Effortful verb retrieval from semantic memory drives beta suppression in mesial frontal regions involved in action initiation

The contribution of the motor cortex to the semantic retrieval of verbs remains a subject of debate in neuroscience. Here, we examined whether additional engagement of the cortical motor system was required when access to verbs semantics was hindered during a verb generation task. We asked participants to produce verbs related to presented noun cues that were either strongly associated with a single verb to prompt fast and effortless verb retrieval, or were weakly associated with multiple verbs and more difficult to respond to. Using power suppression of magnetoencephalography beta oscillations (15–30 Hz) as an index of cortical activation, we performed a whole‐brain analysis in order to identify the cortical regions sensitive to the difficulty of verb semantic retrieval. Highly reliable suppression of beta oscillations occurred 250 ms after the noun cue presentation and was sustained until the onset of verbal response. This was localized to multiple cortical regions, mainly in the temporal and frontal lobes of the left hemisphere. Crucially, the only cortical regions where beta suppression was sensitive to the task difficulty, were the higher order motor areas on the medial and lateral surfaces of the frontal lobe. Stronger activation of the premotor cortex and supplementary motor area accompanied the effortful verb retrieval and preceded the preparation of verbal responses for more than 500 ms, thus, overlapping with the time window of verb retrieval from semantic memory. Our results suggest that reactivation of verb‐related motor plans in higher order motor circuitry promotes the semantic retrieval of target verbs.     

中国西南地区汉族脊肌萎缩症患者SMA相关基因分子特征

目的 以中国西南地区汉族人群为研究对象,构建脊肌萎缩症（SMA）相关基因拷贝数变化频率,为SMA的临床诊断和分型提供依据。方法 收集62例临床诊断为SMA的无亲缘关系患者,以及50例无亲缘关系的正常人作为健康对照组,采用多重连接酶依赖的探针扩增技术（MLPA）分析运动神经元基因（SMN）和神经原凋亡抑制蛋白基因（NAIP）的拷贝数。 结果 62例患者中,SMAⅠ～Ⅳ型分别占30.65%（19/62）、41.94%（26/62）、16.13%（10/62）、11.29%（7/62）。SMN1基因外显子7纯合缺失占98.38%（61/62）,SMN1基因外显子8纯合缺失占82.26%（51/62）。SMAⅠ型患者中NAIP基因外显子5有68.42%（13/19)纯合缺失,26.32%（5/19）杂合缺失;SMAⅡ～Ⅳ型患者中NAIP基因外显子5有13.95%（6/43）纯合缺失,62.79%（27/43）杂合缺失。SMAⅠ型患者中68.42%（13/19）有1～2拷贝的SMN2基因,SMAⅡ型中84.62%（22/26)有2拷贝以上的SMN2基因,90.00%（9/10)SMAⅢ型和85.71%（6/7)SMAⅣ型患者有2拷贝以上的SMN2基因,且发现有5拷贝和6拷贝SMN2基因。结论 SMN1基因缺失是SMA的主要致病原因,SMN2和NAIP基因拷贝数变化可以影响SMA病情严重程度。     

PDGF-α受体反义寡核苷酸对体外视网膜色素上皮细胞增殖和凋亡的影响

目的:探讨血小板源性生长因子-α受体反义寡核苷酸(PDGFR-αASODN)对体外人视网膜色素上皮(humanretinal pigment epithelium,HRPE)细胞增殖和凋亡的作用。方法:使用阳离子脂质体lipofectamineTM2000将靶向PDGFR-α基因的ASODN转染至细胞株HRPE细胞,MTT法检测对HRPE细胞增殖的影响;Hoechst33258荧光染色观察凋亡细胞;流式细胞仪检测HRPE细胞的周期和凋亡率。结果:PDGFR-αASODN转染组细胞增殖抑制率和凋亡率均明显高于对照组(P<0.05)。结论:沉默PDGFR-α基因表达可显著抑制HRPE细胞的增殖,并能诱导其凋亡。     

儿童急性淋巴细胞白血病雌激素受体α与β的表达及临床意义

[摘要] 目的：研究雌激素受体（ER）α与β在儿童急性淋巴细胞白血病（ALL）中的表达水平及与临床疗效的关系。方法：先采用白细胞免疫标记技术APAAP法对30例儿童急性淋巴细胞白血病（ALL）患儿进行免疫学分型,然后采用免疫组织化学SP法检测30例儿童急性淋巴细胞白血病患儿骨髓单个核细胞ERα与ERβ的表达;对照组为15例非恶性血液病患儿。结果：30例初诊组中ERα、ERβ阳性表达率分别为65.7%和70.7%,明显高于对照组（P<0.05）;ERα阳性表达者与阴性表达者之间缓解率无显著差异（P>0.05）,ERβ阳性表达者缓解率明显高于ERβ阴性表达者,两者比较有显著差异（P<0.05）;在缓解组与未缓解组之间ERα阳性表达率无显著差异（P>0.05）,在缓解组与未缓解组之间ERβ阳性表达率有显著差异（P<0.05）。在ALL-B和ALL-T中ERα、ERβ表达均无统计学意义。结论：儿童急性淋巴细胞白血病可能有一定的激素依赖性,ERβ在儿童急性淋巴细胞白血病发生、发展、预后评估上发挥重要角色。     

hif-1α基因沉默对宫颈癌HeLa细胞增殖及对顺铂敏感度的影响

目的研究靶向干扰hif-1α基因表达后,对HeLa细胞增殖及其对顺铂敏感度的影响。方法构建针对hif-1α基因的干扰载体并转染HeLa细胞,G418筛选阳性克隆,经RT-PCR与Western blot鉴定抑制效果,用MTT法观察抑制hif 1α基因表达后,HeLa细胞增殖的变化,RT-PCR检测在低氧培养条件下HeLa/shRNA-i细胞葡萄糖转运蛋白1 mRNA的水平,利用MTT法观察抑制hif-1α表达后HeLa细胞对顺铂敏感性的改变。结果HeLa/shRNA-i细胞与对照细胞组相比,hif-1α基因mRNA表达降低了62%,蛋白表达明显降低,MTT显示细胞吸光度值降低,低氧条件下葡萄糖转运蛋白1 mRNA表达降低,对顺铂药物的敏感度增高,与对照组比较差异有统计学意义（P<0.05）。结论hif-1α基因的沉默可以抑制HeLa细胞的增殖并且能够增强HeLa细胞对顺铂的敏感度。     

HIF-1α、CAIX在胃癌组织中的表达及意义

目的探讨HIF-1α、CAIX表达与胃癌临床病理特征的关系及两者相关性。方法应用免疫组织化学方法,检测84例胃癌组织及癌旁正常组织中HIF-1α、CAIX的表达,并分析其与胃癌临床病理特征的关系及相互间的关系。结果 84例胃癌组织及癌旁内正常胃组织中CAIX阳性表达率分别为76.2%,26.0%(P<0.05)。有、无淋巴结转移的癌组织中CAIX阳性表达率分别为95.3%、56.1%(P<0.05),浸润至黏膜或黏膜下、肌层或浆膜下、浆膜层癌组织中CAIX阳性表达率分别为41.7%、89.2%、91.3%(P<0.05)。未或低分化、中或高分化癌组织中CAIX阳性表达率分别为88.0%、71.2%(P>0.05)。肿瘤直径≤5cm、>5cm的癌组织中CAIX阳性表达率分别为55.9%、90.0%(P<0.05)。男性和女性患者CAIX阳性表达率分别为71.7%和81.5%(P>0.05),<60岁和≥60岁患者CAIX阳性表达率分别为72.7%和80.0%(P>0.05)。HIF-1α在胃癌组织中阳性表达率为60.7%。结论 CAIX表达与胃癌浸润、淋巴结转移和肿瘤大小有关,并与HIF-1α表达具有明显相关性...     

Myofibroblast Stromal Presence and Distribution in SquamousEpithelial Carcinomas,Oral Dysplasia and Hyperkeratosis

Purpose: Stromal elements play a key role in growth and development of different neoplasms. Myofibroblastsare the major components and occur in stromal tissue during carcinogenesis processes. The purpose of this studywas to review the frequency and the distribution pattern of myofibroblasts(αSMA-positive) in the stroma ofsquamous epithelial carcinoma and to compare values with those for with oral dysplasia and hyperkeratosis.Methods: we evaluated αSMA protein frequency in hyperkeratosis (N =18), oral epithelial dysplasia (N=18)and oral squamous cell carcinoma (N=18) using immunohistochemistry. Results: αSMA-positive expressionwas observed in 67% of OSCC tissue samples with network and spindle patterns, whereas it was seen in 22%with a focal pattern in dysplasia and in 6% with a scanty pattern in hyperkeratosis cases. Conclusion: Thesefindings suggest that an increase in number of myofibroblasts and change in their distribution pattern occursduring carcinogenesis which can be an expression of their role in tumor invasive characteristics.     

氢醌对人骨髓单个核细胞拓扑异构酶Ⅱα表达的影响

目的 研究苯代谢物氢醌(hydroquinone,HQ)对人骨髓单个核细胞中拓扑异构酶(TOPO)Ⅱα表达的影响,探讨TOPOⅡα在HQ所致造血毒性中的作用及调控机制.方法 50μmol/LHQ处理的正常人骨髓单个核细胞为实验组,设立对照组(等体积灭菌蒸馏水培养),应用TOPOⅡ检测试剂盒检测TOPOⅡ的活力,免疫印迹法(Western blotting)检测TOPOⅡα含量的变化,反转录-聚合酶链反应(RT-PCR)法检测TOPOⅡα mRNA表达水平的改变,染色质免疫沉淀分析法(ChIp)检测TOPOⅡα含量的变化.结果 (1)正常人骨髓单个核细胞50 μmol/LHQ处理10 h后,TOPOⅡ的活力下降,TOPOⅡα含量以及TOPOⅡαmRNA水平分别为0.017±0.029、0.610±0.128,较对照组明显下降,差异有统计学意义(P<0.01);(2)TOPOⅡα含量降低伴随着TOPOⅡα启动子组蛋白H4乙酰化水平的明显降低(分别为1.198±0.056、0.324±0.229),差异有统计学意义(P<0.01),不伴有组蛋白H3乙酰化水平的改变,分别为1.253±0.045、1.177±0.025;(3)HQ接触不同时间TOPOⅡαmRNA水平呈动态变化,且TOPOⅡα启动子水平的变化早于mRNA水平的变化.结论 HQ可抑制造血细胞TOPOⅡα的表达.组蛋白化学修饰水平的改变在苯代谢物所致的造血毒性中发挥一定的作用.     

CLU、PKCα基因过度表达与卵巢癌化疗耐药相关的研究

目的:对比CLU、PKCα基因在化疗前及化疗后卵巢癌组织表达的差异。方法:卵巢癌患者60例,包括紫杉醇化疗组(Ⅰ组)和未化疗组(Ⅱ组)各30例,提取卵巢癌组织总RNA,反转录为cDNA。用荧光实时定量PCR方法检测60份标本中CLU、PKCα,MDR基因的表达。结果:CLU、PKCα基因在Ⅰ组、Ⅱ组均有较高的表达阳性率,分别为96.67%与100%、100%与100%,两组间无显著差异(P0.05)。PKCα基因在化疗组表达Ct值3.530±0.99584,显著高于未化疗组3.003±0.65074(P0.05)。但术前化疗组及化疗复发组之间无显著差异(P0.05)。MDR表达阳性组织中,CLU基因的表达Ct值4.3487±1.41353,显著高于MDR表达阴性组织的3.2955±1.52114(P0.05)。结论:PKCα在化疗后卵巢癌组织中高表达,可能在卵巢癌紫杉醇化疗耐药中起重要作用。CLU可能与MDR介导的卵巢癌多药耐药有关。CLU、PKCα表达显著相关,提示两个基因共同参与了卵巢癌耐药机制。