黄素化颗粒细胞survivin蛋白的表达与卵巢反应性的相关研究

目的探讨Survivin蛋白在人卵巢黄素化颗粒细胞表达与超排卵周期卵巢反应性的关系。方法收集32例行体外受精-胚胎移植（IVF-ET）患者的卵巢黄素化颗粒细胞,根据取卵时卵泡发育数不同将卵巢反应性分为高反应组（n=7）、中反应组（n=20）及低反应组（n=5）。应用流式细胞仪Annex-inV-PI双染法检测颗粒细胞凋亡;采用免疫细胞化学方法检测黄素化颗粒细胞Survivin蛋白的表达,分析它们与卵巢反应性的关系。结果黄素化颗粒细胞的凋亡率与HCG日E2水平呈负相关（r=0.637,P〈0.01）,高反应组、中反应组和低反应组颗粒细胞凋亡率分别为（8.8±2.7）%、（11.8±4.1）%及（19.4±5.8）%,3组比较差异有统计学意义（P〈0.01）;黄素化颗粒细胞Survivin蛋白的表达HCG日E2水平呈正相关（P〈0.01）,高反应组、中反应组和低反应组Survivin蛋白的表达分别为2.591±0.167、2.44±0.229及2.016±0.140,差异有统计学意义（P〈0.01）。结论黄素化颗粒细胞Survivin蛋白的表达水平可反映卵巢储备功能与超促排卵过程中卵巢反应性。     

补肾调周法对超排卵周期颗粒细胞CYP19 A1 mRNA表达的影响

目的：探讨补肾调周法对超体外受精与胚胎移植（ in vitro fertilization and embryo transfer, IVF－ET ）控制性超排卵（controlled ovarian hyperstimulation,COH）周期中颗粒细胞CYP19A1 mRNA表达的影响。方法：将24例因输卵管因素不孕行IVF－ET的患者以随机数字表法分为治疗组（育泡组方联合COH治疗）和对照组（ COH治疗）各12例。对比分析2组患者卵巢颗粒细胞CYP19A1 mRNA的相对表达量及其与IVF参数的相关性。结果：治疗组中2例患者未按规定用药而退出研究,对照组中1例患者降调后妊娠而取消周期。 COH治疗后,2组患者肾虚证候积分的差异有统计学意义（ P＜0．05）;2组患者重组人促卵泡激素（ rFSH）使用时间、rFSH总用量、雌二醇／获卵数、MⅡ卵子数／获卵数及优质胚胎率的差异有统计学意义（ P＜0．05）;治疗组患者卵巢颗粒细胞CYP19A1 mRNA相对表达量明显高于对照组,差异有统计学意义（P＜0．05）;CYP19A1 mRNA相对表达量与MⅡ卵子数／获卵数及雌二醇／获卵数呈正相关（ P＜0．05）。结论：在IVF－ET治疗周期,配合使用具有补肾益精作用的中药可明显改善患者所表现出的肾虚症状,减少rFSH用量,提高成熟卵子率及优质胚胎率。补肾益精类中药可提高颗粒细胞CYP19A1 mRNA的表达,改善颗粒细胞的分泌功能,这可能是补肾益精类中药改善IVF最终结果的机制之一。     

微刺激和温和刺激促排方案对卵巢低反应患者体外受精-胚胎移植的对比研究

目的:探讨卵巢低反应助孕患者在进行体外受精-胚胎移植(IVF-ET)治疗中微刺激方案与温和刺激方案的治疗效果。方法:将2012年9月1日—2013年9月30日在山西省妇幼保健院生殖中心接受IVF/ICSI-ET(ICSI为卵胞浆内单精子注射技术)治疗并预测卵巢低反应的120周期患者分为微刺激组(42例)与温和刺激组(78例)。比较两组的一般资料、促性腺激素(Gn)用量、Gn天数以及平均获卵数、成熟卵数、人绒毛膜促性腺激素(HCG)日血清激素水平、周期取消率、新鲜周期移植妊娠率。结果:两组治疗后超排卵Gn用量、HCG日黄体生成素(LH)及孕酮(P)水平、成熟卵子数、无优势卵泡发育率、提前排卵率比较,差异均无统计学意义(P>0.05);微刺激方案组的Gn天数、HCG日雌二醇(E2)水平低于温和刺激方案组,差异有统计学意义(P<0.05)。微刺激方案组的周期取消率明显高于温和刺激方案组,差异有统计学意义(P<0.05)。结论:温和刺激方案简单、经济,同时相对于微刺激方案降低了周期取消率,是卵巢低反应患者较理想的促排卵方案。     

重组人生长激素在ART超排周期中的观察

目的 观察卵巢低反应患者行IVF／ICSI（体外受精／单精子卵泡浆内注射）治疗周期使用重组人生长激素（GH）辅助超排卵对其治疗结果的影响。方法回顾性分析2005年1月～2007年10月在我中心行IVF／ICSI治疗的卵巢低反应患者218例（218个周期）,按自愿原则分为两组,其中加用GH的86例（86个周期）为研究组,未用GH者132例（132个周期）为对照组,分析两组获卵数,受精数及妊娠率的差异。结果两组在获卯数,受精数上有明显差异（P〈0．05）,但妊娠率无明显差异（P〉0．05）。结论对卵巢低反应的患者在IVF／ICSI治疗周期使用GH辅助超排卵可以减少卵巢不良反应,可能提高获卵数和受精率。     

卵巢低反应预处理后对IVF-ET结局的影响

目的 探讨在超排卵前补佳乐人工周期处理3个周期后对卵巢反应不良患者IVF-ET结局的影响.方法 选择2005年1月～2006年12月在我中心接受IVF-ET或ICSI治疗中预测将出现卵巢低反应的患者,21例设为研究组,在超排卵前给予补佳乐行人工周期3个周期;22例作为对照组,分析两组超排卵前不孕原因、不孕时间、基础内分泌以及超排卵时所用Gn天数、Gn支数、获卵数、受精数、优质胚胎数、妊娠率、早期流产率.结果 两组在不孕原因、不孕时间、基础内分泌无统计学差异性(P＞0.05);两组Gn天数、Gn支数、获卵数、受精数和优胚数亦无统计学差异性(P＞0.05),研究组妊娠率高于对照组,早期流产率低于对照组(P＜0.05).结论 补佳乐预处理后,可以提高卵巢反应不良患者的妊娠率,降低流产率.     

卵泡冲洗在卵巢功能减退患者实施辅助生殖助孕中的应用

目的:研究卵泡冲洗在卵巢功能减退患者行体外授精-胚胎移植(IVF-ET)助孕中的作用。方法:选择行IVF-ET助孕的卵巢储备功能差的患者共100个取卵周期,分为常规取卵组(对照组)50例和卵泡冲洗取卵组(冲洗组)50例。比较两组的获卵及胚胎情况、临床结局。结果:卵泡冲洗组的获卵率高于常规取卵组(P<0.05),其临床妊娠率有增高趋势,但差异无统计学意义(P>0.05)。结论:卵泡冲洗可以提高卵巢储备功能差的患者的获卵数,因此卵泡数少的患者取卵时,卵泡冲洗是必要的。     

来曲唑配合中药治疗多囊卵巢综合征排卵障碍的疗效观察

目的:观察来曲唑配合中药治疗多囊卵巢综合征(PCOS)所致排卵障碍的临床效果及安全性。方法:选取门诊PCOS患者300例,随机分为3组:枸橼酸氯米芬(CC)组100例(188周期)、尿促性腺激素(HMG)组100例(104周期)、来曲唑(LE)组100例(155周期)。比较3组治疗后成熟卵泡出现率、排卵率、妊娠率、流产率、多胎畸胎率、取消周期数、无优势卵泡发生数、发生卵巢过度刺激综合征(OHSS)等参数。结果:CC组出生30人,HMG组出生34人,LE组出生43人;在成熟卵泡出现率、排卵率、妊娠率方面,LE组高于CC组、HMG组(P<0.05),HMG组高于CC组(P<0.05);在流产率、畸胎率、取消周期数、无优势卵泡发育数、OHSS方面,LE组低于CC组、HMG组(P<0.05),CC组、HMG组比较差异无统计学意义(P>0.05);多胎率HMG组高于CC组、LE组(P<0.05)。结论:应用来曲唑配合中药可治疗PCOS排卵障碍引起的不孕,排卵率及妊娠率较高,经济、方便、安全。     

二硫化碳对雌性小鼠的性腺毒作用

进行了雌性小鼠CS_2染毒后卵巢连续切片的组织学观察和超数排卵(人工诱发排卵)试验。<1>卵巢组织学观察结果:原始卵泡数在各实验组间无显著性差异;初级卵泡和次级卵泡数CS_2高剂量组均显著低于CS_2低剂量组和对照组(P<0.05);闭锁卵泡呈明显增多趋势;<2>超数排卵试验结果:GS_2染毒组与对照组间平均超排卵数无显著性差异(P>0.05)。提示CS_2性腺毒作用可以表现为卵泡生长发育成熟的明显障碍,而卵巢对于超量促性腺激素作用的反应机能基本正常。     

来曲唑治疗排卵异常的临床疗效评价

目的:观察、比较来曲唑(letrozole,LE)治疗各种排卵异常的疗效,以探讨其适应症及不良反应等。方法:选取排卵异常患者313例,观察871个治疗周期,按排卵异常类型分成4组:除多囊卵巢综合征(polycysticovariansyndrome,PCOS)外的无排卵组(A组)、PCOS组(B组)、小卵泡排卵组(C组)、未破裂卵泡黄素化综合征(luteinizedunrupturedfolliclesyn-drome,LUFS)组(D组)。4组均自月经d5起,口服LE2.5mgq.d.×5,后酌情或加用人绝经促性腺激素(humanmenopausalgonadotropin,HMG)。当优势卵泡平均直径(MFD)≥18mm,或尿黄体生成素(lutein-izinghormone,LH)测定(+),肌注人绒毛膜促性腺激素(humanchorionicgonadotropin,HCG)10000IU。比较4组的排卵率、妊娠率、流产率等。结果:4种排卵异常中,仅B组有因无优势卵泡发育或有卵巢过度刺激综合征(ovarianhyperstimulationsyndrome,OHSS)危险而取消周期者;单用LE的优势卵泡出现率:B组明显低于另3组;HCG肌注日最大卵泡平均直径(middlefollicledominant,MFD):C组明显低于另3组;HCG(humanchorionicgonadotropin)肌注日MFD≥15mm卵泡个数:B组明显高于另3组;排卵率:A、C组明显高于B、D组;妊娠率C组最低;早期流产率C组最高,其次为B组;PCOS患者刺激卵泡前的窦卵泡数≤8个/侧者较≥9个/侧者取消周期率、HCG肌注日MFD≥15mm卵泡个数低而单用LE的优势卵泡出现率、排卵率高;刺激卵泡日数:≤6d者无妊娠,7~13d者较≥14d者妊娠率高而早期流产率低;不良反应:全部患者均诉月经经期延长,仅有7个周期有患者诉服LE期间轻微胃肠道反应。结论:LE对除PCOS外的无排卵、PCOS、LUFS均有疗效,对小卵泡排卵者的卵泡发育无明显改善;刺激卵泡前窦卵泡数目可预测PCOS患者对LE的敏感;刺激卵泡日数7~13d疗效最佳;服用LE不良反应少。     

控制性超排卵下血管内皮生长因子与卵巢反应性的研究

目的探讨控制性超排卵周期卵巢反应不良组、对照组血清和卵泡液中血管内皮生长因子(VEGF)、性激素水平与卵巢反应性及妊娠结局的关系,以揭示卵巢反应不良的发病机制。方法行体外受精胚胎移植反应不良的不孕患者29例、对照组43例,采集其取卵日血清和卵泡液,应用酶联免疫吸附试验(ELISA)检测其性激素水平和VEGF。结果①卵泡液中的VEGF明显高于血清,约为血清中的6倍;②反应不良组卵泡液中VEGF浓度高于对照组(P<0.05);③反应不良组血清中的VEGF与对照组差异无统计学意义(P>0.05);④VEGF不能反映妊娠结局。结论卵泡液中的VEGF通过负反馈机制以及与酪氨酸受体结合,介导一氧化氮释放,使VEGF浓度增加;结合基础卵泡刺激素(FSH)值、雌激素水平以及卵泡液中VEGF能够预测卵巢的反应性。     

Human controlled ovarian hyperstimulation outcome is a polygenic trait

This study aimed to evaluate the association between follicle-stimulating hormone (FSH) hormone efficacy and FSHR, CYP19, ESR1 and ESR2 genes using single nucleotide polymorphism analyses. One hundred and seventy women with conserved ovarian function undergoing controlled ovarian stimulation (COS) with daily exogenous recombinant FSH administration. Women were categorized as poor responders to FSH (three or less ovarian follicles observed at the end of cycle) or normal responders (more than three follicles). The outcome is the number of normal/poor responders as defined by the number of follicles obtained during COS. The DNA markers studied are located in genes related to the FSH mechanism of action (FSH receptor, CYP19 aromatase and oestrogen receptors alpha and beta genes). We conducted an association study between the COS outcome and selected DNA markers using two-point and multi-locus genetic association studies. Genotype pattern tracking in extreme phenotypes and multi-locus analysis using Sumstat and PM algorithms provided significant evidences of genetic interaction between FSHR, ESR1 and ESR2 markers in relation to COS outcome (P = 0.0015). Our results support the hypothesis that a discrete set of genes, related to the FSH hormone mechanism of action, controls the ovarian response to FSH in humans. An oligogenic model including specific FSHR, ESR1 and ESR2 genotype patterns may partially explain the poor response to FSH hormone during controlled ovarian stimulation treatments. The existence of genetic heterogeneity is also suspected.     

Early neuroleptic response: clinical profiles and plasma catecholamine metabolites

Forty-seven psychotic inpatients who required neuroleptic treatment were studied with respect to some clinical and biochemical variables associated with early neuroleptic response. Compared to poor early responders, good responders were older at onset of illness and at index admission, less likely to have had a schizoid developmental history, and more likely to be married. There was a trend for good early responders to have received a diagnosis of affective psychosis or atypical psychotic disorder rather than schizophrenia or schizophreniform disorder. However, no behavioral symptom or sign differentiated good from poor early responders with the possible exception of pretreatment psychomotor retardation, which showed some association with poor response. Fasting plasma-free homovanillic acid was significantly higher in the good response group and 3-methoxy-4-hydroxyphenethylene glycol showed a similar trend.     

维持性血液透析对T细胞亚群与红细胞生成素低反应性的影响

目的 通过对红细胞生成素(rHuEPO)不同反应的患者用流式细胞仪检测T细胞亚群以了解rHuEPO低反应与细胞免疫的关系及可能的作用机制.方法 将40例维持性血液透析(MHD)患者按照rHuEPO反应的不同分为第一组和第二组,rHuEPO反应低下的18例为第一组,rHuEPO反应良好的22例为第二组,另设一健康对照组20例.应用流式细胞仪检测各组患者T淋巴细胞表面CD+4、CD+8、CD+4/CD+28、CD+8/CD+28抗原的表达情况.结果 rHuEPO反应良好组和反应低下组的CD+4 T细胞、CD+8 T细胞百分比差异无统计学意义,但均显著低于对照组;rHuEPO反应低下组的CD+4 CD+28/CD+4、CD+8 CD+28/CD+8 T细胞的百分比明显低于反应良好组和对照组,而反应良好组与对照组之间无明显差异.结论 尿毒症MHD患者存在T细胞免疫表型的改变.     

Aromatase inhibitors for the treatment of infertility

Ovarian stimulation during infertility treatment is used either alone or in conjunction with intrauterine insemination and assisted reproductive technologies. At the present time, the two main medications used for ovarian stimulation include an oral antioestrogen, clomiphene citrate and injectable gonadotrophins. In spite of the high ovulation rate, the use of clomiphene citrate is associated with adverse side effects and low pregnancy rates. In clomiphene citrate failures, gonadotrophin injections are generally the next treatment option but, especially in polycystic ovarian syndrome, are associated with increased risk of severe ovarian hyperstimulation syndrome and high multiple pregnancies. Therefore, an effective oral treatment that could be used without risk of ovarian hyperstimulation syndrome and with minimal monitoring is preferred. It was hypothesised that aromatase inhibitors can be administered early in the follicular phase to induce ovulation by releasing the hypothalamus and/or pituitary from oestrogen negative feedback. The success of aromatase inhibitors in induction and augmentation of ovulation has been reported. In addition, increased intraovarian androgen levels may synergise with central effects of decreased oestrogen to enhance ovarian response to gonadotrophin stimulation. This increased sensitivity to follicle-stimulating hormone may be especially useful in poor responders. The potential future applications for aromatase inhibitors in infertility management are also discussed.     

Aromatase inhibitors for the treatment of infertility

Ovarian stimulation during infertility treatment is used either alone or in conjunction with intrauterine insemination and assisted reproductive technologies. At the present time, the two main medications used for ovarian stimulation include an oral antioestrogen, clomiphene citrate and injectable gonadotrophins. In spite of the high ovulation rate, the use of clomiphene citrate is associated with adverse side effects and low pregnancy rates. In clomiphene citrate failures, gonadotrophin injections are generally the next treatment option but, especially in polycystic ovarian syndrome, are associated with increased risk of severe ovarian hyperstimulation syndrome and high multiple pregnancies. Therefore, an effective oral treatment that could be used without risk of ovarian hyperstimulation syndrome and with minimal monitoring is preferred. It was hypothesised that aromatase inhibitors can be administered early in the follicular phase to induce ovulation by releasing the hypothalamus and/or pituitary from oestrogen negative feedback. The success of aromatase inhibitors in induction and augmentation of ovulation has been reported. In addition, increased intraovarian androgen levels may synergise with central effects of decreased oestrogen to enhance ovarian response to gonadotrophin stimulation. This increased sensitivity to follicle-stimulating hormone may be especially useful in poor responders. The potential future applications for aromatase inhibitors in infertility management are also discussed.     

Differential expression of GAS5 in rapamycin‐induced reversion of glucocorticoid resistance

This study evaluates the association between the long noncoding RNA GAS5 levels and the anti‐proliferative effect of the glucocorticoid (GC) methylprednisolone (MP) alone and in combination with rapamycin in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. The effect of MP, rapamycin, and MP plus rapamycin was determined in 17 healthy donors by labelling metabolically active cells with [methyl‐3H] thymidine and the expression levels of GAS5 gene were evaluated by real‐time RT‐PCR TaqMan analysis. We confirmed a role for GAS5 in modulating GC response: poor responders presented higher levels of GAS5 in comparison with good responders. Interestingly, when PBMCs were treated with the combination of rapamycin plus MP, the high levels of GAS5 observed for each drug in the MP poor responders group decreased in comparison with rapamycin (P value = 0.0134) or MP alone (P value = 0.0193). GAS5 is involved in GC resistance and co‐treatment of rapamycin with GCs restores GC effectiveness in poor responders through the downregulation of the long noncoding RNA. GAS5 could be considered a biomarker to personalize therapy and a novel therapeutic target useful for the development of new pharmacological approaches to restore GC sensitivity.     

Cortisol and treatment of depression: predictive value of spontaneous and suppressed cortisol levels and course of spontaneous plasma cortisol

In 72 consecutive depressed hospitalized patients afternoon plasma cortisol was measured in three ways before treatment with antidepressants: 1) Spontaneous (n=72), 2) 2 h after oxazepam suppression (45 mg, n=28; 60 mg, n=37) and 3) 16 h after dexamethasone suppression (2 mg, n=71). In addition, spontaneous cortisol was measured after 3 weeks' treatment (n=55) and 5 weeks' treatment (n=36). Both spontaneous and suppressed cortisol levels seemed to have a predictive value in the endogenously depressed patients: complete responders had significantly lower pretreatment cortisol levels compared to poor responders. However, other covarying factors such as distress and age may as well account for the differences in treatment effect. During treatment a significant decrease of spontaneous cortisol was found from about 400 nM in poor responders and 325 nM in complete responders to about 300 nM in all groups. There was a positive correlation between pre- and post-treatment cortisol levels and between pretreatment levels and per cent fall in spontaneous cortisol levels.     

Phase II study of high-dose megestrol acetate in platinum-refractory epithelial ovarian cancer

Our objective was to determine the efficacy of megestrol acetate in the treatment of platinum-refractory epithelial ovarian cancer (EOC), and to evaluate the toxicities and quality of life (QOL) associated with this therapy. Patients with platinum-resistant epithelial ovarian cancer were treated with megestrol acetate (800 mg/day) orally for 28 days and then 400 mg/day for a minimum of 28 days before being assessed ready for evaluation of response to therapy. Patients who demonstrated a complete response (CR), partial response (PR) or stable disease were continued in the study until there was objective evidence of disease progression. All patients who went off study were followed up at regular intervals, every 2 months, to assess overall survival. Thirty-six patients were enrolled. Response was observed in seven of 36 patients (three CR and four PR). The response rate was 19.4% (95% CI 9-36). Four of the responders had the endometrioid cell type, while two were clear cell carcinoma and one was serouscystadenocarcinoma. All three CR patients had the histology of endometrioid carcinoma with the tumors located in the pelvis. Median survival of the study population was 5.8 months. Median survival in the responders was 12 months, while median survival in the non-responders was 5.5 months. Median progression-free survival in the responders was 8.3 months, while median progression-free survival in the non-responders was only 2 months. The majority of patients gained weight and had a fair quality of life score during treatment. The only toxicity observed was alopecia (grade 1) in four patients. We conclude that megestrol acetate has modest but definite activity in patients with platinum-refractory EOC, particularly in a small subset of the endometrioid subtype with limited disease in the pelvis. Only minimal toxicity was observed and the patients had a fair QOL score during the treatment.     

Inhibition of Hec1 expression enhances the sensitivity of human ovarian cancer cells to paclitaxel

Aim:

Hec1, a member of the Ndc80 kinetochore complex, is highly expressed in cancers. The aim of this study was to explore the role and mechanism of action of Hec1 with respect to the cytotoxicity of paclitaxel in ovarian cancer.

Methods:

Thirty ovarian cancer samples and 6 normal ovarian samples were collected. Hec1 expression in these samples was determined with immunohistochemistry. Ovarian cancer cell lines A2780, OV2008, C13K, SKOV3, and CAOV3 and A2780/Taxol were examined. Cell apoptosis and cell cycle analysis were detected with flow cytometric technique. siRNA was used to delete Hec1 in the cells. The expression of related mRNAs and proteins was measured using RT-PCR and Western blot analysis, respectively.

Results:

Hec1 expression was significantly higher in ovarian cancer samples than in normal ovarian samples, and was associated with paclitaxel-resistance and poor prognosis. Among the 6 ovarian cancer cell lines examined, Hec1 expression was highest in paclitaxel-resistant A2780/Taxol cells, and lowest in A2780 cells. Depleting Hec1 in A2780/Taxol cells with siRNA decreased the IC₅₀ value of paclitaxel by more than 10-fold (from 590±26.7 to 45.6±19.4 nmol/L). Depleting Hec1 in A2780 cells had no significant effect on the paclitaxel sensitivity. In paclitaxel-treated A2780/Taxol cells, depleting Hec1 significantly increased the cleaved PARP and Bax protein levels, and decreased the Bcl-xL protein level.

Conclusion:

Hec1 overexpression is associated with the progression and poor prognosis of ovarian cancer. Inhibition of Hec1 expression can sensitize ovarian cancer cells to paclitaxel.     

卵巢上皮性癌P53和c—erbB—2的表达及其临床意义

目的：探讨卵巢上皮性癌（简称卵巢癌）Ｐ５３和ｃ－ｅｒｂＢ－２表达的临床意义。方法：用免疫组织化学法检测Ｐ５３和ｅ－ｅｒｂＢ－２,结合临床病理及肿瘤的生物学行为进行分析。结果：Ｐ５３在高分化卵巢癌中的表达频率显著低于中,低分化癌,Ｐ５３表达阳性组的卵巢癌对化疗不敏感,其预后亦明显劣于阴性卵巢癌。卵巢癌的ｃ－ｅｒＢ－２表达与临床期别,组织学类型和分级,残余瘤大小,化疗疗效和预后均无显著相关性,结论：Ｐ