Selective antiaggressive effect of an alpha-2 adrenoceptor agonist naphthylmedetomidine in mice

Alpha-2 adrenoceptors (alpha(2)-ARs) are critically involved in regulating neurotransmitter release from sympathetic nerves and neurons and play an important role in the regulation of awareness, arousal and vigilance. In our recent study, dexmedetomidine, a full alpha(2)-AR agonist, produced antiaggressive effects in the social conflict test in mice at doses that were twice smaller than those producing sedation. The aim of this study was to ascertain antiaggressive effect of a novel drug naphthylmedetomidine, with a more selective alpha(2)-AR activity. Behavioral effects of naphthylmedetomidine (150-1200 microg/kg i.p.) were studied in the activity cage and in the social conflict tests in mice. Naphthylmedetomidine dose dependently decreased aggressive behavior during social conflict in aggressive mice with significant reduction already at the lowest doses tested (150 microg/kg), whereas locomotion and social investigation were significantly decreased only after four times bigger dose of naphthylmedetomidine (600 microg/kg) in aggressive mice. Naphthylmedetomidine had no effect on aggression in nonaggressive mice. Naphthylmedetomidine reduced locomotion in the activity cage significantly only at the highest doses tested (600 and 1200 microg/kg), and this effect was only partially reversed by administration of high doses of an alpha-2 antagonist atipamezole (3 and 10 mg/kg). In nonaggressive mice, the difference between the dose reducing dominant social behavior (social investigation) and locomotion (150 and 300 microg/kg, respectively) was smaller than in aggressive mice. In conclusion, naphthylmedetomidine showed a very strong and selective antiaggressive effect in aggressive mice, which was devoid of locomotion-inhibiting/sedative effect. This study suggests that naphthylmedetomidine may have clinical potential as antiaggressive drug.     

糖尿病高血压和糖尿病肾病患者血清MMP-2及TIMP-1的表达及意义

为了探讨MMP-2、TIMP-1在DMEH和DN发病中的意义,随机收集T2DM患者146例,其中SDM 57例,DMEH 38例,DN 51例,健康对照38例。用ELISA法测定MMP-2、TIMP-1的含量。结果显示,DM患者尤其是DMEH和DN患者血清MMP-2明显低于健康对照组,P均〈0.01,且随病情发展呈逐渐降低趋势。而血清TIMP-1随病情的发展则呈现明显的上升趋势,SDM、DMEH组和DN组与健康对照组比较,分别为P〈0.05,P〈0.01和P〈0.01。因此,MMP-2和TIMP-1可能参与了DMEH和DN的发生发展过程,定期检测DM患者血清MMP-2和TIMP-1的含量变化有助于DM并发症的早期诊断和疗效观察。     

不同条件下拟合指数的表现及临界值的选择

在本模拟研究中设计了6种样本容量,6种因子载荷,和4种评分等级,并考察了正态和非正态分布两种情况。采用的错误模型为参数误置（真模型中每个因子各由5个题目来测量,错误模型中则是第一个因子由6个题测量,另两个因子各由4个和5个题来测量,即有一个因子载荷被误置）模型。结果发现（1）样本量、载荷量、评分等级数和分布形态都对GOF的取值确有影响。其中分布形态的影响最大。NNFI、IFI在不同条件下的平均值是最稳定的,其次是CFI、RMSEA和SRMR。它们都算是值得推荐的GOF,尤其是NNFI和IFI。（2）在正态分布中,当样本量≥1000时,根据NNFI、IFI、CFI、RMSEA、SRMR对模型是否拟合做出判断时有很低的两类错误率,在样本量<1000时则不理想。在偏态条件下无论选择哪个GOF两类错误率都很高。（3）采用2指数策略在很多情况下也不能显著降低两类错误率。（4）由于在数据分布非正态,或正态但样本量<1000时是难判断模型是否拟合的。因此我们提出了2界值策略。即为每个GOF确定上下两个界值。低于下界值时可判断模型是不正确的,而高于上界值时则可判断模型是正确的。GOF取值处于上下界值之间时难以判断模型是否拟合,只能说越高拟合的可能性越大。这时就要通过跨样本验证和增加样本量来确定模型是否正确     

论内隐学习在二语习得中的作用

简要地介绍了内隐学习的内涵、机制等内容,进而分析其在二语习得语音、词汇、语法、阅读和写作中的作用。     

Plasma BDNF is reduced among middle-aged and elderly women with impaired insulin function: Evidence of a compensatory mechanism

Brain-derived neurotrophic factor (BDNF) plays a regulatory role in neuronal differentiation and synaptic plasticity and has been linked to glucose regulation and cognition. Associations among plasma BDNF, cognition, and insulin function were explored. Forty-one participants with impaired insulin function (IIF), ranging from insulin resistance to type 2 diabetes mellitus (T2DM), were matched with 41 healthy controls on gender, age, education, and IQ. Participants received complete medical, neurological, psychiatric, and neuropsychological evaluations. IIF individuals had significantly lower plasma BDNF levels than controls, particularly females, and higher BDNF levels were associated with poorer explicit memory in IIF females, suggesting that higher levels within this group may reflect the body’s efforts to respond to damage. After accounting for age, education, and HbA1c, BDNF significantly predicted 13.1–23.5% of the variance in explicit memory in IIF women. These findings suggest that BDNF elevations within diseased groups may not always be a marker of health.     

The influence of perceptual and semantic categorization on inhibitory processing as measured by the N2–P3 response

In daily activities, humans must attend and respond to a range of important items and inhibit and not respond to unimportant distractions. Our current understanding of these processes is largely based on perceptually simple stimuli. This study investigates the interaction of conceptual-semantic categorization and inhibitory processing using Event Related Potentials (ERPs). Participants completed three Go–NoGo tasks that increased systematically in the degree of conceptual-semantic information necessary to respond correctly (from single items to categories of objects and animals). Findings indicate that the N2 response reflects inhibitory processing but does not change significantly with task difficulty. The P3 NoGo amplitude, on the other hand, is attenuated by task difficulty. Further, the latency of the peak of the P3 NoGo response elicited by the most difficult task is significantly later than are the peaks detected during performance of the other two tasks. Thus, the level of complexity of conceptual-semantic representations influences inhibitory processing in a systematic way. This inhibition paradigm may be a key for investigating inhibitory dysfunction in patient populations.     

情绪干扰听觉反应冲突的ERP研究

采用ERP技术研究13例正常青年人在声音诱发的不同情绪条件下,对反应抑制加工过程的影响,并试图阐明其潜在脑机制。实验中选择正、中、负三种声音各50种,作为诱发情绪的刺激材料。结果发现Go条件下的反应时在负性、中性、正性条件下依次减短;Go与Nogo刺激均诱发出显著的N1成分,中性条件下波幅显著大于正负性情绪条件。此外,三种情绪背景下, Nogo刺激诱发出显著的N2与P3成分。Nogo-N2主要分布在头皮前中部,在Fz点波幅最大。Nogo-P3主要分布在头皮中部,Pz点波幅最大。中性条件下Nogo-N2波幅显著大于负性与正性条件,而正性和负性之间差异不显著。行为结果表明,听觉负性情绪诱发对反应执行有干扰作用;ERP结果表明声音诱发的情绪对早期听觉选择性注意具有调节作用。听觉情绪诱发对反应抑制加工过程有显著影响,且该影响在早期反应冲突监控阶段最为明显。     

治疗糖尿病创新药物研究

本论文从治疗2型糖尿病药物应用现状出发,通过对2型糖尿病病理的认识,新发现的主要受体和相关药靶等方面进行分析。指出随着对糖尿病认识的深入发展,治疗糖尿病创新药物研究的发展趋势也发生了相应的变化,就是从局部治疗到全身综合考虑,从药物外部直接地干预到增强自身调节功能。为治疗2-型糖尿病药物发展指明了方向。     

2型糖尿病患者抑郁患病率调查与分析

调查2型糖尿病（T2DM）患者抑郁患病率,探讨影响抑郁发生的因素。从青岛市城区常住居民中随机抽取40岁以上者5000人,选取其中已诊T2DM患者440例,运用Zung抑郁自评量表等进行调查、测定临床生化指标,进行分析。T2DM患者抑郁患病率为21．82％,抑郁对血糖控制不利,病程长、收入低、应用胰岛素、有并发症、不运动、血糖控制差为T2DM患者抑郁患病的危险因素。     

原发性骨肉瘤中EGFR和C—erbB-2的表达及其意义

检测20例原发性骨肉瘤和10例骨纤维结构不良中EGFR和C-erbB-2的表达;两者在骨肉瘤中表达的阳性率分别为50%和40%（P＜0.05）,而在骨纤维结构不良中分别为10%和0%（P＜0.05）;骨肉瘤中EGFR和C-erbB-2表达均高于骨纤维结构不良,且呈正相关,这为骨肉瘤的诊疗提供了理论依据。