An N-terminal splice variant of human Stat5a that interacts with different transcription factors is the dominant form expressed in invasive ductal carcinoma

We have identified a new variant of human Stat5a, found at higher ratios to full-length Stat5a in invasive ductal carcinoma versus contiguous normal tissue. The variant, missing exon 5, inhibits p21 and Bax production and increases cell number. After prolactin stimulation, only full-length Stat5a interacts with the vitamin D and retinoid X receptors, whereas only Δ5 Stat5a interacts with activating protein 1–2 and specificity protein 1. Prolactin also oppositely regulates interaction of the two Stat5a forms with β-catenin. We propose that a change in splicing leading to upregulation of this new isoform is a pathogenic aspect of invasive ductal carcinoma.     

The Effects of Invigorating Qi, Removing Blood Stasis and Tonifying the Kidney on the Expression of Ⅱ Collagen Mrna Inside the Degenerated Intervertebral Discs

It has been found from the clinical observa-tion that the method of Invigorating Qi,Remov-ing Blood Stasis and Tonifying the Kidney canhave a good regulatory effect on cervical spondy-losis.But whether this method can be effectiveor not for the tissue of degenerated interverte-bral disc is still unknown.Itwill be of greatsig-nificance for the prevention and treatmentof cer-vical spondylosis if this method can improve andpostpone the course of degeneration of the de-generated intervertebral d…     

转录因子S tat5a对乳腺癌细胞增殖的影响及其表观遗传学机制探讨

目的：探讨转录因子Stat5a对人类乳腺癌细胞（MCF‐7）增殖的影响及表观遗传学机制。方法利用腺病毒介导的基因转移技术,使MCF‐7大量表达转录因子Stat5a ,应用活细胞计数（M TS）法检测细胞增殖情况,并以染色质免疫共沉淀（ChIP）方法,检测p53基因启动子区域组蛋白甲基化程度。最后以实时定量 PCR进一步确认 p53基因表达水平。结果携带Stat5a cDNA的腺病毒感染后,MCF‐7的数量呈剂量依赖式地增加。当病毒感染增殖活性（MOI）分别为10、20及30时,MCF‐7的细胞密度较对照组细胞分别增加7．6031％、18．1237％及24．8987％。染色质免疫共沉淀分析表明,Stat5a明显导致p53基因启动子区域组蛋白甲基化（H3K27Me3）增加,p53基因表达水平下降。结论 Stat5a导致MCF‐7抑癌基因p53启动子组蛋白甲基化,使启动子活性降低,导致细胞的异常增殖。     

卵巢切除后骨质疏松大鼠股骨颈质量的力学特征及外展肌群重链肌球蛋白基因的表达

目的 研究卵巢切除术诱导的绝经后骨质疏松症大鼠模型股骨颈质量的力学表达与附着肌群肌强度基因表达的变化,探讨股骨颈骨质疏松性骨折风险升高的肌肉-骨骼机制。方法 将20只8月龄Wistar雌性大鼠随:饥分为对照组(10只,双侧卵巢假切除)和模型组(10只,为双侧卵巢切除)。手术后180 d,分别测定股骨颈质量的结构强度、结构硬度和结构韧性与附着股骨颈的外展肌群肌强度的重链肌球蛋白基因的表达。结果 模型组的结构强度(168.09±25.20)N、结构硬度(682±131)N/mm和结构韧性(0.04±0.07)J与对照组比较都显著下降(P<0.05);附着的外展肌群肌强度的基因表达,对照组重链肌球蛋白ImRNA表达量高,模型组表达量低。结论 股骨颈质量的低结构强度、低结构硬度与低结构韧性的力学表达导致股骨颈骨质疏松性骨折风险升高;附着肌群肌强度的重链肌球蛋白ImRNA低表达对于造成骨质量力学表达变化的骨重建高转换的调控机制具有重要的作用。     

Early infection and risk of childhood brain tumors (Canada)

Objective Up to 15% of human cancers can be attributed to infections. Currently there are no known associations between infective agents and childhood brain tumors. We explored childhood brain tumor risk associated with a variety of indicators of infection during gestation and childhood. Methods Two hundred and seventy-two cases of childhood brain tumor diagnosed in children less then 15 years of age in the province of Quebec between 1980 and 1999 were included in the study. An equal number of sex and age matched population based controls were recruited from family allowance or provincial health insurance files. Conditional logistic regression was used to estimate the risk of developing childhood brain tumors associated with self-reported exposure to infection. Results Childhood brain tumor risk was weakly to moderately elevated after maternal reported exposure to several indicators of infection: use of antibiotics during gestation (OR = 1.7, 95% CI = 0.8–3.6) or childhood (OR = 1.4, 95% CI = 0.7–2.9), removal of tonsils, adenoids or appendix (OR = 1.2, 95% CI = 0.6–2.4), having siblings (OR = 1.4, 95% CI = 0.9–2.3), and being at least second born (OR = 1.7, 95% CI = 1.2–2.4). Moreover, childhood brain tumor risk was reduced for some subjects who were breastfed or attended daycare for more than 1 year. Risk varied by sex, age at diagnosis and tumor type. Conclusion Childhood brain tumor risk may be associated with exposure to infective agents.     

益肾、健脾和柔肝中药抗炎镇痛作用的比较研究

比较治疗ＯＡ常用的益肾方,健脾方和柔肝方的抗炎镇痛效应。方法以小鼠热反法缩腿反应,耳廓肿度及佐剂性关了炎大鼠的踝关节肿胀指数为指标,观察益肾方,健脾方和柔肝方的抑炎镇痛效应。     

糖皮质激素诱导的骨质疏松大鼠模型综合评价

综合评价糖皮质激素诱导的大鼠骨质疏松模型停用激素后该模型的变化特点及其在骨质疏松研究中的地位与作用.雄性大鼠肌肉注射醋酸泼尼松龙5mg/kg/次,每周2次,12周后停止注射,继续观察14周,用骨密度、骨生物力学指标和骨组织计量学等三方面的指标对造模8周、12周及停止注射糖皮质激素8周、11周和14周的骨质疏松状况作综合评价.结果显示造模8周模型组腰椎骨密度、胫骨生物力学性能显著低于对照组,造模12周时模型组腰椎和股骨骨密度及胫骨生物力学指标都显著低于对照组.但停药8周～14周,股骨骨密度、胫骨最大载荷值、类骨质宽及双标表面等指标都有所恢复.提示该模型与原发性骨质疏松的发病机理和病程发展不尽一致,所以在以此模型评价药物对原发性骨质疏松的作用时应持谨慎态度.     

大鼠中缝背核向缰核投射的5-羟色胺能神经元对躯体伤害性刺激的fos表达

用WGA-HRP逆行追踪与抗FOS和抗5-羟色胺免疫组化的三重标记方法,观察向大鼠一侧有前跖部皮下注射8%福尔马林50μl后,中缝背核至缰核5-羟色胺能神经元的FOS表达.光镜下发现中缝背核内有七种阳性神经元.即HRP、FOS、5-HT单标细胞;FOS/HRP、FOS/5-HT、HRP/5-HT双标细胞;FOS/HRP/5-HT三标细胞.结果表明中缝背核至缰核的5-HT能投射神经元对躯体伤害性刺激起反应.     

冠部牙本质深龋细菌学分析

目的：探明牙本质深龋中的主要相关菌。方法：利用色谱法、裂解法等对龋坏牙本质分三层作细菌分离、鉴定、分析。结果：牙本质龋中的主要相关菌为乳杆菌和变链菌,龋内层牙本质中的细菌含量较外层少。结论：乳杆菌促进牙本质龋的发展,在牙本质龋进展中脱矿在先,细菌入侵在后。     

Pyrotinib Sensitizes 5-Fluorouracil-Resistant HER2⁺ Breast Cancer Cells to 5-Fluorouracil

5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent for breast cancer. However, acquired chemoresistance leads to a loss of its efficacy; methods to reverse are urgently needed. Some studies have shown that pyrotinib, an ErbB receptor tyrosine kinase inhibitor, is effective against HER2+ breast cancer. However, whether pyrotinib sensitizes 5-FU-resistant breast cancer cells to 5-FU is unknown. We hypothesized that the combination of pyrotinib and 5-FU would show synergistic antitumor activity, and pyrotinib could reverse 5-FU resistance in HER2+ breast cancer cells in vitro and in vivo. Our data showed that pyrotinib inhibited the growth of 5-FU-resistant SKBR-3/FU and MDA-MB-453/FU cell lines and the parental cell lines. 5-FU remarkably suppressed the growth of SKBR-3 and MAD-MB-453 cells. However, SKBR-3/FU and MADMB-453/FU cells showed resistance to 5-FU. A combination of pyrotinib and 5-FU resulted in the synergistic inhibition of the growth of the 5-FU-resistant SKBR-3/FU and MDA-MB-453/FU cell lines and the parental cell lines. Pyrotinib decreased significantly the IC50 values of 5-FU and the thymidylate synthase (TS) mRNA expression levels in the 5-FU-resistant SKBR-3/FU and MDA-MB-453/FU cell lines and the parental cell lines and increased significantly the intracellular concentration of 5-FU in SKBR-3/FU and MDA-MB-453/FU cells. In addition, pyrotinib reduced the ABCG2 mRNA and protein expression levels in SKBR-3/FU and MDA-MB- 453/FU cells and downregulated the protein expression levels of pAKT, pHER2, and pHER4 in all four cell lines. After TS or ABCG2 in 5-FU-resistant breast cancer cells was knocked down, the sensitivity of SKBR-3/ FU and MDA-MB-453/FU cells to 5-FU was restored. Moreover, in vivo experiments demonstrated that pyrotinib in combination with 5-FU more effectively inhibited SKBR-3/FU tumor growth than either pyrotinib or 5-FU alone. In conclusion, our findings suggest that pyrotinib could restore sensitivity of 5-FU-resistant HER2+ breast cancer cells to 5-FU through downregulating the expression levels of TS and ABCG2.