DNA甲基化在复发性流产病因中的研究进展

复发性流产（recurrent spontaneous abortion,RSA）是一种常见病理性妊娠,其中有约50%的患者病因和发病机制不明确。随着表观遗传学研究领域的发展,尤其是近年来DNA甲基化的研究,为RSA的病理生理机制提供了一个新视角。研究发现,基因DNA甲基化的功能缺陷、DNA的甲基化修饰调控及DNA甲基化介导的其他表观遗传修饰方式与RSA密切相关,印迹基因DNA甲基化、胎盘特有基因DNA甲基化以及精子DNA甲基化异常都直接或间接地影响胚胎的着床、生长及发育过程,最终导致RSA的发生。现阐述DNA甲基化在RSA发生、发展中的作用及其研究进展。     

子宫内膜异位症不孕的表观遗传学研究进展

子宫内膜异位症是生育年龄妇女不孕的主要原因之一,其机制仍不清楚.最新研究发现,子宫内膜异位症可能是一种表观遗传性疾病.DNA甲基化异常和印记功能紊乱是表现遗传异常的主要形式.在子宫内膜异位症中存在DNA的异常甲基化,这种异常甲基化与子宫内膜异位症不孕有关;印记基因对胎儿及胎盘的发育具有十分重要的作用,子宫内膜异位症相关的印记功能紊乱可能影响胚胎着床和发育.该文就DNA甲基化、基因印记与子宫内膜异位症不孕的研究进展作以综述,为子宫内膜异位症不孕新治疗方法的提出提供理论依据.     

亚甲基四氢叶酸还原酶及甲硫氨酸合成酶基因多态性与男性不育

易感基因、环境及营养等因素在疾病发生过程中起到了重要作用.亚甲基四氢叶酸还原酶(MTHFR)、甲硫氨酸合成酶(MS)是叶酸和同型半胱氨酸(Hcy)代谢中的重要酶,其活性缺陷可能引起体内高同型半胱氨酸血症和DNA甲基化异常而导致多种疾病.目前对MTHFR基因单核苷酸多态性C677T与男性不育的相关性报道结论不一,而对另两...     

恶性转化人支气管上皮细胞基因组甲基化观察

目的对反式二氢二醇环氧苯并芘（anti-BPDE）和结晶型硫化镍（NiS）恶性转化人支气管上皮细胞（Hu-man bronchial epithelia,16HBE）基因组DNA甲基化状况进行研究,寻找DNA甲基化异常的基因片段,探讨反式-BPDE和NiS的表遗传致癌机制.方法采用限制性指纹识别技术（MSRF）,对反式-BPDE和NiS分别诱导转化及裸鼠成瘤的4种人支气管上皮细胞株基因组进行分析;对异常甲基化基因阳性片断采用TA克隆技术构建测序载体,对测序结果进行同源性分析比较.结果发现结晶型NiS恶性转化人支气管上皮细胞基因组存在高甲基化的DNA片段,其中一基因片段与编码鼻咽癌易感性蛋白ANKRD11基因序列99%同源.另一基因片段与HOXA3基因序列99%同源;未发现反式BPDE恶性转化人支气管上皮细胞基因组DNA异常甲基化基因片段.结论结晶型NiS恶性转化人支气管上皮细胞DNA的高度甲基化可能导致基因表达抑制.可能是结晶型NiS致癌的一种表遗传机制;反式BPDE致癌过程可能与基因组磷酸胞苷酰（CpG）岛甲基化异常关系不明确.     

巢式甲基化特异性聚合酶链反应法检测甲状腺患者血浆p16基因启动子区域异常甲基化及其临床意义

目的 探讨甲状腺癌患者血浆p16基因启动子区域异常甲基化及其在甲状腺癌筛查及早期诊断中的价值,为甲状腺癌的早期诊断提供依据.方法 利用巢式甲基化特异性聚合酶链反应(nested methylation specific PCR,nMSP)法检测50例甲状腺癌患者和32例结节性甲状腺肿患者组织和血浆中p16基因启动子区域的异常甲基化情况;分析p16基因异常甲基化与甲状腺癌临床特征的相关性及血浆p16基因异常甲基化与肿瘤组织检测结果之间的一致性.结果 甲状腺癌患者组织中p16基因启动子区甲基化率为54％(27/50),血浆标本中p16基因启动子区甲基化率为52％(26/50),两者有很好的一致性(P＞0.05);结节性甲状腺肿患者组织标本和血浆标本中均未见p16基因启动子区甲基化,与甲状腺癌患者相比,差异均有统计学意义(P＜0.01);血浆标本p16基因甲基化检测敏感度为52％,特异度为100％.结论 血浆中p16基因启动子区域异常甲基化的检测有望成为甲状腺癌筛查和早期诊断的有效指标.     

抑癌基因甲基化与乙型肝炎病毒相关性肝癌研究进展

抑癌基因DNA高度甲基化后可以引起基因的转录抑制,从而可以导致细胞异常增殖,甚至发生癌变,而甲基转移酶抑制剂如5-脱氧杂氮胞苷等通过DNA去甲基化,可以恢复多种抑癌基因的正常表达,使细胞的异常增殖受阻.抑癌基因P16、P15、RASSF1A等在肝癌中存在DNA甲基化失活,乙型肝炎病毒(HBV)相关性肝癌的发生发展与P16、P15、RASSFA等基因甲基化失活有密切的关系,因此抑癌基因去甲基化有望成为肝癌基因治疗的一种有效手段.     

肝癌患者血浆RASSF1A及p16基因异常甲基化检测

目的探讨血浆RASSF1A基因(Ras association domain family 1 gene)和p16基因的启动子区异常甲基化与原发性肝癌关系。方法采用甲基化特异性PCR(MSP)法,对100例原发性肝癌(HCC)患者、30例乙肝患者、30例肝硬化患者和30名健康体检者血浆中RASSF1A和p16基因的启动子区异常甲基化状况进行检测。结果 HCC患者血浆RASSF1A和p16基因异常甲基化检出率分别为38.0%(38/100)和65.0%(65/100),而乙肝患者、肝硬化患者和健康体检者均未检出,与HCC组比较,差异均有统计学意义(P=0.000);Logistic回归分析发现,患者年龄、性别、血浆甲胎蛋白(AFP)、HBsAg、p16基因(RASSF1A基因)甲基化状况等与血浆中RASSF1A基因(p16基因)异常甲基化检测结果无关(P0.05)。结论原发性肝癌患者血浆DNA中可检测到RASSF1A基因和p16基因的甲基化;RASSF1A基因和p16基因的甲基化检测对肝癌筛查有重要意义。     

差异甲基化杂交在发现卵巢癌相关基因中的应用

目的:探讨差异甲基化杂交结合生物信息学在发现新的人上皮性卵巢癌相关基因中的应用价值。方法:采用基于芯片技术的差异甲基化杂交(differential methylation hybridization,DMH)的方法检测5例原发性上皮性卵巢癌患者癌组织(以癌旁组织为对照)的DNA异常甲基化位点。利用生物信息学,通过序列比对分析,筛选新的候选的卵巢癌相关基因。结果:上皮性卵巢癌患者癌组织与癌旁组织相比,5张差异甲基化杂交芯片共筛出异常甲基化位点62个;DNA序列比对分析发现,基因EGFLAM启动子区CpG岛(CpG island,CGI)在上皮性卵巢癌中出现低甲基化,提示该基因可能是通过启动子区的异常甲基化参与卵巢癌的发生发展。结论:将基于芯片技术的差异甲基化杂交技术与现代生物信息学相结合,可以有效地发现新的人上皮性卵巢癌相关基因。     

DNA甲基化与肝癌关系研究进展

DNA甲基化是哺乳动物最常见的表观遗传学修饰方法之一,它能调控正常基因的表达、维持染色体的完整性,是调节DNA重组的关键环节,具有重要的生物学意义。DNA甲基化是肿瘤抑癌基因的沉默机制之一,普遍存在于所有基因类型,当正常甲基化过程发生异常变化时,会引起机体的一系列分子改变导致肿瘤的发生。DNA甲基化异常在肝癌的发生中发挥了重要作用,且与肝癌的进展与转移也存在相关性,但是其具体机制仍有待进一步研究阐明。本文就DNA甲基化与肝癌关系的研究进展及其可能的作用机制进行了总结,并对DNA甲基化抑制剂作为潜在抗癌药物的可能性进行了探讨,同时为肝癌的早期诊断与治疗提供新的研究思路。     

硅转化BALB/c-3T3细胞基因组DNA异常甲基化的研究

目的 对硅转化细胞基因组DNA异常甲基化进行研究，探讨硅的表遗传致癌机制。方法 从结晶型硅(Si)转化BALB/c-3T3细胞中提取基因组DNA，经Msel(甲基化非敏感性酶)单独消化或Msel和BstU1(甲基化敏感性酶)联合消化，消化产物用甲基化敏感性内切酶指纹法(MSRF)进行分析，差异显示出异常甲基化基因片段，进一步将异常甲基化DNA片段亚克隆和序列测定，再与基因文库中的基因进行类比分析。结果发现硅转化细胞存在6条异常甲基化DNA(其中1条为高甲基化，5条有低甲基化现象)，序列测定显示这些异常甲基化基因片段似乎来源于一些RNA转录和蛋白质翻译等基因家族。结论DNA异常甲基化会导致基因表达激活或抑制，因此硅转化细胞基因组某些功能基因DNA异常甲基化导致的异常表达，可能间接是硅诱导细胞转化及其致癌作用的一种表遗传机制。     

Investigation and Control of Anthrax Outbreak at the Human–Animal Interface,Bhutan, 2010

In 2010, we investigated anthrax outbreak in Bhutan. A total of 43 domestic animals died, and cutaneous anthrax developed in 9 persons, and 1 died. All affected persons had contact with the carcasses of infected animals. Comprehensive preparedness and response guidelines are needed to increase public awareness of anthrax in Bhutan.     

Risk for Travel-associated Legionnaires’ Disease,Europe, 2009

Legionnaires’ disease is underreported in Europe; notification rates differ substantially among countries. Approximately 20% of reported cases are travel-associated. To assess the risk for travel-associated Legionnaires’ disease (TALD) associated with travel patterns in European countries, we retrieved TALD surveillance data for 2009 from the European Surveillance System, and tourism denominator data from the Statistical Office of the European Union. Risk (number cases reported/number nights spent) was calculated by travel country. In 2009, the network reported 607 cases among European travelers, possibly associated with 825 accommodation sites in European Union countries. The overall risk associated with travel abroad was 0.3 cases/million nights. We observed an increasing trend in risk from northwestern to southeastern Europe; Greece had the highest risk (1.7). Our findings underscore the need for countries with high TALD risks to improve prevention and control of legionellosis; and for countries with high TALD risks, but low notification rates of Legionnaires’ disease to improve diagnostics and reporting.     

Travel-associated Diseases,Indian Ocean Islands, 1997–2010

Data collected by the GeoSentinel Surveillance Network for 1,415 ill travelers returning from Indian Ocean islands during 1997–2010 were analyzed. Malaria (from Comoros and Madagascar), acute nonparasitic diarrhea, and parasitoses were the most frequently diagnosed infectious diseases. An increase in arboviral diseases reflected the 2005 outbreak of chikungunya fever.     

Haemophilus ducreyi Associated with Skin Ulcers among Children,Solomon Islands

During a survey of yaws prevalence in the Solomon Islands, we collected samples from skin ulcers of 41 children. Using PCR, we identified Haemophilus ducreyi infection in 13 (32%) children. PCR-positive and PCR-negative ulcers were phenotypically indistinguishable. Emergence of H. ducreyi as a cause of nongenital ulcers may affect the World Health Organization’s yaws eradication program.     

Dengue Virus Transmission by Blood Stem Cell Donor after Travel to Sri Lanka; Germany, 2013

Three days after donation of peripheral blood stem cells to a recipient with acute myeloblastic leukemia, dengue virus was detected in the donor, who had recently traveled to Sri Lanka. Transmission to the recipient, who died 9 days after transplant, was confirmed.     

Long-Term Survival Among Histological Subtypes in Advanced Epithelial Ovarian Cancer: Population-Based Study Using the Surveillance,Epidemiology, and End Results Database

BackgroundActual long-term survival rates for advanced epithelial ovarian cancer (EOC) are rarely reported.ObjectiveThis study aimed to assess the role of histological subtypes in predicting the prognosis among long-term survivors (≥5 years) of advanced EOC.MethodsWe performed a retrospective analysis of data among patients with stage III-IV EOC diagnosed from 2000 to 2014 using the Surveillance, Epidemiology, and End Results cancer data of the United States. We used the chi-square test, Kaplan–Meier analysis, and multivariate Cox proportional hazards model for the analyses.ResultsWe included 8050 patients in this study, including 6929 (86.1%), 743 (9.2%), 237 (2.9%), and 141 (1.8%) patients with serous, endometrioid, clear cell, and mucinous tumors, respectively. With a median follow-up of 91 months, the most common cause of death was primary ovarian cancer (80.3%), followed by other cancers (8.1%), other causes of death (7.3%), cardiac-related death (3.2%), and nonmalignant pulmonary disease (3.2%). Patients with the serous subtype were more likely to die from primary ovarian cancer, and patients with the mucinous subtype were more likely to die from other cancers and cardiac-related disease. Multivariate Cox analysis showed that patients with endometrioid (hazard ratio [HR] 0.534, P<.001), mucinous (HR 0.454, P<.001), and clear cell (HR 0.563, P<.001) subtypes showed better ovarian cancer-specific survival than those with the serous subtype. Similar results were found regarding overall survival. However, ovarian cancer–specific survival and overall survival were comparable among those with endometrioid, clear cell, and mucinous tumors.ConclusionsOvarian cancer remains the primary cause of death in long-term ovarian cancer survivors. Moreover, the probability of death was significantly different among those with different histological subtypes. It is important for clinicians to individualize the surveillance program for long-term ovarian cancer survivors.     

Outbreak of Panton-Valentine Leukocidin–Associated Methicillin-Susceptible Staphylococcus aureus Infection in a Rugby Team,France, 2010–2011

Staphylococcus aureus strains that produce Panton-Valentine leukocidin are known to cause community infections. We describe an outbreak of skin abscesses caused by Panton-Valentine leukocidin–producing methicillin-susceptible S. aureus (clonal complex 121) in a professional rugby team in France during July 2010–February 2011. Eight team members were carriers; 7 had skin abscesses.     

大龄单身女性寻求生育力保存的伦理问题探析

近年来,在肿瘤和卵巢相关疾病发生率逐年增加、不少大龄单身女性渴望为自己购买一份“生殖保险”等社会及个人因素催化下,人类对于生育力保存的需求急剧增加,满足这一需求正在或将成为重大挑战。对于寻求进行生育力保存的大龄单身女性来说,在合适的年龄应用玻璃化冷冻技术将其卵母细胞冻存是目前可采用的最佳生育力保存手段。而单身女性卵子冷冻将面临来自伦理道德、社会乃至法律的巨大挑战。本文概述国内外大龄单身女性卵子冷冻的现状,并对其可能涉及的相关伦理问题及解决途径进行综述,以促进理性正视单身女性卵子冷冻问题。     

Reemergence and Autochthonous Transmission of Dengue Virus,Eastern China, 2014

In 2014, 20 dengue cases were reported in the cities of Wenzhou (5 cases) and Wuhan (15 cases), China, where dengue has rarely been reported. Dengue virus 1 was detected in 4 patients. Although most of these cases were likely imported, epidemiologic analysis provided evidence for autochthonous transmission.