超促排卵周期胚胎移植日血清孕酮/雌二醇比值对胚胎着床的影响

目的：探讨超促排印周期胚胎移植日血清孕酮／雌二醇（P／E2）比值对子宫内膜容受性的影响。方法：将96例体外受精-胚胎移植患者按胚胎移植日（ET）血清P／E2比值分为5组,对其实验室结果和临床结局进行比较。结果：5组患者的平均年龄、ET日内膜厚度、受精率、印裂率、可移植胚胎数及移植胚胎数均无差异（P〉0．05）。组1的取卵数最多,妊娠率低;组5的取卵数最少,无1例妊娠。而组3（P／E2为100～150）获得显著高于其他组的妊娠率和单胚种植率（P〈0．05）。结论：恰当的P／E2比值可提高子宫内膜的容受性,在促排卵周期测定ET日的P／E2比值对预测妊娠成功与否有参考作用。     

Aspirin Enhances the Protective Effect of Progesterone on Trophoblast Cell from Oxidative Stress and Apoptosis

Objective::Clinically, low-dose aspirin and progesterone are frequently used to prevent pregnancy loss. We investigated the effect of these drugs on the biologi...     

补肾凉血安胎法治疗肾虚血热型先兆流产合并官腔积液临床研究

目的:研究补肾凉血安胎法治疗肾虚血热型先兆流产合并宫腔积液的效果。方法:选择肾虚血热型先兆流产合并宫腔积液患者160例,按随机数字表法分为对照组和观察组各80例。对照组给予黄体酮联合酚磺乙胺治疗,观察组采用补肾凉血安胎法治疗,连续治疗2周。观察2组临床疗效,比较2组孕酮(P)、雌二醇(E2)、人绒毛膜促性腺激素(HCG),以及中医症候评分。结果:观察组总有效率为85.00%,高于对照组70.00%(P<0.05)。治疗前,2组P、HCG、E2水平比较,差异无统计学意义(P>0.05)。治疗后,2组P、HCG、E2水平较治疗前升高(P<0.05),且观察组P、HCG、E2水平高于对照组(P<0.05)。治疗前,2组各项中医症状评分比较,差异无统计学意义(P>0.05)。治疗后,2组各项中医症状评分较治疗前降低(P<0.05),且观察组各项中医症状评分低于对照组(P<0.05)。结论:采用补肾凉血安胎汤治疗肾虚血热型先兆流产合并宫腔积液患者,不仅能改善患者血液指标,有利于保胎,还能促进宫腔积液的吸收,效果显著,值得临床应用。     

Evaluation of NMU-Induced Breast Cancer Treated with Sirolimus and Sunitinib on Breast Cancer Growth

Objective: To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib. Methods: Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis. Results: Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring. Conclusion: Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment.     

Development of a Nomogram to Predict the Recurrence Score of 21-Gene Prediction Assay in Hormone Receptor–Positive Early Breast Cancer

IntroductionA 21-gene prediction assay (Oncotype DX) is helpful to estimate benefit from adjuvant chemotherapy in patients with hormone receptor–positive, lymph node–negative early breast cancer. This study was conducted to develop a model to estimate high recurrence score (RS) using easily available clinicopathologic parameters in limited-resource countries.Patients and MethodsHormone receptor–positive, lymph node–negative early breast cancer patients who underwent Oncotype DX were enrolled onto the training set (n = 192). The risk category range of the RS was the same as in the TAILORx study. The multivariable logistic regression model was used to identify significant variables associated with high RS. The independent validation set (n = 264) was established from patients of a different time period.ResultsThe median age in the training set was 47 years, and 78.0% were premenopausal. The number of patients with low RS (< 11), intermediate RS (11-25), and high RS (> 25) were 42 (22.0%), 122 (63.9%), and 27 (14.1%), respectively. High nuclear grade, no progesterone receptor expression, and high Ki-67 were associated with high RS, and these variables were used to construct the nomogram. It had significant discriminatory power in internal validation (area under the curve = 0.856) and in the validation set (area under the curve = 0.828). The calibration plot showed optimal agreement between predicted and actual probabilities in both sets.ConclusionA nomogram was successfully developed with 3 simple parameters. The probability of high RS can be easily and conveniently estimated using our nomogram. It might be useful to determine whether or not Oncotype DX is conducted in the TAILORx era. Future large-scale prospective studies are warranted.     

黄体酮对脑缺血再灌注大鼠紧密连接蛋白ZO-1和occludin表达的影响

目的探讨黄体酮对大鼠局灶性脑缺血再灌注后血脑屏障紧密连接蛋白ZO-1、occludin表达及血脑屏障通透性的影响。 方法将42只健康雄性SD大鼠按随机数字表法分为假手术组（6只）和缺血再灌注组,后者再按再灌注时间分为缺血2h再灌注3h、6h、12h、24 h、48 h及72h组（各6只）。缺血再灌注组用线栓法制备成大鼠大脑中动脉缺血再灌注模型。采用荧光分光光度法测定缺血侧脑组织中伊文氏蓝(EB)含量来评价血脑屏障的通透性,Western blotting法检测脑组织ZO-1和occludin的表达。取EB漏出最多组的时间点,增设黄体酮干预组和溶剂对照组（各6只）,与相同时间点的缺血再灌注组比较,观察黄体酮对ZO-1、occludin表达及血脑屏障通透性的影响。 结果 缺血2h再灌注3h时脑组织EB含量开始增加,再灌注24 h时达高峰;ZO-1、occludin的表达在缺血2h再灌注3h时开始下降,再灌注24 h时达最低。黄体酮干预组EB含量明显低于缺血2h再灌注24 h组,差异有统计学意义(P＜0.05)。黄体酮干预组ZO-1和occludin的表达水平均明显高于缺血2h再灌注24 h组,差异有统计学意义(P＜0.05)。 结论 黄体酮町抑制缺血再灌注大鼠紧密连接蛋白ZO-1和occludin表达的降低,从而起到保护血脑屏障的作用。     

雌激素和孕激素对人乳腺癌细胞MCF-7 RCAS1表达的影响

目的探讨体外雌激素和孕激素对人乳腺癌细胞MCF-7表达SiSo细胞上的受体结合肿瘤抗原(RCAS1)分子的影响。方法用浓度为10-12~10-8mol/L的雌激素或浓度为10-9~10-5mol/L的孕激素作用乳腺癌细胞MCF-7后,用半定量逆转录聚合酶链反应(RT-PCR)检测MCF-7细胞RCAS1 mRNA水平的变化,用蛋白免疫印迹试验分析MCF-7细胞表达RCAS1蛋白水平的变化。结果在10-12~10-8mol/L范围内随着雌激素浓度的增加,MCF-7细胞RCAS1 mRNA的表达呈递增趋势,在10-11、10-10、10-9、10-8mol/L范围内雌激素组与未处理对照组比较,差异有统计学意义(P<0.05)。随着10-9~10-5mol/L的孕激素浓度的增加,MCF-7细胞RCAS1 mRNA的表达呈下降趋势,孕激素各组与未处理对照组比较,差异有统计学意义(P<0.05)。用RCAS1单克隆抗体能检出相对分子质量为32 000的条带,其灰度随着雌激素浓度的增加而增强,随孕激素浓度的增加而减弱。结论雌激素可上调MCF-7细胞的RCAS1分子表达,孕激素可下调MCF-7细胞的RCAS1分子表达。     

Progestin-inducible EDD E3 ubiquitin ligase binds to α4 phosphoprotein to regulate ubiquitination and degradation of protein phosphatase PP2Ac

Mammalian α4 phosphoprotein binds to the protein phosphatase 2A catalytic subunit (PP2Ac) to regulate PP2A activity, and to poly(A)-binding protein (PABP) and progestin-inducible EDD E3 ubiquitin ligase. This study showed induction of the EDD protein by progesterone, 17β-estradiol and prolactin in breast cancer cells. Co-immunoprecipitation analyses, using lysates of COS-1 cells transfected with α4-deletion constructs, showed the α4 N-terminus binding to endogenous PP2Ac and PABP, and the C-terminus to EDD. Monoubiquitinated α4 in MCF-7 cells was unaffected by EDD-targeting siRNA (siEDD) nor by non-targetting siNT, thus, EDD does not ubiquitinate α4. PP2Ac is polyubiquitinated, and 36-kDa PP2Ac only was detected in siEDD- or siNT-transfected cells. However, treatment with proteasomal inhibitor MG132 showed polyubiquitinated-PP2Ac molecules (∼65–250 kDa) abundantly in siNT controls but low in siEDD-transfectants, implicating PP2Ac as an EDD substrate. Finally, progesterone induction of EDD in MCF-7 cells correlated with decreased PP2Ac levels, further implicating hormone-inducible EDD in PP2Ac turnover.     

左炔诺孕酮宫内节育系统治疗无排卵型功能失调性子宫出血的疗效

目的观察左炔诺孕酮宫内节育系统(曼月乐,LNG-IUS)治疗无排卵型功能失调性子宫出血(AUB-O)的疗效及其对子宫内膜血管内皮细胞生长因子、雌激素受体和孕激素受体的影响。方法将2015年6月~2016年9月我院收治的78例AUB-O患者,随机分为对照组和观察组,每组39例。在常规治疗基础上,对照组予去氧孕烯炔雌醇片(妈富隆)口服,观察组予曼月乐治疗。比较两组治疗前与治疗12个月后血红蛋白水平(HGB)、血清雌二醇(E_2)、孕酮(P)、垂体分泌卵泡刺激素(FSH)、黄体生成素(LH)激素水平及子宫内膜厚度,采用SP免疫组织化学检测两组治疗前及12个月后子宫内膜腺体和间质中的血管内皮生长因子(VEGF)、雌激素受体(ER)、孕激素受体(PR)的阳性表达。比较两组的临床疗效、不良反应。结果观察组的控制出血及完全止血时间均显著短于对照组,差异均有统计学意义(P0.01)。治疗后,两组的血红蛋白水平均较治疗前显著升高(P0.01),子宫内膜厚度显著减少(P0.01),E_2均较治疗前显著降低,P显著升高,且观察组改善程度较对照组更加明显,差异亦有统计学意义(P0.01)。观察组患者治疗后的子宫内膜腺体及间质中的VEGF阳性率显著高于治疗前,ER、PR阳性率显著低于治疗前(P0.01)。且治疗后观察组的VEGF阳性率高于对照组,ER、PR阳性率低于对照组(P0.01)。观察组的的总有效率为94.9%,显著高于对照组的79.5%(P0.05)。两组的不良反应发生情况无统计学差异(P0.05)。结论曼月乐治疗AUB-O能更好的通过调节子宫内膜ER、PR、VEGF的表达,达到临床治疗效果,且较口服妈富隆更加简便、有效、安全。     

乳腺癌组织中HER2、ERα、ERβ、PR的表达及其相关性分析

目的探讨雌激素受体α（ERα）、雌激素受体β（ERβ）、孕激素受体（PR）、人类表皮生长因子受体2（HER2）在乳腺癌组织中的表达及其与TNM分期和腋窝淋巴结状况的关系。方法随机选择我院在2004年12月至2007年12月收治的HER2高表达（＋＋＋）51例与无表达（-）53例乳腺浸润性导管癌病例，分别检测乳腺癌组织的ERα、ERβ、PR的表达水平，分析其与TNM分期、腋窝淋巴结转移等临床指标的相关性。结果104例乳腺癌患者，TNM分期为I期的占14．42％，Ⅱ期占62．50％，Ⅲ期占19．23％，Ⅳ期占3．85％；HER2阳性的淋巴结转移率为41．18％，HER2阴性的转移率为47．5％；ERα、ERβ、PR的阳性表达率分别为52．88％、63．46％、73．08％。ERβ与ERα、PR的表达呈正相关（P〈0．01），与HER2的表达负相关（P〈0．01）；ERα与PR的表达正相关（P〈0．01），与HER2负相关（P〈0．01），PR与HER2的表达负相关（P〈0．05）；ERα、ERβ、PR、HER2的表达与淋巴结转移情况及TNM分期无显著相关性。结论HER2作为乳腺癌预后不良的重要指标与作为乳腺癌预后良好的重要指标ERα、ERβ、PR的表达呈负相关，与TNM分期及腋窝淋巴结转移状态未显示明显相关性。