血清血管内皮生长因子及可溶性血管内皮生长因子受体1在系统性红斑狼疮患者中的表达及其意义

目的 研究血清中血管内皮生长因子(VEGF)及可溶性血管内皮生长因子受体1(sFlt-1)在活动期系统性红斑狼疮(SLE)及不同肾脏病理类型的狼疮肾炎(LN)患者中表达的意义. 方法 采用双抗体夹心酶联免疫吸附法(ELISA)对60例SLE患者及30名健康人血清中VEGF及sFlt-1的水平同时进行检测,结合临床资料及肾脏病理进行相关分析. 结果 活动期SLE患者血清VEGF及sFlt-1水平均明显升高;血清中VEGF/sFlt-1的比值健康对照组较活动期SLE、非活动期SLE及LN组患者降低(P＜0.01),Ⅴ型LN组该比值较Ⅱ、Ⅲ、Ⅳ型LN组升高(P＜0.05);血清sFlt-1的浓度与尿蛋白呈正相关(rs=0.6244,P＜0.01),血清VEGF的浓度与尿蛋白无明显相关(rs=0.1807,P＞0.05);血清sFlt-1的浓度与ESR正相关(rs=0.4235,P＜0.01),血清VEGF的浓度与ESR无明显相关(rs=0.0532,P＞0.05);血清VEGF及sFlt-1浓度与SLE疾病活动指数(SLEDAI)均呈正相关(rs=0.5046,P＜0.01,rs=0.5152,P＜0.01);血清VEGF浓度与肾组织活动指数(RAI)呈正相父(r=0.3386,P＜0.05),血清sFlt-1浓度与RAI无明显相关(rs=0.0240,P＞0.05);SLE患者中VEGF、sFlt-1水平与血压、血肌酐、尿素氮、C3、C4、C反应蛋白(CRP)无明显相关. 结论 血清VEGF及sFlt-1的水平可作为SLE病情活动评价指标,VEGF的高表达可能与增殖性肾小球病变相关,sFlt-1的表达与蛋白尿关系密切.     

缺氧诱导因子-1α血管内皮生长因子在胶原诱导性关节炎滑膜中的表达及其与血管生成的关系

目的 探讨缺氧诱导因子(HIF)-1α和血管内皮生长因子(VEGF)在类风湿关节炎(RA)血管生成中的作用.方法 建立大鼠胶原诱导性关节炎(CIA)模型,采用苏木素-伊红(HE)染色评估滑膜病理血管生成、SP法免疫组织化学染色检测HIF-1α和VEGF的表达,动态观察HIF-1α表达与VEGF表达及血管生成之间的关系.结果 CIA大鼠滑膜HIF-1α及VEGF表达增加,且随发病时间的延长而逐渐增加,两者均与滑膜病理血管生成评分呈显著正相关,同时滑膜衬里层和衬里下层HIF-1α表达又与相应部位的VEGF表达呈显著正相关.结论 HIF-1α可能参与上调VEGF表达促进血管生成,从而在RA关节破坏中起一定作用.     

类风湿关节炎滑膜组织人糖皮质激素诱导型肿瘤坏死因子受体表达的免疫组织化学研究

目的 观察研究人糖皮质激素诱导型肿瘤坏死因子受体(hGITR)在类风湿关节炎(RA)滑膜组织和软骨组织中的表达及其与滑膜炎性病变程度的相关性.方法 用免疫组织化学的方法对16例RA患者、9例骨关节炎(OA)患者及4例无关节病变的截肢患者滑膜组织和软骨组织中hGITR的表达进行描述分析,并对hGITR表达情况与RA患者滑膜炎性病变程度相关性进行分析.结果 hGITR在RA滑膜组织主要分布于血管翳周围,如血管内皮细胞和炎性细胞等,hGITR阳性细胞数约为69%.而该受体在RA患者软骨组织细胞中的表达率与对照组比较差异无统计学意义.OA滑膜组织和软骨组织细胞中hGITR也呈现不同程度的阳性表达,但与RA比较阳性程度较弱,阳性细胞数量较少;对hGITR表达与RA滑膜炎性程度的相关性分析发现,hGITR与RA滑膜炎性程度呈正相关(r=0.895,P<0.01).结论 hGITR在RA滑膜组织炎性细胞及血管内皮细胞上的异常表达可能是其参与RA血管翳的形成及滑膜组织的侵袭等病理过程导致RA患者滑膜损伤的一个重要机制.     

实验性关节炎大鼠血浆肿瘤坏死因子-α和滑膜血管内皮生长因子表达相关性分析

目的　同步观察实验性关节炎大鼠不同时间点的血浆肿瘤坏死因子 α (TNF α)含量与滑膜内皮生长因子 (VEGF)表达变化 ,探讨TNF α和VEGF在类风湿关节炎 (RA)发病机制中的作用及其相关性。方法　采用Ⅱ型胶原与完全福氏佐剂诱导SD大鼠实验性关节炎 (CIA)模型 ,同步检测CIA大鼠不同时间点的血浆TNF α含量和滑膜组织VEGF的表达水平 ,并同时观察其发病时间与滑膜新生血管形成、关节炎指数积分以及TNF α和VEGF之间关系。用直线相关分析法分析TNF α与VEGF之间的关系 ,用等级相关分析法分析关节炎指数积分与VEGF及TNF α之间的关系。结果　随着CIA发病时间的延长 ,滑膜新生血管逐渐增多 ,滑膜增厚 ,关节炎指数积分逐渐增加 ,TNF α含量和VEGF水平也随之升高 ;其关节炎指数积分与VEGF表达水平呈正相关关系 (r =0 5 35、P <0 0 5 ) ,与TNF α含量虽有相关增高趋势 ,但差异无显著性 (r =0 371 ,P >0 0 5 )。血浆TNF α含量与VEGF表达水平呈显著正相关关系 (r =0 893,P <0 0 1 )。结论　TNF α与VEGF在RA炎症反应 ,滑膜新生血管形成的细胞因子网络中起重要作用 ,二者可能具有互相影响 ,相互促进 ,充当恶性网络循环的调控作用 ;是介导RA发生和发展以及骨质侵蚀、致残的众多因子中的关键因子。     

α1抗胰蛋白酶在强直性脊柱炎患者滑膜组织中表达的研究

目的 观察α1抗胰蛋白酶(ATA1)在强直性脊柱炎(AS)滑膜组织中的表达分布,并探讨编码该蛋白的基因对AS的遗传效应.方法 选用8例AS,9例类风湿关节炎(RA)和9例骨关节炎患者关节滑膜样本,用蛋白免疫印迹定量分析ATA1的表达水平,用免疫组织化学法定位ATA1在滑膜组织中表达分布.分别选用32例AS、RA、骨关节炎滑液样本分析ATAl在滑液中的表达水平.选用56例AS血液样本,260例RA和160名健康者样本作对照,用水解探针法对标签单核苷酸多态性位点(SNP)(rs2753934,rs2749531和rs6575424)进行基因分型.采用单因素方差分析、LSD检验和x2检验进行统计分析.结果 与RA、骨关节炎滑膜比较,ATA1在AS滑膜中呈高表达,表达率为100％.同样,ATA1在AS滑液中表达量(1.6±0.6)也高于RA(1.4±0.5)和骨关节炎(1.2±0.5)的表达量(P＜0.05).基因分型发现ATAl SNP与AS和RA无明显关联(P＞0.05).单体型分析没有检测到与AS相关的或与RA相关的单体型.结论 ATA1在AS滑膜组织中高表达,提示ATA1及关节滑膜在AS发病过程中起重要作用.     

血管内皮细胞生长因子在骨关节炎患者膝关节滑膜和滑液中的表达及其意义

目的 检测不同阶段的骨关节炎患者膝关节滑膜组织和滑液中血管内皮细胞生长因子(VEGF)的表达情况,评价VEGF作为进展期骨关节炎的标志的可行性。方法 临床收集膝关节镜或关节置换手术患者的滑液和滑膜组织,根据X线平片的K-L分级进行分组。以Kellegren-Lawrence (K-L)分级均为0级的单纯膝关节半月板损伤的患者作为对照组。酶联免疫吸附测定( ELISA)法检测各组滑液中VEGF的含量,免疫组织化学染色方法检测VEGF在滑膜组织中的原位表达。统计学方法采用方差分析。结果 骨关节炎滑膜组织普遍存在不同程度的炎症,滑膜色泽变暗红,组织增生,甚至呈绒毛样改变。免疫组织化学染色显示,VEGF在滑膜衬里层及血管平滑肌细胞表达。2～4组的滑液中VEGF水平逐级增高,从(1181±116)、(1632±140)到(2252±216) pg/ml,明显高于对照组(648±129) pg/ml,差异均有统计学意义（P＜0.01）;免疫组织化学阳性细胞分数对照组和第2～4组分别为(5±4)％和(9±4)％、(16±6)％、(21±6)％,差异有统计学意义(P＜0.01)。结论 关节滑膜产生的VEGF参与了骨关节炎软骨损害的病理过程,滑液中VEGF水平的持续升高可作为判断骨关节炎病情活动的一个指标。     

低氧诱导因子-1α在大鼠胶原诱导性关节炎中的表达及与血管生成的关系

目的制备牛Ⅱ型胶原诱导性大鼠关节炎(CIA)模型,探讨低氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)在类风湿关节炎(RA)组织中的动态表达及其相关性作用。方法 50只SD大鼠,随机分为对照组与模型组。建立CIA模型,动态观察各项关节炎活动指标,于造模21、28、35、42d取踝关节行HE染色及HIF-1α、VEGF免疫组化染色,分析两者在CIA中的相关性及与关节炎活动指标、滑膜病理学评分之间的关系。结果 CIA大鼠关节滑膜层和滑膜下层均表达HIF-1α、VEGF,第21天阳性表达量最高,随病程进展,表达逐渐下降,与滑膜病理学评分、滑膜增生评分及血管生成评分呈显著正相关,与炎症浸润评分无明显相关。结论Ⅱ型胶原可成功诱导大鼠关节炎模型。HIF-1α、VEGF在RA组织中的表达,与炎症严重程度呈明显正相关。HIF-1α可能通过调控一系列下游靶基因,如VEGF等,促进滑膜增生及血管生成,影响RA的发生、发展。     

维生素D结合蛋白在类风湿关节炎滑膜中表达的研究

目的 本研究通过蛋白质组学的方法比较类风湿关节炎(RA)、骨关节炎及强直性脊柱炎(AS)滑膜组织中表达的蛋白,筛选RA滑膜中表达特异性下调的蛋白,并通过单核苷酸多态性(SNPs)分析方法分析靶蛋白编码基因对RA的遗传易感性.方法 提取RA( 10例)、骨关节炎(10例)及AS(10例)滑膜组织总蛋白,每类疾病的样本等比例混合,然后用2-D凝胶电泳进行分析,对RA样本中表达量明显低于骨关节炎和AS的蛋白进行飞行时间质谱鉴定,检测结果用蛋白印迹法验证.用Taqman方法对中国人群中267例RA患者和160名健康对照的维生素D结合蛋白(VDBP)编码基因的标签SNPs进行基因分型,并扩大样本量(389例RA和371名健康对照)验证分型结果.采用单因素方差分析和Fisher确切概率法进行检验.结果 蛋白质组学研究发现,在RA患者滑膜中VDBP表达量明显下降,蛋白印迹法也验证了这一结果.基因分型研究发现,SNP位点rs2282679与RA密切相关(P=0.026 794).进一步扩大样本实验也得出了一致结果,rs2282679与RA有相关性[比值比(OR )=0.678 639,95％可信区间(CI)0.541 113～0.851 118,P=0.000 776].结论 与骨关节炎和AS患者相比,VDBP在RA患者滑膜中表达量明显下降.VDBP基因上的SNP位点rs2282679与RA有相关性.VDBP在RA中的表达下调及其基因的遗传效应显示VDBP可能参与RA的病理过程.     

HBx和VEGF与HBV相关性肝癌组织血管生成及转移的关系

目的探讨乙型肝炎病毒X蛋白(HBx)和血管内皮生长因子(VEGF)与HBV相关性肝癌组织血管生成及转移的关系。方法选择84例HBV相关性肝癌组织和22例非HBV相关性肝癌组织,免疫组织化学法检测HBx、VEGF及血管内皮细胞表面抗原(CD34)表达,光镜下记录微血管计数(MVD)。结果84例HBV相关性肝癌组织中HBx阳性表达率为73.81%(62/84),阴性率为26.19%(22/84);62例HBx阳性表达组中的VEGF阳性率为74.19%(46/62),明显高于22例HBx阴性组36.36%(8/22)和非HBV相关性肝癌组36.36%(8/22)(P0.05);HBx阴性表达的HBV相关性肝癌组和非HBV相关性肝癌组中VEGF阳性表达差异无统计学意义(P0.05);HBx和VEGF的表达呈正相关(r=0.552,P0.01);二者在高分化肿瘤组织中的表达高于低分化组织(P0.05),且转移组表达高于无转移组;HBx阳性表达组平均MVD值明显高于HBx阴性组和非HBV相关性肝癌组(P0.01),有转移组MVD高于无转移组(P0.01);有门脉侵犯组高于非侵犯组(P0.05)。结论HBx和VEGF广泛表达于HBV相关性肝癌组织中,二者呈正相关;HBx可能通过上调VEGF的表达在HBV相关性肝癌组织血管生成及转移中起促进作用。     

硫氧还蛋白5在类风湿关节炎患者滑膜组织滑液及血液中表达的研究

目的 在蛋白和mRNA水平上进一步研究硫氧还蛋白5(TXNDC5)在类风湿关节炎(RA)患者滑膜和血液中的表达水平与临床指标的关系,探讨该基因对RA的病理作用.方法 用免疫组织化学法、免疫荧光定量分析、实时荧光定量聚合酶链反应(PCR)、蛋白免疫印迹定量分析TXNDC5在RA滑膜中的表达水平;以骨关节炎(OA)、系统性红斑狼疮(SEE)、强直性脊柱炎(AS)及健康人为对照,用夹心酶联免疫吸附法(Sandwich-ELISA)分析TXNDC5在RA患者血液和滑液中的表达水平.采用单因素方差分析,LSD检验、Spearman相关分析进行统计学处理.结果 免疫组织化学法和免疫荧光定量分析显示TXNDC5在RA滑膜组织中高表达(100%,40±9),在OA滑膜中无表达,在AS滑膜中表达量(200%.4±4)也较低.实时定量PCR和Western blotting均证实TXNDC5在RA滑膜中高表达(P均<0.01).SandwichELISA显示,TXNDC5在RA患者血液及滑液中高表达(A值=1.31±0.37),但在OA、SEE、AS以及健康人低表达或无表达(P均<0.05).RA血液中TXNDC5的水平(A值=0.8185±0.299)与抗环瓜氨酸肽(CCP)抗体水平存在正相关(r=0.350,P=0.027).结论 TXNDC5在RA滑膜和血液中表达量明显升高,可能通过刺激RA滑膜血管翳形成参与RA病理进程.     

A Call to Action to Enhance Filovirus Disease Outbreak Preparedness and Response

The frequency and magnitude of recognized and declared filovirus-disease outbreaks have increased in recent years, while pathogenic filoviruses are potentially ubiquitous throughout sub-Saharan Africa. Meanwhile, the efficiency and effectiveness of filovirus-disease outbreak preparedness and response efforts are currently limited by inherent challenges and persistent shortcomings. This paper delineates some of these challenges and shortcomings and provides a proposal for enhancing future filovirus-disease outbreak preparedness and response. The proposal serves as a call for prompt action by the organizations that comprise filovirus-disease outbreak response teams, namely, Ministries of Health of outbreak-prone countries, the World Health Organization, Médecins Sans Frontières, the Centers for Disease Control and Prevention—Atlanta, and others.     

Control of intraabdominal hemorrhage and shock: a comparison of fluid resuscitation, MAST, and balloon occlusion

Our study examined the efficacy of four treatment modalities in controlling hemorrhage and achieving hemodynamic stabilization in hemorrhagic shock: intravenous fluid replacement (IV); military antishock trousers used concomitantly with fluids (MAST); balloon occlusion at the level of the diaphragm with concomitant fluid replacement (balloon); and a combination of MAST inflation, balloon occlusion, and fluid resuscitation (MAST and balloon). Twenty-eight mongrel dogs were anesthetized, and the spleen was exposed and completely crushed. The abdomen was closed, and treatment was initiated and continued for four hours or until the dog died. For all conditions the hematocrit dropped during the course of the experiment; balloon occlusion was effective at slowing this drop (P less than .0001), but MAST had no statistically significant effect. Animals with balloons bled more slowly into the abdominal cavity than did animals in the other two groups (P less than .0001). MAST also were effective at slowing the bleeding (P less than .05). Of the balloon and the MAST and balloon dogs, all except one survived the entire four hours; this difference between balloon and nonballoon dogs is significant (P = .002). MAST did not have a statistically significant effect on survival. Perfusion pressure (PP) declined during the course of the experiment, and the balloon was effective at slowing this decline (P less than .0001); none of the other comparisons was statistically significant.     

Interplay between interferon-mediated innate immunity and porcine reproductive and respiratory syndrome virus

Innate immunity is the first line of defense against viral infection, and in turn, viruses have evolved to evade host immune surveillance. As a result, viruses may persist in host and develop chronic infections. Type I interferons (IFN-α/β) are among the most potent antiviral cytokines triggered by viral infections. Porcine reproductive and respiratory syndrome (PRRS) is a disease of pigs that is characterized by negligible induction of type I IFNs and viral persistence for an extended period. For IFN production, RIG-I/MDA5 and JAK-STAT pathways are two major signaling pathways, and recent studies indicate that PRRS virus is armed to modulate type I IFN responses during infection. This review describes the viral strategies for modulation of type I IFN responses. At least three non-structural proteins (Nsp1, Nsp2, and Nsp11) and a structural protein (N nucleocapsid protein) have been identified and characterized to play roles in the IFN suppression and NF-κB pathways. Nsp's are early proteins while N is a late protein, suggesting that additional signaling pathways may be involved in addition to the IFN pathway. The understanding of molecular bases for virus-mediated modulation of host innate immune signaling will help us design new generation vaccines and control PRRS.     

Disease Pandemics and Major Epidemics Arising From New Encounters between Indigenous Viruses and Introduced Crops

Virus disease pandemics and epidemics that occur in the world’s staple food crops pose a major threat to global food security, especially in developing countries with tropical or subtropical climates. Moreover, this threat is escalating rapidly due to increasing difficulties in controlling virus diseases as climate change accelerates and the need to feed the burgeoning global population escalates. One of the main causes of these pandemics and epidemics is the introduction to a new continent of food crops domesticated elsewhere, and their subsequent invasion by damaging virus diseases they never encountered before. This review focusses on providing historical and up-to-date information about pandemics and major epidemics initiated by spillover of indigenous viruses from infected alternative hosts into introduced crops. This spillover requires new encounters at the managed and natural vegetation interface. The principal virus disease pandemic examples described are two (cassava mosaic, cassava brown streak) that threaten food security in sub-Saharan Africa (SSA), and one (tomato yellow leaf curl) doing so globally. A further example describes a virus disease pandemic threatening a major plantation crop producing a vital food export for West Africa (cacao swollen shoot). Also described are two examples of major virus disease epidemics that threaten SSA’s food security (rice yellow mottle, groundnut rosette). In addition, brief accounts are provided of two major maize virus disease epidemics (maize streak in SSA, maize rough dwarf in Mediterranean and Middle Eastern regions), a major rice disease epidemic (rice hoja blanca in the Americas), and damaging tomato tospovirus and begomovirus disease epidemics of tomato that impair food security in different world regions. For each pandemic or major epidemic, the factors involved in driving its initial emergence, and its subsequent increase in importance and geographical distribution, are explained. Finally, clarification is provided over what needs to be done globally to achieve effective management of severe virus disease pandemics and epidemics initiated by spillover events.     

岳阳市城区小学生血吸虫病防治健康教育现状调查

目的 调查湖南省岳阳市城区小学生血吸虫病防治知识、行为现状及健康教育需求情况,为制定科学有效的小学生血吸虫病健康教育方案提供参考依据。方法 采用分层整群抽样方法,抽取岳阳市城区洞庭湖湖畔学校和中心城区学校各2所,每所再从五、六年级分别抽取2个班的学生,通过调查问卷了解小学生血吸虫病相关知识、预防行为及健康教育需求,并进行统计分析。结果 共调查湖畔小学353人、中心城区小学363人,两组学校小学生年龄、性别、年级构成差异无统计学意义（t=-0.494,χ²_性别=1.615,χ²_年级=2.152;P均>0.05）。学生血吸虫病防治知识总知晓率为42.60%（305/716）,其中,湖畔学校小学生血防知识知晓率（52.97%）高于中心城区（32.51%）,差异有统计学意义（χ²=30.661,P<0.05）;学生行为正确率为76.68%（549/716）,血防知识知晓组行为正确率（81.31%）高于不知晓组（71.24%）,差异有统计学意义（χ²=6.384,P<0.05）。学生血防知识主要来源于老师（47.49%）;91.90%的学生愿意了解更多的血防知识,最喜欢的血防知识学习方式是参加课外活动（50.42%）。结论 岳阳市城区小学生的血防知识知晓率及行为正确率偏低,对血吸虫病防治健康教育需求较高。建议针对学生开展形式多样的血防健康教育,以增强学生的血吸虫病防护意识,提高自我防护能力。     

Barrett's Esophagus: Where Do We Stand?

Barrett''s esophagus (BE) is a precursor for esophageal adenocarcinoma, which has an increased incidence rate over the last few decades. Its importance stems from the poor five-year survival of esophageal adenocarcinoma and current data that suggest a survival benefit when surveillance programs are implemented. In this review, we will cover the pathophysiology and natural history of BE and the different endoscopic findings. The prevalence of BE in different geographic areas and the incidence of high-grade dysplasia and adenocarcinoma in this patient population is reviewed. Recent recommendation for screening and surveillance of BE has been covered in this review as well as the efficacy of nonconventional imaging modalities and endoscopic ablation therapies.