TnT-Hs和NSE在手足口病患儿中的表达水平及临床意义

目的：探讨TnT-Hs和NSE水平在手足口病患儿中的表达及临床意义。方法：选择我院2012年6月-2013年6月确诊为手足口病的住院患儿68例作为观察组,选择同期入院健康体检的68例正常儿童作为对照组,对比两组心肌钙蛋白T（TnT—Hs）与血清神经元特异性烯醇化酶（NSE）水平;并对观察组EV71阳性患儿与阴性患儿TnT-Hs与NSE水平进行比较。结果：①相比健康对照组,观察组TnT-Hs与NSE水平均较高,差异有统计学意义（P〈0．01）。②EV71阳性患儿46例,阴性患儿22例,阳性患儿相比阴性患儿TnT-Hs与NSE水平较高,差异均有统计学意义（P〈0．05）。结论：Tn—T-Hs和NSE水平可反映手足口病患儿病情进展变化,其可作为早期预测手足口病患儿心肌损害及脑损伤的依据及重症病例的预警指标。     

ICAM-1K469E 位点A 等位基因可降低EV71 手足口病发生率

目的:研究ICAM-1基因K469E位点、MCP-1A2518G位点基因多态性及sICAM-1、MCP-1在血清中表达水平与EV71手足口病的关系,探讨EV71型手足口病的遗传易感因素。方法:运用限制性片段长度多态性-聚合酶链反应(PCR-RFLP)检测急性期EV71感染阳性的手足口病患儿和正常儿童中ICAM-1K469E位点及MCP-1A2518G位点碱基变异情况,同时采用双夹心抗体法(ELISA)检测血清sICAM-l和MCP-1水平。结果:EV71手足口病组患儿血清中sICAM-l和MCP-1水平均显著高于正常对照组(P均<0.01)。EV71手足口病组ICAM-1K469E位点中,A等位基因的频率显著低于对照组(x2=6.897,P<0.01)。EV71手足口病组患儿MCP-1基因型分布、等位基因频率与对照组比较均无统计学意义(P>0.05)。结论:sICAM-1表达水平和其基因K469E位点多态性与EV71手足口病有关,A等位基因可降低EV71手足口病发生率。MCP-1表达水平与EV71手足口病感染有关,但MCP-1A-2518G位点基因多态性与EV71手足口病感染无关。     

免疫反应及相关细胞因子在EV71 相关手足口病 合并肺水肿中的作用

目的:探讨细胞、体液免疫应答以及相关的细胞因子在EV71相关手足口病合并肺水肿中的作用。方法:将90例经鉴定为EV71感染患儿分为手足口病合并肺水肿组38例,手足口病无并发症组52例,并设查体健康对照组28例。ELISA法检测90例EV71感染引起的手足口病患儿血清IL-6、IL-10、TNF-α及IFN-γ含量;采用流式细胞仪对血液中CD3+T、CD4+及CD8+T细胞百分比进行检测;采用免疫比浊法对90例EV71感染引起的手足口病患儿血清免疫球蛋白(IgG、IgA及IgM)及补体C3、C4含量进行检测。结果:手足口病合并肺水肿组患儿血清IL-6、IL-10及IFN-γ含量明显升高,同时伴随CD4+及CD8+T细胞百分比下降;手足口病合并肺水肿组,无并发症组及健康对照组患儿血清IgM分别为1.85±0.73,1.46±0.790和0.88±0.39,三组之间差别具有统计学意义(F=14.967,P<0.05)。而IgG与IgA在三组之间无明显变化(X2=5.535,P>0.05;F=1.988,P>0.05);手足口病患儿血清C3及C4含量均明显低于健康对照组(F=46.079;62.794,P<0.05)。结论:由IL-10及IFN-γ的异常释放而引起的广泛的中枢及外周神经系统炎症反应和T淋巴细胞衰竭是引起EV71合并肺水肿病程进展的重要原因;在EV71感染后引发的手足口病进程中存在IgM的大量释放,且伴随补体C3、C4的消耗。     

菏泽地区2009年肠道病毒71型与其他肠道病毒所致手足口病临床差异研究

目的:探讨EV71引起小儿手足口病与其他肠道病毒所致手足口病的临床特点的差异.方法:回顾性分析2009年3月-9月菏泽地区各定点医院收治的病原学检测为阳性的320例小儿手足口病的临床资料,筛出EV71感染的手足口病患儿进行分析,其他肠道病毒所致手足口痛患儿作为对照组.结果:菏泽地区2009年抽取的病原学检测为阳性的320例患儿,肠道病毒71型引起手足口病占106例,其余为其他肠道病毒所致手足口病.(1)男女发病基本相同,发病年龄1～3岁居多,农村患儿占绝大多数.(2)EV71感染的患儿临床主要表现高热、神经系统症状、无皮疹,大多数外周血象高、血糖高,可合并心肌损害,心电图异常、部分发现胸片、脑电图及核磁异常,部分符合重症手足口病标准.(3)其他肠道病毒感染的惠儿临床症状以皮疹、低热、上感症状为主,少数患儿有精神差,基本不出现神经系统症状,少数发现外周血象高、血糖高、合并心肌损害,一般胸片不会发现异常.(4)56例出现神经系统症状的患儿收集脑脊液进行两次RT-PCR扩增,发现50例EV71阳性.结论:EV71导致的手足口病,病情凶险,易致神经损害及肺水肿,早期识别重症病例,及时救治,普及病原体的检测对提高诊治能力,加强疾病的认识,对减少致残率及死亡率很有帮助.     

TLR3和TLR4基因多态性与EV71感染手足口病严重性及易感性的关系研究

手足口病(Hand-foot-and-mouth disease,HFMD)是5岁以下婴幼儿常见的病毒性肠道传染病,该病主要由人肠道病毒71型(Enterovirus 71,EV71)型及柯萨奇A组16型(Coxsackievirus A16,CV-A16)引起,但关于TLR3、TLR4基因多态性与EV71感染手足口病的报道较少。为探讨EV71感染手足口病患儿TLR3和TLR4基因多态性与EV71感染手足口病严重性及易感性的关系,本研究选择2016年8月至2017年8月就诊于安徽医科大学第一附属医院的EV71感染手足口病患儿166例,其中重症组76例,轻症组90例,并选择同期来院体检的健康者120例作为对照组。收集患者入院时的年龄、性别、发热天数等基线资料,采集血液检测白细胞计数(White blood cell count,WBC)、丙氨酸转氨酶(Alanine aminotransferase,ALT)、谷草转氨酶(Glutamate transaminase,AST)、酶联免疫吸附试验(Enzyme-linked immunosorbent assay,ELISA)检测血清C反应蛋白(C reactive protein,CRP)、干扰素-γ(Interferon-γ,IFN-γ)水平;分离外周血单个核细胞提取DNA,琼脂糖凝胶电泳检测DNA情况;聚合酶链反应(Polymerase chain reaction,PCR)扩增TLR3c.1377C/T和TLR4-896A/G,限制性内切酶Tap I(TthHB8 I)、Nco I分别酶切TLR3、TLR4 PCR扩增产物,凝胶成像系统记录实验结果,对扩增产物进行测序,分析其基因多态性结果。结果显示,对照组与EV71感染组TLR3c.1377C/T位点的基因型分布与C、T等位基因频率均无显著统计学意义(P0.05);EV71感染组中重症组TT基因型较轻症组显著升高(P0.05);重症组T等位基因频率显著高于轻症组(P0.05),C等位基因频率显著低于轻症组(P0.05);EV71感染组中,TLR3c.1377C/T位点不同基因型患儿在年龄、性别及ALT、AST、CKMB水平上无显著差异(P0.05);TLR3c.1377C/T位点TT型患儿的发热时间及WBC、CRP水平显著高于CT和CC型,CT型患儿的发热时间及WBC、CRP水平显著高于CC型(P0.05);CC型患儿的IFN-γ水平显著高于CT和TT型(P0.05);TLR4-896A/G基因电泳条带为140bp的特异性扩增产物,为野生型Asp/Asp基因型,对照组和EV71感染组均未出现A→G的突变。本研究得出结论,TLR3c.1377C/T位点有CC、TT、CT三个基因型,且携带T等位基因EV71感染手足口病患儿进展为重症的风险较高;TLR4-896A/G基因无突变,与EV71感染手足口病患儿疾病严重性和易感性无关。     

热毒宁注射液治疗CoxA16、EV71肠道病毒感染手足口病的效果与安全性分析

目的探讨热毒宁注射液治疗CoxA16、EV71肠道病毒感染手足口病的效果与安全性。方法选择2015年10月~2016年5月在我院治疗的CoxA16、EV71肠道病毒感染的手足口病患儿96例,随机分为两组,其中对照组48例给予利巴韦林注射液治疗,研究组48例给予热毒宁注射液治疗,比较两组的治疗效果与安全性。结果研究组治疗总有效率(97.92%)明显高于对照组(83.33%),差异有统计学意义(P0.05);两组均无严重不良反应(P0.05)。结论热毒宁注射液治疗CoxA16、EV71肠道病毒感染手足口病患儿的效果显著,安全可靠,值得推广。     

2007年北京地区儿童手足口病病原的初步筛查

2007年4～6月儿童手足口病流行期间,对北京地区51例皮损症状典型、伴/不伴发热、无重症合并症的手足口病患儿采样,建立RT-PCR方法,以5'非编码区(5'UTR)肠道病毒通用引物、CA16和EV71 VP1区特异性引物直接对82份临床标本进行了初步筛查,肠道病毒阳性率达70.6%。检测病例中CA16阳性25例(25/51)、EV71阳性4例(4/51)、非CA16和EV71的肠道病毒阳性病例7例(7/51),三者比例约为6:1:2。2007年北京地区儿童轻症手足口病主要病原包括CA16和EV71,同时还存在一定比例其它肠道病毒。部分EV71毒株经测序验证及系统进化分析显示为C4基因亚型。     

肠道病毒71型感染小鼠心肌损害与CXCL12/CXCR4通路激活的关系

重症手足口病患儿中心肌损害常见,肠道病毒71型(Enterovirus 71,EV71)是引起手足口病的主要病原体之一,EV71感染小鼠可以出现心肌炎的病理改变,但EV71引起心肌损害的机制尚不明确。为了阐明EV71引起心肌损害的机制,本实验观察了EV71感染小鼠心肌损害与CXC趋化因子配体12(CXC chemokine ligand 12,CXCL12)/CXC趋化因子受体4(CXC chemokine receptor 4,CXCR4)通路激活的关系。BALB/c乳鼠随机分为对照组、EV71组、EV71+AMD3100组、AMD3100组,对照组、AMD3100组给予生理盐水腹腔注射,EV71组、EV71+AMD3100组给予EV71病毒液腹腔注射;而后EV71+AMD3100组、AMD3100组给予CXCR4抑制剂AMD3100腹腔注射、连续7d。比较四组间血清中CXCL12、磷酸肌酸激酶同工酶(CreatineKinase-MB,CK-MB)、乳酸脱氢酶(Lactate dehydrogenase,LDH)含量、心肌病理改变及细胞凋亡率、心肌中CXCR4、含半胱氨酸的天冬氨酸蛋白水解酶-3(caspase-3)表达及肿瘤坏死因子-α(Tumor necrosis factor,TNF-α)、白介素-6(Interleukin-6,IL-6)含量的差异。与对照组比较,EV71组血清中CXCL12、CK-MB、LDH的含量明显增加,心肌出现了典型的心肌炎病理改变且细胞凋亡率、CXCR4及caspase-3表达水平、TNF-α及IL-6含量明显增加;与EV71组比较,EV71+AMD3100组血清中CXCL12、CK-MB、LDH的含量明显降低,心肌的病理改变改善且细胞凋亡率、CXCR4及caspase-3表达水平、TNF-α及IL-6含量明显降低。以上结果表明EV71感染小鼠心肌中CXCL12/CXCR4通路过度激活,该通路的激活介导了心肌细胞凋亡及炎症反应。本研究创新点为阐明了CXCL12/CXCR4通路在EV71病毒感染引起心肌损害中的作用,CXCL12/CXCR4通路激活能够激活EV71感染小鼠心肌的炎症反应及细胞凋亡,这为今后研究手足口病发病过程中心肌损害的机制提供了依据。     

白介素18启动子区基因多态性与儿童EV71感染相关性研究

目的:研究白介素18基因启动子多态性与儿童EV71感染遗传易感性的关系.方法:收集EV71感染患儿177例,单纯HFMD组127例,HFMD并脑炎组50例,提取外周血DNA,用序列特异性引物-聚合酶链反应(SSP-PCR)技术及基因测序法检测IL-18启动子区-137G/C、-607A/C位点的基因多态性.结果:EV71感染患儿与健康儿童IL-18-607基因型以CA为主,AA、CC次之,EV71感染患儿AA基因型、A等位基因分布频率显著高于健康儿童.EV71感染HFMD并脑炎组患儿AA基因型分布显著高于单纯HFMD组患儿,差异有统计学意义.EV71感染患儿与健康儿童IL-18-137基因型以CC为主,CG次之,GG占少数.该位点基因型及等位基因在EV71感染组与健康儿童、单纯HFMD与HFMD并脑炎组的分布无显著差异.结论:IL-18基因多态性与EV71感染相关,IL-18-607AA基因型、A等位基因携带儿童更易感染EV71病毒,且AA基因型患儿易并发脑炎,-607AA基因型可能为EV71感染的易感基因型.-137C/G位点基因多态性与EV71感染无相关性.     

Race and Racism in America and in Anthropology

Race in North America: Origin and Evolution of a Worldview . Audrey Smedley
Anthropology and Race . Eugenia Shanklin     

Electroejaculation in chimpanzees and gorillas and artificial insemination in chimpanzees

Electroejaculation was performed in 3 chimpanzees, 1 pygmy chimpanzee, and 2 gorillas with an instrument that delivers a modified sine wave current with a frequency of 24 Hz. The current stimuli were applied by a rectal probe with longitudinal electrodes. The electrical parameters varied from 6 to 12 V and from 30 to 40 mA for response of erection and lay between 8 and 18 V and between 40 and 145 mA during semen emission. Eleven chimpanzee semen samples showed the following data (x ± SD): total volume 1.9 ± 1.3 ml, volume of the liquid fraction 0.3 ± 0.2 ml, spermatozoa per ejaculate 743 ± 376 × 10⁶, sperm motility 52.7 ± 9.6%, morphologically abnormal spermatozoa 12.2 ± 7.5%. From an adult gorilla, three semen samples were collected, in each case without spermatozoa. The electrostimulation of a 6-year-old gorilla led to an erection, but not to semen emission. Three female chimpanzees were inseminated with fresh or frozen semen, each of them within three different estrous cycles. None of these inseminations led to a pregnancy.     

Degradation and conversion of somatostatin in normal and diabetic rats in vivo and in vitro

Plasma somatostatin-like immunoreactivity in the portal and jugular veins of streptozotocin diabetic rats was compared with that in normal control rats. In the diabetic group, somatostatin levels in the portal (p less than 0.05) and jugular (p less than 0.01) veins were both elevated compared with those in the control group. Moreover, the degree of elevation was greater in the jugular vein than in the portal vein. To further investigate the role of the liver in the clearance of somatostatin-28 in vivo, 2 micrograms of somatostatin-28 was administered as a bolus into the external jugular vein of intact and functionally hepatectomized rats. The mean half-time of somatostatin-28 was significantly longer in intact diabetic rats than in controls (p less than 0.05). The functional hepatectomy did not cause a significant difference in the half-time in diabetic rats but made it longer in control rats. These results suggest that the longer half-time of somatostatin-28 in diabetic rats in vivo is due to its slower hepatic clearance. The hepatic clearance of somatostatin-28 and somatostatin-14 was further studied in vitro using a recirculating liver perfusion method. The hepatic clearance of 1.2 nM of either somatostatin-28 or somatostatin-14 was significantly lower in diabetic rats than in controls (p less than 0.01). This indicates that elevated plasma somatostatin levels in diabetic rats are caused at least in part by decreased hepatic clearance of somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Trajectories and Constraints in Brain Evolution in Primates and Cetaceans

A negative allometric relationship between body mass (BM) and brain size (BS) can be observed for many vertebrate groups. In the past decades, researchers have proposed several hypotheses to explain this finding, but none is definitive and some are possibly not mutually exclusive. Certain species diverge markedly (positively or negatively) from the mean of the ratio BM/BS expected for a particular taxonomic group. It is possible to define encephalization quotient (EQ) as the ratio between the actual BS and the expected brain size. Several cetacean species show higher EQs compared to all primates, except modern humans. The process that led to big brains in primates and cetaceans produced different trajectories, as shown by the organizational differences observed in every encephalic district (e.g., the cortex). However, these two groups both convergently developed complex cognitive abilities. The comparative study on the trajectories through which the encephalization process has independently evolved in primates and cetaceans allows a critical appraisal of the causes, the time and the mode of quantitative and qualitative development of the brain in our species and in the hominid evolutionary lineage.     

Variation in infectivity and aggressiveness in space and time in wild host-pathogen systems: causes and consequences

Variation in host resistance and in the ability of pathogens to infect and grow (i.e. pathogenicity) is important as it provides the raw material for antagonistic (co)evolution and therefore underlies risks of disease spread, disease evolution and host shifts. Moreover, the distribution of this variation in space and time may inform us about the mode of coevolutionary selection (arms race vs. fluctuating selection dynamics) and the relative roles of G × G interactions, gene flow, selection and genetic drift in shaping coevolutionary processes. Although variation in host resistance has recently been reviewed, little is known about overall patterns in the frequency and scale of variation in pathogenicity, particularly in natural systems. Using 48 studies from 30 distinct host–pathogen systems, this review demonstrates that variation in pathogenicity is ubiquitous across multiple spatial and temporal scales. Quantitative analysis of a subset of extensively studied plant–pathogen systems shows that the magnitude of within‐population variation in pathogenicity is large relative to among‐population variation and that the distribution of pathogenicity partly mirrors the distribution of host resistance. At least part of the variation in pathogenicity found at a given spatial scale is adaptive, as evidenced by studies that have examined local adaptation at scales ranging from single hosts through metapopulations to entire continents and – to a lesser extent – by comparisons of pathogenicity with neutral genetic variation. Together, these results support coevolutionary selection through fluctuating selection dynamics. We end by outlining several promising directions for future research.     

Aminoacylation in Sulfolobus acidocaldarius and in methanogenic and halophilic archaebacteria

Abstract Phenylalanyl-tRNA synthetase (PRS) from the sulphur-metabolizing thermoacidophilic archaebacterium Sulfolobus acidocaldarius has been purified 150-fold using different chromatographic steps. The enzyme has a M _r of 270 000 and exhibits considerable thermostability in a temperature range up to 90°C with optimal activity at 70°C. Conservation of antigenic determinants could not be detected by antibodies against various PRS of all primary kingdoms. As a further means to detect traits of phylogenetic relationship, the cross-species reactivity between PRS and tRNAs of organisms from the three branches of archaebacteria and from all primary kingdoms reveals the group character of all 3 branches of the archaebacterial domain, the sulphur-metabolizing, methanogenic and halophilic archaebacteria.