高危局部进展期前列腺癌手术后复发、转移风险高，指南推荐以手术为主的综合治疗，包括新辅助治疗及辅助治疗。我们收治1例高危局部进展期前列腺癌，术前采用最大雄激素阻断治疗及4个周期多西他赛＋泼尼松(DP)方案化疗，后行根治性前列腺切除术，术后予辅助内分泌治疗及放疗。术后2.5年疾病进展为转移性去势抵抗性前列腺癌，予DP方案化疗10个周期，PSA控制良可。

Objective:Real-word data on long-acting luteinizing hormone-releasing hormone(LHRH)agonists in Chinese patients with prostate cancer are limited.This study aimed to determine the real-world effectiveness and safety of the LHRH agonist,goserelin,particularly the long-acting 10.8-mg depot formulation,and the follow-up patterns among Chinese prostate cancer patients.Methods:This was a multicenter,prospective,observational study in hormone treatment-na?ve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen.The patients had follow-up evaluations for 26 weeks.The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen(PSA)levels.The secondary outcomes included testosterone and PSA levels,attainment of chemical castration(serum testosterone<50 ng/dL),and goserelin safety.The exploratory outcome was the monitoring pattern for serum testosterone and PSA.All analyses were descriptive.Results:Between September 2017 and December 2019,a total of 294 eligible patients received≥1 dose of goserelin;287 patients(97.6％)were treated with goserelin 10.8-mg depot.At week 24±2,the changes from baseline[standard deviation(95％confidence interval)]in serum testosterone(n = 99)and PSA(n = 131)were-401.0 ng/dL[308.4 ng/dL(-462.5,-339.5 ng/dL)]and-35.4 ng/mL[104.4 ng/mL(-53.5,-17.4 ng/mL)],respectively.Of 112 evaluable patients,100(90.2％)achieved a serum testosterone level<50 ng/dL.Treatment-emergent adverse events(TEAEs)and severe TEAEs occurred in 37.1％and 10.2％of patients,respectively.The mean testing frequency(standard deviation)was 1.6(1.5)for testosterone and 2.2(1.6)for PSA.Conclusions:Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

目的:研究小于8岁性早熟女童阴道出血的病因.方法:对宁波市北仑区小港医院儿科2014年1月到2016年12月收治的68例小于8岁性早熟女童的临床资料进行回顾性分析,对所有患儿的病史进行详细询问,对其进行身高,体重,乳房,外阴等项目的体检,并对其骨龄片进行摄取,并对其进行B超检查,主要对其卵巢,子宫进行扫描,对其进行头颅MRI检查,LHRH激发试验,运用化学发光法检测其PRL,FSH,E2,T水平.结果:68例患儿中,54例为假性性早熟,其中24例为外源性性早熟,18例为卵巢囊肿,12例病因不明,分别占44.4％,33.3％,22.2％;14例为真性性早熟,分别占总数的79.4％,20.6％.假性性早熟患儿中外源性性早熟,卵巢囊肿患儿均有一定程度的色素沉着在乳晕及外阴,而和假性性早熟患儿相比,真性性早熟患儿具有显著较大的乳房发育,同时外阴阴唇阴蒂均已发育.结论:小于8岁性早熟女童阴道出血的病因主要为假性性早熟,而假性性早熟的病因主要为外源性性早熟,卵巢囊肿.临床应该依据病因及时给予患儿有针对性的治疗,从而将不良后果的发生几率降低到最低限度.

目的 研究不同剂量及注射时间的促黄体素释放激素(LHRH-A2)、孕马血清促性腺激素(PMSG)、人绒毛膜促性腺激素(hCG)、抑制素抗血清(IAS)对小鼠超排卵效果的影响.方法 以BALB/c近交系小鼠为实验对象,160只雌性小鼠随机分为4组,每组40只,按照注射剂量不同分为4组,A组:腹腔注射5 IU LHRH-A2,间隔72 h后注射10 IU PMSG,间隔48 h后注射10 IUhCG;B组:腹腔注射5IU LHRH-A2,间隔48 h后注射10 IU PMSG,间隔48 h后注射10 IU hCG;C组:腹腔注射10 IU PMSG,间隔48h后注射10 IU hCG;D组:腹腔注射0.2 mL IAS,间隔48h后注射10 IU hCG.次日早取卵、体外受精(IVF)培养,统计排出卵母细胞的数量,IVF率(IVF％)和异常率.结果 D组平均超数排卵数高于另外3组(P＜0.05),但同时IVF率低于另外3组(P＜0.05).A、B、C组平均超数排卵数,IVF率,异常率均无统计学差异(P＞0.05).结论 对于BALB/c小鼠,采用IAS和hCG超排激素组合,得到的卵子数目比另外3组显著增多,但2-细胞期胚胎数少.采用LHRH-A2、PMSGT和hCG超排激素组合,得到的2-细胞期胚胎数比另外3组更多,异常卵数少.

目的 制备一种载紫杉醇的靶向相变型纳米级超声造影剂,并评价其一般特性.方法 通过薄膜水化法、乳化法制备载紫杉醇的非靶向脂质纳米粒(PTX-LNP),通过生物素-亲和素法将生物素化的促黄体生成素释放激素(LHRH)连接于非靶向脂质微球制备载紫杉醇的LHRH靶向相变型脂质纳米粒(PTX-LNP-LHRH),检测PTX-LNP-LHRH的粒径以及表面电位,载药量及包封率,分别观察其声致相变及热致相变情况,检测纳米粒的LHRH靶连接率及其致人卵巢癌OVCAR3细胞的凋亡率.结果 成功制备靶向相变型脂质纳米粒,LHRH的靶连接率为(98.85±0.75)％,共聚焦显微镜下可见PTX-LNP-LHRH聚集在OVCAR3细胞周围,PTX-LNP-LHRH组致OVCAR3细胞的凋亡率明显高于PTX-LNP组.结论 成功制备靶连接率高且致靶细胞凋亡率较高的PTX-LNP-LHRH,其体外声致相变后可增强超声显影的效果.

制备重组蛋白pET28a-LHRH-PTD-GFP, 利用绿色荧光蛋白GFP, 研究LHRH的介导和PTD蛋白的转膜作用.以重组质粒pET28a-PTD-GFP为模板, 设计含有LHRH基因序列的PCR引物, 经过PCR扩增后双酶切, 克隆到原核表达载体p ET28 (a) 中, 构建重组表达质粒pET28a-LHRH-PTD-GFP, 并在大肠杆菌中诱导表达, 纯化目的蛋白.通过GFP的荧光特性, 检测LHRH介导的PTD蛋白的转膜作用.成功构建LHRH-PTD-GFP原核表达载体, 融合蛋白相对分子质量约为30 k, 纯化得到蛋白浓度为1.62 mg/m L的LHRH-PTD-GFP重组蛋白.荧光显微镜检测结果显示, He La细胞内显现明显的绿色荧光, 证明LHRH介导的PTD蛋白具有很好的跨膜特性.该研究结果为下一步构建以LHRH为靶向, 以PTD为转膜作用的肿瘤治疗药物提供了理论基础和技术支撑.

[目的]探讨黑升麻提取物莉芙敏预防乳腺癌患者促黄体生成素释放激素类似物(luteinizing hormone release hormone analogue,LHRH-a)治疗后围绝经期综合征的临床价值.[方法]前瞻性纳入了2017年1月至12月浙江省肿瘤医院收治的绝经前乳腺癌病例85例.将患者以随机数字表法分为A组(实验组)42例和B组(对照组)43例,A组予以LHRH-a联合莉芙敏20mg口服,2次/d,共12周,B组予以LHRH-a治疗同时无其他干预措施.比较两组患者不同时期Kupperman绝经指数(Kupperman menopausal index,KMI)、雌二醇(Estradiol,E2)、促黄体生成素(luteinizing hormone,LH)、卵泡刺激素(follicle-stimulating hormone,FSH)和妇科相关并发症(子宫内膜增厚、子宫肌瘤、卵巢囊肿、宫颈囊肿)的差异.[结果]两组间治疗前比较,KMI、E2、LH、FSH差异均无统计学意义(P>0.05).治疗4、8、12周时,A组患者KMI均显著低于B组,差异有统计学意义(P<0.01).而治疗的相同时期,两组之间E2、LH、FSH水平差异均无统计学意义(P>0.05).另外,治疗各时点两组患者的E2水平均较基线水平明显降低(P<0.01).A组除宫颈囊肿发生率高于B组(21.43％vs 4.65％,P<0.05)外,其余妇科相关并发症差异均无统计学意义(P>0.05).[结论]乳腺癌患者在LHRH-a治疗时联合莉芙敏可明显降低围绝经期综合征的发生率和程度,总体副反应较小.使用莉芙敏预防LHRH-a引起的围绝经期综合征安全可靠.

We aimed to evaluate the current nationwide trend,efficacy,safety,and quality of life (QoL) profiles of hormone treatment in real-world practice settings for prostate cancer (PCa) patients in Korea.A total of 292 men with any biopsy-proven PCa (TanyNanyMany)from 12 institutions in Korea were included in this multi-institutional,observational study of prospectively collected data.All luteinizing hormone-releasing hormone (LHRH) agonists were allowed to be investigational drugs.Efficacy was defined as (1) the rate of castration (serum testosterone ≤50 ng dl-1) at 4-week visit and (2) breakthrough (serum testosterone ＞50 ng dl-1 after castration).Safety assessments included routine examinations for potential adverse events,laboratory tests,blood pressure,body weight,and bone mineral density (BMD,at baseline and at the last follow-up visit).QoL was assessed using the Expanded Prostate Cancer Index Composite-26 (EPIC-26).The most common initial therapeutic regimen was LHRH agonist with anti-androgen (78.0％),and the most commonly used LHRH agonist for combination and monotherapy was leuprolide (64.0％ for combination and 58.0％ for monotherapy).The castration and breakthrough rates were 78.4％ and 6.6％,respectively.The laboratory results related to dyslipidemia worsened after 4 weeks of hormone treatment.In addition,the mean BMD T-score was significantly lower at the last follow-up (mean:-1.950) compared to baseline (mean:-0.195).The mean total EPIC-26 score decreased from 84.8 (standard deviation [s.d.]:12.2) to 78.3 (s.d.:8.1),with significant deterioration only in the urinary domain (mean:23.5 at baseline and 21.9 at the 4-week visit).These findings demonstrate the nationwide trend of current practice settings in hormone treatment for PCa in Korea.

目的 制备促黄体激素释放激素(luteinizing hormone releasing hormone,LHRH)-TAT-p53融合蛋白,探讨其抗肿瘤作用.方法 以重组质粒pET28a-p53为模板,经PCR扩增目的基因,双酶切,克隆至原核表达载体pET20b中,构建重组表达质粒pET20b-LHRH-TAT-p53,并在E coli中IPTG诱导表达,经金属螯合层析、DEAE弱阴离子交换层析纯化目的蛋白.取对数生长期的HeLa、BGC及MDCK细胞进行细胞活性试验,检测pET28a-p53蛋白活性.结果 经双酶切及测序鉴定,重组质粒pET20b-LHRH-TAT-p53构建正确;融合蛋白相对分子质量约54000,主要以包涵体形式存在,表达量约占菌体总蛋白55％;HeLa及BGC细胞加入纯化复性的重组蛋白后,细胞变圆、色暗、折光性变差,甚至裂解死亡,细胞死亡数增加,而MDCK细胞无变化;一定浓度范围内(25～120 μg/mL)蛋白对HeLa及BGC细胞有明显的抑制作用.结论 成功制备了LHRH-TAT-p53融合蛋白,该蛋白具有生物活性,对肿瘤细胞有杀伤作用.本研究为下一步制备靶向LHRH的肿瘤治疗药物提供了参考.

本文报道20例正常男子和2例IHH患者对脉冲式皮下注射LHRH后促性腺激素和睾酮的反应。正常人LH峰值出现在注射后30分钟（小剂量组）和45分钟（大剂量组），分别为基值的2.5和2.6倍。FSH峰值均在45分钟时出现，分别为基值的1.55和1.94倍。T仅在30分钟后稍有升高趋势。三种激素对不同剂量的反应值之间在各时相均无统计学区别（ P>0.05）。IHH患者对一次脉冲无反应，治疗第4天后三种激素开始升高，第8天时例1对单一脉冲剂量的反应达正常人水平。本文对轻便脉冲给药泵的使用方法，以及LHRH剂量与反应的关系进行了讨论。