2型糖尿病降糖治疗对癌症风险的影响

2型糖尿病患者实性肿瘤的发生风险可能受降糖治疗的影响。为了了解肿瘤的发生风险与口服降糖药物、人胰岛素、胰岛素类似物治疗的关系,研究者对62809例患者进行了一项回顾性队列研究。所有患者年龄〉40岁,并且在2000年后开始应用胰岛素或口服药物治疗。患者被分成4个治疗组：单独应用二甲双胍、单独应用磺脲类、上述两种药物联用、应用胰岛素。应用胰岛素治疗的患者又被分为4个亚组：甘精胰岛素、长效人胰岛素、双相胰岛素类似物、双相人胰岛素。     

Kinetics and 28-day test–retest repeatability and reproducibility of [11C]UCB-J PET brain imaging

[¹¹C]UCB-J is a novel radioligand that binds to synaptic vesicle glycoprotein 2A (SV2A). The main objective of this study was to determine the 28-day test–retest repeatability (TRT) of quantitative [¹¹C]UCB-J brain positron emission tomography (PET) imaging in Alzheimer’s disease (AD) patients and healthy controls (HCs). Nine HCs and eight AD patients underwent two 60 min dynamic [¹¹C]UCB-J PET scans with arterial sampling with an interval of 28 days. The optimal tracer kinetic model was assessed using the Akaike criteria (AIC). Micro-/macro-parameters such as tracer delivery (K₁) and volume of distribution (V_T) were estimated using the optimal model. Data were also analysed for simplified reference tissue model (SRTM) with centrum semi-ovale (white matter) as reference region. Based on AIC, both 1T2k_V_B and 2T4k_V_B described the [¹¹C]UCB-J kinetics equally well. Analysis showed that whole-brain grey matter TRT for V_T, DVR and SRTM BP_ND were –2.2% ± 8.5, 0.4% ± 12.0 and –8.0% ± 10.2, averaged over all subjects. [¹¹C]UCB-J kinetics can be well described by a 1T2k_V_B model, and a 60 min scan duration was sufficient to obtain reliable estimates for both plasma input and reference tissue models. TRT for V_T, DVR and BP_ND was <15% (1SD) averaged over all subjects and indicates adequate quantitative repeatability of [¹¹C]UCB-J PET.     

B细胞能够部分自主控制命运

最近,澳大利亚和爱尔兰科学家在B细胞研究中证实B细胞可在某种程度上控制自己的命运.这一发现在很大程度上会改变科学家们对于细胞命运决定因素的理解.在淋巴结中增殖的B细胞面临着多种命运的抉择：常见的包括细胞死亡、细胞分裂、成为能够分泌抗体的细胞或是改变它们产生的抗体.过去科学界普遍认可的观点是B细胞的命运取决于例如特定激素或细胞信号分子等外部信号.而新研究发现B细胞的命运在很大程度上是由内部的程序所决定.他们开发了新型技术与图像分析方法,通过重建B细胞分化形成不同细胞类型所需的条件,对B细胞进行了追踪成像观测.结果 表明不同的细胞命运是细胞内竞争的结果.即使这些细胞获得相同的外部信号,细胞群体中发生的事件仍会出现相当大的差异.这表明激素或细胞信号分子等外部因素并非是B细胞命运的主宰因子,它们只不过能改变细胞命运选择的概率.     

安颤灵对泛素-蛋白酶体通路损伤细胞模型的保护作用

目的 利用中药血清药理学方法探讨安颤灵含药血清对lactacystin诱导PC12细胞损伤的保护作用及其可能机制. 方法 按照血清药理学实验方法制备安颤灵含药血清,将含药血清分为大、中、小剂量组(分别按7.3 g/kg、3.65 g/kg、1.83 g/kg添加药物),用lactacystin建立PC12细胞泛素-蛋白酶体系统(UPS)损伤模型.MTT方法检测各组的细胞活力.将对数生长期的PC12细胞分为正常组(DMEM+10%空白鼠血清)、损伤组(DMEM+10%空白鼠血清+10 μmol/Llactacystin)、安颤灵中剂量组(含DMEM+10%中剂量安颤灵含药血清+10 μmol/L lactacystin),通过免疫组化方法,观察各组细胞α-突触核蛋白、酪氨酸羟化酶(TH)表达的情况. 结果 与大、小剂量组相比,中剂量组细胞的存活率明显升高,差异有统计学意义(P＜0.05);与正常组相比,损伤组细胞α-突触核蛋白阳性细胞数增多,而TH阳性细胞明显减少,差异有统计学意义(P＜0.05);与损伤组相比,安颤灵中剂量组细胞α-突触核蛋白阳性细胞数减少,TH阳性细胞明显增加,差异有统计学意义(P＜0.05). 结论 安颤灵含药血清能改善细胞UPS的功能,降低细胞内α-突触核蛋白的聚集并上调TH表达,从而起到提高细胞存活率,保护神经元的作用.     

New Insights on Adenovirus as Vaccine Vectors

Adenovirus (Ad) vectors were initially developed for treatment of genetic diseases. Their usefulness for permanent gene replacement was limited by their high immunogenicity, which resulted in rapid elimination of transduced cells through induction of T and B cells to antigens of Ad and the transgene product. The very trait that excluded their use for sustained treatment of genetic diseases made them highly attractive as vaccine carriers. Recently though results showed that Ad vectors based on common human serotypes, such as serotype 5, may not be ideal as vaccine carriers. A recently conducted phase 2b trial, termed STEP trial, with an AdHu5-based vaccine expressing antigens of human immunodeficiency virus 1 (HIV-1) not only showed lack of efficacy in spite of the vaccine''s immunogenicity, but also suggested an increased trend for HIV acquisition in individuals that had circulating AdHu5 neutralizing antibodies prior to vaccination. Alternative serotypes from humans or nonhuman primates (NHPs), to which most humans lack pre-existing immunity, have been vectored and may circumvent the problems encountered with the use of AdHu5 vectors in humans. In summary, although Ad vectors have seen their share of setbacks in recent years, they remain viable tools for prevention or treatment of a multitude of diseases.