...Objective The study aimed to synthesize and characterize pyrimidine-linked benzimidazole hybrids,define their antimicrobial and antifungal activities in vitro,and determine their ability to inhibit the main protease and spike glycoprotein of SARS-CoV-2.Methods The ability of the synthesized compounds to inhibit the main protease and spike glycoprotein inhibitory of SARS-CoV-2 was investigated by assessing their mode of binding to the allosteric site of the enzyme using molecular docking.The structures of pyrimidine-linked benzimidazole derivatives synthesized with microwave assistance were confirmed by spectral analysis.Antibacterial and antifungal activities were determined by broth dilution.Results Gram-negative bateria(Escherichia coli and Pseudomonas aeruginosa)were more sensitive than gram-positive bateria(Staphylococcus aureus and Streptococcus pyogenes)to the derivatives.Candida albicans was sensitive to the derivatives at a minimal inhibitory concentration(MIC)of 250μg/mL.The novel derivatives had better binding affinity(kcal/mol)than nelfinavir,lopinavir,ivermectin,remdesivir,and favipiravir,which are under investigation as treatment for SARS-CoV-2 infection.Compounds 2c,2e,and 2g formed four hydrogen bonds with the active cavity of the main protease.Many derivatives had good binding affinity for the RBD of the of SARS-CoV-2 spike glycoprotein with the formation of up to four hydrogen bonds.Conclusion We synthesized novel pyrimidine-linked benzi-midazole derivatives that were potent antimicrobial agents with ability to inhibit the SARS-CoV-2 spike glycoprotein.Understanding the pharmacophore features of the main protease and spike glycoprotein offers much scope for the development of more potent agents.We plan to optimize the properties of the derivatives using models in vivo and in vitro so that they will serve as more effective therapeutic options against bacterial and SARS-CoV-2 infections.展开更多
Objective: To explore the relationship between C-reactive protein(CRP) concentration and severity of coronary artery lesion. Methods: The plasma CRP concentration were tested in 166 cases who underwent coronary angiog...Objective: To explore the relationship between C-reactive protein(CRP) concentration and severity of coronary artery lesion. Methods: The plasma CRP concentration were tested in 166 cases who underwent coronary angiography(CAG),coronary heart disease(CHD) was presented in 86 patients and absent in 80 cases as normal control group, and results of the two groups and different numbers of diseased coronary vessels in CHD group were analyzed. Results: The plasma CRP concentration were 2293±198, 5126±508, 12969±1076 μg/L, respectively,for the normal control group, the stable angina group and the unstable angina group. The CRP concentration in the stable angina group and unstable angina group were significantly higher than those of the normal control group (P<0.05, P<0.01, respectively). In the CHD group, the plasma CRP concentration were 5131±513, 7024±689, 11970±2075 μg/L, respectively,for the 1-vessel-disease-group, the 2-vessel-disease-group and the 3-vessel-disease-group. The CRP concentration of the three groups were significantly higher than those of the normal control group (P<0.01). Conclusion: CRP concentration is closely associated with severity of coronary artery lesion.展开更多
Single nucleotide polymorphisms (SNP) of ATP-binding cassette transporter A1 (ABCA1) gene are related to plasma lipid and susceptibility to coronary artery disease (CAD). Our first goal was to screen all 50 codi...Single nucleotide polymorphisms (SNP) of ATP-binding cassette transporter A1 (ABCA1) gene are related to plasma lipid and susceptibility to coronary artery disease (CAD). Our first goal was to screen all 50 coding regions of ABCA1 to find new SNPs. Our second goal was to investigate the frequency distribution of R1587K and M883I polymorphisms of ABCA1 gene, which are the variant occurred most frequently, in Chinese people and to evaluate their association with the CAD phenotype and plasma lipids. Methods: Single-strand conformation polymorphism (SSCP) and DNA sequence were used for confirming new SNP of ABCA1, and restriction fragment length polymorphism (RFLP) were applied for confirming genotypes of R1587K and M883I in 112 CAD cases and 108 healthy people. Results: We discovered a new ABCA1 SNP in Chinese population, which converse 233 amino acids from Methionine to Valine (M233V). This new ABCA1 SNP located in exon7, and might potentially modulate the biological function of lipid metabolism. For R1587K and M883I SNPs, the K allele and I allele frequency was 28.9% and 31.1%, respectively. The K allele at R1587K conferred lower mean values of HDL-C in a dose-dependent manner in both CAD patients and healthy people. However, 883I allele was not associated with plasma lipid level. Neither 1587KK nor 883II associated with increased risk of CAD. Conclusion: Our study finds a potential functional ABCA1 SNPs and revealed K allele of R1587K associated decreased HDL-C level in Chinese population.展开更多
Objective The platelet membrane glycoprotein (GP)Ⅰa/Ⅱa plays a major part as a primary colla-gen receptor in platelet function. Previous studies indicated that variations of GPⅠa/Ⅱa density and function are associ...Objective The platelet membrane glycoprotein (GP)Ⅰa/Ⅱa plays a major part as a primary colla-gen receptor in platelet function. Previous studies indicated that variations of GPⅠa/Ⅱa density and function are associated with the 807 C/T polymorphism of GPⅠa gene in American and Spanish Cau-casian populations. This study investigated the correlation between acute coronary syndrome (ACS) and 807 C/T dimorphism of GPⅠa gene in Chinese of Han ethnicity. Methods A case-control study was carried out, including 75 patients with either acute myocar-dial infarction (AMI) or unstable angina pectoris (UAP), and 65 controls with no history of coronary heart disease, thrombogenic and hemorrhagenic diseases. Genotypes of GPⅠa were checked by polymerase chain reaction-sequence specific primers(PCR-SSP)technique. Results The frequencies of both homozygotes and heterozygotes for T807 allele(TT+TC)were significantly higher in patients with AMI than in controls(62.16% vs 33.85%, P < 0.01; odds ratio 3.21). The prevalence of (TT+TC) genotypes was also markedly higher in patients with UAP than in controls(65.79% vs 33.85%, P < 0.005; odds ratio 3.76). There was significant difference in the distribution of(TT+TC)genotypes not only between all patients and controls(64.00% vs 33.85%, P <0.005; odds ratio 3.47)but also between the two subgroups aged < 60 years(70.00% vs 38.24%, P <0.005; odds ratio 3.77). However, there was no significant difference in the distribution of(TT+TC)genotypes between patients with AMI and with UAP. Platelet GPⅠa T807 allele remained significantly associated with AMI and UAP by multiple logistic regression(odds ratio 4.94). Conclusion This study suggests a strong association between presence of GPⅠa T807 allele and ACS. T807 allele can be a marker of genetic susceptibility to ACS.展开更多
Objective To analyze the current usage of optimal medical therapy (OMT), influencing factors, and the predictive value of OMT for all-cause mortality in coronary artery disease (CAD) patients with different subgro...Objective To analyze the current usage of optimal medical therapy (OMT), influencing factors, and the predictive value of OMT for all-cause mortality in coronary artery disease (CAD) patients with different subgroups. Methods A total of 3176 CAD patients confirmed by coronary angiography were included. OMT was defined as the combination of anti-platelet drugs, statins, beta blockers, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Factors for OMT and its prognostic value were analyzed in CAD patients across different subgroups. Results Out of 3176 patients, only 39.8% (n = 1265) were on OMT at discharge. Factors associated with OMT at discharge were pre-admission OMT and discharge department. All-cause mortality occurred in 6.8% (n = 217) of patients. Multivariate analyses indicated that OMT was significantly associated with reduced all-cause mortality (HR: 0.65, 95% CI: 0.45~0.95; P = 0.025). Sub-group analyses indicate that male acute coronary syndrome (ACS) patients were more likely to receive survival benefits with OMT at discharge. The positive impact of OMT at discharge was more apparent after 24 months, regardless of revascularization therapy. Four-drug combination of OMT was superior to 3-drug combination therapy in ACS patients but not in stable patients. Conclusions OMT was asso- ciated with significant improvement in survival in patients with CAD. The positive impact of OMT was distinct in the CAD patients with different characteristics.展开更多
In order to establish the eukaryotic cell lines for inducible control of SARS-CoV nucleocapsid gene expression.The recombinant plasmid of pTRE-Tight-SARS-N was constructed by using the plasmid p8S as the PCR template ...In order to establish the eukaryotic cell lines for inducible control of SARS-CoV nucleocapsid gene expression.The recombinant plasmid of pTRE-Tight-SARS-N was constructed by using the plasmid p8S as the PCR template which contains a cDNA clone covering the nucleocapsid gene of SARS-CoV HKU-39449. Restriction enzymes digestion and sequence analysis indicated the recombinant plasmid of pTRE-Tight-SARS-N contained the nucleocapsid gene with the optimized nucleotide sequence which will improve the translation efficiency. Positive cell clones were selected by cotransfecting pTRE-Tight-SARS-N with the linear marker pPUR to BHK-21 Tet-on cells in the presence of puromycin. A set of double-stable eukaryotic cell lines (BHK-Tet-SARS-N) with inducible control of the SARS-CoV neucleocapsid gene expression was identified by using SDS-PAGE and Western-blot analysis. The expression of SARS-CoV nucleocapsid protein was tightly regulated by the varying concentration of doxcycline in the constructed double-stable cell line. The constructed BHK-Tet-SARS-N cell strains will facilitate the rescue of SARS-CoV in vitro and the further reverse genetic research of SARS-CoV.展开更多
Background There is great debate on the possible adverse interaction between proton pump inhibitors (PPIs) and clopidogrel. In ad- dition, whether the use of PPIs affects the clinical efficacy of ticagrelor remains ...Background There is great debate on the possible adverse interaction between proton pump inhibitors (PPIs) and clopidogrel. In ad- dition, whether the use of PPIs affects the clinical efficacy of ticagrelor remains less known. We aimed to determine the impact of concomi- tant administration of PPIs and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome (ACS) after percuta- neous coronary intervention (PCI). Methods We retrospectively analyzed data fi'om a "real world", international, multi-center registry between 2003 and 2014 (n = 15,401) and assessed the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year composite primary endpoint (all-cause death, re-infarction, or severe bleeding) in patients with ACS after PCI. Results Of 9429 patients in the final cohort, 54.8% (n = 5165) was prescribed a PPI at discharge. Patients receiving a PPI were older, more often female, and were more likely to have comorbidities. No association was observed between PPI use and the primary endpoint for patients receiving clopidogrel (ad- justed HR: 1.036; 95% CI: 0.903-1.189) or ticagrelor (adjusted HR: 2.320; 95% CI: 0.875-45.151) (Pinteraction = 0.2004). Similarly, use of a PPI was not associated with increased risk of all-cause death, re-infarction, or a decreased risk of severe bleeding for patients treated with either clopidogrel or ticagrelor. Conclusions In patients with ACS following PCI, concomitant use of PPIs was not associated with in- creased risk of adverse outcomes in patients receiving either clopidogrel or ticagrelor. Our findings indicate it is reasonable to use a PPI in combination with clopidogrel or ticagrelor, especially in patients with a higher risk of gastrointestinal bleeding.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) relies on the central molecular machine RNA-dependent RNA polymerase(Rd Rp) for the viral replication and transcription. Remdesivir at the template strand h...Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) relies on the central molecular machine RNA-dependent RNA polymerase(Rd Rp) for the viral replication and transcription. Remdesivir at the template strand has been shown to effectively inhibit the RNA synthesis in SARS-Co V-2 Rd Rp by deactivating not only the complementary UTP incorporation but also the next nucleotide addition. However, the underlying molecular mechanism of the second inhibitory point remains unclear. In this work, we have performed molecular dynamics simulations and demonstrated that such inhibition has not directly acted on the nucleotide addition at the active site. Instead, the translocation of Remdesivir from +1 to-1 site is hindered thermodynamically as the posttranslocation state is less stable than the pre-translocation state due to the motif B residue G683. Moreover, another conserved residue S682 on motif B further hinders the dynamic translocation of Remdesivir due to the steric clash with the 1′-cyano substitution. Overall,our study has unveiled an alternative role of motif B in mediating the translocation when Remdesivir is present in the template strand and complemented our understanding about the inhibitory mechanisms exerted by Remdesivir on the RNA synthesis in SARS-Co V-2 Rd Rp.展开更多
Thromboembolic complications have been frequently re- ported in patients with long-lasting nephrotic syndrome (NS). Although thrombotic complications in the venous system are common in patients with NS, arterial thr...Thromboembolic complications have been frequently re- ported in patients with long-lasting nephrotic syndrome (NS). Although thrombotic complications in the venous system are common in patients with NS, arterial thromboses associated with NS are much less common. However, coronary thromboses are extremely rarely observed. So, NS is a rare cause of acute coronary syndrome (ACS). As such, the incidence, pathogenesis, and treatment of these patients have yet to be clearly defined. In the current litera- ture, publications contain less than 15 patients, most of whom are young children.展开更多
Let G be a connected graph of order p, and let γ7(G) denote the domination number of G. Clearly, γ(G) ≤[p/2]. The aim of this paper is to characterize the graphs G that reaches this upper bound. The main results ar...Let G be a connected graph of order p, and let γ7(G) denote the domination number of G. Clearly, γ(G) ≤[p/2]. The aim of this paper is to characterize the graphs G that reaches this upper bound. The main results are as follows: (1) when p is even, γ(G) = p/2 if and only if either G C4 or G is the crown of a connected graph with p/2 vertices; (2) when p is odd, γ(G) = (p-1)/2 if and only if every spanning tree of G is one of the two classes of trees shown in Theorem 3.1.展开更多
A series of macrocycles, including crown ethers, cyclodextrins, calixarenes, pillararenes and cucurbiturils, are well known to be able to associate various organic/inorganic/biological guest molecules and ions in thei...A series of macrocycles, including crown ethers, cyclodextrins, calixarenes, pillararenes and cucurbiturils, are well known to be able to associate various organic/inorganic/biological guest molecules and ions in their well-defined cyclic cavities to form stable host-guest complexes and supramolecular systems through the cooperative contributions of various non-covalent interactions.When one or more functional groups are attached to the cavity of macrocycles or guest molecules, enhanced and/or controlled host-guest associations may take place, leading to not only improved host-guest binding abilities but also fascinating properties.In this review, some representative contributions in the construction of controllable macrocyclic supramolecular assemblies in aqueous solution are presented with an emphasis on the stimuli-responsive control manner and wide applications of this property.展开更多
Forced response analysis of a rocket engine turbine blade was conducted by a decoupled fluid-structure interaction procedure.Aerodynamic forces on the rotor blade were obtained using 3D unsteady flow simulations. The ...Forced response analysis of a rocket engine turbine blade was conducted by a decoupled fluid-structure interaction procedure.Aerodynamic forces on the rotor blade were obtained using 3D unsteady flow simulations. The resulting aerodynamic forces were interpolated to the finite element(FE) model through surface effect elements prior to conducting forced response calculations.Effects of axial gap on aerodynamic forces were studied. In addition, influence of axial gap on the response of the shrouded blade was compared with that on the response of the unshrouded blade. Results demonstrated that as the axial gap increases,time-averaged pressure on the blade surface changes very little, while the pressure fluctuations decrease significantly. Pressure and aerodynamic forces on the blade surface display periodic variation, and the vane passing frequency component is dominant.Amplitudes of aerodynamic forces decrease with increasing axial gap. Restricted by the shroud, deformation and response of shrouded blade are much lower than those of the unshrouded blade. The response of unshrouded blade shows obvious beat vibration phenomenon, while the response of the shrouded blade does not have this characteristic because the shroud restrains multiple harmonics. Blade response in time domain was converted to frequency domain using fast Fourier transformation(FFT).Results revealed that the axial gap mainly affects the forced harmonic at the vane passing frequency, while the other two harmonics at natural frequency are hardly affected. Amplitudes of the unshrouded blade response decrease as the axial gap increases, while amplitudes of the shrouded blade response change very little in comparison.展开更多
文摘Objective: Using receiver operating characteristics (ROC) curve to evaluate the value of pulse wave velocity (PWV) in the diagnosis of coronary heart disease (CHD). Methods: By using coronary angiography as golden diagnostic standard of CHD, 218 patients were divided into both CHD group (n=121) and non-CHD group (n = 97). All these patients received PWV test. The efficacy of PWV of each artery segments in the diagnosis of CHD was evaluated by ROC curve. The sensitivity and specificity were calculated with the golden diagnostic standard of CHD. Results:The PWV of right carotid to femoral artery (Rc-f), left carotid to femoral artery (Lc-f), right radial to carotid artery (Rc-r), left radial to carotid artery (Lc-r) in CHD group were significantly higher than that of non-CHD group (9. 31±1. 75 vs 7.60±1.59, P<0. 01; 9. 02±1.71 vs 7. 52±1.50, P<0. 01; 8. 69±1. 37 vs 8. 00±1. 27, P<0. 01; 8.52±1. 03 vs 8. 03±1. 2, P<0. 01 respectively). However, the PWV of both right and left femoral to ankle artery (Rf-a and Lf-a) had no significant differences between the two groups. We then compared the area under curve (AUC) of each ROC(AUCROC) of PWV of Rc-f, Lc-f Rc-r and Lc-r to evaluate their diagnostic efficacy for CHD. We found that AUCROC of Rc-f PWV was the biggest (AUCROC = 0. 818), at the peak point of its ROC curve, the PWV was 8. 32 m/s. PWV>8. 32 m/s of Rc-f could predict the presence of CHD with a sensitivity of 79% and specificity of 77%. Conclusion: The PWV of Rc-f, Lc-f, Rc-r, Lc-r are significantly higher in CHD group than that in non-CHD group, and PWV of Rc-f is the most accurate in the detection of CHD. The PWV>8. 32 m/s of RC-F is a valuable predictor of CHD.
文摘Objective The study aimed to synthesize and characterize pyrimidine-linked benzimidazole hybrids,define their antimicrobial and antifungal activities in vitro,and determine their ability to inhibit the main protease and spike glycoprotein of SARS-CoV-2.Methods The ability of the synthesized compounds to inhibit the main protease and spike glycoprotein inhibitory of SARS-CoV-2 was investigated by assessing their mode of binding to the allosteric site of the enzyme using molecular docking.The structures of pyrimidine-linked benzimidazole derivatives synthesized with microwave assistance were confirmed by spectral analysis.Antibacterial and antifungal activities were determined by broth dilution.Results Gram-negative bateria(Escherichia coli and Pseudomonas aeruginosa)were more sensitive than gram-positive bateria(Staphylococcus aureus and Streptococcus pyogenes)to the derivatives.Candida albicans was sensitive to the derivatives at a minimal inhibitory concentration(MIC)of 250μg/mL.The novel derivatives had better binding affinity(kcal/mol)than nelfinavir,lopinavir,ivermectin,remdesivir,and favipiravir,which are under investigation as treatment for SARS-CoV-2 infection.Compounds 2c,2e,and 2g formed four hydrogen bonds with the active cavity of the main protease.Many derivatives had good binding affinity for the RBD of the of SARS-CoV-2 spike glycoprotein with the formation of up to four hydrogen bonds.Conclusion We synthesized novel pyrimidine-linked benzi-midazole derivatives that were potent antimicrobial agents with ability to inhibit the SARS-CoV-2 spike glycoprotein.Understanding the pharmacophore features of the main protease and spike glycoprotein offers much scope for the development of more potent agents.We plan to optimize the properties of the derivatives using models in vivo and in vitro so that they will serve as more effective therapeutic options against bacterial and SARS-CoV-2 infections.
文摘Objective: To explore the relationship between C-reactive protein(CRP) concentration and severity of coronary artery lesion. Methods: The plasma CRP concentration were tested in 166 cases who underwent coronary angiography(CAG),coronary heart disease(CHD) was presented in 86 patients and absent in 80 cases as normal control group, and results of the two groups and different numbers of diseased coronary vessels in CHD group were analyzed. Results: The plasma CRP concentration were 2293±198, 5126±508, 12969±1076 μg/L, respectively,for the normal control group, the stable angina group and the unstable angina group. The CRP concentration in the stable angina group and unstable angina group were significantly higher than those of the normal control group (P<0.05, P<0.01, respectively). In the CHD group, the plasma CRP concentration were 5131±513, 7024±689, 11970±2075 μg/L, respectively,for the 1-vessel-disease-group, the 2-vessel-disease-group and the 3-vessel-disease-group. The CRP concentration of the three groups were significantly higher than those of the normal control group (P<0.01). Conclusion: CRP concentration is closely associated with severity of coronary artery lesion.
基金Supported by the Natural Scientific Foundation of China (30471929)
文摘Single nucleotide polymorphisms (SNP) of ATP-binding cassette transporter A1 (ABCA1) gene are related to plasma lipid and susceptibility to coronary artery disease (CAD). Our first goal was to screen all 50 coding regions of ABCA1 to find new SNPs. Our second goal was to investigate the frequency distribution of R1587K and M883I polymorphisms of ABCA1 gene, which are the variant occurred most frequently, in Chinese people and to evaluate their association with the CAD phenotype and plasma lipids. Methods: Single-strand conformation polymorphism (SSCP) and DNA sequence were used for confirming new SNP of ABCA1, and restriction fragment length polymorphism (RFLP) were applied for confirming genotypes of R1587K and M883I in 112 CAD cases and 108 healthy people. Results: We discovered a new ABCA1 SNP in Chinese population, which converse 233 amino acids from Methionine to Valine (M233V). This new ABCA1 SNP located in exon7, and might potentially modulate the biological function of lipid metabolism. For R1587K and M883I SNPs, the K allele and I allele frequency was 28.9% and 31.1%, respectively. The K allele at R1587K conferred lower mean values of HDL-C in a dose-dependent manner in both CAD patients and healthy people. However, 883I allele was not associated with plasma lipid level. Neither 1587KK nor 883II associated with increased risk of CAD. Conclusion: Our study finds a potential functional ABCA1 SNPs and revealed K allele of R1587K associated decreased HDL-C level in Chinese population.
文摘Objective The platelet membrane glycoprotein (GP)Ⅰa/Ⅱa plays a major part as a primary colla-gen receptor in platelet function. Previous studies indicated that variations of GPⅠa/Ⅱa density and function are associated with the 807 C/T polymorphism of GPⅠa gene in American and Spanish Cau-casian populations. This study investigated the correlation between acute coronary syndrome (ACS) and 807 C/T dimorphism of GPⅠa gene in Chinese of Han ethnicity. Methods A case-control study was carried out, including 75 patients with either acute myocar-dial infarction (AMI) or unstable angina pectoris (UAP), and 65 controls with no history of coronary heart disease, thrombogenic and hemorrhagenic diseases. Genotypes of GPⅠa were checked by polymerase chain reaction-sequence specific primers(PCR-SSP)technique. Results The frequencies of both homozygotes and heterozygotes for T807 allele(TT+TC)were significantly higher in patients with AMI than in controls(62.16% vs 33.85%, P < 0.01; odds ratio 3.21). The prevalence of (TT+TC) genotypes was also markedly higher in patients with UAP than in controls(65.79% vs 33.85%, P < 0.005; odds ratio 3.76). There was significant difference in the distribution of(TT+TC)genotypes not only between all patients and controls(64.00% vs 33.85%, P <0.005; odds ratio 3.47)but also between the two subgroups aged < 60 years(70.00% vs 38.24%, P <0.005; odds ratio 3.77). However, there was no significant difference in the distribution of(TT+TC)genotypes between patients with AMI and with UAP. Platelet GPⅠa T807 allele remained significantly associated with AMI and UAP by multiple logistic regression(odds ratio 4.94). Conclusion This study suggests a strong association between presence of GPⅠa T807 allele and ACS. T807 allele can be a marker of genetic susceptibility to ACS.
文摘Objective To analyze the current usage of optimal medical therapy (OMT), influencing factors, and the predictive value of OMT for all-cause mortality in coronary artery disease (CAD) patients with different subgroups. Methods A total of 3176 CAD patients confirmed by coronary angiography were included. OMT was defined as the combination of anti-platelet drugs, statins, beta blockers, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Factors for OMT and its prognostic value were analyzed in CAD patients across different subgroups. Results Out of 3176 patients, only 39.8% (n = 1265) were on OMT at discharge. Factors associated with OMT at discharge were pre-admission OMT and discharge department. All-cause mortality occurred in 6.8% (n = 217) of patients. Multivariate analyses indicated that OMT was significantly associated with reduced all-cause mortality (HR: 0.65, 95% CI: 0.45~0.95; P = 0.025). Sub-group analyses indicate that male acute coronary syndrome (ACS) patients were more likely to receive survival benefits with OMT at discharge. The positive impact of OMT at discharge was more apparent after 24 months, regardless of revascularization therapy. Four-drug combination of OMT was superior to 3-drug combination therapy in ACS patients but not in stable patients. Conclusions OMT was asso- ciated with significant improvement in survival in patients with CAD. The positive impact of OMT was distinct in the CAD patients with different characteristics.
基金This work was supported by the European Commission (SARS-DTV ) SP22-CT-2004–511064)the State Key Laboratory of Pathogen and Biosecunity SKLPBS0918
文摘In order to establish the eukaryotic cell lines for inducible control of SARS-CoV nucleocapsid gene expression.The recombinant plasmid of pTRE-Tight-SARS-N was constructed by using the plasmid p8S as the PCR template which contains a cDNA clone covering the nucleocapsid gene of SARS-CoV HKU-39449. Restriction enzymes digestion and sequence analysis indicated the recombinant plasmid of pTRE-Tight-SARS-N contained the nucleocapsid gene with the optimized nucleotide sequence which will improve the translation efficiency. Positive cell clones were selected by cotransfecting pTRE-Tight-SARS-N with the linear marker pPUR to BHK-21 Tet-on cells in the presence of puromycin. A set of double-stable eukaryotic cell lines (BHK-Tet-SARS-N) with inducible control of the SARS-CoV neucleocapsid gene expression was identified by using SDS-PAGE and Western-blot analysis. The expression of SARS-CoV nucleocapsid protein was tightly regulated by the varying concentration of doxcycline in the constructed double-stable cell line. The constructed BHK-Tet-SARS-N cell strains will facilitate the rescue of SARS-CoV in vitro and the further reverse genetic research of SARS-CoV.
文摘Background There is great debate on the possible adverse interaction between proton pump inhibitors (PPIs) and clopidogrel. In ad- dition, whether the use of PPIs affects the clinical efficacy of ticagrelor remains less known. We aimed to determine the impact of concomi- tant administration of PPIs and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome (ACS) after percuta- neous coronary intervention (PCI). Methods We retrospectively analyzed data fi'om a "real world", international, multi-center registry between 2003 and 2014 (n = 15,401) and assessed the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year composite primary endpoint (all-cause death, re-infarction, or severe bleeding) in patients with ACS after PCI. Results Of 9429 patients in the final cohort, 54.8% (n = 5165) was prescribed a PPI at discharge. Patients receiving a PPI were older, more often female, and were more likely to have comorbidities. No association was observed between PPI use and the primary endpoint for patients receiving clopidogrel (ad- justed HR: 1.036; 95% CI: 0.903-1.189) or ticagrelor (adjusted HR: 2.320; 95% CI: 0.875-45.151) (Pinteraction = 0.2004). Similarly, use of a PPI was not associated with increased risk of all-cause death, re-infarction, or a decreased risk of severe bleeding for patients treated with either clopidogrel or ticagrelor. Conclusions In patients with ACS following PCI, concomitant use of PPIs was not associated with in- creased risk of adverse outcomes in patients receiving either clopidogrel or ticagrelor. Our findings indicate it is reasonable to use a PPI in combination with clopidogrel or ticagrelor, especially in patients with a higher risk of gastrointestinal bleeding.
基金supported by the National Key RD program of China(No.2021YFA1502300)the National Natural Science Foundation of China(No.21733007)。
文摘Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) relies on the central molecular machine RNA-dependent RNA polymerase(Rd Rp) for the viral replication and transcription. Remdesivir at the template strand has been shown to effectively inhibit the RNA synthesis in SARS-Co V-2 Rd Rp by deactivating not only the complementary UTP incorporation but also the next nucleotide addition. However, the underlying molecular mechanism of the second inhibitory point remains unclear. In this work, we have performed molecular dynamics simulations and demonstrated that such inhibition has not directly acted on the nucleotide addition at the active site. Instead, the translocation of Remdesivir from +1 to-1 site is hindered thermodynamically as the posttranslocation state is less stable than the pre-translocation state due to the motif B residue G683. Moreover, another conserved residue S682 on motif B further hinders the dynamic translocation of Remdesivir due to the steric clash with the 1′-cyano substitution. Overall,our study has unveiled an alternative role of motif B in mediating the translocation when Remdesivir is present in the template strand and complemented our understanding about the inhibitory mechanisms exerted by Remdesivir on the RNA synthesis in SARS-Co V-2 Rd Rp.
基金The program is supported by grants from the National Na tural Science Foundation of China (No.81400238).
文摘Thromboembolic complications have been frequently re- ported in patients with long-lasting nephrotic syndrome (NS). Although thrombotic complications in the venous system are common in patients with NS, arterial thromboses associated with NS are much less common. However, coronary thromboses are extremely rarely observed. So, NS is a rare cause of acute coronary syndrome (ACS). As such, the incidence, pathogenesis, and treatment of these patients have yet to be clearly defined. In the current litera- ture, publications contain less than 15 patients, most of whom are young children.
基金Supported by the National Science Foundation of Jiangxi province.
文摘Let G be a connected graph of order p, and let γ7(G) denote the domination number of G. Clearly, γ(G) ≤[p/2]. The aim of this paper is to characterize the graphs G that reaches this upper bound. The main results are as follows: (1) when p is even, γ(G) = p/2 if and only if either G C4 or G is the crown of a connected graph with p/2 vertices; (2) when p is odd, γ(G) = (p-1)/2 if and only if every spanning tree of G is one of the two classes of trees shown in Theorem 3.1.
基金supported by the National Natural Science Foundation of China (91527301, 21432004)
文摘A series of macrocycles, including crown ethers, cyclodextrins, calixarenes, pillararenes and cucurbiturils, are well known to be able to associate various organic/inorganic/biological guest molecules and ions in their well-defined cyclic cavities to form stable host-guest complexes and supramolecular systems through the cooperative contributions of various non-covalent interactions.When one or more functional groups are attached to the cavity of macrocycles or guest molecules, enhanced and/or controlled host-guest associations may take place, leading to not only improved host-guest binding abilities but also fascinating properties.In this review, some representative contributions in the construction of controllable macrocyclic supramolecular assemblies in aqueous solution are presented with an emphasis on the stimuli-responsive control manner and wide applications of this property.
文摘Forced response analysis of a rocket engine turbine blade was conducted by a decoupled fluid-structure interaction procedure.Aerodynamic forces on the rotor blade were obtained using 3D unsteady flow simulations. The resulting aerodynamic forces were interpolated to the finite element(FE) model through surface effect elements prior to conducting forced response calculations.Effects of axial gap on aerodynamic forces were studied. In addition, influence of axial gap on the response of the shrouded blade was compared with that on the response of the unshrouded blade. Results demonstrated that as the axial gap increases,time-averaged pressure on the blade surface changes very little, while the pressure fluctuations decrease significantly. Pressure and aerodynamic forces on the blade surface display periodic variation, and the vane passing frequency component is dominant.Amplitudes of aerodynamic forces decrease with increasing axial gap. Restricted by the shroud, deformation and response of shrouded blade are much lower than those of the unshrouded blade. The response of unshrouded blade shows obvious beat vibration phenomenon, while the response of the shrouded blade does not have this characteristic because the shroud restrains multiple harmonics. Blade response in time domain was converted to frequency domain using fast Fourier transformation(FFT).Results revealed that the axial gap mainly affects the forced harmonic at the vane passing frequency, while the other two harmonics at natural frequency are hardly affected. Amplitudes of the unshrouded blade response decrease as the axial gap increases, while amplitudes of the shrouded blade response change very little in comparison.