Effect of polymorphism and type II diabetes on aspirin resistance in patients with unstable coronary artery disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Aspirin is widely used in the secondary prevention of coronary artery diseases, including myocardial infarction, stroke, and vascular related deaths. However, the antiplatelet effect of aspirin appears to be variable and aspirin resistance (AR) is currently still controversial for Chinese patients. The aim of this study was to describe the prevalence of AR, and identify possible risk factors associated with a lack of response to aspirin treatments in patients with unstable coronary artery disease.</p><p><b>METHODS</b>Platelet function tests with arachidonic acid (ARA) and urinary 11-dehydro-thromboxane B2 (11-DH-TXB2) concentrations were performed in 262 patients with unstable coronary artery disease who had not been taking aspirin before admission. ARA induced platelet aggregation and 11-DH-TXB2 were detected to evaluate the functional and biochemical responses to aspirin before and on days 1, 4, and 10 after aspirin administration. Six-month follow-up was completed in patients who developed AR to evaluate the effect of aspirin in a long-term treatment. GP1Bα (C1018T), Pl (A1/A2), P2Y1 (A1622G), TBXA2R (T924C) were also detected to evaluate the influence of genetic variant on aspirin responsiveness.</p><p><b>RESULTS</b>A total of 8.8% of patients were indentified as AR at the first day after aspirin treatment. The level of urine 11-DH-TXB2 in the AR group was higher compared to non-AR group (P < 0.05). There was no relationship between ARA induced platelet aggregation and urinary 11-DH-TXB2 levels (r = 0.038, P = 0.412). The results of DNA sequencing showed that TBXA2R-924TT homozygotes had a significantly high rate of AR. Logistic regression demonstrated that diabetes was an independent risk factor of AR.</p><p><b>CONCLUSIONS</b>In the beginning period of administration, aspirin was not a sufficient factor that inhibits platelet aggregation. TBXA2R-924T allele was involved in AR. Diabetes was an independent risk factor of AR.</p>

Early and long-term results of combined cardiac surgery and neoplastic resection in patients with concomitant severe heart disease and neoplasms / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is a surgical dilemma when patients present with both severe heart disease and neoplasms. The best surgical treatment remains controversial. This study aimed to analyze the early and long-term results of simultaneous surgical treatment of severe heart disease and neoplasms.</p><p><b>METHODS</b>We reviewed the clinical records of 15 patients who underwent simultaneous neoplastic resection and cardiac surgery between September 2006 and January 2011. There were 5 male and 10 female patients. The mean age was (59.2 ± 12.5) years and the mean left ventricular ejection fraction was (57.4 ± 11.0)%. All patients were followed up completely for a period of 12 to 51 months (mean, (33.1 ± 11.2) months).</p><p><b>RESULTS</b>Fifteen patients underwent simultaneous cardiac surgery and neoplastic resection. Cardiac procedures consisted of off pump coronary artery bypass grafting (n = 7), aortic valve replacement (n = 3), mitral valve replacement (n = 3), mitral valve replacement with coronary artery bypass grafting (n = 1) and left atrial myxoma resection (n = 1). Neoplastic resection consisted of lung cancer resection (n = 5), colonic cancer resection (n = 3), gallbladder resection (n = 1), colonic cancer resection with gallbladder resection (n = 1), hysterectomy (n = 2), hysterectomy with bilateral salpingo-oophorectomy (n = 2) and left ovariectomy (n = 1). Pathological examination confirmed malignant disease in 10 patients and benign disease in 5 patients. There were no perioperative myocardial infarctions, stroke, pericardial tamponade, renal failure or hospital deaths. The most frequent complications were atrial fibrillation (33.3%), pneumonia (26.7%), low cardiac output syndrome (6.7%) and delayed healing of surgical wounds (6.7%). There was 1 late death 42 months after surgery for recurrent malignant disease. At 1 and 3 years, survival rates were 100% (Kaplan-Meier method).</p><p><b>CONCLUSIONS</b>Simultaneous cardiac surgery and neoplastic resection was not associated with increased early or late morbidity or mortality. Cardiopulmonary bypass does not appear to adversely affect survival in patients with malignant disease. The long-term survival was determined by tumor stage.</p>

Association of polymorphisms of cytochrome P450 2C9 exon 4 and -65G>C with warfarin sensitivity / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of the polymorphisms of cytochrome P450 2C9 (CYP2C9) exon 4 608T/G, 561A/C, 537A/C and 527A/C, and -65G/C with warfarin sensitivity.</p><p><b>METHODS</b>A total of 102 patients under warfarin anticoagulant therapy were selected. During follow-up, warfarin dosage and associated Prothrombin Time-International Normalized Ratio (P-INR) values were recorded. Simultaneous monitoring of incidence of bleeding and thrombosis adverse effect was recommended. Genetic polymorphisms of the above mentioned loci were identified by polymerase chain reaction and DNA sequencing.</p><p><b>RESULTS</b>The average age of the 102 patients was (62.1+/-10.5) years. The body mass index (BMI) was (24.7+/-3.8) kg/m2. Mean daily warfarin requirement was from 1.250 to 5.077 mg/day when therapeutic PT-INR (1.5-2.5) was maintained. DNA sequencing showed no polymorphisms of 608T/G, 561A/C, 537A/C, 527A/C in CYP2C9 exon 4. Warfarin daily dosage in CYP2C9 exon 4 -65C carriers was 3.106+/-0.619 mg/d, while it was (2.555+/-0.708) mg/d in individuals with wild-type -65G (P=0.020). Receiver operating characteristic (ROC) analysis showed that warfarin daily dosage of more than 2.5 mg/d can be used to predict the CYP2C9 exon 4 -65GC genotype (AUC: 0.770, P=0.005, 95%CI:0.626-0.915). Logistic regression indicated that BMI was an independent factor of bleeding during anti-coagulation therapy (OR=0.794, 95%CI: 0.651-0.970, P=0.024).</p><p><b>CONCLUSION</b>The Chinese population are, generally, warfarin-sensitive. Exon 4 of the CYP2C9 gene is highly conserved in this population. The warfarin maintenance dosage in CYP2C9 exon 4 -65CG carriers was significantly higher than those with wild-type -65GG. The clinical significance needs further investigation with more large-scale, multi-center trials.</p>

Molecular biological analysis of genotyping and phylogeny of severe acute respiratory syndrome associated coronavirus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>SARS-CoV is the causative agent of severe acute respiratory syndrome (SARS) which has been associated with outbreaks of SARS in Guangdong, Hong Kong and Beijing of China, and other regions worldwide. SARS-CoV from human has shown some variations but its origin is still unknown. The genotyping and phylogeny of SARS-CoV were analyzed and reported in this paper.</p><p><b>METHODS</b>Full or partial genomes of 44 SARS-CoV strains were collected from GenBank. The genotype, single nucleotide polymorphism and phylogeny of these SARS-CoV strains were analyzed by molecular biological, bioinformatic and epidemiological methods.</p><p><b>RESULTS</b>There were 188 point mutations in the 33 virus full genomes with the counts of mutation mounting to 297. Further analysis was carried out among 36 of 188 loci with more than two times of mutation. All the 36 mutation loci occurred in coding sequences and 22 loci were non-synonymous. The gene mutation rates of replicase 1AB, S2 domain of spike glycoprotein and nucleocapsid protein were lower (0.079% - 0.103%). There were 4 mutation loci in S1 domain of spike glycoprotein. The gene mutation rate of ORF10 was the highest (3.333%) with 4 mutation loci in this small domain (120 bp) and 3 of 4 loci related to deletion mutation. By bioinformatics processing and analysis, the nucleotides at 7 loci of genome (T:T:A:G:T:C:T/C:G:G:A:C:T:C) can classify SARS-CoV into two types. Therefore a novel definition is put forward that according to these 7 loci of mutation, 40 strains of SARS-CoV in GenBank can be grouped into two genotypes, T:T:A:G:T:C:T and C:G:G:A:C:T:C, and named as SARS-CoV Yexin genotype and Xiaohong genotype. The two genotypes can be further divided into some sub-genotypes. These genotypes can also be approved by phylogenetic tree of three levels of 44 loci of mutation, spike glycoprotein gene and complete genome sequence. Compared to various strains among SARS-CoV Yexin genotype and Xiaohong genotype, GD01 strain of Yexin genotype is more closely related to SARS-CoV like-virus from animals.</p><p><b>CONCLUSION</b>The results mentioned above suggest that SARS-CoV is responding to host immunological pressures and experiencing variation which provide clues, information and evidence of molecular biology for the clinical pathology, vaccine developing and epidemic investigation.</p>