骨碎补化学成分和生物活性研究进展＊

骨碎补是历代临床常用中药，具有疗伤止痛、补肾强骨、消风祛斑等功效。其主要含黄酮、苯丙素、三萜、酚酸及其苷等类化学成分，现代研究表明骨碎补具有抗骨质疏松、促进骨折愈合、促软骨再生、护牙健齿、保护肾功能、抗炎、防治中毒性耳聋、降血脂等多种生物活性，开发前景广阔。本文对近年来骨碎补的化学成分、药理作用及临床应用研究进行综述，以期为骨碎补的进一步深入系统的研究和开发利用提供依据。     

Relation between active mediation,exposure to Daniel Tiger’s Neighborhood,and US preschoolers’ social and emotional development

This study explored the relationship between active mediation, exposure to Daniel Tiger’s Neighborhood, and key indicators of preschoolers’ social and emotional development. One hundred and twenty-seven children aged 2–6 either watched or did not watch 10 episodes of Daniel Tiger’s Neighborhood over a two-week period. Results revealed that preschoolers who watched the program exhibited higher levels of empathy, self-efficacy, and emotion recognition when their regular TV-watching experiences are frequently accompanied by active mediation. This was especially true for younger preschoolers and preschoolers from low-income families. Implications for policy-makers, parents, producers of prosocial programming, and educators are discussed.     

依维莫司联合全反式维甲酸逆转急性早幼粒细胞白血病细胞耐药的研究

目的探讨依维莫司联合全反式维甲酸(简称维甲酸)逆转急性早幼粒细胞白血病(APL)细胞株NB4-R1耐药的作用。方法应用CD11b染色流式细胞术及硝基四唑氮蓝(NBT)还原实验检测两药联合应用对细胞分化的影响, 流式细胞术检测细胞周期情况, Annexin V/PI双染色检测细胞凋亡情况, 蛋白质印迹法检测自噬相关蛋白微管结合蛋白轻链3(LC3)、Beclin 1及早幼粒白血病-维甲酸受体融合蛋白(PML-RARα)、磷酸化核糖体S6激酶(P-P70S6K)、磷酸化4E结合蛋白1(P-4E-BP1) 等表达水平。结果与维甲酸组比较, 联用组能诱导耐药细胞株NB4-R1细胞的分化, 并将细胞增殖阻止在G ₁期而对细胞凋亡无明显影响。100 nmol/L依维莫司组、1μmol/L维甲酸组、联用组、对照组NB4-R1细胞培养48 h后分化百分率分别为(2.29±0.57)%、(17.06±2.65)%、(54.47±4.91)%、(2.54±0.53)%; 处于G ₁期的细胞百分率分别为(35.20±11.97)%、(33.54±6.25)%、(53.70±8.73)%、(27.40±6.01)%; 四组细胞凋亡细胞百分率分别为(2.30±0.14)%、(2.25±0.21)%、(2.40±0.28)%、(1.95±0.07)%。与维甲酸组比较, 联用组mTOR信号通路下游的P70S6K、4E-BP1分子磷酸化水平下降, LC3-II和Beclin 1的表达上调, 且能部分降解融合蛋白PML-RARα。 结论依维莫司联合维甲酸能诱导NB4-R1细胞分化, 且能阻滞细胞周期而不致细胞凋亡, 其机制可能与依维莫司联合维甲酸抑制mTOR信号通路激活自噬作用从而降解PML-RARα蛋白有关。     

A Reminder of Methylene Blue's Effectiveness in Treating Vasoplegic Syndrome after On-Pump Cardiac Surgery

The inflammatory response induced by cardiopulmonary bypass decreases vascular tone, which in turn can lead to vasoplegic syndrome. Indeed the hypotension consequent to on-pump cardiac surgery often necessitates vasopressor and intravenous fluid support. Methylene blue counteracts vasoplegic syndrome by inhibiting the formation of nitric oxide.We report the use of methylene blue in a 75-year-old man who developed vasoplegic syndrome after cardiac surgery. After the administration of methylene blue, his hypotension improved to the extent that he could be weaned from vasopressors. The use of methylene blue should be considered in patients who develop hypotension refractory to standard treatment after cardiac surgery.     

溴氰菊酯对白纹伊蚊（Aedesalbopictus）C6／36细胞株的细胞遗传学效应

本研究选择１０μｇ／ｍｌ、２０μｇ／ｍｌ、４０μｇ／ｍｌ浓度的溴氰菊酯处理白纹伊蚊Ｃ６／３６细胞，以ＭＭＣ作为阳性对照物，观察溴氰菊酯处理２４ｈ后对Ｃ６／３６细胞染色体畸变率和姐妹染色单体互换（ＳＣＥ）频率的影响。结果显示，三个浓度的溴氰菊酯对Ｃ６／３６细胞染色体畸变率均没有显著影响（Ｐ＜０．０５）；溴氰菊酯浓度在４０μｇ／ｍｌ时可诱导Ｃ６／３６细胞ＳＣＥ频率轻度增高（Ｐ＞０．０５），而溴氰菊酯浓度在１０μｇ／ｍｌ、２０μｇ／ｍｌ时，对Ｃ６／３６细胞ＳＣＥ频率没有诱导作用。表明溴氰菊酯对Ｃ６／３６细胞的遗传学效应较弱     

Bayesian estimation of a random effects heteroscedastic probit model

Summary Bayesian analysis is given of a random effects binary probit model that allows for heteroscedasticity. Real and simulated examples illustrate the approach and show that ignoring heteroscedasticity when it exists may lead to biased estimates and poor prediction. The computation is carried out by an efficient Markov chain Monte Carlo sampling scheme that generates the parameters in blocks. We use the Bayes factor, cross‐validation of the predictive density, the deviance information criterion and Receiver Operating Characteristic (ROC) curves for model comparison.     

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.     

纸本与数字的交互：手机阅读的最佳效果

随着全球3G商用的推进和拥有大容量存储能力的智能终端的日益普及,手机正逐步演变成为一个新型的数字阅读终端。利用手机进行电子阅读的全新模式,正以前所未有的普及速度冲击着人们的阅读习惯。而这趋势也逐渐为"阅读"进行重新的定义。对于每一个读者而言,在这样一个信息化的时代里,手机阅读和纸本阅读的交互使用、取长补短,才是获得最佳阅读效果的最有效方式。     

Fisher information matrix for nonlinear mixed effects multiple response models: Evaluation of the appropriateness of the first order linearization using a pharmacokinetic/pharmacodynamic model

We focus on the Fisher information matrix used for design evaluation and optimization in nonlinear mixed effects multiple response models. We evaluate the appropriateness of its expression computed by linearization as proposed for a single response model. Using a pharmacokinetic–pharmacodynamic (PKPD) example, we first compare the computation of the Fisher information matrix with approximation to one derived from the observed matrix on a large simulation using the stochastic approximation expectation–maximization algorithm (SAEM). The expression of the Fisher information matrix for multiple responses is also evaluated by comparison with the empirical information obtained through a replicated simulation study using the first‐order linearization estimation methods implemented in the NONMEM software (first‐order (FO), first‐order conditional estimate (FOCE)) and the SAEM algorithm in the MONOLIX software. The predicted errors given by the approximated information matrix are close to those given by the information matrix obtained without linearization using SAEM and to the empirical ones obtained with FOCE and SAEM. The simulation study also illustrates the accuracy of both FOCE and SAEM estimation algorithms when jointly modelling multiple responses and the major limitations of the FO method. This study highlights the appropriateness of the approximated Fisher information matrix for multiple responses, which is implemented in PFIM 3.0, an extension of the R function PFIM dedicated to design evaluation and optimization. It also emphasizes the use of this computing tool for designing population multiple response studies, as for instance in PKPD studies or in PK studies including the modelling of the PK of a drug and its active metabolite. Copyright © 2009 John Wiley & Sons, Ltd.     

Long-term effectiveness and quality of life improvement in entacapone-treated Parkinson's disease patients: the effects of an early therapeutic intervention

To evaluate the long-term effects of entacapone on both mean daily 'on' time and health-related quality of life (QoL) in patients with Parkinson's disease (PD) experiencing 'end-of-dose' motor fluctuations and the benefits of an early therapeutic intervention. A prospective, multicenter, observational, 12-month study was performed with an initial 3-month intervention phase, consisting of a phone call to half of the patients from randomly selected investigators to assess if dose adjustment was necessary. Effectiveness was determined by home diaries ('on' time), subscales II and III of the Unified Parkinson's Disease Rating Scale (UPDRS), and the Parkinson's Disease Questionnaire (PDQ-8). After 3 months of treatment, 4.0% of the intervention group patients discontinued the study, versus 18.4% in the control group ( P  < 0.01). The improvement in 'on' time was significantly increased since the 3-month visit (21%, P  < 0.0001) until the end of the study (23% at 12 months, P  < 0.0001). Entacapone also induced significant reductions in the UPDRS scores for subscales II and III and in the PDQ-8 score. 11.2% of patients experienced at least one adverse reaction. This study confirms the effectiveness of entacapone in reducing motor fluctuations by increasing 'on' time, and in improving QoL of PD patients. An early adjustment of entacapone and levodopa doses reduces the number of treatment discontinuations during the first months of treatment.