检测病变组织中CD146、MMP-9及TIMP-2对完全性葡萄胎恶变的预测价值

目的探讨黏附分子CD146、基质金属蛋白酶9（MMP-9）及基质金属蛋白酶抑制剂2（TIMP-2）的表达对完全性葡萄胎恶变的预测价值。方法采用免疫组化二步法检测80例完全性葡萄胎（恶变组36例,未恶变组44例）组织中CD146、MMP-9及TIMP-2的表达,分析其对完全性葡萄胎恶变的预测价值。结果完全性葡萄胎恶变组中CD146、MMP-9的表达明显高于未恶变组,P均〈0.01;TIMP-2在两组中的表达相近（P〉0.05）。联合检测CD146、MMP-9的表达对完全性葡萄胎恶变的阳性预测值和阴性预测值分别为84.1%和72.2%。结论CD146和MMP-9对完全性葡萄胎恶变的预测有一定价值,TIMP-2无预测价值。     

妊娠滋养细胞疾病患者病变组织中CD146的表达及意义

目的探讨妊娠滋养细胞疾病（包括完全性葡萄胎、侵蚀性葡萄胎及绒毛膜癌）病变组织中细胞黏附分子CD146的表达变化及意义。方法采用免疫组化二步法检测80例完全性葡萄胎、37例侵蚀性葡萄胎、39例绒毛膜癌患者病变组织中CD146的表达，与30例正常胎盘绒毛中CD146的表达作比较。结果完全性葡萄胎恶变者CD146的表达较正常胎盘绒毛和完全性葡萄胎未恶变者显著增强（P均〈0．01）；CD146预测完全性葡萄胎恶变的敏感度和特异性分别为71．05％和78．57％。侵蚀性葡萄胎和绒毛膜癌组织中CD146的表达较完全性葡萄胎显著增强（P均〈0．01）。CD146在滋养细胞肿瘤（包括侵蚀性葡萄胎及绒毛膜癌）晚期的表达显著强于早期（P〈0．01），且预后高危者CD146表达显著强于低危者（P〈0．01）。结论CD146对完全性葡萄胎恶变有一定的预测价值，其表达与滋养细胞肿瘤的临床分期及预后有关。     

P16、P15基因蛋白与葡萄胎恶变关系探讨

目的探讨P16、P15基因蛋白与葡萄胎恶变的关系.方法采用免疫组化PV9000方法对40例葡萄胎和25例早孕患者绒毛P16、P15蛋白进行检测.结果早孕绒毛组织中P16、P15基因蛋白表达均阳性.葡萄胎中P16、P15基因蛋白阴性表达率分别为42.5%、30%,与早孕绒毛组织相比,差异有显著性(P均＜0.05).葡萄胎恶变组(7例)P16、P15基因蛋白表达均阴性者4例,占57.1%,高于无恶变组的18.2%(6/33),差异有显著性(P＜0.05);恶变组中,清宫前子宫大于妊娠月份,同时发生黄素囊肿且囊肿＞6cm,清宫后人绒毛膜促性腺激素(β-HCG)持续2个月后消退者,其P16、P15基因蛋白联合阴性率高于非恶变组,差异有显著性(P＜O.05).结论葡萄胎的发生、发展与P16、P15基因蛋白缺失有关.P16、P15基因蛋白缺失有望成为预测葡萄胎恶变的指标.     

HBV父婴垂直传播的研究进展

HBV感染是一个严重威胁人类健康的全球性公共卫生问题。父婴垂直传播(P-FT)是HBV持续感染的主要来源之一,其传播率与母婴垂直传播相当,近几年受到越来越多的关注,成为一个国内外研究的热点。P-FT通过精子途径传播已得到证实,但相关机制尚未阐明。研究显示父方血清、精液HBV DNA高载量及血清HBe Ag阳性是P-FT发生的主要危险因素。HBV DNA一旦随机整合入精子后可影响精子质量,引起男性不育,甚至可能影响母亲妊娠结局。目前孕前干预是阻断P-FT的最主要措施,包括父亲抗病毒治疗及母亲主动免疫。     

精浆锌含量与精液质量及体外受精结局的相关性

目的探讨精浆锌含量对精液质量及体外受精(IVF)结局的影响。方法采用5-Br-PAPS显色法检测81例不育男性患者精浆锌含量,Spearman相关分析法分析精浆锌含量与精液常规参数、成熟精子率及IVF结局的关系。结果 Spearman相关分析显示精浆锌含量与精子密度、精子活率、IVF受精数呈显著正相关(r=0.49、0.305、0.289,P均<0.05,与不成熟精子率呈负相关(r=-0.278,P<0.05),与精子正常形态率及IVF卵裂率、优胚率无相关性(P均>0.05)。结论适量的精浆锌含量能够促进精子核成熟,精浆锌含量降低可致精子密度和活率下降,使IVF受精数降低;但是对精子的正常形态率,IVF卵裂率和优质胚胎率无显著影响。     

精索静脉曲张对精子DNA碎片和体外受精结局的影响

目的探讨精索静脉曲张（VC）对精子DNA碎片、活力、形态和体外受精（IVF）结局的影响。方法采用染色质扩散实验（scD）对103例VC所致男性不育患者和37例正常生育男性进行精子DNA碎片率（DW）检测;采用计算机辅助精液分析仪,按照WHO标准进行精液常规分析;采用苏木素一伊红染色、Kruger评分标准进行精子形态学分析。男性不育患者中有75例进入试管婴儿周期,统计其IVF受精率、卵裂率和妊娠结局,并与本中心同期数值比较。结果与正常生育男性相比,VC所致男性不育患者的精子DFI升高（P〈0．05）;而精液量、精子密度、前向精于活动百分率和正常精子形态百分率下降（P〈0．05）;VC所致男性不育患者IVF受精率和卵裂率与我中心同期IVF受精率、卵裂率相比下降（P〈0．05）,但两组优质胚胎率和生化妊娠率无统计学差异（P〉0．05）。结论VC可导致精子DFI增加和精液常规参数下降,还可导致IVF受精率和卵裂率下降。     

原发性高血压及血压的遗传性

原发性高血压是一种遗传性疑病,证据是:①在本病的家族中,其发生频度要比一般人口中高;②一卵双生的一致率,比之二卵双生的一致率高得多。许多研究者认为,高血压的遗传是单一基因,与性别无关,为常染色体显性遗传;然而作者却主张多因子遗传学说。作者最近研究了血压的遗传样式,结果如下:①双亲血压皆正常者,子代血压为正规分布的常态曲线型,其峰顶位于-0.2～+0.2(血压补正值),只有很少的子代有高或低血压;②血压正常或低的双亲的     

不同时间去除卵丘细胞对短时受精结果的影响

目的：探讨短时受精技术进行体外受精（ IVF）时,不同时间去除卵丘细胞对短时受精结果的影响。方法选择行IVF助孕的原发不孕且取卵后本周期移植的患者226例,随机分为A组119例和 B组107例,A组移植精卵结合4～6 h后去除卵丘细胞发育来的胚胎,B组移植精卵结合4～6 h后保留卵丘细胞发育来的胚胎。比较两组的胚胎种植率和妊娠率。结果 A、B组胚胎种植率分别为36．51％和52．09％,两组比较有统计学差异（ P＜0．05）;妊娠率分别为52．94％和66．35％,两组比较无统计学差异（ P＞0．05）。结论短时受精过程中,在保证患者受精的情况下,将剩余的卵母细胞保留卵丘细胞可以提高胚胎的种植率。     

妊娠滋养细胞疾病组织中MMP-9的表达及意义

采用免疫组化法对30例正常早孕绒毛组织及32例部分性葡萄胎、93例完全性葡萄胎、30例侵蚀性葡萄胎5、例绒毛膜癌组织中的基质金属蛋白酶-9（MMP-9）进行检测。结果显示,MMP-9在正常早孕绒毛组织、部分性葡萄胎、完全性葡萄胎、侵蚀性葡萄胎、绒毛膜癌组织中均有表达,但随着滋养细胞疾病恶性程度的增加,其表达强度显著升高（P〈0.05）。认为MMP-9与滋养细胞的侵袭过程及其恶性程度有关。     

精液白细胞与精子DNA完整性、精子参数的关系

目的探讨精液白细胞与精子DNA完整性、精子参数的关系。方法分析156例男性不育患者精液标本,采用联苯胺染色法检测精液白细胞,吖啶橙荧光染色检测精子DNA完整性。采用计算机自动分析精子密度与活力,采用精子形态检测系统下人工修正方法进行精子形态分析。结果精液白细胞异常者精子密度、精子活力降低（P〈0.05）,精子DNA完整率异常率增高（P〈0.05）。精子DNA完整率异常者精子密度、活力降低（P〈0.05）,精子形态无明显变化（P〉0.05）。结论精液白细胞可直接影响精子参数、精子DNA完整率,又可能通过精子DNA完整率异常影响精子参数。     

Diagnosis of hydatidiform mole and persistent trophoblastic disease: diagnostic accuracy of total human chorionic gonadotropin (hCG), free hCG {alpha}- and {beta}-subunits, and their ratios

OBJECTIVE: Human chorionic gonadotropin (hCG) is widely used in the management of hydatidiform mole and persistent trophoblastic disease (PTD). Predicting PTD after molar pregnancy might be beneficial since prophylactic chemotherapy reduces the incidence of PTD. DESIGN: A retrospective study based on blood specimens collected in the Dutch Registry for Hydatidiform Moles. A group of 165 patients with complete moles (of which 43 had PTD) and 39 patients with partial moles (of which 7 had PTD) were compared with 27 pregnant women with uneventful pregnancy. METHODS: Serum samples from patients with hydatidiform mole with or without PTD were assayed using specific (radio) immunoassays for free alpha-subunit (hCGalpha), free beta-subunit (hCGbeta) and 'total' hCG (hCG + hCGbeta). In addition, we calculated the ratios hCGalpha/hCG + hCGbeta, hCGbeta/hCG + hCGbeta, and hCGalpha/hCGbeta. Specificity and sensitivity were calculated and paired in receiver-operating characteristic (ROC) curve analysis, resulting in areas under the curves (AUCs). RESULTS: hCGbeta, hCGbeta/hCG + hCGbeta and hCGalpha/hCGbeta show AUCs ranging between 0.922 and 0.999 and, therefore, are excellent diagnostic tests to distinguish complete and partial moles from normal pregnancy. To distinguish partial from complete moles the analytes hCGbeta, hCG + hCGbeta and the ratio hCGalpha/hCGbeta have AUCs between 0.7 and 0.8. Although hCGalpha, hCGbeta and hCG + hCGbeta concentrations are significantly elevated in patients who will develop PTD compared with patients with spontaneous regression after evacuation of their moles, in predicting PTD, these analytes and parameters have AUCs <0.7. CONCLUSIONS: Distinction between hydatidiform mole and normal pregnancy is best shown by a single blood specimen with hCGbeta, but hCGbeta/hCG + hCGbeta and hCGalpha/hCGbeta are also excellent diagnostic parameters. To predict PTD, hCGalpha, hCGbeta, hCG + hCGbeta and hCGalpha/hCGbeta are moderately accurate tests, although they are not accurate enough to justify prophylactic chemotherapy treatment for prevention of PTD.     

Molecular analysis of Duffy, Yt and Colton blood groups in Taiwanese, Filipinos and Thais

We used a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for DNA-based typing of Duffy, Yt and Colton blood groups in Taiwanese, Filipinos and Thais. A total of 200 Taiwanese, 115 Filipinos and 105 Thais were studied. In the Duffy blood group in Taiwanese, 180 cases (90%) were homozygote of Fya, 18 cases (9%) were double heterozygote of Fya and Fyb, and 2 cases (1%) were homozygote of Fyb. In Filipinos, 98 cases (85.2%) were homozygote of Fya, 16 cases (14.0%) were double heterozygote of Fya and Fyb and 1 case (0.8%) was homozygote of Fyb. In Thais, 87 cases (82.9%) were homozygote of Fya, 18 cases (17.1%) were double heterozygote of Fya and Fyb, and no case of Fyb was found. These results correlate well with serological phenotype. For the Yt blood group, only YT1 was found in Taiwanese. Among Filipinos, 114/115 (99.1%) was YT1/1 and 1/115 (0.9%) was YT1/2. In Thais, 103/105 (98.1%) was YT1/1 and 2/105 (1.9%) was YT1/2. For the Colton blood group, the results showed that there was only Coa allele in these three populations. Our results provide the first data of the Yt and Colton blood groups in these three populations.     

Overexpression of type IV collagen in chorionic villi in hydatidiform mole

To investigate the characteristic structure of hydatidiform mole, type IV collagen expression was determined in human villous tissues obtained from normal pregnancies (n = 17) and complete hydatidiform moles (n = 10). Indirect immunofluorescent staining was performed to detect type IV collagen with specific monoclonal antibody, and Northern blot analysis was performed to assess expression of messenger ribonucleic acid for the alpha1(IV) chain. In addition, serum levels of type I, III, and IV collagen were measured by RIA. Immunohistochemical staining for type IV collagen revealed stronger staining of the trophoblastic basement membrane in hydatidiform mole than in normal pregnancy. Northern blot analysis revealed that the villous expression of messenger ribonucleic acid for the alpha1(IV) chain was significantly increased in hydatidiform moles compared with normal pregnancy (P < 0.01). Although there were no differences in the serum type I and III collagen levels between hydatidiform mole and normal pregnancy, the type IV collagen level was significantly higher in patients with hydatidiform mole than in normal pregnancy (P < 0.05). These results suggest that type IV collagen might play an important role in determining the pathophysiology and structure of hydatidiform mole.     

Segregation patterns of polymorphic restriction sites of the gene encoding the alpha subunit of human chorionic gonadotropin in trophoblastic disease.

The gene encoding the alpha subunit of human chorionic gonadotropin contains at least two polymorphic sites in its 3' flanking region detected by restriction enzymes HindIII and EcoRI. We used these polymorphic sites as markers of tissue genotype in normal placenta, hydatidiform mole, choriocarcinoma, and peripheral leukocytes. As expected, inheritance patterns of most hydatidiform moles showed only a paternal genetic contribution. However, one uncommon DNA polymorphism pattern, homozygosity for the absence of the EcoRI site and the presence of the HindIII site, predominated in choriocarcinoma. Thus, our results suggest that moles which have this uncommon polymorphism pattern appear particularly likely to develop into choriocarcinoma.     

PTEN、VEGF在葡萄胎组织中的表达及临床意义

目的探讨人第10号染色体缺失的磷酸酶及张力蛋白同源的基因(PTEN)、血管内皮生长因子(VEGF)在葡萄胎组织中的表达及意义。方法选择我院手术切除的完全性葡萄胎(CHM)标本20份(CHM组)、部分性葡萄胎(PHM)标本20份(PHM组)、水肿性流产(HA)组织标本30份(HA组)及正常绒毛(NP)标本20份(NP组),采用免疫组化SP法检测各组标本中PTEN、VEGF的表达水平,并分析PTEN、VEGF在各组中表达的相关性。结果CHM组和PHM组PTEN、VEGF阳性表达率均明显高于HA组、NP组,P均<0.05;Spearman等级相关检验示PTEN和VEGF在CHM组、PHM组、HA组、NP组组织中表达均无明显相关性(P均>0.05)。结论 PTEN、VEGF在葡萄胎中的表达变化为其早期诊断提供一定参考依据。     

Gestational trophoblastic tumors

Although virtually 100% of women who develop gestational trophoblastic tumors enter a long-term complete remission, there are many aspects of trophoblastic disease that arouse interest. Epidemiological studies have shown a large geographical variation in the percentage of conceptions that result in a hydatidiform mole and have stimulated studies on the immunological differences of the low and high risk populations. Chromosomal analysis is now complementing the pathological differentiation between complete and partial moles. There is still debate as to which factors are positively associated with the progression of a hydatidiform mole through invasive mole to choriocarcinoma. There are also considerable differences in the proportion of molar patients receiving chemotherapy in different centers. In addition to these topics, this article will review several recently introduced treatment regimens which show improved results with reduced toxicity.     

Decreased type III and V collagen expression in chorionic villi of hydatidiform mole.

To investigate the characteristic structure of hydatidiform mole, various types of collagen expression were determined in human villous tissues obtained from normal pregnancies (n = 17) and complete hydatidiform moles (n = 10). Indirect immunofluorescent staining was performed to detect type I, III, and VI collagen with specific monoclonal antibodies. Collagens were also extracted from the villous tissues obtained from normal pregnancy and hydatidiform mole by the salt precipitation method. Immunohistochemical staining for type I, III, and VI collagen revealed weak staining of the villous stroma in hydatidiform mole compared with that in normal pregnancy. Both the ratios of type III to type I collagen and the ratios of type V to type I collagen in the villous tissues were significantly decreased (P < 0.05) in molar pregnancy compared with those in normal pregnancy. These results suggest that alterations in the distribution and composition of collagen might play an important role in determining the pathophysiology and structure of hydatidiform mole.     

Paternal Hemizygosity in 11p15 in Mole-like Conceptuses: Two Case Reports

Hydatidiform mole is an abnormal human pregnancy characterized by the fetus being absent or nonviable, and the chorionic villi being vesicular and with trophoblastic hyperplasia. Most often, the mole phenotype is seen in conceptuses with an excess of paternally inherited genome set(s) relative to maternally inherited genome set(s), suggesting that the phenotype is caused by an excess of genome with a paternal imprinting pattern. However, it is unknown if correct parental origin of every imprinted gene is crucial for normal early differentiation or if abnormal parental imprinting of only one, or some, gene(s) can cause the mole phenotype.Two conceptuses included in the Danish Mole Project stood out since they presented with vesicular chorionic villi and without signs of fetal differentiation, and had apparently biparental diploid genomes, and no mutations in NLRP7 or KHDC3L were detected in the mothers. These conceptuses were subjected to a centralized histopathological revision and their genetic complements were scrutinized using fluorescence in situ hybridization, and DNA-marker and array comparative genomic hybridization analyses. Both conceptuses showed dysmorphic chorionic villi with some similarities to hydatidiform moles; however, no definite florid trophoblast hyperplasia was observed. Both conceptuses showed paternal hemizygosity of 11pter-11p15.4, most likely in nonmosaic state.Our findings suggest that the product of one (or a few) maternally expressed gene(s) on the tip of chromosome 11 is necessary for normal early embryonic differentiation. However, since the present two cases did not exhibit all features of hydatidiform moles, it is likely that abnormal parental imprinting of genes in other regions contribute to the phenotype of a hydatidiform mole.     

The expression of human chorionic gonadotropin/human luteinizing hormone receptors in human gestational trophoblastic neoplasms.

Normal human placental trophoblasts have recently been shown to contain receptors for hCG/hLH. The present studies investigated the expression of these receptors in hyperplastic and anaplastic trophoblasts in gestational trophoblastic neoplasms. The results demonstrated that both hydatidiform moles and choriocarcinomas contained receptor messenger RNA (mRNA) and receptor protein. A variety of nontrophoblast tumors, on the other hand, contained neither receptor mRNA nor receptor protein. Choriocarcinomas contained more receptor mRNA and receptor protein than hydatidiform moles which in turn contained more than normal human placenta. Midluteal phase human corpus luteum contained more receptor mRNA than normal human placenta and about the same as choriocarcinomas. The hyperplastic and anaplastic trophoblasts in hydatidiform moles and choriocarcinomas contained more receptor immunostaining than the normal trophoblasts in the same tissue or those from normal placentas from about the same gestational age. The receptor immunostaining increased as the degree of trophoblast hyperplasia increased in hydatidiform moles. Anaplastic trophoblasts of choriocarcinomas contained a similar amount of receptor immunostaining as severely hyperplastic trophoblasts of hydatidiform moles. Invading anaplastic trophoblasts of choriocarcinoma contained greater amount of receptor immunostaining than the surrounding endometrial stromal and myometrial smooth muscle cells. In summary, this is the first study to our knowledge demonstrating the expression of hCG/hLH receptor gene in gestational trophoblastic neoplasms. The increased receptor expression in these neoplasms suggests that hCG, via its receptors, could play a fundamental and previously unsuspected autocrine role in the regulation of trophoblast transformation, growth, invasion, and high hCG secretion.