Objective :The Hutchinson-Gilford progeria syndrome (HGPS or progeria) is a childhood disorder with features of premature aging and is caused by mutations in the lamin A gene resulting in the production of an abnormal protein, termed progerin. To investigate the underlying pathogenic mecha-nism, we studied the nuclear co-localization and association of progerin interactive partner proteins (PIPPs) with lamina proteins. Methods:Both wild-type (WT) and progeria fibroblasts were studied by various methods including eonfocal microscopy, immunopreeipitation and Western blot. Results:All PIPPs discovered so-far co-localized with lamin A/C. In addition, the PIPPs were selectively associated with lamina proteins. An increased immunofluorescent staining signal was found for Mel18 in HGPS as com-pared to WT cells. An association of Me118 with emerin was observed in HGPS, but not in WT cells.Conclusion: Based on these findings, we propose that PIPPs, along with associated lamina proteins may form a pathogenic progerin-containing protein complex.
作者： 刊期： 2009年第04期
目的:比较国际抗痈联盟(International Union Against Cancer,UICC)和美国癌症联合会(American Joint Committe on Cancer,AJCC)于1997年公布的第6版非小细胞肺癌TNM分期方案(以下简称第6版方案),与国际肺癌研究会(International Association for the Study of Lung Cancer,IASLC)2007年提山的非小细胞肺癌TNM分期的修改方案(以下简称新方案)对中国非小细胞肺痛患者预后预测的不同点.方法:根据2003年9月至2005年10月北京大学临床肿瘤学院胸外科手术治疗的136例非小细胞肺癌患者的存档资料,分别按照第6版方案和新方案进行病理分期,主要观察目标为不同分期下的两年无复发转移生存率和无复发转移生存期,用Kaplan-Meier和Log-rank法进行统计学检验.结果:(1)第6版方案中Ⅰ、Ⅱ、Ⅲ和Ⅳ期患者例数分别为56、23、53和4例;在新方案中Ⅰ、Ⅱ、Ⅲ和Ⅳ期患者例数分别为50、31、54和1例,其中第6版方案中有6例Ⅰ期在新方案中变成Ⅱ期,1例Ⅱ期变成Ⅲ期,3例Ⅲ期变成Ⅱ期,1例Ⅲ期变成Ⅳ期,4例Ⅳ期变成Ⅲ期.(2)第6版方案中Ⅰ a、Ⅰ b、Ⅱ a、Ⅱb、Ⅲa、Ⅲb和Ⅳ期患者的两年无复发转移生存率分别为95.5%、82.4%、100.0%、63.6%、52.1%、80.0%和50.0%;新方案中Ⅰa、Ⅰb、Ⅱa、Ⅱb、Ⅲa、Ⅲb和Ⅳ期患者的两年无复发转移生存率分别为95.5%、89.3%、68.4%、63.6%、52.8%、50.0%和0.0%.(3)按照第6版方案,经Log-rank法分析后显示,Ⅰ期和Ⅱ期患者的2年无复发转移生存期差异无统计学意义(P=0.232),Ⅱ期和Ⅲ期患者的无复发转移生存期差异有统计学意义(P=0.023);按照新方案,Ⅰ期和Ⅱ期,以及Ⅱ和Ⅲ期患者之间的无复发转移生存期差异均有统计学意义(P值分别为0.023和0.014).(4)新方案中新增的2和5 cm这两个节点上下的患者的无复发转移生存期差异有统计学意义(P值分别为0.025和0.023).结论:IASLC 2007版非小细胞肺癌TNM分期方案较UICC和AJCC的第6版非小细胞肺癌TNM分期方案显示了更好的分期特异性,且新方案一样适用于中国非小细胞肺癌患者.
作者：王嘉；吴楠；郑庆锋；冯源；阎石；杨跃 刊期： 2009年第04期
目的:探讨MTHFR基因C677T多态性与非综合征型唇腭裂(nonsyndromic cleft lip with or without cleft palate,NSCI/P)相关性.方法:收集97个核心家庭和104个对照家庭,用聚合酶链式反应-限制性片段长度多态性方法,进行MTHFR基因C677T位点多态性检测;用人群关联研究、传递不平衡检验(transmission-disequlibrium test,TDT)、单倍型相对风险率(haplotype-based haplotype relative risk,HHRR)、家系为基础的关联检验(family-based association test,FBAT)等进行统计分析.结果:人群关联研究分析表明,子代、父亲、母亲的病例组和对照组之间基因型和等位基因的分布差异无统计学意义(P>0.05);子代、父亲、母亲组,CT基因型携带者相对于CC基因型携带者的OR分别为1.02(95%CI 0.47～2.21)、0.62(95%CI 0.29～1.32)、0.66(95%CI 0.31～1.40);TT基因型携带者相对于CC基因型携带者的OR分别为1.10(95%CI 0.44～2.74)、0.95(95%CI 0.39～2.32)、0.68(95%C/0.28～1.66);T相对于C基因的OR分别为1.07(95%CI 0.72～1.58)、0.98(95%CI 0.66～1.46)、0.83(95%C/0.56～1.24).携带有突变基因T并不能增加患NSCL/P的危险.病例组核心家庭分析表明,TDT检验X2=1.817,P>0.05;HHRR检验X2=1.76,P>0.05;FBAT检验Z=1.348,P>0.05.结论:没有发现MTHFR C677T多态性和NSCLP无关联性,该基因位点的变异可能不会导致中国东北地区人群NSCLP的发生.
作者：郭晋臻；宋晓明；汪云；朱文丽；李书琴；李勇 刊期： 2009年第04期
目的:探讨听觉统合训练(auditory integration training,AIT)对儿童孤独症的近期疗效,为孤独症儿童的康复治疗提供临床依据.方法:将88例孤独症患儿随机分为实验组和对照组,两组均进行综合治疗,实验组在其基础上进一步行AIT治疗,疗效评估主要采用韦氏幼儿(或儿童)智力测验(WPPSI或WISC-R)或Gesell量表、孤独症儿童行为检查量表(Autism Behavior Checklist,ABC)等方法,对患儿进行治疗前后临床症状、ABC分值及智商(intelligence quotient,IQ)分值变化的比较.结果:有7例患儿失访.实验组经过AIT治疗6个月后,与对照组比较,患儿在语言障碍、社会交往障碍、某些行为特征方面有明显的改善(P<0.05);但在异常行为方而两组比较差异无统计学意义.实验组IQ明显提高、ABC分值明显降低,两组之间差异有统计学意义(P<0.05).ABC分值下降的程度和IQ分值升高程度与患儿年龄呈负相关;ABC分值下降的程度与患儿基础智商呈正相关.结论:AIT可以改善孤独症患儿的语言障碍、社会交往障碍、某些行为特征和发育水平,其对儿童孤独症的近期疗效比较肯定.
作者：张改巧；龚群；张凤玲；陈孙敏；胡立群；刘锋；崔瑞华；何琳 刊期： 2009年第04期
Objective: To investigate the association between the polymorphism of HLA-A, HLA-B genes and pre-eclampsia. Methods: HLA-A, HLA-B genotyping was performed by polymerase chain reaction sequence-specific primer (PCR-SSP) in 119 preeclampsia patients, 117 normal pregnant women and their neonates. Results: The study showed that 16 HLA-A and 39 HLA-B alleles were obtained in pre-eclamptic patients and normal pregnant women. 15 HLA-A and 37 HLA-B alleles were obtained in their neonates. No significant difference was found in maternal or neonatal HLA-A, HLA-B alleles be-tween pre-eclampsia group and control group (Pc>0. 05). The frequencies of HLA-A11, HLA-A24,HLA-B13, HLA-B14, HLA-B15, HLA-B52 maternal/fetus genetic assoications were significantly different between pre-eclampsia group and control group (P<0. 05). Conclusion: Some HLA-A, HLA-B maternal/fetus special bindings may be associated with the susceptibility or protective of pre-eclampsia.
作者：张展；贾莉婷；张琳琳 刊期： 2009年第04期
目的:研究包载碘油的海藻酸钙微球(lipiodoi-containing calcium alginate microspheres,LAMs)的制备方法、理化性质、栓塞性能和不透X射线的效果.方法:采用滴制法制备LAMs.通过正交实验考察乳剂处方中碘油与水相的比例、滴制操作中气流大小、砝码重量这3个因素对微球的数均粒径、粒径多分散性及碘油包封率的影响.以光学显微镜观察微球的形态,以物性测定仪考察微球的弹件,以视频旋转滴张力仪考察微球在导管内的推注性能,以X射线摄影系统考察微球在大鼠血管内的显影效果.结果:制备微球的佳条件是碘油与水相的比例为3:10,气流速度为40 g/mL,所用砝码质量为100 g.按正交实验优化工艺制备的微球,平均数均粒径为(493.9±42.6)μm,多分散性系数为1.02,碘油包封率为(88.97±1.09)%,微球圆整、表面光滑,微球,变形60%时可承受的大力平均值为(1.09±0.18)N,导管内推注性能良好.微球注人大鼠血管后,在X射线下显影效果清晰.结论:研制出的不透X射线微球外观圆整、粒径在栓塞所需范围内、弹性良好、导管内易推注、动物体内显影清晰,为介入栓塞治疗提供了一种新型的栓塞剂.
作者：张苑；袁惠燕；吴瑨威；范田园 刊期： 2009年第04期
Objective:To explore the relationship between the polymorphisms in gene FGFR1, FGF10, FGFI8 and the nonsyndromic cleft lip with or without cleft palate (NS CLP) in Chinese population. Methods: Genomic DNA was isolated from peripheral lymphocytes of 75 patients with NS CLP and their parents and 75 unimpaired healthy children. The polymorphisms in FGFRI gene rs13317, p. E467K, p. M3691 and p. S393S, FGF10 gene rs1448037 and FGFI8 gene rs4043716 were detected by applying three-dimensional (3-D) polyacrylamide gel microarray technology. The data were performed using statis-tical analysis : the genotype frequenc+ y and allele frequency between patients with NSCL/P and control subjects were performed. Haplotype relative risk (HRR) , family based association test (FBAT) , and transmission disequilibrium test (TDT) in nuclear family were performed. Results: There were no poly-morphism in FGFR1 gene p. E467K, p. M369I and p. $393S site, the corresponding base was all G. The polymorphisms of rs13317 and rs1448037 were detected and their genotype frequency and allele frequen-cy showed no significant difference between 75 patients with NSCL/P and 75 normal children. TDT, HRR and FBAT were also no significant differences. The genotype frequency of gene FGF18 rs4043716 showed significant difference, but allele frequency were no significant difference. TDT, HRR and FBAT were also no significant difference. Conclusion: Our studies suggest an association between gene FGF18 rs4043716 and the NS CLP in Chinese population, and no association among gene FGFR1 rs13317, p. FA67K, p. M3691, p. S393S and gene FGF10 rs1448037.
作者：万伟东；杨顺露；刘嘉茵；崔毓桂；周小平；郭芳芳；程宏宇；程璐；肖鹏峰；陆祖宏 刊期： 2009年第04期
目的:研究人端粒酶催化亚单位(hTERT)反义分子探针(99mTc-hTERT ASON)在体外靶细胞摄取动力学情况,以及特异识别靶基因的生物学性质.方法:以双功能螯合剂法,制备放射性核素99mTc标记的针对hTERTmRNA的反义分子探针(99mTc-hTERT ASON).培养hTERT表达阳性的人肝细胞癌细胞株(HepG2细胞).观察在有/无脂质体介导下,细胞对99mTc-hTERT ASON的摄取动力学情况.阳离子脂质体介导99mTc-hTERT ASON转染细胞,逆转录聚合酶链反应(reverse transcriptase polymerase chain reaction,RT-PCR)分析其特异识别靶基因的生物学活性.结景: 99mTc-hTERT ASON的标记率达到(76±5)%(n=5),放射性化学纯度达到96%,比活度为1.850×106Bq/μg.不论脂质体介导与否,99MTc-hTERT ASON在不同时相的细胞摄取率均高于对照组(P<0.05);脂质体明显提高细胞对99MTc-hTERT ASON的摄取(P<0.05);通过脂质体介导,细胞对99,Tc-hTERT ASON的摄取高峰值提前至2 h,并保持稳定水平至3 h.RT-PCR结果显示99,Tc-hTERT ASON转染细胞后,hTERT mRNA表达量明显降低.结论:脂质体在体外能有效提高99mTc-hTERT ASON的细胞摄取率.分子探针99mTc-hTERT ASON能特异识别靶基因.为进一步开展99mTc-hTERT ASON体内研究奠定了基础.
作者：王荣福；刘萌；张春丽；闫平；于明明 刊期： 2009年第04期
Objective: To investigate the birth defect condition in Haidian district of Beijing city, 61 272 live-born infants who were delivered in Haidian Maternal and Child Health Hospital from 2003 to the March of 2009 are analyzed. Methods: Data was collected from the hospital' s medical records and from the birth defect surveillance. Results: Among the newborns studied, 1 076 were found having birth defect (17.56‰). The most common birth defects are congenital heart defect, followed by dysmorphosis of external ear, polydactyly, hypospadia, cleft lip and palate. In addition, three birth defects that are not included in the birth defect surveillance list were enorchia, renal agenesis and giant hemangioma. The birth defect rates of preterm and small for gestational age infants are significantly higher than it of the term infants. The birth defect patterns for these two types of abnormal infants are distinct. Conclusion: We have determined the pattern of birth defects in Beijing, which may help in policy-making regarding the prevention and intervention of birth defects.
作者：李瑛；刘晓红；王粉燕；赵心亮；张羲；张运平 刊期： 2009年第04期
Objective:To study the clinical effect of neural stem cell transplantation in the treatment of inherited cerebellar atrophy (CA). Methods: The cells from human fetal cerebellum (8-10 weeks of gestation) were grown and expanded in vitro. The cultured neurospheres were then implanted into the dentate nuclei of patients by stereo tactic operation. Totally, 12 patients (7 males and 5 females with age ranging 22-62 years, mean 43 years) were treated by this operation from August 2006 to August 2008. Results: The cells of fetal cerebellum were expanded by 107folds in undifferentiated state in the culture. After the operation, no rejection was detected. Follow up, the effective rates were 58. 3% after 3 months, 75.0% after 6 months, and 66.7% for 12-24 months (mean 18 months). Conclusion: the transplantation of in vitro cultured neural stem cell is a feasible and effective treatment for inherited CA, but the long term effectiveness need to be taken in consideration.
作者：田增民；陈涛；Nanbert ZHONG；李志超；尹丰；刘爽 刊期： 2009年第04期
目的:对300例骨骼肌活组织检查(活检)标本进行组织学切片和染色,总结分析技术方法的操作过程和改进,重点探讨各种肌酶及非酶组织化学染色技术在神经肌肉病诊断中的应用选择和价值.方法:将标本经异戊烷-液氮速冻后进行冰冻切片,应用HE及Gomori三色(GMR)、糖原(PAS)、脂肪(油红O)等特殊染色,肌球蛋白三磷酸腺苷酶(ATP酶)、还原型辅酶Ⅰ四唑氮还原酶(NADH-TR)等酶组织化学染色,并对各种染色技术进行调整和改进.结果:标本经异戊烷-液氮速冻及恒冷切片,可以有效避免产生冰晶.GMR染色主要显示线粒体及肌纤维变性坏死的病变,油红O染色显示肌纤维内有无脂质增多,PAS染色主要显示糖原和糖蛋白.对于肌肉组织,应用冰冻切片优于石蜡切片.NADH-TR及ATP酶染色可以区分两型肌纤维,并可观察肌纤维内部结构及线粒体酶的变化等.结论:通过骨骼肌酶与非酶组织化学染色技术,可以清晰地显示出两型肌纤维的分布情况及各种特征性的病理改变,几种方法可互为补充.
作者：张燕；韩志慧；钟延丰；王盛兰；李玲玲；郑丹枫 刊期： 2009年第04期
The most frequent chromosomal rearrangement reported in acute promyelocytic leukemia (APL) is t(15 ;17)(q22;q21). The t(15;17) generates the PML/RARA fusion gene that blocks the transcription of genes involved in myeloid cell differentiation. A small number of simple and complex variants of the classical t(15;17) have been reported. We report two complex three-way translocation variants, t(3;17;15) (q27;q21 ;q22) and t(8;17;15) (q24.3;q12;q22) in which the PML/RARA fusion gene has been created on the derivative 15 chromosomes. Many of these variant translocations are suspected by conventional cytogenetics but need to be confirmed with additional molecular testing. We discuss the importance of supplementing conventional cytogenetic testing with FISH and RT-PCR to accurately diagnose APL variant patients.
作者： 刊期： 2009年第04期
脊髓脊膜膨出(meningomyelocele)是神经管发育畸形中的常见类型,其膨出物一旦破溃,容易出现感染、脑膜炎,其转化为鳞状细胞癌(squamous cell carcinoma,SCC)极为罕见.本文报道北京大学第一医院神经外科收治的l例脊髓脊膜膨出合并SCC患者,并结合文献复习,以探讨其形成原因、疾病特点以及治疗方法.
作者：段鸿洲；张扬；张家涌；鲍圣德；周长青 刊期： 2009年第04期
Rearrangements involving chromosome region at 12p13 are common abnormalities in hematological malignancies, including myeloid and lymphoid types. ETV6 gene is usually involved in the 12p13 region. ETV6 rearrangements are more often observed in acute lymphoblastic leukemia than in acute myeloid leukemia (AML), where ETV6 gene deletions are more common than rearrangements.Here, we report an AML case with the recurrent t(10;12) (q24;p13) as the sole abnormality. Fluorescence in situ hybridization with mapping back to metaphases confirmed that the ETV6 gene splits, and rearranges with a locus at 10q24. In review of the literature, this is the first report of AML case with the novel abnormality as the sole change. Complete laboratory findings from bone marrow examination, flow cytometry analysis, cytogenetie studies, molecular analysis, and clinical features are also described in the report.
作者： 刊期： 2009年第04期
This short report describes a model for international collaboration on perinatal health that is innovative,highlyproductive and challenging.
作者： 刊期： 2009年第04期
1 The need to extend and expand the maternal, neonatal and child health (MNCH) continuum to include preconception healthThe provision of care along the MNCH continuum is currently the core strategy for reducing maternal, neonatal and infant mortality [1-5]. Yet, gaps in the MNCH continuum persist. Reductions in maternal mortality have stagnated in many parts of the world. With the lowering of infant and child mortality, approximately 40% of infant deaths now occur in the neonatal period[6].
作者： 刊期： 2009年第04期
Since the sequencing of the human genome was announced in 2001, researchers have an increased ability to discern the genetic basis for diseases. This reference genome has opened the door to translational medicine which may be defined as the use of data acquisition and analysis to improve medical care, including prognostics, diagnos-tics, preventive intervention, therapeutic selection, and individualized treatment based on the complex interaction between inherited and acquired elements of human variation. It is an approach that will build on the comprehensive nature of the genome sciences. It aims at detecting and understanding of all genetic variations of the human genome that contribute to the manifestation and progression of disease.
作者： 刊期： 2009年第04期
Array-based comparative genomic hybridization (array CGH), a method used to detect gains or losses of genetic material, has recently been applied to prenatal diagnosis of genomic imbalance in the clinical laboratory setting. This new and exciting diagnostic tool represents a major technological step forward in cytogenetic testing and addresses many of the limitations of current cytogenetic methods.Conventional chromosome analysis, the current gold standard in prenatal diagnosis, focuses primarily on the detection of common aneuploidies and is limited by its capacity to detect only those copy number changes that are large enough to be microscopically visible (typically 5-6 Mb in size at the 500 band level). In contrast, array CGH analysis simultaneously evaluates regions across the entire genome and al-lows for detection of unbalanced structural and numerical chromosome abnormalities of less than one hun-dred kb. Array CGH analysis also overcomes some of the limitations of chromosome analysis, such as the requirement for cell culture and longer reporting time, by using direct uncultured fetal specimens. With many diagnostic laboratories now embracing this technology, the past year has seen tremendous growth in the use of array CGH analysis for prenatal diagnosis. This review aims to summarize array CGH methodology and its current applications in prenatal diagnosis.
作者：Amy M. BREMAN；毕为民；张秀慧 刊期： 2009年第04期
主动脉内球囊反搏(intra-aortic balloon pump counterpulsation,IABP)是一种通过主动脉内球囊与心动周期同步地充放气,以增加心肌氧供,减少心肌氧耗的治疗方法.据国外近20年的统计,急性心肌梗死合并心源性休克的发生率为5%～15%,国内约为6%～20%.国外报道在溶栓前时代其死亡率在90%以上,IABP联合血管重建治疗可使其死亡率降至50%～74%[1-2].
作者：陈明；王新刚；霍勇 刊期： 2009年第04期
Objective:To present clinical and pathologic features of pulmonary hyalnizing granuloma through analyzing three cases found in our institution and reviewing cases reported in the English language literature. Methods and Results: Three eases of pulmonary hyalnizing granuloma identified at our institu-tion during the past ten years were reviewed. In the first case, the patient presented with concurrent pulmonary hyalinizing granuloma and histoplasmosis. In the second case, the patient presented with a 5.5 cm lung mass and a separate smaller lesion radiologically resembling bronchogenic carcinoma. There was very prominent polyclonal lymphocytic proliferation at the periphery especially of the smaller lesion likely representing an early stage of the disease process. In the third case, the patient presented with multiple subpleural plaque-like lesions in addition to nodular lesions of the lung. All cases also demonstrated various degrees of lymphocytic infiltration within the lesions. The English literature has been reviewed through searching the PubMed. Conclusion: Since patients with pulmonary hyalinizing granuloma demonstrated a spectrum of clinical presentations, radiologic changes and histologic features with a variety of associated clinical disorders, pulmonary hyalnizing granuloma is more in keeping with a clinicopathologic entity rather than a specific pathologic disease.
作者： 刊期： 2009年第04期
前列腺癌是男性生殖系统常见的恶性肿瘤.在世界范围内男性癌症中,前列腺癌以年新增病例782 600例排名第2位,以254 000例排名年死亡病例第6位[1].近年来,发达国家前列腺癌的死亡率有所下降,然而,在亚洲前列腺癌的死亡率有上升的趋势[2].
作者：吕冬姣；张珏；王霄英；郭雪梅；王翠艳 刊期： 2009年第04期
The 4th International Conference on Birth Defects and Disa-bilities in the Developing World is being held at New Delhi,In-dia from 4th to 9th October 2009 at Hotel Le Meridien,New Delhi.
作者：北京大学医学遗传中心 刊期： 2009年第04期
