激素受体阳性乳腺癌的内分泌治疗

乳腺癌是我国女性最常见的恶性肿瘤之一,也是一种激素依赖性肿瘤.近年来,针对乳腺癌内分泌激素通路的药物陆续得到开发和应用,一些药物已被证明可以改善乳腺癌患者的预后.内分泌治疗在乳腺癌中取得了良好的效果,对于乳腺癌患者的治疗方案正在迅速改变,内分泌治疗已成为激素受体阳性乳腺癌患者的主要治疗手段.本文对乳腺癌患者内分泌治疗的...     

米非司酮治疗子宫肌瘤后患者血清VEGF及VEGFR2水平的变化

目的探讨米非司酮对子宫肌瘤患者血清血管内皮生长因子(VEGF)及血管内皮生长因子受体2(VEGFR2)的影响。方法选择71例至少有1个瘤体≥3 cm的子宫肌瘤患者,自月经来潮第5天开始,口服米非司酮25 mg,每日2次,连续服用3个月。分别在服药前后测定血清VEGF、VEGFR2、促卵泡生成素、促黄体生成素、雌激素、孕激素的浓度,同时用B超检测服药前后子宫和最大肌瘤体积、肌瘤数量及子宫动脉搏动指数和阻抗指数。结果服药后患者血清VEGF及VEGFR2水平较服药前显著减低,子宫动脉搏动指数明显下降,而阻抗指数明显升高。结论米非司酮可通过抑制血清VEGF和VEGFR2水平及有效减少子宫动脉血流来缩减肌瘤体积。     

基于5-LOX体外代谢途径的火绒草抗炎活性部位筛选

目的:筛选火绒草中的抗炎活性部位。方法:采用系统溶剂法按照极性由低到高的顺序分离得到火绒草石油醚提取物、乙酸乙酯提取物、正丁醇萃取物、水提取物。采用酶联免疫法(ELISA)建立花生四烯酸(AA)的5-脂氧合酶(5-LOX)体外代谢途径,检测火绒草提取物抑制5-LOX活性的能力。结果:火绒草乙酸乙酯提取物对5-LOX活性有76.92%强度的抑制作用。结论:火绒草乙酸乙酯提取物具有较强的抗炎活性,可作为潜在的抗炎活性成分筛选药物。     

CCL_4诱导大鼠肝损伤模型的代谢组学及茵陈蒿汤的干预作用研究

基于代谢组学的系统化理论,以UPLC/QTOF分析系统为核心手段,结合生物样品分析制备方法,研究CCL_4诱导肝损伤大鼠的代谢组变化,以及茵陈蒿汤干预后的肝损伤大鼠代谢组的回调趋势。同时,借助MS解析理论和主成分分析软件,明晰表征大鼠肝损伤的5个内源性特征生物标记物,并结合系统生物学的理论还原肝损伤的机理与实质,以及茵陈蒿汤的肝损伤防治机理,从药物代谢组学角度对经典方剂防治肝损伤给出全新解释。     

D101大孔吸附树脂纯化苦玄参总皂苷的研究

目的 研究D101大孔吸附树脂纯化苦玄参总皂苷的工艺条件，建立苦玄参总皂苷的分析方法。方法 以TLC为检测手段，考察D101大孔吸附树脂对苦玄参总皂苷的吸附和洗脱条件，并采用分光光度法测定提取物中苦玄参皂苷的含量。结果 D101大孔吸附树脂可以将苦玄参总皂苷含量由浸膏中的8．7％提高至27．3％，增加20％乙醇洗脱操作可进一步提高至52．1％；苦玄参总皂苷的最大吸收波长为261nm，与苦玄参苷IA一致。苦玄参苷IA在4．56～91．2μg／mL与吸光度呈良好的线性关系，平均回收率为96.3％。结论 D101大孔吸附树脂能有效富集并纯化苦玄参总皂苷；分光光度法测定苦玄参总皂苷含量具有快捷、准确的特点。     

Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay

Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M1- dG have not been applied to a large number of individuals or variety of samples. Often, only a few microg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M1-dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of MI-dG in 1 microg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M1-dG per 10(8) normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/32P-post- labelling (HPLC/PPL) method previously developed and indicated a high correlation between M1-dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 microg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.      

Normalizing GDNF expression in the spinal cord alleviates cutaneous hyperalgesia but not ongoing pain in a rat model of bone cancer pain

Bone cancer pain (BCP) is the most common complication in patients with bone cancer. Glial cell line‐derived neurotrophic factor (GDNF) is believed to be involved in chronic pain conditions. In this article, the expression and roles of GDNF were studied in a rat model of BCP induced by tibia injection of Walker 256 rat mammary gland carcinoma cells. Significant mechanical and thermal hyperalgesia and ongoing pain were observed beginning as early as day 5 post injection. The expression level of GDNF protein examined on day 16 after tibia injection was decreased in the L3 dorsal root ganglion (DRG) and lumbar spinal cord, but not in other spinal levels or the anterior cingulate cortex. Phosphorylation of Ret, the receptor for GDNF family ligands, was also decreased. Furthermore, normalizing GDNF expression with lentiviral vector constructs in the spinal cord significantly reduced mechanical and thermal hyperalgesia, spinal glial activation, and pERK induction induced by tibia injection, but did not affect ongoing pain. Together these findings provide new evidence for the use of GDNF as a therapeutic treatment for bone cancer pain states.     

bcl-2抑制剂联合地西他滨治疗慢性粒-单核细胞白血病转化型急性髓系白血病一例并文献复习

目的 提高对转化型急性髓系白血病(AML)及其治疗方法的认识.方法 报道1例慢性粒-单核细胞白血病(CMML)转化为AML患者的诊断及治疗过程,并进行文献复习.结果 患者为老年男性,初步诊断为CMML,并快速转化为AML-M4.初始给予小剂量地西他滨(10 mg/周,皮下注射)诱导分化治疗,3周后联合bcl-2抑制剂(venetoclax)治疗,取得了较好的疗效.但患者年龄较大,合并脏器功能受损,最终因呼吸衰竭,进而多器官衰竭死亡.结论 转化型AML目前尚无标准的治疗方案,预后差,长期生存率低,需要探索新的治疗方法来提高患者生存率.     

Zebularine对HL-60及K562细胞株WWOX基因甲基化的影响

目的:探讨去甲基化药物1-(β-D-呋喃核糖苷)-1,2-二氢嘧啶-2-酮(Zebularine,Zeb,折布拉林)处理HL-60及K562细胞后WWOX甲基化水平的变化,分析Zeb在白血病治疗中的意义。方法:Zeb处理HL-60及K562细胞,以5-氮杂-2脱氧胞苷(5-Aza-CdR,地西他滨)作为阳性对照,MSP法检测WWOX基因启动子及第一外显子甲基化状态;QRT-PCR检测WWOXmRNA的表达,并分析不同细胞株药物处理组与处理前组甲基化情况与mRNA表达的关系。结果:1.药物处理前,K562细胞WWOX基因启动子甲基化PCR扩增出阳性条带,非甲基化扩增阴性;第一外显子甲基化PCR扩增阴性,而非甲基化PCR扩增出阳性条带;药物处理后启动子及第一外显子甲基化PCR均不能扩增出阳性条带,而非甲基化扩增阳性。2.Zeb与5-AzaCdR处理前后,HL-60细胞WWOX基因启动子及第一外显子甲基化PCR扩增均阴性,非甲基化均扩增出阳性条带。3.经Zeb与5-Aza-CdR处理后,K562细胞WWOX基因mRNA表达升高,处理前后比较差异有统计学意义(P<0.05),不同浓度的Zeb处理组间比较差异有统计学意义(P<0.05)。4.Zeb与5-Aza-CdR处理前后,HL-60细胞WWOX基因mRNA表达差异无统计学意义(P>0.05)。结论:Zeb能够发挥去甲基化作用,上调K562细胞WWOX基因mRNA表达,具有浓度依赖性,对HL-60细胞WWOX基因mRNA表达无明显影响。     

CT平扫定量评定门脉高压及其对周围器官的影响

目的 探讨CT平扫定量在评定门脉高压及其对周围实质器官影响中的价值.方法 回顾分析86例患者的CT平扫资料,其中45例为门脉高压患者,设为门脉高压组,41例为正常人群,设为正常组,观测2组的门脉左右肢汇合部、门脉汇合部同一扫描层腹主动脉、胰腺、双肾及脾脏的CT值,门脉高压组按肝功能分级对以上各部位所对应的CT值计数并进行统计分析.结果 门脉高压组门脉左右支汇合部、同一扫描层腹主动脉、胰腺、双肾及脾脏的CT值分别为(36.97±5.81)、(41.06 ±7.22)、(42.64±6.07)、(33.18 ±4.20)及(45.29±4.60) HU;正常组相应部位CT值分别为(43.92±5.71)、(47.19±5.80)、(50.06 ±7.80)、(36.12 ±4.50)及(52.38 ±4.95) HU;以上部位肝功能A、B及C级对应CT值分别为(39.57±4.56)、(36.56 ±5.46)、(31.24±5.23);(45.23 ±6.73)、(40.86 ±6.92)、(36.06 ±7.12);(45.97 ±6.07)、(42.76±6.35)、(38.67 ±7.35);(37.33 ±4.09)、(33.46 ±3.97)、(28.23 ±4.13);(48.66 ±4.38)、(45.03 ±4.43)、(40.12 ±5.32) HU;方差分析显示,门脉高压组与正常组的门脉、腹主动脉、胰腺、双肾及脾脏的CT值差异有统计学意义(P＜0.05),肝功能A、B和C级各部位组内差异有统计学意义(P＜0.05).结论 门脉高压时,门脉、腹主动脉、胰腺、双肾及脾脏的CT值将降低,而且肝功能分级越高,CT值越低,提示门脉高压时,对周围器官的功能及主动脉血流动力学有一定的影响.