eIF4E和 VEGF C在大肠癌中的表达及其意义

目的探讨大肠癌组织中真核细胞翻译起始因子4E(eIF4E)和血管内皮生长因子 C(VEGF C)的表达及意义.方法应用免疫组织化学技术检测46例大肠癌及20例正常大肠组织中 eIF4E和 VEGF C的表达,同时结合患者的临床病理资料进行分析.结果46例大肠癌组织中的 elF4E和 VEGF C的表达阳性率分别为91.3和76.1%.而正常大肠组织中 elF4E和 VEGF C的表达阳性率分别为10%和20%.eIF4E和 VEGF的表达都与大肠癌患者性别、年龄、肿瘤病理分化程度无明显相关,但与肿瘤浸润深度、临床分期、有无淋巴结转移有关(P<0.05);两者的表达具有正相关(r=0.347,P<0.05).结论 eIF4E和 VEGF C与大肠癌的发生发展密切相关,可作为判断大肠癌侵袭转移及预后的重要指标     

P16及COX-2蛋白在宫颈癌中表达及意义

目的 探讨P16及COX-2蛋白在宫颈癌中表达及意义.方法 收集宫颈活检或手术标本138例,采用免疫组织化学方法分别检测P16及COX-2蛋白的表达,并分析结果.结果 正常宫颈组织、宫颈低级别上皮内瘤变(LSIL)、宫颈高级别上皮内瘤变(HSIL)、宫颈癌中P16蛋白阳性表达分别为0％(0/30)、42.3％ (11/26)、71.9％(23/32)、92％(46/50).COX-2蛋白阳性表达分别为3.3％(1/30)、50％(13/26)、75％(24/32)、88％ (44/50).随着宫颈病变分级升高,P16及COX-2蛋白阳性率逐渐上升,统计学差异有显著性(p＜0.05)；结论 P16及COX-2的高表达在宫颈癌的发生、发展中均起作用.     

PD-L1在人子宫颈癌细胞异常表达并促T细胞凋亡

目的 探讨人子宫颈癌中负性协同刺激分子PD-L1的表达和它与肿瘤浸润淋巴细胞的关系以及PD-L1融合蛋白促宫颈癌患者外周血活化T细胞凋亡的作用.方法 采用免疫组化S-P法检测67例宫颈癌组织及20例正常宫颈组织中PD-L1的表达,分析PD-L1同临床病理特征的相关性,免疫荧光观察肿瘤浸润淋巴细胞数量,TUNEL法检测T细胞凋亡,体外实验将PD-L1融合蛋白细胞加入PHA刺激活化的宫颈癌患者外周血T细胞中共同培养,流式细胞术分析T细胞凋亡率和CD8+/CD4+T细胞比例.结论 正常子宫颈组织不表达PD-L1；宫颈癌组织中PD-L1的表达率为70％.宫颈癌PD-L1的表达与宫颈癌浸润深度相关(P＜0.05).PD-L1阳性病例肿瘤局部浸润淋巴细胞存在凋亡且CD8+T细胞数量明显减少；PD-L1融合蛋白组T细胞凋亡率明显高于抗PD-1组和空白对照组T细胞,分别为32.7％、18.3％和17.9％；CD8+T/CD4+T细胞的比值低于加入抗PD-1组和空白对照组,分别为0.864、0.894和0 907.结论 PD-L1在子宫颈癌中高表达且与肿瘤浸润程度及肿瘤浸润淋巴细胞数量减少有关,PD-L1能促进活化的T细胞尤其是CD8+T细胞的凋亡.     

热性惊厥儿童血液IL-6、IL-10和MMP-9表达的研究

目的 热性惊厥是儿童痫性发作最常见的形式.炎性细胞因子可能导致热性惊厥的发展.本研究探讨白介素-6(IL-6)、白介素-10(IL-100和金属蛋白酶-9(MMP-9)等炎性细胞因子在小儿热性惊厥中是否被激活以及其表达与原发性癫痫中的不同.方法 回顾性研究自2010年12月到2012年11月入院的相关病人资料.分热性惊厥组(N=43)、高热对照组(N=40)、原发性癫痫组(N=32)及正常儿童组(N=15).在惊厥发生的24h内收集病人血液.酶联免疫吸附试验(ELISA)进行IL-6、IL-10和MMP-9等细胞因子水平测定.结果 IL-6、IL-10和MMP-9在热性惊厥组的表达均高于原发性癫痫组(p＜0.05)和正常组(p＜0.05).IL-6与MMP-9在热性惊厥组的表达高于高热对照组,IL-10的表达在热性惊厥组与高热对照组之间无明显差异(P＞0.05).结论 IL-6、IL-10和MMP-9在热性惊厥儿童表达明显升高;炎性因子可能参与热性惊厥的病理过程,且其参与机制可能不同于其在原发性癫痫病理过程中的作用.     

鸟苷酸交换因子DOCK1对心肌细胞存活的影响

目的 探讨鸟苷酸交换因子DOCK1对心肌细胞存活的影响.方法 用重组真核质粒pCXN2-Flag-hDOCK1(人DOCK1过表达质粒),pCXN2-Flag(空质粒)及空白试剂分别转染大鼠源H9C2心肌细胞,并给予缺氧/复氧(H/R)干预.将心肌细胞分为空白组,空质粒组,DOCK1过表达组,空白+-H/R组,空质粒+H/R组,DOCK1过表达+H/R组.用RT-PCR测定DOCK1mRNA水平.流式细胞术、MTT分别测定细胞的凋亡率和增殖率.结果 DOCK1过表达组(1.51 ±0.169)％,(2.49±0.442)％,(38.94±0.580)％,(P＜0.05)较空白组(-),(3.61±0.334)％,(20.64±0.720)％,(P＜0.05)和空质粒组(-),(3.66±0.373)％,(22.29±0.838)％,(P＜0.05),DOCK1过表达+H/R组1.03±0.171,(5.38±0.431)％,(17.33±0.343)％,(P＜0.05)较空白+H/R组[(-),(2.49±0.442)％,(7.95±0.322)％,(P＜0.05)和空质粒+H/R组(-),(10.32±0.388)％,(7.92±0.351％,(P＜0.05),人的DOCK1RNA分别显著增加、心肌细胞凋亡率分别显著降低及增殖率分别显著增加.较DOCK1过表达组.DOCK1过表达+H/R组人的DOCK1 mRNA显著降低.较空白组(0.64±0.145),(P＜0.05)、空质粒组(0.60±0.182),(P＜0.05)及DOCK1过表达组(0.60±0.182),(P＜0.05),空白+H/R组(0.30±0.115),(P＜0.05)、空质粒+H/R组(0.36±0.101),(P＜0.05)及DOCK1过表达+H/R组(1.03±0.171),(P＜0.05)大鼠的DOCK1 mRNA分别显著降低、心肌细胞凋亡率分别显著增加及增殖率分别显著降低.结论 DOCK1可抑制H9C2心肌细胞的凋亡,促进H9C2心肌细胞的增殖、存活；且DOCK1可抑制H/R诱导的H9C2心肌细胞凋亡增加及增殖、存活的降低.     

益气化瘀化痰法对肺纤维化大鼠肺组织结构及血清MMP-9、TIMP-1的影响

目的 观察益气化瘀化痰法(YHH)对肺纤维化大鼠肺组织结构、血清基质金属蛋白酶-9(MMPO)和金属蛋白酶组织抑制物-1(TIMP-1)水平的影响,探讨其防治肺纤维化的可能机制.方法 健康SD大鼠采用博来霉素建立肺纤维化模型,随机分成7组:正常对照组(Z组)、模型组(M组)、氢化可的松组(QK组)、益气组(YQ组)、化瘀组(HY组)、化痰组(HT组)、益气化瘀化痰组(YHH组).HE、Masson染色光镜观察肺组织病理形态变化;电镜观察肺组织超微结构变化;酶联免疫吸附法(ELISA)检测血清MMP-9、TIMP-1含量.结果 1)与M组比较,各治疗组均能减少肺间质胶原沉积,减轻肺纤维化程度,尤以YHH组较为明显2)与Z组比较,M组血清MMP-9水平有所升高,TIMP-1水平显著升高,MMP-9/TIMP-1比值降低(P＜0.05);与M组比较,各治疗组均能升高血清MMP-9水平,降低TIMP-1水平,升高MMP-9/TIMP-1比值,以YHH组作用更显著(P＜0.05).结论 益气化瘀化痰法可能在一定程度上通过调整MMP-9/TIMP-1的比值,使其趋于平衡,从而延缓肺纤维化的进程.     

COX-2与CYPlBl在人乳腺癌中的表达及意义

目的探讨人乳腺癌组织中COX-2和CYPlBl的表达规律及与临床病理特征的关系，对认识其在乳腺癌发生发展中的作用奠定初步病理学基础。方法应用免疫组织化学方法检测42例乳腺癌组织中COX-2和CYPlBl的表达情况，结合临床病理指标进行研究分析。结果在乳腺癌中COX-2和CYPIBl表达阳性率分别为78．6％和73．8％。COX-2的阳性表达与乳腺癌淋巴结转移、组织学分级显著相关（P〈0．05）；CYPlBI的阳性表达与组织学分级、ER表达显著相关（P〈0．05）。乳腺癌COX-2与CYPlBI表达呈正相关（r=0．481，P〈0．01）。结论人乳腺癌组织存在COX-2与CYPlBl的共同阳性表达，COX-2可能促进CYPlBl表达，共同作用参与乳腺癌的发生发展。     

FGFR1、FGFR3和Pokemon在膀胱癌中的表达及相关性研究

目的通过观察FGFR1、FGFR3和Pokemon在膀胱癌组织的表达情况,探讨它们在膀胱癌发生、发展中的作用。方法采用免疫组化检测296例膀胱癌和48例正常膀胱组织中FGFR1、FGFR3和Pokemon蛋白的表达情况。结果 1)FGFR1在膀胱癌不同病理分期、分级及初发复发的表达率为:Ta-T1期7.5%,T2-T4期18.1%(p0.01);低级别2.8%,低-高级别11.9%(p0.05),高级别14.3%的(p0.01);初发表达6.8%,复发表达率17.1%(p0.01)。2)FGFR3在膀胱癌不同病理分期、分级的表达率为:Ta-T1期68.1%,T2-T4期35.0%(p0.01));低级别75.0%,低-高级别60.3%(p0.05),高级别44.9%(p0.01)。3)Pokemon在膀胱癌不同病理分级及初发复发的表达率为:低级别47.2%,低-高级别66.7%(p0.01),高级别80.6%(p0.01);初发59.2%,复发80.0%(p0.01)。结论 FGFR1在膀胱癌中的表达与病理分级、分期成正相关,复发表达明显高于初发;Pokemon在膀胱尿路上皮癌中的表达与病理分级成正相关,复发表达也明显高于初发,表明它们可能主要参与膀胱癌发展及转移等过程。FGFR3在膀胱癌中的表达与病理分级、分期成负相关,表明它可能在膀胱癌发展早期及低级别肿瘤发展中发挥着重要作用。     

胃癌组织中EGFL7的表达及其临床病理特征的关系研究

目的：探讨胃癌组织中表皮生长因子样结构域（EGFL7）的表达及其与胃癌临床病理特征的关系。方法：采用免疫组织化学SP法分别检测45例胃癌组织中EGFL7的表达水平及微血管密度（MVD，CD34标记），分析EGFL7的表达与MVD及胃癌临床病理特征之间的关系。结果：EGFL7的表达在有淋巴结转移组中的阳性率（84．6％）高于无淋巴结转移组（57．9％），在浸润浆膜层组中的阳性率（84．4％）高于未浸润浆膜层组（46．2％）。胃癌组织中EGFL7的表达与淋巴结转移和浸润程度呈正相关（P〈0．05），但与患者的年龄、性别、肿瘤的分化程度无关（P〉0．05）。胃腺癌低分化纽MVD（37．62±10．42）高于高分化组（27．91±9．93）和中分化组（28．40±9．18）；浸润至浆膜层组MVD（34．25±10．43）高于未至浆膜层组（26．69±8．66）；有淋巴结转移组MVD（33．00±9．99）高于无淋巴结转移组（25．94±9．34）。癌组织中MVD值与分化程度、浸润深度及有无淋巴结转移呈正相关（P〈0．05），但与年龄、性别无关（P〉0．05）。在EGFL7表达阳性的肿瘤纽织中MVD均值为33．80±10．56，高于EGFL7表达阴性的肿瘤组织中MVD均值26．004-7．21（P〈0．05），采用Pearson积差相关系数进行分析，发现MVD值与EGFL7的表达成正相关（r=0．313，P〈0．05）。结论：EGFL7的高表达可能促进了胃癌的浸润和转移，其机制可能与促进胃癌组织中的血管新生有关。     

microRNA-451对人结肠癌细胞SW620裸鼠皮下种植瘤生长的抑制作用及机制探讨

目的 探讨microRNA-451(miR-451)对人结肠癌细胞系SW620裸鼠皮下种植瘤生长的影响,并探讨其可能机制.方法 18只裸鼠随机分为3组,实验组(SW-620-451组)、阴性对照组(SW-620-NC)、空白对照组(SW-620组),每组6只,分别皮下接种转染miRNA-451 agomir的SW620细胞、转染了阴性片段agomir Negative Control(NC)的SW620细胞和不经处理的结肠癌SW620细胞,并每周两次于瘤体内分别注射miRNA-451 agomir、miRNA-451 agomir NC片段及生理盐水.比较各组裸鼠皮下形成瘤体的大小并计算抑瘤率,接种四周后处死裸鼠取组织,用免疫组化法和Western-blot法定性定量分析和比较肿瘤相关基因c-myc的表达.结果 各组裸鼠皮下接种肿瘤细胞6天后均有瘤体形成,成瘤率100％,实验组(SW-620-451组)瘤体生长速度明显低于其他两组(p＜0.05)；时间终点为第30天时,实验组(SW-620-451组)裸鼠皮下种植瘤的体积为(0.95±0.13)cm3,阴性对照组(SW-620-NC组)为(2.25±0.50) cm3,空白对照组(SW-620组)为(2.46±0.59)cm3;实验组(SW-620-451组)瘤体体积显著小于其他两组体积(p＜0.05)；实验组(SW-620-451组)瘤体质量为(1.15±0.13)g,明显低于SW-620-NC组(2.59±0.46)g及SW-620组(2.76±0.44)g(p ＜0.05).实验组种植瘤中c-myc的表达量较另外两组下降(p＜0.05).结论 转染miR-451后可以抑制结肠癌细胞SW620裸鼠皮下移植瘤的生长,其机制可能与下调c-myc表达有关.     

草地与农牧交错带退化生态系统重建及防治途径

草地不仅是草地畜牧业的基地，而且在生态环境保护与建设方面的作用尤为重要。草原与农牧交错带，即不同于西部牧区，也不同于东部农区。根据它在地理、气候、农林牧产业结构、生态、经济、文化、社会等方面具有自己独特地位的实际情况，因地制宜提出了相应之对策，为国家在西部大开发和草地与农牧交错带生态环境的恢复提供科学依据。     

Telomeres and meiosis in health and disease

Telomeres are important segments of chromosomes that protect chromosome ends from nucleolytic degradation and fusion. At meiosis telomeres display an unprecedented behavior which involves their attachment and motility along the nuclear envelope. The movements become restricted to a limited nuclear sector during the so-called bouquet stage, which is widely conserved among species. Recent observations suggest that telomere clustering involves actin and/or microtubules, and is altered in the presence of impaired recombinogenic and chromosome related functions. This review aims to provide an overview of what is currently known about meiotic telomere attachment, dynamics and regulation in synaptic meiosis.     

Telomeres and meiosis in health and disease

Telomeres are important segments of chromosomes that protect chromosome ends from nucleolytic degradation and fusion. At meiosis telomeres display an unprecedented behavior which involves their attachment and motility along the nuclear envelope. The movements become restricted to a limited nuclear sector during the so-called bouquet stage, which is widely conserved among species. Recent observations suggest that telomere clustering involves actin and/or microtubules, and is altered in the presence of impaired recombinogenic and chromosome related functions. This review aims to provide an overview of what is currently known about meiotic telomere attachment, dynamics and regulation in synaptic meiosis.     

Structure and function of desmosomal proteins and their role in development and disease

Desmosomes represent major intercellular adhesive junctions at basolateral membranes of epithelial cells and in other tissues. They mediate direct cell-cell contacts and provide anchorage sites for intermediate filaments important for the maintenance of tissue architecture. There is increasing evidence now that desmosomes in addition to a simple structural function have new roles in tissue morphogenesis and differentiation. Transmembrane glycoproteins of the cadherin superfamily of Ca²⁺-dependent cell-cell adhesion molecules which mediate direct intercellular interactions in desmosomes appear to be of central importance in this respect. The complex network of proteins forming the desmosomal plaque associated with the cytoplasmic domain of the desmosomal cadherins, however, is also involved in junction assembly and regulation of adhesive strength. This re-view summarizes the structural features of these desmosomal proteins, their function during desmosome assembly and maintenance, and their role in development and disease.Received 5 February 2003; received after revision 14 March 2003; accepted 1 April 2003     

Linear and threshold forecasts of output and inflation using stock and housing prices

This study examines whether simple measures of Canadian equity and housing price misalignments contain leading information about output growth and inflation. Previous authors have generally found that the information content of asset prices in general, and equity and housing prices in particular, are unreliable in that they do not systematically predict future economic activity or inflation. However, earlier studies relied on simple linear relationships that would fail to pick up the potential nonlinear effects of asset price misalignments. Our results suggest that housing prices are useful for predicting GDP growth, even within a linear context. Meanwhile, both stock and housing prices can improve inflation forecasts, especially when using a threshold specification. These improvements in forecast performance are relative to the information contained in Phillips‐curve type indicators for inflation and IS‐curve type indicators for GDP growth. Copyright © 2008 John Wiley & Sons, Ltd.     

Geopsychology and geopsychopathology: Mental processes and disorders associated with geochemical and geophysical factors

Summary Temporal and regional variations in psychological processes have been associated with three geological factors. They are geochemical profiles, geomagnetic variations, and tectonic stresses. In the geochemical domain, copper, aluminum, zinc, and lithium may influence the incidence of thought disorders such as schizophrenia and senile dementia. These common elements are found in many soils and ground water. Geomagnetic variations have been correlated with enhanced anxiety, sleep disturbances, altered moods, and greater incidences of psychiatric admissions. The effects are usually brief but pervasive. Transient and very local epidemics of bizarre and unusual behaviors are sociological phenomena that sometimes precede increases in earthquake activity within a region; they have been hypothesized to be associated with tectonic strain. Many of the contemporary correlations between geological factors and human behavior are also apparent within historical data. The effects of geophysical and geochemical factors upon human behavior are not artifactual, but they are complex and often not detected by the limited scope of most studies.     

Mutagenicity and toxicity of chloroethylene oxide and chloroacetaldehyde

Summary Exposure of severaltrp-auxotrophicEscherichia coli strains, carrying base0pair substitutions, to chloroethylene oxide or chloroacetaldehyde (two metabolites of vinyl chloride) increased the mutation frequency to tryptophan prototrophy. Strong cytotoxic and mutagenic effects were observed with 2.5 mM chloroethylene oxide, while a higher concentration of chloroacetaldehyde (100 mM) exhibited a mutagenic effect which was 400 times lower.I am grateful to Prof. G. Michel, Laboratoire de Biochimie Microbienne, and to Dr H. Bartsch, International Agency for Research on Cancer, for the support of this work. I wish to thank Dr F. Besson-Simien and Dr A. Barbin for their collaboration.     

Histone methylation and ubiquitination with their cross-talk and roles in gene expression and stability

Methylation of lysine residues of histones is associated with functionally distinct regions of chromatin, and, therefore, is an important epigenetic mark. Over the past few years, several enzymes that catalyze this covalent modification on different lysine residues of histones have been discovered. Intriguingly, histone lysine methylation has also been shown to be cross-regulated by histone ubiquitination or the enzymes that catalyze this modification. These covalent modifications and their cross-talks play important roles in regulation of gene expression, heterochromatin formation, genome stability, and cancer. Thus, there has been a very rapid progress within past several years towards elucidating the molecular basis of histone lysine methylation and ubiquitination, and their aberrations in human diseases. Here, we discuss these covalent modifications with their cross-regulation and roles in controlling gene expression and stability. Received 24 September 2008; received after revision 21 November 2008; accepted 28 November 2008     

Hyaluronan synthesis and degradation in cartilage and bone

Hyaluronan (HA) is a large but simple glycosaminoglycan composed of repeating D-glucuronic acid, β1–3 linked to N-acetyl-D-glucosamine β1–4, found in body fluids and tissues, in both intra- and extracellular compartments. Despite its structural simplicity, HA has diverse functions in skeletal biology. In development, HA-rich matrices facilitate migration and condensation of mesenchymal cells, and HA participates in joint cavity formation and longitudinal bone growth. In adult cartilage, HA binding to aggrecan immobilises aggrecan, retaining it at the high concentrations required for compressive resilience. HA also appears to regulate bone remodelling by controlling osteoclast, osteoblast and osteocyte behaviour. The functions of HA depend on its intrinsic properties, which in turn rely on the degree of polymerisation by HA synthases, depolymerisation by hyaluronidases, and interactions with HA-binding proteins. HA synthesis and degradation are closely regulated in skeletal tissues and aberrant synthetic or degradative activity causes disease. The role and regulation of HA synthesis and degradation in cartilage, bone and skeletal development is discussed. Received 5 August 2007; received after revision 19 September 2007; accepted 20 September 2007