破壁灵芝孢子粉与雌二醇抗肝纤维化的比较研究

目的：通过破壁灵芝孢子粉和雌二醇对CCl4诱导的肝纤维化大鼠肝组织转化生长因子β1（TGF-β1）影响的实验研究,比较破壁灵芝孢子粉和雌二醇的作用效果。方法：使用CCl4诱导大鼠肝纤维化动物模型,分别给予雌二醇和高低剂量的破壁灵芝孢子粉处理。通过免疫组化染色半定量分析TGF-β1的表达状况。结果：TGF-β1雌二醇组与破壁灵芝袍子粉高剂量组之间无统计学差异（P〉0.05）,均值小于低剂量组高于对照组,其他各组间两两比较均有统计学差异（P〈0.05）。结论：破壁灵芝袍子粉高剂量组与雌二醇在抗肝纤维化中的作用效果接近,低剂量组作用效果低于雌二醇组。     

戊酸雌二醇片/雌二醇环丙孕酮片复合包装治疗围绝经期功能失调性子宫出血的临床效果观察

目的：探讨戊酸雌二醇片/雌二醇环丙孕酮片复合包装治疗围绝经期功能失调性子宫出血的临床效果。方法选取本院2013年3月～2014年2月收治的96例围绝经期功能失调性子宫出血患者,随机分为治疗组与对照组各48例。治疗组口服戊酸雌二醇片/雌二醇环丙孕酮片复合包装进行治疗,对照组应用炔诺酮片进行治疗。比较两组的临床疗效及治疗前后月经周期、经期、经量的变化情况。结果治疗组痊愈率为75.0%,总有效率为93.75%;对照组痊愈率为41.67%,总有效率为56.25%;治疗组痊愈率及总有效率明显高于对照组（P＜0.05）。两组治疗后月经周期、经期、经量与治疗前比较,差异有统计学意义（P＜0.05）;治疗后治疗组月经周期、经期、经量与对照组比较,差异有统计学意义（P＜0.05）。结论戊酸雌二醇片/雌二醇环丙孕酮片复合包装治疗围绝经期功能失调性子宫出血效果显著,值得临床进一步推广应用。     

Characterization of a membrane-associated estrogen receptor in a rat hypothalamic cell line (D12)

The ability of estrogens to produce rapid changes in cellular function has been firmly established. The question remains whether these changes are mediated by a modified form of the nuclear estrogen receptor (ER) that is associated with the plasma membrane (mER) or by a completely novel membrane receptor. Therefore, we characterized the biochemical properties of the nuclear and membrane-associated ERs expressed endogenously in a rat hypothalamic endothelial cell line (D12). Radioligand binding experiments using D12 membrane fractions showed that these cells exhibit properties consistent with a binding site specific for estrogens (mER). Equilibrium binding assays using [¹²⁵I]16-α-iodo-3,17-β-estradiol revealed saturable binding to mER, an affinity value similar to nuclear ER, with differing receptor expression levels. Competition assays revealed that 9 of 12 ER ligands tested had comparable affinities for mER and ER. For example, 17-α-estradiol and estrone had similar binding characteristics for both receptors while differences were noted for raloxifene, 17β-estradiol (E2), and genistein. Western blot and immunocytochemical analyses using antibodies specific for ERα confirmed that D12 cells expressed a membrane-associated protein with a molecular mass (67 kDa) similar to that of ERα that colocalized with caveolae-enriched membranes. A rapid increase in intracellar Ca²⁺ levels in the presence of E2 suggests that mER can mediate physiologic changes through calcium mobilization. These data support the expression of mER in these brain-derived endothelial cells that is similar to, but biochemically distinguishable from, nuclear ERα.     

【特刊综述】睾酮和雌二醇检测方法面临的挑战和取得的进展

在患者护理、公共卫生、科学研究过程中类固醇激素的检测方法需要正确而精准,因为这些检测的标准可以保证所有的临床机构和研究机构的结果具有可比性。本文陈述了目前有关检验结果易变的主要问题以及最近美国疾病预防控制中心（CDc）针对提升检验效果所做的工作。目前,睾酮和雌二醇的检测方法还无法达到高度的正确性和精准性。虽然类固醇激素检测方法已经有了长足的进步,但是实验室内部和实验室之间的检测差异仍然未能得到相应的改善。检测标准和特异性的差异被认为是测量精度变异性的来源。最终认为,类固醇激素检测的不准确性似乎是由综合因素造成的,其中不一致的检验标准和缺乏特异性被认为是产生结果变异的两个主要因素。目前,同一批次内的化验结果也变异较大,特别是在样本浓度低的情况下。2007至2011年间的质谱分析法和CDC参考方法之间的平均绝对偏差下降了50％,由此可以看出CDC激素标准化测试程序正在提高临床化验的准确性。这种测试程序可以为CDC参考方法提供追朔源头的途径,从而减少产生测量结果变异的因素。     

CA125、孕酮联合雌二醇预测先兆流产的价值

目的 探讨血清癌抗原125（CA125）、孕酮联合雌二醇预测先兆流产的临床价值。方法 回顾性分析2012年3月至2014年3月解放军第一零一医院收治的孕龄在6～8周的单胎孕妇,按照妊娠结局将其分为3组：先兆流产组、难免流产组以及正常妊娠组,分别测定三组的CA125、孕酮以及雌二醇水平。结果 3组的CA125、孕酮、雌二醇经方差分析比较,差异均有统计学意义（F值分别为15．731、3．608、26．253,均P＜0．05）,两两比较后发现正常妊娠组的CA125显著低于先兆流产组和难免流产组（t 值分别为12．183、16．065,均P＜0．05）,先兆流产组的CA125低于难免流产组（t＝9．187,P＜0．05）,正常妊娠组的孕酮、雌二醇显著高于先兆流产组和难免流产组（t值分别为10．073、12．685、9．936、18．187,均P＜0．05）,先兆流产组孕酮、雌二醇显著高于难免流产组（t值分别为9．637、10．098,P＜0．05）。 CA125、孕酮、雌二醇检测的灵敏度、特异度、准确性差异无统计学意义（χ^2分别为1．962、1．734、0．985,P＞0．05）,CA125、孕酮联合雌二醇对先兆流产患者预后的灵敏度、特异度、准确性均显著高于其它三组（χ^2分别为5．184、6．861、4．086,均P＜0．05）。结论 CA125、孕酮联合雌二醇对先兆流产进行预测具有准确性高的特点,临床有重要参考价值。     

雌二醇联合孕激素对卵巢癌细胞凋亡及microRNA-15a表达的影响

目的 探讨雌二醇（E2）联合孕激素（P4）对microRNA-15a （miR-15a）表达的影响。方法 采集手术中切除的卵巢癌组织标本进行细胞培养,分3个处理组：E2组,P4组和雌二醇联合孕激素（E2+P4）组。激素处理后,MTT法检测细胞存活率;流式细胞技术检测细胞凋亡与细胞周期;qRT-PCR法检测Bcl-2,Bax和miR-15a的相对表达量。结果 高浓度（浓度均为10^-4 mol·L^-1）的E2,P4,E2+P4能够降低卵巢癌细胞的存活率,并表现为时间依赖性;低浓度（≤ 10^-8 mol·L^-1） E2能够提高卵巢癌细胞的存活率。与对照组相比,高浓度E2,P4和E2+P4能够增加卵巢癌细胞的凋亡率（P<0.001）,并且E2+P4的作用最明显;低浓度E2能够抑制肿瘤细胞的凋亡（P<0.001）。E2,P4和E2+P4对细胞周期的影响没有统计学差异。高浓度的E2,P4和E2+P4能够下调Bcl-2的表达（P<0.05或P<0.001）,上调Bax的表达（P<0.001）;但是低浓度E2作用却相反。高浓度的E2+P4能够促进miR-15a的表达（P<0.001）。结论 高浓度的E2,P4和E2+P4能够降低细胞的存活率促进细胞凋亡,下调Bcl-2的表达,上调Bax的表达;低浓度E2的作用则相反;高浓度的E2+P4能够促进miR-15a的表达。     

The comparison of the effectiveness and safety of drospirone ethinyl estradiol and ethinyl estradiol cyproterone in the treatment of polycystic ovarian syndrome: A protocol for systematic review and meta-analysis

Background:Polycystic ovarian syndrome (PCOS) is an endocrine disorder syndrome with reproductive dysfunction and abnormal glucose metabolism. Persistent non-ovulation, excessive androgens and insulin resistance are important features and they are the most common causes of menstrual disorders in women during childbearing years. At present, the cause of PCOS is not clinically clear. Current studies suggest that it may be due to the interaction of certain genetic genes with environmental factors. It is an important cause of infertility or early miscarriage with the characteristics of various causes and complex clinical manifestations. At present, for the treatment of PCOS patients, clinical treatment mainly includes hypoglycemia, insulin and menstrual regulation and other symptomatic and supportive treatment. Drospirone ethinyl estradiol and ethinyl estradiol cyproterone are 2 of the most commonly used drugs in clinical treatment of PCOS, but there is lack of the evidence of evidence-based medicine. Therefore, this study systematically evaluates the therapeutic effect and safety of PCOS patients with 2 short-acting oral contraceptives, drospirone ethinyl estradiol and ethinyl estradiol cyproterone, which provides the guidance for clinically selecting the appropriate drug to treat PCOS.Methods:Searching CNKI, WanFang Data, VIP, SinoMed, PubMed, EMbase, Web of Science, and The Cochrane Library database by computer, collecting the randomized controlled studies of DEE and EEC in the treatment of PCOS. The retrieval time limit is from the establishment of each database to July 1, 2020. In addition, tracing the references incorporated into the literature to supplement to the relevant literature. Using the retrieval method by combining the free words and the subject words, and the individual search of different databases is carried out. Meta-analysis is performed using RevMan 5.3 software after 2 researchers independently screens the literature, extracts the data, and evaluates the bias risk included in the study.Results:This study will systematically evaluate the DEE and EEC in the treatment of PCOS by collecting the required evidence to understand the effects of the 2 drugs on hypersotrophicemia, insulin resistance, lipid metabolism, and the safety during drug use in patients of this class, and the results will be published in highly influential academic journals.Conclusion:The results of this study will provide theoretical basis for the drug treatment of polycystic ovarian syndrome and provide help in the decision-making of clinical treatment of the disease.Ethics and dissemination:In this study, meta-analysis was used to conduct a second study on the published literature. Therefore, this type of systematic review research does not need to be approved by ethics.OSF Registration DOI:10.17605/OSF.IO/8GW9M.     

Estrogen potentiates the behavioral and nucleus accumbens dopamine response to continuous haloperidol treatment in female rats

Estrogen has been shown to enhance the effects of antipsychotics in humans. To investigate the mechanisms of how this may occur, the current study examined estradiol's effects on dopaminergic transmission and behavior in amphetamine‐sensitized and non‐sensitized female rats. Sixty‐four ovariectomized female Sprague–Dawley rats were used for this study. Half of the rats were sensitized to four once‐daily injections of 1 mg/kg amphetamine and the other half served as controls. Rats received chronic administration of either low‐dose haloperidol (0.25 mg/kg/day) or saline vehicle via osmotic minipumps implanted subcutaneously. The groups were further subdivided with respect to estradiol treatment: low chronic estrogen (subcutaneous estradiol implant, 0.36 mg/pellet: 90‐day release, plus an additional oil vehicle injection every second day) and high pulsatile estrogen (subcutaneous estradiol implant plus an additional 10 μg/kg estradiol injection every second day). Motor activity was assessed at day 2 and day 12 during haloperidol treatment, while nucleus accumbens dopamine availability was assessed via microdialysis 10 days into antipsychotic treatment. Haloperidol treatment along with high, but not low, estradiol replacement was effective in reducing amphetamine‐induced locomotor activity in sensitized rats. High estradiol treatment also augmented the effects of chronic haloperidol in reducing dopaminergic release in sensitized rats. These data suggest that estradiol levels affect both the behavioral and the dopamine responses to chronic antipsychotic treatment.