Optimal treatment allocation for placebo‐treatment comparisons in trials with discrete‐time survival endpoints

In many randomized controlled trials, treatment groups are of equal size, but this is not necessarily the best choice. This paper provides a methodology to calculate optimal treatment allocations for longitudinal trials when we wish to compare multiple treatment groups with a placebo group, and the comparisons may have unequal importance. The focus is on trials with a survival endpoint measured in discrete time. We assume the underlying survival process is Weibull and show that values for the parameters in the Weibull distribution have an impact on the optimal treatment allocation scheme in an interesting way. Additionally, we incorporate different cost considerations at the subject and measurement levels and determine the optimal number of time periods. We also show that when many events occur at the beginning of the trial, fewer time periods are more efficient. As an application, we revisit a risperidone maintenance treatment trial in schizophrenia and use our proposed methodology to redesign it and compare merits of our optimal design. Copyright © 2015 John Wiley & Sons, Ltd.     

两种不同有创动脉血压监测护理方法应用于儿童的效果比较

[目的]比较两种不同有创动脉血压监测的护理方法应用于儿童的临床效果。[方法]对使用有创动脉血压监测的58例患儿采用随机方法分为生理盐水组(30例)和肝素盐水组(28例),予以持续冲洗管路,比较两种不同冲洗方法在48h内的临床效果。[结果]生理盐水组和肝素盐水组在24h内均未发生管路堵塞,在36h内分别堵塞2例(6.6%)和1例(3.6%),在48h内分别累计堵塞3例(9.9%)和2例(7.1%)。两种护理方法在血栓形成和患儿使用前后凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)变化方面差异无统计学意义(P0.05)。[结论]使用生理盐水和肝素盐水冲洗管路对有创动脉血压监测管路在血栓形成和患儿凝血功能方面差异不明显,对于儿童特别是低体重患儿建议使用生理盐水1mL/h冲洗。     

JAK2/STAT3信号通路介导灯盏花乙素抗人心脏微血管内皮细胞缺氧-复氧损伤

Objective: To investigate the antagonistic cell injury effect and molecular mechanism of scutellarin(SCU)in hypoxia reoxygenation(HR) treated human cardiac microvascular endothelial cells(HCMECs).Methods: The method of 12 h hypoxia following by 12 h reoxygenation was used to culture HCMECs in vitro to built cell injury model. The groups were divided into control group, model(HR) group, and HR + SCU(0.1 μmol/L, 1 μmol/L, and 10 μmol/L) group. The cell viability was determined by MTT, and oxidative stress was detected by malondialdehyde(MDA) levels by biochemical assay kit. Protein expression of JAK2/p-JAK2 and STAT3/p-STAT3 were evaluated by Western blot.Results: The results of MTT and MDA showed that HR decreased the cell viability(P 0.05) and increased MDA level significantly(P 0.05), SCU played a contrary role in these processes. Western blot analysis indicates that, the expression of JAK2 and p-JAK2, STAT3, and p-STAT3 were increased in model group when compared with control group(P 0.05); Compared with model group, their expression were reduced by SCU(P 0.05).Conclusion: SCU took a protective effect on HR-treated HCMECs, and the molecular mechanism may be associated with the inhibition of JAK2/STAT3 signal transduction pathway.     

谷氨酸受体在左旋多巴诱导的异动症中的相关研究进展

在帕金森病(PD)患者中,长期使用左旋多巴而诱导的异动症(LID)显著影响着左旋多巴的疗效及患者的生活质量,现有的应对方案效果也均不甚理想,其原因与LID的机制目前尚未完全阐明密切相关。近年来越来越多的研究证实,谷氨酸能系统与多巴胺能系统紧密关联,谷氨酸受体在LID中的作用也日益凸显,特别是代谢型谷氨酸受体(mGluR)4、mGluR5以及部分离子型谷氨酸受体(iGluRs)在LID的机制研究和临床药物研究中更是关注热点。笔者现对各类谷氨酸受体在LID中的变化、作用以及相关的临床研究进展进行综述,以期为PD患者中LID的诊治和机制阐明提供新思路。     

Feasibility and efficacy evaluation of metallic biliary stents eluting gemcitabine and cisplatin for extrahepatic cholangiocarcinoma

BACKGROUND Effective endoscopic management is fundamental for the treatment of extrahepatic cholangiocarcinoma(ECC). However, current biliary stents that are widely used in clinical practice showed no antitumor effect. Drug-eluting stents(DESs) may achieve a combination of local chemotherapy and biliary drainage to prolong stent patency and improve prognosis.AIM To develop novel DESs coated with gemcitabine(GEM) and cisplatin(CIS)-coloaded nanofilms that can maintain the continuous and long-term release of antitumor agents in the bile duct to inhibit tumor growth and reduce systemic toxicity.METHODS Stents coated with different drug-eluting components were prepared by the mixed electrospinning method, with poly-L-lactide-caprolactone(PLCL) as the drug-loaded nanofiber membrane and GEM and/or CIS as the antitumor agents. Four different DESs were manufactured with four drug-loading ratios(5%, 10%, 15%, and 20%), including bare-loaded(PLCL-0), single-drug-loaded(PLCL-GEM and PLCL-CIS), and dual-drug-loaded(PLCL-GC) stents. The drug release property, antitumor activity, and biocompatibility were evaluated in vitro and in vivo to confirm the feasibility and efficacy of this novel DES for ECC.RESULTS The in vitro drug release study showed the stable, continuous release of both GEM and CIS, which was sustained for over 30 d without an obvious initial burst, and a higher drug-loaded content induced a lower release rate. The drug-loading ratio of 10% was used for further experiments due to its ideal inhibitory efficiency and relatively low toxicity. All drug-loaded nanofilms effectively inhibited the growth of EGI-1 cells in vitro and the tumor xenografts of nude mice in vivo; in addition, the dual-loaded nanofilm(PLCL-GC) had a significantly better effect than the single-drug-loaded nanofilms(P 0.05). No significant differences in the serological analysis(P 0.05) or histopathological changes were observed between the single-loaded and drug-loaded nanofilms after stent placement in the normal porcine biliary tract.CONCLUSION This novel PLCL-GEM and CIS-eluting stent maintains continuous, stable drug release locally and inhibits tumor growth effectively in vitro and in vivo. It can also be used safely in normal porcine bile ducts. We anticipate that it might be considered an alternative strategy for the palliative therapy of ECC patients.     

Fe-Ga合金磁特性测试装置的设计与实验

设计了一种新型Fe-Ga合金磁特性测试装置。建立了该测试装置磁路部分三维有限元磁场分析模型，在该模型基础上通过调整结构和元件尺寸优化了磁路结构，并制作了样机。搭建了磁特性测试装置的实验平台，进行了Fe-Ga合金磁特性测试。实验结果表明，该装置可对Fe-Ga合金磁致伸缩棒材磁致伸缩效应和逆磁致伸缩效应进行静态、准静态和动态测量，测量结果与国外报道的结果一致。设计的磁特性测试装置具有稳定可靠、精度高、操作简单、自动记录等优点。该装置还适用于Fe-Ni、Fe-Co等饱和磁场低的磁致伸缩材料的磁特性测量。