Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

Misdiagnosis of attention deficit hyperactivity disorder: ‘Normal behaviour’ and relative maturity

Attention deficit hyperactivity disorder (ADHD) is one of the most frequently diagnosed disorders in children, yet it remains poorly understood. Substantial controversy exists regarding correct diagnosis of ADHD, and areas of subjectivity in diagnosis have been identified. Concerns for appropriate diagnosis are critical in terms of children’s educational outcomes, as well as health concerns associated with the use and potential overuse of stimulant medications. There exists a relative-age effect in which children who are relatively younger than their peers and born closest to the school start age cut-off are more frequently diagnosed and treated for ADHD. Additionally, substantial variation exists in ADHD diagnosis between boys and girls, with boys often presenting with more stereotypical symptoms. Both the relative-age effect and variation in sex diagnosis, as well as the challenges of early preschool diagnosis, emphasize the importance of considering relative maturity in ADHD diagnosis of children. Implications and knowledge translation strategies for practitioners, parents and the education system are presented.     

椎弓根螺钉三椎体内固定对脊椎爆裂性骨折患者椎体与神经功能状态的影响观察

目的:探讨椎弓根螺钉三椎体内固定对脊椎爆裂性骨折患者椎体与神经功能状态的影响.方法:选取2013年7月至2015年1月于本院进行治疗的58例脊椎爆裂性骨折患者为研究对象,对其进行回顾性研究,将其根据手术方式不同分为对照组(短节段椎弓根内固定组)29例和观察组(椎弓根螺钉三椎体内固定组)29例,然后将两组患者手术前与手术后不同时间的伤椎恢复指标与血清神经功能相关指标进行比较.结果:观察组手术后不同时间的伤椎恢复指标中的后凸Cobb角、椎体平移率、椎体高度丢失率与血清神经功能相关指标中的BDNF、NSE、NGF及S100B均显著好于同期的对照组指标,并且明显好于其治疗前,均有显著性差异(P＜0.05).结论:椎弓根螺钉三椎体内固定可更为有效地恢复脊椎爆裂性骨折患者椎体参数,并且更有助于神经功能状态的恢复.     

烯烃的热力学性质的拓扑研究

目的：寻找一种性能优良的拓扑指数，方法：根据分子图的邻接矩阵和距离矩阵提出一种新的拓扑指数P1^*,P2^*,P3^*,p^4*。结果，拓扑指数P1^*,P2^*,P3^*,p^4*与烯烃的热力学函数－△Hf(g),S(g),△Gf(g)均有相关性，其复相关系数均在99．6％以上。结论：拓扑指数P1^*,P2^*,P3^*,p^4*与烯烃的热力学函的多种物理化学性质均有良好的相关性。     

Ill-health as a household norm: Evidence from other people's health problems

This paper proposes that an individual's self-assessed health (SAH) does not only suffer from systematic reporting bias and adaptation bias but is also biased owing to confounding health norm effects. Using 13 waves of the British Household Panel Survey covering the period 1991–2005, I show that, while there is a negative and statistically significant correlation between SAH and individuals' own health problem index, this negative effect reduces with the average number of health problems per (other) family member. The relative health bias is small, however, which implies that measures of SAH may not suffer seriously from systematic health norm bias. This is an important finding for researchers working with SAH data as it indicates that we do not have to worry too much about controlling for confounding influences from the health of other household members when estimating SAH regression equations.     

美国头颈癌患者生存资料分析

为使国内头颈癌生存分析的基本方法与国际一致，规范生存率分析的基本方法，以利于相互比较．本文以文字及表格方式，简述生存分析基本术语的概念、意义和应用，并介绍2002年第6版《美国头颈部肿瘤TNM分期》的1-5年观察生存率、相对生存率。     

重质石油中含氮化合物的形态及分布分析Ⅱ．含氦杂环化合物的定性方法

探索了色谱保留值与质谱信息相结合的定性分析方法。用ＳＥ－５４柱代替ＳＥ－５２柱，选用六个多环芳烃化合物作为标准计算保留指数，从而改善了Ｍ．Ｌ．Ｌｅｅ保留指数的应用条件和范围；用文献值转换扩充了Ｌｅｅ的含氮杂环化合物保留指数表，并利用保留时间与沸点的关系作定性佐证。应用该法鉴定了重质石油样品子组分及萘油中的４６个含氮杂环化合物及其异构体，为质谱在异构体鉴定以及缺乏标样所产生的困难提供了可信、简便的定性鉴定方法。     

乙型肝炎与肝癌关系的流行病学研究—广西HBsAg携带者及肝损害者的分布及发生肝癌的前瞻性研究

本文对20岁以上22830人按HBsAg状况和肝损害表现分队列进行随访,平均追踪6.8年,在肝癌高发区和低发区均以HBsAg携带者并有重度肝损害者(肝大+肝功能异常)的肝癌死亡率和相对危险性最高,相对危险性分别为37.3和22.5倍。以无肝大和肝功能异常的非携带者最低,肝癌的发生和肝损害的程度呈平行关系。HBsAg携带者发生肝癌死亡的相对危险性高于非携带者7倍,并发现HBsAg携带并有重度肝损害的肝癌死亡的平均年龄显著提前。认为肝癌高发区人群中HBV的持续感染和肝损害的广泛存在是导致肝癌高发和早发的重要因素。     

不同饮水类型的若干癌症发病率研究

应用回顾前瞻性方法，在海宁市随机选择了８个乡（镇）作为研究区。１９７７至１９８８年间，研究区共有癌症病例１９８８人。研究结果示，饮用池塘水的肝、肺、胃、食道及结直肠的癌症平均发病率男女均为最高；而饮用井水的上述５种癌症的平均发病率最低。在各饮水类型问对各种癌症的平均发病率作了Ｐｏｉｓｓｏｎ检验，结果差异有统计学意义。将饮用井水作为非暴露，作相对危险度分析。表明饮用河水的ＲＲ值高达７．７９～１４．２５；饮用池塘水的ＲＲ则更高（２．５５～３６．９９）。本文揭示了不同饮水类型癌症发病率的差异及其联系。     

相对湿度对空调环境至适温度影响的研究

本文研究空调室内相同温度（夏季：２４℃，２８℃：冬季：１９℃；２２℃）条件下相对湿度（分别为３０～７０％；８５～９５％）对至适温度的影响。以健康成年人为研究对象，以体温、皮温、皮温差、温热感和舒适感为观察指标。结果表明：空调室内气温相同时，皮温差、温热感、舒适感均随气湿不同而出现差异。夏季空调温度为２８℃、气湿为８５～９５％时，皮温差（２．１℃）已超出生理至适范围，温热感（１２．５％）和舒适感（０％）也随湿度增高而下降（Ｐ＜０．０１）。提出在制订空调至适温度卫生标准时，应考虑空气湿度对至适温度的影响。