Association of SNP rs6903956 on chromosome 6p24.1 with angiographical characteristics of coronary atherosclerosis in a chinese population

Objective

To explore the association between rs6903956 and severity of coronary artery disease (CAD) in a Chinese population.

Methods

A cohort of 1075 consecutive patients who underwent coronary arteriography for suspected or known coronary atherosclerosis was enrolled in our study. Coronary atherosclerosis severity was defined by Gensini''s Score System and counts of diseased vessels.

Results

Gensini score frequencies and counts of diseased vessels differed among GG, AG, AA genotype groups at the rs6903956 locus (p = 0.025 for Gensini score frequencies vs. p = 0.024 for counts of diseased vessels, respectively). A univariate logistic regression analysis revealed that the genotype distribution of this SNP was associated significantly with angiographical characteristics of coronary atherosclerosis risk (p = 0.030, odds ratio (OR) = 1.444, 95% confidence interval (CI) = 1.036∼2.013 for AG vs. GG; p = 0.021, OR = 5.896, 95% CI = 1.299∼26.750 for AA vs. GG and p = 0.007, OR = 1.564, 95% CI = 1.132∼2.162 for combined (AG+AA) vs. GG). A multivariate logistic regression analysis indicated that the genotype distribution of the rs6903956 polymorphism be associated significantly with the angiographical characteristics of coronary atherosclerosis risk (p = 0.004, OR = 1.578, 95% CI = 1.155∼2.154 for GG vs. AG vs. AA; p = 0.013, OR = 1.541, 95% CI = 1.097∼2.163 for GG vs. GA+ AA). A stratification analysis revealed that male subjects and smoking subjects had a higher frequency of the rs6903956 heterozygous mutant among higher Gensini score subjects than among lower Gensini score subjects (p = 0.023, OR = 1.579, 95% CI = 1.064∼2.344 for male subgroup; p = 0.005, OR = 2.075, 95% CI = 1.249∼3.448 for smoking subgroup).

Conclusions

Allele A is a risk factor for CAD and the G-to-A allele substitution may underlie the association between rs6903956 and CAD.     

不同磷效率小麦品种对缺磷胁迫反应的比较

在营养液培养条件下,以根据相对产量为指标筛选出的6个不同磷效率的小麦(Triticum aestivum L.)品种为材料,对其苗期在缺磷条件下生长、根冠磷含量及其分配,以及叶片韧皮部汁液中磷浓度等进行了比较研究。结果表明,缺磷抑制植株地上部生长,但刺激根系生长,导致植株根／冠比增加。无论在供磷或缺磷条件下,磷高效品种的根冠生长速率都低于磷低效品种。缺磷导致植株体内的磷含量下降与根系相比,地上部磷含量的下降速率更快。但在缺磷条件下,不同磷效率的小麦品种根冠间的磷分配变化没有差异。研究发现,在正常供磷条件下,磷高效小麦品种的叶片韧皮部汁液中磷浓度较低,而磷低效品种的叶片韧皮部汁液中磷浓度较高。但开始缺磷后,磷高效品种的叶片韧皮部汁液中的磷浓度下降较慢,使其相对磷浓度较高。缺磷后10天,磷低效品种叶片韧皮部汁液中的磷浓度为供磷对照的35．9％,而磷高效品种叶片韧皮部汁液中的磷浓度为供磷对照的59％。     

Combined Effects of Admission Serum Creatinine Concentration with Age and Gender on the Prognostic Significance of Subjects with Acute ST-Elevation Myocardial Infarction in China

Objective

to explore the impact of admission serum creatinine concentration on the in-hospital mortality and its interaction with age and gender in patients with acute ST-segment elevation myocardial infarction (STEMI) in China.

Methods

1424 acute STEMI patients were enrolled in the study. Anthropometric and laboratory measurements were collected from every patient. A Cox proportional hazards regression model was used to determine the relationships between the admission serum creatinine level (Cr level), age, sex and the in-hospital mortality. A crossover analysis and a stratified analysis were used to determine the combined impact of Cr levels with age and gender.

Results

Female (HR 1.687, 95%CI 1.051∼2.708), elevated Cr level (HR 5.922, 95%CI 3.780∼9,279) and old age (1.692, 95%CI 1.402∼2.403) were associated with a high risk of death respectively. After adjusting for other confounders, the renal dysfunction was still independently associated with a higher risk of death (HR 2.48, 95% CI 1.32∼4.63), while female gender (HR 1.19, 95%CI 0.62∼2.29) and old age (HR 1.77, 95%CI 0.92∼3.37) was not. In addition, crossover analysis revealed synergistic effects between elevated Cr level and female gender (SI = 3.01, SIM = 2.10, AP = 0.55). Stratified analysis showed that the impact of renal dysfunction on in-hospital mortality was more pronounced in patients <60 years old (odds ratios 11.10, 95% CI 3.72 to 33.14) compared with patients 60 to 74 years old (odds ratios 5.18, 95% CI 2.48∼10.83) and patients ≥75years old (odds ratios 3.99, 95% CI 1.89 to 8.42).

Conclusion

Serum Cr concentration on admission was a strong predictor for in-hospital mortality among Chinese acute STEMI patients especially in the young and the female.     

Ligation or cross-linking of CD40 has different effects on AGS gastric cancer cells

A gastric cancer (GC) cell line, AGS, has high-level expression of CD40, a tumor necrosis factor receptor (TNFR) family member. CD40 is present on the surfaces of a large variety of cells, including B cells, endothelial cells, dendritic cells and some carcinoma cells, and delivers signals regulating diverse cellular responses, such as proliferation, differentiation, growth suppression, and cell death. In this research, we studied the effects of different forms of CD40 stimulation on AGS cells by flow cytometry, Western blotting and siRNA transfection. We found that different forms of CD40 stimulation, either recombinant soluble CD40L (sCD40L, ligation) or agonist anti-CD40 antibody (cross-linking), induced different effects in AGS gastric cancer cells, proliferation or apoptosis. We also showed that VEGF provided a significant contribution to sCD40L-induced proliferation, while agonist anti-CD40 antibody induced GADD45 upregulation and promoted apoptosis.     

Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease

Objective Therapeutic angiogenesis is a new strategy for treatment of vascular insufficiency. Hepatocyte growth factor (HGF)-induced angiogenesis has been applied to induce the neovascularization of ischemic adult tissues in preclinical studies. This report summarizes a phase I clinical trial on the safety of adenovirus-mediated human HGF (Ad-HGF) gene transfer to treat clinically significant coronary artery disease. Methods The 18 patients with severe and diffused triple vessel disease determined by coronary angiography, 1–3 of the main coronary arteries not amenable to bypassing grafting and to catheter-based revascularization were assigned to 3 study groups according to the dose of Ad-HGF (from low to high), and the total dose as follows: 5 × 10⁹ pfu (group A, n = 6); 1 × 10¹⁰ pfu (group B, n = 6); 2 × 10¹⁰ pfu (group C, n = 6). Arterial gene transfer was performed by over-the wire balloon to the distal of the accessible artery or otherwise the ostium of the target vessels by diagnostic coronary catheter. General safety parameters and cardiac-specific parameters were measured through the preoperative period and on day 7, 21, and 35 postoperatively. The safety and tolerance of Ad-HGF for patients were evaluated according to functional and cytological assessments. Results During the acute phase up to day 35 and at 11–14 months of follow-up there were no serious adverse events. A mild fever during the first 3 days was not present at day 4, and no long term or paroxysmal fever was found. There were no acute alterations in hemodynamic parameters and the electrocardiogram remained normal. No serious pericardial effusion was reported and there were no arrhythmia on Holter registrations. Moreover, the serum levels of HGF were not changed and the serum anti-adenovirus in the patients was not detected up to day 35. Conclusions The present study demonstrates that it is feasible to safely use an adenovirus gene-transfer vector to deliver the human hepatocyte growth factor gene to individuals with clinically significant coronary artery disease by direct intracoronary injection. However, a great deal of additional work must be done before administration of Ad-HGF can be recommended for clinical practice.     

濒危植物野生东北红豆杉群落特征及保护策略

以长白山自然保护区野生东北红豆杉种群为研究对象,在野生东北红豆杉的主要分布区设置4块标准地(50 m×50 m),运用群落生态学方法统计野生东北红豆杉的树木特征(树高、胸径、冠幅等),立地条件,林分状况等,分析野生东北红豆杉在分布地区的群落物种多样性特征。所调查的4个样地共有木本植物32种,隶属17科24属,草本植物53种,隶属于23科41属。不同样地的Simpson指数和Shannon指数变化一致,样地C4的均匀度Pielou指数为草本层>灌木层>乔木层,其余的样地均为灌木层>乔木层>草本层。Margalef丰富度指数显示,除了样地C4的草本层物种丰富度最大之外,其余3个样地都是乔木层物种丰富度指数最大。在4个样地中,野生东北红豆杉的重要值偏低,在群落中不占优势。野生东北红豆杉所在的群落主要以红松、长白鱼鳞云杉、紫椴等针阔叶树种组成的混交林。根据这种现象,提出了野生东北红豆杉的保护策略,为野生东北红豆杉资源的保护、繁育和利用提供了合理建议和有效途径。     

Autologous dendritic cell vaccine for estrogen receptor (ER)/progestin receptor (PR) double-negative breast cancer

Purpose

A wealth of preclinical information, as well as a modest amount of clinical information, indicates that dendritic cell vaccines have therapeutic potential. The aim of this work was to assess the immune response, disease progression, and post-treatment survival of ER/PR double-negative stage II/IIIA breast cancer patients vaccinated with autologous dendritic cells pulsed with autologous tumor lysates.

Methods

Dendritic cell (DC) vaccines were generated from CD14+ precursors pulsed with autologous tumor lysates. DCs were matured with defined factors that induced surface marker and cytokine production. Individuals were immunized intradermally four times. Specific delayed type IV hypersensitivity (DTH) reaction, ex vivo cytokine production, and lymphocyte subsets were determined for the evaluation of the therapeutic efficiency. Overall survival and disease progression rates were analyzed using Kaplan–Meier curves and compared with those of contemporaneous patients who were not administered DC vaccines.

Results

There were no unanticipated or serious adverse effects. DC vaccines elicited Th1 cytokine secretion and increased NK cells, CD8+ IFN-γ+ cells but decreased the percentage of CD3+ T cells and CD3+ HLA-DR+ T cells in the peripheral blood. Approximately 58% (18/31) of patients had a DTH-positive reaction. There was no difference in overall survival between the patients with and without DC vaccine. The 3-year progression-free survival was significantly prolonged: 76.9% versus 31.0% (with vs. without DC vaccine, p?Conclusion Our findings strongly suggest that tumor lysate-pulsed DCs provide a standardized and widely applicable source of breast cancer antigens that are very effective in evoking anti-breast cancer immune responses.     

喜树碱和10—羟基喜树碱受喜树生长发育调控的不同特点

为了揭示喜树碱（camptothecin,CPT)和10-羟基喜树碱（10-hydroxycamptothecin,HCPT)在喜树（Camptotheca acuminata Decaisne)体内代谢的生理调控机制及这两种类似物之间的关系和作用。运用高效液相色谱技术对种子形成,成熟,萌发和幼苗生长过程中喜树三和10-羟基喜树碱的代谢动态进行了全面的研究。结果表明,喜树碱相对稳定地存在于成熟的幼嫩的组织中;10-羟基喜树碱特异性地积累在乳熟期的种子,种芽的子叶,幼嫩的真叶等幼嫩组织中,随着组织的进一步发育和成熟,其含量快速减少,成熟组织中积累极少,并且这两种生物碱的代谢在时间和数量上都呈现出相互消长的特点,由此推断,这两种生物碱不同程度地受生长发育调控的特点可能与喜树的化学防御策略密切相关。并且,它们之间可以相互转化以充分利用有限的氮素资源。     

Fe Accumulation and Mobilization in Root Apoplast of Soybean Seedlings Under Fe deficiency Condition

Fe accumulation and mobilization in root apoplast of soybean ( Clycine max (L.) Merr. ) seedlings grown under Fe supplement of 10-6 mol/L FeEDTA, or Fe-deficient condition were studied. Under Fe sufficient condition, the content of the root apoplastic Fe pools of soybean seedlings changed in a rhythmic fashion of alternative accumulation and mobilization in every three-day cycling, together with orchestrated rhythmic changes of root Fe ( Ⅲ )-reduction capacity and peroxidase activity. In Fe deficient condition, Fe content in the root apoplastic pools deceased steadily almost to nil, and the root Ye( Ⅲ )-reduction capacity and peroxidase activity, ahhrough under went rhythmic changes but only in 2-day cycling. The results showed an important relation among root apoplastic Ye pools, Fe( Ⅲ )-reduction capacity and peroxidase activity.     

乙烯在豌豆植株顶端优势中的作用

用人工合成细胞分裂素BAP和CPPU处理豌豆植株叶腋可诱导处理部位侧芽的生长,同时伴有大量乙烯产生;用乙烯合成抑制剂AVG处理或植株去顶同样可导致创芽生长,但乙烯释放量却明显少于对照,表明侧芽的生长与乙烯释放量的多少无关。而3种物质处理后诱导产生的侧芽的数目、长度及其鲜重与处理部位内源IAA含量的增加则呈正相关。