Isolation of Growth Hormone-Releasing Hormone and Its Receptor Genes from Scatophagus argus and Their Expression Analyses

The teleost Scatophagus argus is a species whose females grows faster than males.Growth hormone(gh)mRNA abundance in females pituitary is higher than that in males;however the mechanism underlining such differential is still unknown.Growth hormone(GH)is tightly associated with GH-releasing hormone(Ghrh)in vertebrates.In this study,Ghrh gene(ghrh)and its receptor gene,ghrhr,were isolated from S.argus.Tissue expression analysis showed that ghrh and ghrhr were mainly expressed in hypothalamus while ghrhr was expressed in pituitary and gh was predominantly expressed in pituitary.Twenty cultured S.argus individuals were used to compare ghrh,ghrhr and gh mRNA abundances,120 g and 181 g average weight for male(n=11)and female(n=9),respectively.Real-time PCR indicated that the ghrh and ghrhr mRNA abundances in male hypothalamus were significantly higher than those in female hypothalamus while that of gh mRNA abundance was significantly higher in female pituitary than in male pituitary.The ghrh and ghrhr mRNA abundances were significantly up-regulated in female hypothalamus 3 h after injection of 0.1 mg kg^-1 body weight Ghrh while pituitary ghrhr and gh mRNA abundances were not affected.In female hypothalamus,ghrh and ghrhr m RNA abundances were not affected at 6 h post-injection of 4 mg kg^-1 body weight 17α-methyltes-tosterone(17α-MT)or 17β-Estradiol(E2).In female pituitary,ghrhr m RNA abundance was down-regulated by 17α-MT while that of gh m RNA abundance was up-regulated by E2.Our findings indicated that E2,rather than Ghrh,plays an important role in up-regulating the expression of gh in female S.argus,which should aid to understand the sexual dimorphism of teleost growth.

Combination immunotherapy with Survivin and luteinizing hormone-releasing hormone fusion protein in murine breast cancer model

AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6 leu)-LTB] for immunotherapy of breast cancer.METHODS Murine 4 T-1 breast cancer model was used to evaluate the efficacy of recombinant proteins in vivo. Twenty four Balb/c mice were divided into 4 groups of 6 mice each. Recombinant Survivin and LHRH fusion protein, alone or in combination, were administered along with immunomodulator Mycobacterium indicus pranii (MIP) in Balb/c mice. Unimmunized or control group mice were administered with phosphate buffer saline. Each group was then challenged with syngeneic 4 T-1 cells to induce the growth of breast tumor. Tumor growth was monitored to evaluate the efficacy of immune-response in preventing the growth of cancer cells.RESULTS Preventive immunization with 20 μg recombinant Survivin and MIP was effective in suppressing growth of 4 T-1 mouse model of breast cancer (P = 0.04) but 50 μg dose was ineffective in suppressing tumor growth. However, combination of Survivin and LHRH fusion protein was more effective in suppressing tumor growth (P = 0.02) as well as metastasis in vivo in comparison to LHRH fusion protein as vaccine antigen alone.CONCLUSION Recombinant Survivin and MIP suppress tumor growth significantly. Combining LHRH fusion protein with Survivin and MIP enhances tumor suppressive effects marginally which provides evidence for recombinant Survivin and LHRH fusion protein as candidates for translating the combination cancer immunotherapy approaches.

Long-term effectiveness of luteinizing hormone-releasing hormone agonist or antiandrogen monotherapy in elderly men with localizect prostate cancer （T1-2） ： a retrospective study

Aim： To evaluate the long-term effectiveness, side effects and compliance rates of two types of drugs （luteinizing hormone-releasing hormone [LHRH] agonist and antiandrogen） that were used individually to treat patients with localized prostate cancer （T1-2） at our institution. Methods： Ninety-seven patients who were diagnosed in the period from April 1997 to January 2000 as having clinically localized prostate cancer （T1-2） received either LHRH agonist （leuprolide acetate 7.5 mg/month） monotherapy （group 1, n = 62） or antiandrogen monotherapy （group 2, n = 35; 18 received bicalutamide 50 mg q.d., 13 received nilutamide 150 mg t.i.d, and 4 received flutamide 250 mg t.i.d.）. The mean age in both groups was 76 years. Results： The mean follow-up time was （50.8 ±8.5） months in group 1 and （43.1 ± 2.2） months in group 2. Prostate-specific antigen （PSA） levels rose in only 1 of the 62 patients （1.6%） in group 1, and in 20 of the 35 patients （57.1%） in group 2. In group 2, 10 of the 20 patients （50 %） with increasing PSA levels were treated with LHRH salvage therapy, and eight （80%） responded. Hot flashes （54.8%） and lethargy （41.9%） were the most common side effects in group 1. In contrast, nipple-tenderness （40%） and light-dark adaptation （17.1%） were more often seen in group 2. Only 1 of the 62 patients （1.6%） in group 1 switched to another medication because of adverse side effects; whereas 8 of the 35 patients （22.9%） in group 2 did so. Conclusion： Unlike antiandrogen monotherapy, LHRH agonist monotherapy provided long-term durable control of localized prostate cancer （T1-2）. It can also be an effective treatment option for patients whose disease failed to respond to antiandrogen monotherapy. The limitations of our study are the lack of health outcomes analysis and a small sample size.

Effect of Luteinizing Hormone-Releasing Hormone Analogue on the Sexual Behavior of Sacalia quadriocellata

Luteinizing hormone-releasing hormone(LHRH) is known to influence sexual behavior in many vertebrate taxa, but there have been no systematic studies on the role of LHRH in sexual behavior of turtles. We tested the hypotheses that exogenous LHRH analogues would induce sexual behavior of male Four-eyed turtle, Sacalia quadriocellata. We examined this by challenging males with intramuscular injections of mammalian luteinizing hormone-releasing hormone analogue(LHRH-A), human chorionic gonadotropin(HCG), or a combination of the two, and subsequently exposing them to sexually receptive females for behavioral observation. Our data show that the injection of only HCG could not, while that of only LHRH-A could, facilitate sexual behavior along with testicular recrudescence and spermatogenesis in S. quadriocellata. The injection of both LHRH-A and HCG would induce more drastic sexual behavior of the animals than that of LHRH-A alone, indicating HCG enhances the effects of LHRH-A induced sexual behavior. However, different pharmacological dosages of LHRH-A(0.5 μg, 1 μg, 2 μg per 100 g bodyweight) did not correspond to different activity levels. Though the mechanism of LHRH effect was not determined, this study may support that the sexual behavior of S. quadriocellata which occurs at the beginning of the injection despite regression of the gonads. This is the first report on the exogenous LHRH-A induced sexual behavior for this species.

Preclinical therapy of benign prostatic hyperplasia with neuropeptide hormone antagonists

Benign prostatic hyperplasia(BPH)is a pathologic condition of the prostate described as a substantial increase in its number of epithelial and stromal cells.BPH may significantly reduce the quality of life due to the initiation of bladder outlet obstruction and lower urinary tract syndromes.Current medical therapies mostly consist of inhibitors of 5α-reductase orα1-adrenergic blockers;their efficacy is often insufficient.Antagonistic analogs of neuropeptide hormones are novel candidates for the management of BPH.At first,antagonists of luteinizing hormone-releasing hormone(LHRH)have been introduced to the therapy aimed to reduce serum testosterone levels.However,they have also been found to produce an inhibitory activity on local LHRH receptors in the prostate as well as impotence and other related side effects.Since then,several preclinical and clinical studies reported the favorable effects of LHRH antagonists in BPH.In contrast,antagonists of growth hormone-releasing hormone(GHRH)and gastrin-releasing peptide(GRP)have been tested only in preclinical settings and produce significant reduction in prostate size in experimental models of BPH.They act at least in part,by blocking the action of respective ligands produced locally on prostates through their respective receptors in the prostate,and by inhibition of autocrine insulin-like growth factors-Ⅰ/Ⅱand epidermal growth factor production.GHRH and LHRH antagonists were also tested in combination resulting in a cumulative effect that was greater than that of each alone.This article will review the numerous studies that demonstrate the beneficial effects of antagonistic analogs of LHRH,GHRH and GRP in BPH,as well as suggesting a potential role for somatostatin analogs in experimental therapies.

CORRELATION OF ANNUAL CHANGE OF LUTEINIZING HORMONE-RELEASING HORMONE (LH-RH) WITH GONADAL DEVELOPMENT IN AMPHIOXUS

The present study demonstrates for the first time by RIA that LH-RH is present in the heads as well as the bodies of the amphioxuses of both sexes. Gonadoliberin increases gradually during the course of gonadal development. At the time of gonadal maturity, LH-RH content reaches a maximum. The annual change of LH-RH correlates well with gonadal development and the gonadosomatic index (GSI). The reproductive season of the amphioxus covers about three months from May to July, and LH-RH content starts to increase in May (66.89±5.26 ng) and reaches the peak in June (158.57±3.17 ng), indicating that LH-RH is likely also to be involved in the reproductive activity of the chordate. This finding is of significance in understanding the evolutionary process of the reproductive endocrine in the vertebrate.

IVF促排卵过程中GnRH拮抗剂添加日LH水平对助孕结局的影响

目的 探索体外受精-胚胎移植技术(IVF-ET)助孕过程中促性腺激素释放激素(GnRH)拮抗剂添加日血黄体生成素(LH)水平对妊娠结局和胚胎质量的影响。方法 回顾性分析2018年1月至2022年12月于武汉大学中南医院生殖医学中心接受拮抗剂方案常规IVF-ET治疗且预期卵巢正常反应的女性不孕症患者资料,根据其拮抗剂添加日LH水平进行分组,比较各组临床妊娠率、着床率、卵子成熟度、受精率、卵裂率、2原核胚胎比率、D3优质胚胎率、囊胚形成率,并绘制受试者工作特征(ROC)曲线评估LH水平对临床妊娠的预测价值。结果 研究共纳入188例患者,其拮抗剂添加日LH水平的中位值为3.79(2.48,6.14)mIU/mL。当LH <2.48 mIU/mL时鲜胚移植的临床妊娠率和着床率均最低(P <0.05),而LH> 6.14 mIU/mL时则具有最高的临床妊娠率和着床率(P <0.01),但各组之间的配子和胚胎发育参数差异无统计学意义(P>0.05)。ROC曲线下面积为0.678,LH水平对预测临床妊娠具有一定的准确性。结论 控制性超促排卵过程中LH水平高于6.14 mIU/mL时使用拮抗剂可获得最优的临床妊娠结局。

湖羊和新疆细毛羊妊娠早期内分泌比较

为比较多胎与单胎绵羊妊娠早期生殖内分泌的差异，应用酶免疫测定法（EIA）和放射免疫测定法（RIA）检测江苏湖羊和新疆细毛羊妊娠早期血清孕酮（P）、雌二醇（E2）、促黄体素（LH）、前列腺素和瘦素水平。试验结果表明：湖羊血清孕酮、瘦素水平在妊娠13～43d极显著高于新疆细毛羊（P〈0．01），血清前列腺素水平在妊娠13～30d极显著低于新疆细毛羊（P〈0．01），而雌二醇、促黄体素水平在妊娠13～43d与新疆细毛羊无显著差异（P〉0．05）。这为湖羊多胎作用机制的研究提供了参考。

卵泡中晚期添加HMG对体外受精-胚胎移植结局的影响

目的：探讨促排卵过程中添加人绝经期促性腺激素（HMG）对体外受精-胚胎移植（IVF-ET）结局的影响。方法回顾性分析在解放军105医院生殖中心接受IVF-ET治疗的406例不育患者的临床资料，研究对象均于月经第3～5天行重组人促卵泡激素（r-FSH）促超排卵，当卵泡最大直径达14 mm时，A组（257个周期）每天添加HMG 75～150 U（r-FSH＋ HMG组），B组（149个周期）继续使用r-FSH至HCG注射日。按添加 HMG当日的血清黄体生成素（LH）水平，将A组再分为A1组：LH＜1 U/L ，99个周期；A2组：1 U/L≤L H≤2 U/L ，96个周期；A3组：L H＞2 U/L ，62个周期。比较各组的临床结局。结果 A组促性腺激素（Gn）用量、Gn时间、受精率及妊娠率显著高于B组，流产率显著低于对照组，差异有统计学意义（P＜0．05）；两组间添加HMG日及 HCG日血清LH水平、获卵数、卵裂率及胚胎种植率差异均无统计学意义（P＞0．05）。各亚组 HMG的添加剂量随HMG日LH水平升高逐渐减少，差异有统计学意义（P＜0．05）；A3组的Gn时间显著低于A1、A2组，而受精率则显著高于A1、A2组，差异有统计学意义（P＜0．05）；A2的妊娠率显著高于A1组，差异有统计学意义（P＜0．05）。A1、A2、A33组间r-FSH用量、HCG日LH水平、获卵数、卵裂率、胚胎种植率及流产率差异均无统计学意义（P＞0．05）。结论卵泡中晚期添加HMG可提高妊娠率，降低流产率，尤其血清LH在1～2 U/L时添加 HMG可获较好的临床结局。

2种人卵巢癌裸鼠移植瘤模型的生物学特性比较研究

目的:建立人卵巢癌裸鼠腹腔及皮下移植瘤模型,比较2种模型的生物学特性。方法:采用细胞悬液注射法将人上皮性卵巢癌细胞A2780/DDP注射于裸鼠皮下或腹腔,建立人卵巢癌裸鼠移植瘤模型,观察模型动物肿瘤的生长规律及组织学特性,流式细胞术分析细胞周期分布,免疫组化检测促黄体激素释放激素受体(Luteinzing-hormone releasing hormone receptor,LHRH-R)表达情况。结果:裸鼠腹腔及皮下移植瘤模型的成瘤率均为100%,2组荷瘤鼠中位生存时间分别为(30.000±1.095)d和(41.000±0.894)d,2组移植瘤细胞周期分布与原代细胞周期分布相仿,且2种模型的组织形态学和超微结构相似,免疫组化显示均表达LHRH-R。结论:人卵巢癌细胞株A2780/DDP裸鼠皮下和腹腔移植瘤模型易于建立,腹腔移植瘤模型能更好地模拟人卵巢癌腹腔播散的生物学行为,是研究卵巢癌治疗较理想的动物模型。

促性腺激素释放激素激动剂降调节后血清黄体生成素水平对体外受精-胚胎移植结局的影响

目的探讨促性腺激素释放激素激动剂(GnRH-a)降调节后月经第3天血清黄体生成素(LH)水平对体外受精-胚胎移植(IVF-ET)结局的影响。方法回顾分析2006年6月至2010年6月在我院接受IVF-ET治疗288个周期的临床资料。患者均采用GnRH-a长方案进行垂体降调节,按降调后月经第3天血清黄体生成素(LH)水平分为三组,A组:LH≤1U/L,共57个周期;B组:1U/L<LH≤2.5 U/L,共188个周期;C组:2.5 U/L<LH<5 U/L,共43个周期。比较三组促性腺激素(Gn)使用天数、剂量,人绒毛膜促性腺激素(hCG)注射日血清雌二醇(E_2)、LH水平及子宫内膜厚度、获卵数、受精率、卵裂率、优质胚胎率、临床妊娠率及流产率。结果 hCG注射日血清E_2和LH水平在三组间呈递增趋势,各组间血清LH水平有显著性差异(P<0.05),而Gn天数、Gn用量、获卵数、卵裂率在各组间均无显著性差异(P>0.05);A组的优质胚胎率和临床妊娠率显著低于B、C组(P<0.05),C组的流产率显著高于A、B组(P<0.05)。结论 GnRH-a降调节后月经第3天血清LH水平过低可导致hCG注射日E_2和LH水平下降,影响子宫内膜厚度,并导致受精率、优质胚胎率及临床妊娠率下降,流产率上升,但LH过高也可导致流产率增加。

ELISA测定血清LH、FSH的方法学评价

目的 用酶联免疫法测定血中黄体生成素 ( LH)和卵泡刺激素 ( FSH) ,以对该方法的方法学性能作一评价。方法 以临床血清标本作为检测标本 ,用酶联免疫法测定血中的 L H和 FSH,观察其灵敏度、线性试验及线性范围、精密度、回收率 ,并与放免法做比较。结果 LH、FSH的灵敏度分别为 2 .2 IU/L,1 .3IU/L。线性范围 2 .2～ 2 0 0 IU/L,1 .3～ 1 0 0 IU/L。低、高两种浓度的 LH和 FSH的批内变异分别为8.61 % ,5 .70 %和 9.46% ,6.36% ;批间变异分别为 7.1 4% ,6.0 1 %和 4.46% ,4.69%。回收率 LH为91 .84%～ 1 0 7.66% ,平均 98.1 3% ;FSH为 92 .77%～ 96.88% ,平均 94.5 4 %。与 RIA比较 ,其相关系数LH为 0 .975 9,P<0 .0 0 1 ;FSH为 0 .945 5 ,P<0 .0 0 1。结论 该方法有较高的灵敏度 ,重复性好 ,结果准确可靠等特点 ,与 RIA有良好的相关性 ,且无放射性污染 ,可以替代 RIA用于临床检验。

肝炎后肝硬化的性激素变化及其意义

为了解肝炎后肝硬化的性激素变化及影响性激素改变的有关因素。本文采用放射免疫法对３５例男性肝炎后肝硬化进行了血清睾酮（Ｔ），雌二醇（Ｅ_２），催乳素（ＰＲＬ），黄体生成素（ＬＨ）及卵泡刺激素（ＦＳＨ）的测定。结果发现，肝硬化患者的Ｔ及ＬＨ平均浓度明显低于正常对照组（Ｐ＜０．０１），Ｅ_２及ＰＲＬ的平均浓度明显高于正常人（Ｐ＜０．０１），而ＦＳＨ的平均浓度与正常人相比则无明显改变（Ｐ＞０．０５）。各激素与血清白蛋白，凝血酶原时间及总胆红素之间无明确相关。按Ｃｈｉｌｄ分级，Ｃ级患者的Ｅ_２水平高于Ａ级和Ｂ级患者（Ｐ＜０．０５），而各组间的Ｔ、ＰＲＬ、ＬＨ及ＦＳＨ浓度无统计学意义。３５例肝硬化中，１０例发生女性乳房发育，占２８．６％。有乳房发育和无乳房发育间各激素浓度无统计学差异。这些结果提示，肝炎后肝硬化存在着性激素的改变，肝细胞功能的损害在性激素紊乱中起着某些作用，但其他因素如门体分流可能起着更重要的作用。

重组人黄体生成素在体外受精-胚胎移植高龄患者促排卵中的应用

目的:评价重组人黄体生成素(r-hLH)在高龄患者促排卵中的应用价值以及对临床结局的影响。方法:选择协和医院生殖中心进行试管婴儿治疗,长方案降调节,年龄≥35岁,卵泡刺激素促排卵第7天,血清LH水平低于2U/L的患者146例。根据是否使用r-hLH进行分组:A组78例给予r-hLH治疗,B组68例未给予r-hLH治疗。比较两组患者的血清LH水平变化、平均促性腺激素(Gn)使用量、获卵数、双原核胚胎数、优质胚胎率、着床率及临床妊娠率。结果:两组患者血清LH变化情况、平均Gn用量、获卵数、优质胚胎率差异无统计学意义(P>0.05);A组的平均双原核胚胎数、着床率及临床妊娠率均显著高于B组(P<0.05)。结论:对于卵泡刺激素促排卵第7天血清LH<2U/L的高龄患者,补充r-hLH可以获得较高的双原核胚胎数、着床率及临床妊娠率。

磁分离酶联免疫测定男性生殖激素方法性能评价

目的 :对磁分离酶联免疫测定 (MAIA)法测定男性生殖激素的方法学性能作临床和实验室评价。方法 :将本法与放射免疫测定 (RIA)法进行对比研究。结果 :MAIA法测定促卵泡生成激素 (FSH)、促黄体生成素 (LH)、睾酮 (T)和催乳素 (PRL)的线性分别为 0～ 15 0IU L、0～ 2 0 0IU L、0 .5～ 5 5ng L、0～ 2 5 0ng L ;最小检测量分别为 0 .3mIU ml、0 .2 5mIU ml、4 μIU ml、4 μIU ml;批内CV <4 % ,批间CV <8% ,平均回收率偏差 <5 % ,互感率 <3% ;与RIA法比较 ,两法相关系数分别为 0 .982 6、0 .85 5 0、0 .85 12、0 .9831。临床质控观察 6 0d ,质控稳定 ;成年健康男性 (n =95 )血清FSH、LH、T、PRL的参考范围分别为 :0 .2 5～ 10 .18IU L、0 .33～ 8.95IU L、0 .5 4～ 11.11ng L和 8.77～ 33.4 3ng L。结论 :用MAIA法测定男性生殖激素 ,方法灵敏 ,结果可靠 ,符合临床要求。

^(99)Tc^m-黄体生成素释放激素在荷人乳腺癌裸鼠体内的生物学分布

目的:研究99Tcm-黄体生成素释放激素(99Tcm-LHRH)在荷人乳腺癌裸鼠体内的生物学分布,探讨LHRH用于肿瘤诊断和靶向治疗的价值。方法:直接标记法99Tcm标记LHRH;25只荷瘤鼠随机分成5组,每组5只;荷人乳腺癌SK-BR3裸鼠尾静脉注射99Tcm-LHRH后断头处死小鼠,测定99Tcm-LHRH在各组荷瘤鼠体内的放射性分布,计算每克组织放射性占总注入放射性的百分比。结果:99Tcm-LHRH放化纯度>95%,标志物稳定性好。荷瘤鼠注入99Tcm-LHRH后4 h,肿瘤/血液及肿瘤/肌肉的比值分别为12.89±1.67、36.81±5.64,99Tcm-LHRH主要分布于肿瘤、肝脏、血液,脑、肌肉等组织中放射性分布极低。结论:99Tcm-LHRH高特异地与人乳腺癌细胞结合,在乳腺癌显像和靶向治疗中有潜在的应用前景。

5种化学物质诱导九孔鲍精卵排放的效果比较

九孔鲍是我国东南沿海重要的鲍养殖品种，研究它的精卵排放具有重要意义。试验通过使用过氧化氢、利血平、绒促激素、促黄体素释放激素、孕酮等5种药物，分别配制不同浓度梯度，对壳长6．0～8．0cm，体重约17．0～25．0g的九孔鲍亲鲍个体注射0．02ml溶液，以研究其催产效果。结果表明，过氧化氢的效果最好，利血平次之，绒促激素、促黄体素释放激素和孕酮3种药物在这次的试验浓度中都没有明显效果。设定的4个过氧化氢浓度：4．98×10^-6ml／只、3．73×10^-6ml／只、2．49×10^-6ml／只和1．24×10^-6ml／只，均可使雌、雄亲鲍较快地排放出精卵；尤其以4．98×10^-6ml／只的浓度催产效果最好，不仅效应时间短，而且雌、雄鲍排放率高。试验中的5种药物及浓度未见对亲鲍有明显的损害作用。

早卵泡期长效长方案添加不同外源性黄体生成素制剂对低黄体生成素患者体外受精-胚胎移植临床结局的影响

目的探讨早卵泡期长效长方案添加不同外源性黄体生成素制剂对低黄体生成素(LH)患者体外受精-胚胎移植临床结局的影响。方法选择2017年4月至2020年5月在新乡医学院第三附属医院生殖医学科行体外受精-胚胎移植(IVF-ET)助孕、垂体降调后LH<1.0 U·L^(-1)的238例女性患者为研究对象。所有患者采用早卵泡期长效长方案,给予基因重组促卵泡激素促排卵,在卵泡直径12~14 mm时添加外源性LH制剂,根据添加LH的不同将患者分为重组黄体生成素(r-LH)组(n=116)和人绝经期促性腺激素(HMG)组(n=122)。比较2组患者降调时间、促性腺激素(Gn)启动量、Gn使用时间、Gn总量、添加LH日血LH水平、人绒毛膜促性腺激素(HCG)注射日子宫内膜厚度、HCG注射日LH水平、HCG注射日孕酮(P)水平、HCG注射日雌二醇(E_(2))水平及获卵数、2PN卵数、MII卵数、卵裂数、受精数、优质胚胎数、受精率、2PN卵率、MII卵率、全胚冷冻周期率、优质胚胎率、种植率、临床妊娠率。结果2组患者降调时间、Gn启动量、Gn总量、HCG注射日E_(2)水平、HCG注射日子宫内膜厚度比较差异均无统计学意义(P>0.05),r-LH组患者Gn使用时间、添加LH日血LH水平、HCG注射日P水平显著低于HMG组(P<0.05),HCG注射日LH水平显著高于HMG组(P<0.05)。2组患者获卵数、2PN卵数、MII卵数、卵裂数、受精数、优质胚胎数、受精率、2PN卵率、MII卵率、全胚冷冻期率、种植率、临床妊娠率比较差异均无统计学意义(P>0.05);r-LH组患者优质胚胎率高于HMG组(P<0.05)。结论Gn启动日低LH水平患者在早卵泡期长效长方案促排卵过程中补充r-LH较补充HMG可显著增加体内LH水平,提高优质胚胎率,缩短患者Gn使用时间,临床应用安全性更高。

Hormone naive prostate cancer： predicting and maximizing response intervals

Hormone naive advanced prostate cancer is subdivided into two disease states： biochemical recurrence and traditional M 1 （metastatic） prostate cancer and characterized by no prior hormonal therapy or androgen deprivation therapy （ADT）. In biochemical recurrence/ prostate-specific antigen （PSA） recurrence, men should be risk-stratified based on their PSA doubling time, the Gleason score and the timing of the recurrence. In general, only men who are at high risk should be considered for early/immediate ADT although this is best done using shared decision with the patient. The type of ADT to be used in biochemical recurrence ranging from oral-only peripheral blockade （peripheral androgen deprivation） to complete hormonal therapy （combined androgen blockade [CAB]） remains in debate owing to lack of randomized controlled trials （RCT）. However, there is good RCT support for use of intermittent hormonal therapy （IHT）. There is also limited research on biomarker response （PSA and testosterone decline） to predict prognosis. On the other hand, in the setting of M1 hormone naive prostate cancer, there are many more RCT＇s to inform our decisions. CAB and gonadotrophin-releasing hormone antagonists perhaps provide a slight efficacy advantage while IHT may be slightly inferior with minimal M1 disease. The PSA nadir at 7 months after starting ADT is a powerful prognostic tool for M1 patients. There is growing recognition that serum testosterone （T） control while on ADT is linked to the development of castrate-resistant prostate cancer. Especially for a M 1 patient, maintaining a serum T below 20-30 ng d1-1 prolongs the response to ADT. Novel oral agents （abiraterone and enzalutamide） may soon find use in hormone naive disease and may alter the treatment landscape. Despite over 75 years of experience with ADT, many questions remain, and the field continues to evolve.

Targeted therapy in advanced metastatic colorectal cancer: Current concepts and perspectives

The introduction of new cytotoxic substances as well as agents that target vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) signaling has improved clinical outcome of patients with metastatic colorectal cancer (mCRC). In this review we summarize the most relevant clinical data on VEGF and EGFR targeting regimens in mCRC. The effects of available treatment strategies for mCRC are often temporary, with resistance and disease progression developing in most patients. Thus, new treatment strategies are urgently needed. Some GI peptides including gastrin and gastrin releasing peptide, certain growth factors such as insulin-like growth factor-I&#x02005;and II and neuropeptides such as growth hormone releasing hormone (GHRH) are implicated in the growth of CRC. Experimental investigations in CRC with antagonistic analogs of bombesin/gastrin-releasing peptide, GHRH, and with cytotoxic peptides that can be targeted to peptide receptors on tumors, are summarized in the second part of the review.