Association between the p53 polymorphisms and breast cancer risk: meta-analysis based on case–control study

p53 is a tumor suppressor gene and plays an important role in the etiology of breast cancer. However, studies on the association between p53 polymorphisms and breast cancer risk have yielded conflicting results. We performed a meta-analysis to investigate the association between breast cancer and the p53 polymorphisms codon 72 (27,046 cases and 30,998 controls), IVS3 16 bp (3,332 cases and 3,700 controls) and IVS6+62A>G (8,787 cases and 9,869 controls) in different inheritance models. When all the eligible studies of codon 72 polymorphism were pooled into this meta-analysis, there was no evidence of significant association between breast cancer risk and p53 codon 72 polymorphism in any genetic model. However, in the stratified analysis for Indian population, significantly association was observed in additive model (OR = 0.62, 95% CI = 0.46–0.82, P value of heterogeneity test [P _h] = 0.153) and recessive model (OR = 0.70, 95% CI = 0.50–0.92, P _h = 0.463). IVS3 16 bp was significantly associated with breast cancer risk in a pooled 15 studies dataset (dominant model: OR = 1.14, 95% CI = 1.02–1.27, P _h = 0.30; recessive model: OR = 1.61, 95% CI = 1.21–2.25, P _h = 0.25; additive model: OR = 1.66, 95% CI = 1.24–2.21, P _h = 0.28). No significant association was found between IVS6+62A>G polymorphism and breast cancer risk in a total of 14 studies. In summary, these results indicate that IVS3 16 bp is likely an important genetic marker contributing to susceptibility of breast cancer, and codon 72 homozygous mutants may be associated with decreased breast cancer risk in Indian population.     

太原市无偿献血者职业分布情况分析

目的 通过对无偿献血者的职业分布及血液筛查结果进行分析,为进一步的宣传及招募提供依据.方法 回顾性分析2006～2012年无偿献血志愿者的职业构成及血液筛查结果,并采用SPSS13.0进行统计.结果 七年间无偿献血者共503 823例,基本呈逐年上升趋势,其中职业不详者比例最高（42.82％）,其次为学生（24.32％）,且呈逐年下降趋势,农民比例逐年上升,不合格率以学生为最低.结论 我市无偿献血发展趋势较好,献血人群职业分布波动较大,血源质量也存在差别,需进一步科学深入宣传才能更好地减少浪费,为临床提供充足的血源.     

Fasudil,a Rho kinase inhibitor,drives mobilization of adult neural stem cells after hypoxia/reoxygenation injury in mice

Rho kinase (ROCK) is important in fundamental processes of cell proliferation and survival. Blockade of ROCK promotes stem cell survival in vitro and axonal regeneration in vivo, exhibiting therapeutic potential such as spinal cord injuries and stroke. Here, we used the model of hypoxia/reoxygenation (H/R) injury to explore the possibility whether Fasudil, a ROCK inhibitor in clinical application for subarachnoid hemorrhage and stroke, mobilizes adult neural stem cells in vivo. Most interestingly, Fasudil triggers neurogenesis especially in the subventricular zone after H/R. The increase of Brdu+ cholinergic neurons was observed in striatum and forebrain cortex of Fasudil-treated mice after 30 days. Further observation demonstrates that both levels of granulocyte colony-stimulating factor (G-CSF) and astrocytes expressing G-CSF were elevated in mice treated with Fasudil, as compared to mice injected with saline. In vitro H/R model of cultured astrocytes, Fasudil promoted astrocytes to produce G-CSF in a dose-dependent manner. In addition, antibody neutralization and receptor blocking of the G-CSF pathway clearly demonstrate that Fasudil-induced neurogenesis was mediated partially through astrocyte-derived G-CSF. Our results indicate that Fasudil might represent a promising therapeutic perspective by mobilizating endogenous adult neural stem cells in the CNS.     

铜绿假单胞菌的临床分布及耐药性分析

目的 分析铜绿假单胞菌（Pseudomonas aeruginosa,PAE）的来源分布及其对常用抗菌药物的耐药情况,指导临床合理用药.方法 收集2010年6月至2011年6月晋中市第一人民医院临床送检标本中分离出的PAE菌株222株.采用微生物BioFosun鉴定分析仪及相关鉴定卡对临床分离病原菌进行细菌鉴定,同时做药物敏感试验,用WHONET 5.5软件进行数据分析.结果 分离的222株PAE主要来源于痰标本,占92.79％,主要分布于呼吸科（31.53％）和神经内科（21.62％）等科室.PAE耐药率最低的是头孢吡肟（14.7％）,其次是美洛培南（16.5％）、哌拉西林/他唑巴坦（17.4％）等,耐药率最高的是氨曲南（69.2％）,其次是左旋氧氟沙星（44.4％）.结论 PAE是医院感染的主要病原菌之一,其耐药性监测对指导临床合理应用抗菌药物,控制医院感染的流行十分重要.     

Influence of Progesterone on Sexual Performance in Male Rats

IntroductionIt has been documented that copulatory experience can alter or improve sexual performance in male rats. However, the hormonal basis and the number of sexual encounters needed for a rat to acquire sufficient performance remains unclear.AimThe aim of this study was to examine whether levels of testosterone and progesterone are associated with sexual performance in male rats.MethodsAdult male Wistar Hannover rats were exposed to a receptive female for 15 minutes every other day for 9 days for acquiring sexual experience.Main Outcome MeasuresAfter training protocol, rats were scored as low or high sexual performers. Hormonal levels (testosterone and progesterone) were evaluated in both trained and non-trained control groups.ResultsOur results showed that a 9-day training period was not sufficient for some male rats to acquire a good level of sexual performance. While 42.5% of the rats displayed excellent sexual performance during the training sessions, 17.5% showed adequate performance, 7.5% had low sexual activity, and 32.5% of the rats did not display any sexual behaviors whatsoever. Additionally, after 4 days of training, rats with excellent/adequate performance showed a significant decrease in ejaculation latency relative to the first day of training. The rats with low or no sexual activity had lower progesterone levels relative to those displaying the highest sexual performance after 9 days of training. Testosterone, in turn, was also significantly reduced in animals with low/no sexual performance compared with excellent/adequate rats.ConclusionIn conclusion, progesterone may be a limiting factor to promoting sexual performance in male rats. Alvarenga TA, Andersen ML, and Tufik S. Influence of progesterone on sexual performance in male rats.     

High-throughput liquid–liquid extraction and LCMSMS assay for determination of circulating 25(OH) vitamin D3 and D2 in the routine clinical laboratory

BackgroundIncreasing focus on vitamin D as essential to health has underscored the need for accurate and precise high-throughput measurement of serum 25(OH)D.MethodsSerum was denatured in acetonitrile containing hexadeuterated 25(OH)D3 as internal standard (IS) and automatically applied to filter plates packed with inert diatomous earth material for subsequent heptane extraction. Extracts were chromatographed on a C12 HPLC column, and detected on a triple quadropole mass spectrometer.ResultsThe inter-assay precision was 9.4% and 8.8% respectively at 32.0 and 59.7 nmol/l for 25(OH)D3 and 8.6% and 8.0% at 23.4 and 64.4 nmol/l for 25(OH)D2. The detection limit was 10 nmol/l for both metabolites. Three percent of samples contained > 50 nmol/l 25(OH)D2. Total run time was 4 min. We have performed more than 200,000 routine samples and the method performs well in external control schemes.ConclusionWe describe a robust, high-throughput, LLE-LCMSMS method for accurate and precise quantitation of 25(OH)D3 and 25(OH)D2 in serum. The use of diatomaceous earth material for extraction of vitamin D in 96-well format enables fast, simple and efficient sample preparation. The method offers a cost-effective alternative to immunological methods for use in the routine clinical biochemical laboratory.     

COX-2 (PTGS2) gene methylation in epithelial,subepithelial lymphocyte and stromal tissue compartments in a spectrum of esophageal squamous neoplasia

Background: Previous studies have shown important effects of stromal elements in carcinogenesis. To explore the tumor–stromal relationship in esophageal neoplasia, we examined methylation of COX-2 (PTGS2), a gene etiologically associated with the development of gastrointestinal cancers, in adjacent foci of epithelium, subepithelial lymphocytes and non-lymphocytic stromal cells found in sections of normal squamous epithelium, squamous dysplasia and invasive esophageal squamous cell carcinoma. Methods: Adjacent foci of epithelium, subepithelial lymphocytic aggregates and non-lymphocytic stromal tissues were laser microdissected from six fully embedded, ethanol fixed, esophagectomy samples from Shanxi, China, a high-risk region for esophageal cancer. Promoter CpG site-specific hypermethylation status of COX-2 was determined using real-time methylation-specific PCR (qMS-PCR) based on Taqman Chemistry. The methylation status of a subset of samples was confirmed by pyrosequencing. Results: Forty-nine microdissected foci were analyzed. COX-2 gene methylation was significantly more common in subepithelial lymphocytes (12/16 (75% of all foci)) than in epithelial foci (3/16 (19%)) or foci of non-lymphocytic stromal tissues (3/17 (18%)) (Fisher's exact p = 0.05). Two of three epithelial samples and all three stromal samples that showed COX-2 methylation were adjacent to foci of methylated subepithelial lymphocytes. Pyrosequencing confirmed the methylation status in a subset of samples. Conclusions: In these esopohageal cancer patients, COX-2 gene methylation was more common in subepithelial lymphocytes than in adjacent epithelial or stromal cells in both grades of dysplasia and in foci of invasive cancer. These findings raise the possibility that methylation of subepithelial lymphocytes may be important for tumorigenesis. Future studies of gene methylation should consider separate evaluation of epithelial and non-epithelial cell populations.     

Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: An analysis of Japan Multinational Trial Organisation LC00-03

We examined the impact of pretreatment neutrophil count on survival in patients with advanced non-small-cell lung cancer (NSCLC). A total of 388 chemo-naïve patients with stage IIIB or IV NSCLC from a randomised controlled trial were evaluated. The effects of pretreatment peripheral blood neutrophil, lymphocyte and monocyte counts and neutrophil–lymphocyte ratio on survival were examined using the proportional hazards regression model to estimate hazard ratios after adjustment for covariates. The optimal cut-off value was determined by proportional hazards regression analysis with the minimum P-value approach and shrinkage procedure. After adjustment for prognostic factors, the pretreatment elevated neutrophil count was statistically significantly associated with short overall (P = 0.0008) and progression-free survival (P = 0.024), whereas no association was found between prognosis and lymphocyte or monocyte count. The cut-off value selected for neutrophil count was 4500 mm^–3 (corrected hazard ratio, 1.67; 95% confidence interval (CI), 1.09–2.54). The median survival time was 19.3 months (95%CI, 16.5–21.4) for the low-neutrophil group (?4500 mm^–3, n = 204) and was 10.2 months (95%CI, 8.0–12.3) for the high-neutrophil group (?4500 mm^–3, n = 184). We confirmed that pretreatment elevated neutrophil count is an independent prognostic factor in patients with advanced NSCLC receiving modern chemotherapy. Neutrophil count is easily measured at low cost, and it may be a useful indicator of patient prognosis.     

Role of CD20 Monoclonal Antibodies in Previously Untreated Chronic Lymphocytic Leukemia

Monoclonal antibodies (MoAbs) directed against the CD20 antigen on B cells have dramatically altered the treatment landscape for patients with chronic lymphocytic leukemia (CLL). Rituximab, a chimeric mouse/human MoAb, was the first antibody to be approved for the treatment of indolent B-cell lymphomas. Although single-agent, standard-dose rituximab has limited activity as first-line therapy for patients with CLL, it has synergistic therapeutic activity when combined with chemotherapy. Indeed, chemoimmunotherapy with combined fludarabine (F), cyclophosphamide (C), and rituximab was shown to improve both progression-free and overall survival in a randomized phase III clinical trial compared with FC in previously untreated patients with CLL. In this article, we review important clinical trials that have incorporated rituximab with other agents for treatment-naive patients with CLL. We also highlight second- and third-generation CD20 MoAbs approved or in development for the treatment of CLL.