A dried blood spot assay with HPLC–MS/MS for the determination of larotrectinib in mouse blood and its application to a pharmacokinetic study

Larotrectinib is a first-generation tropomyosin kinase inhibitor, approved for the treatment of solid tumors. In this paper, we present a validated dried blood spot (DBS) method for the quantitation of larotrectinib from mouse blood using HPLC–MS/MS, which was operated under multiple reaction monitoring mode. To the DBS disc cards, acidified methanol enriched with internal standard (IS; enasidenib) was added and extracted using tert-butyl methyl ether as an extraction solvent with sonication. Chromatographic separation of larotrectinib and the IS was achieved on an Atlantis dC₁₈ column using 10 mm ammonium formate–acetonitrile (30:70, v/v) delivered at a flow-rate of 0.80 ml/min. Under these optimized conditions, the retention times of larotrectinib and the IS were ~0.93 and 1.37 min, respectively. The total run time was 2.50 min. Larotrectinib and the IS were analyzed using positive ion scan mode and parent–daughter mass to charge ion (m/z) transitions of 429.1 → 342.1 and 474.1 → 267.1, respectively, were used for the quantitation. The calibration range was 1.06–5,080 ng/ml. No matrix effect or carryover was observed. Hematocrit did not influence DBS larotrectinib concentrations. All of the validation parameters met the acceptance criteria. The applicability of the validated method was shown in a mouse pharmacokinetic study.     

T1Effects in Sequential Dynamic Susceptibility Contrast Experiments

Residual effects of an initial bolus of gadolinium contrast agent have been previously demonstrated in sequential dynamic susceptibility contrast MR experiments. While these residual effects quickly reach a saturation steady state, their etiology is uncertain, and they can lead to spurious estimates of hemodynamic parameters in activation experiments. The possible influence ofT₁effects is now investigated with experiments in whichT₁weighting is varied as well as with serial regionalT₁measurements. Little evidence for significant residualT₁effects is found, suggesting instead that susceptibility effects underlie these observations. An initial saturation dose of contrast agent minimizes this effect.     

世界文化史上的五种科学思维模式

思想方法的更新是人类进步的重要标志之一。对这种标志的认识,在哲学史和文化史研究中通常不被人们所重视。人类思想史上最鲜明、最有意义的科学思维模式,主要表现为本文论及的五种类型,这些思维模式的互补与进步,是东西方文明相互推进的内在标志;对它们的研究和探讨,是把握先进文化前进方向的重要前提。     

Molecular dynamics simulations on the structures and properties of ε-CL-20-based PBXs ——Primary theoretical studies on HEDM formulation design

Five polymer bonded explosives (PBXs) with the base explosive ε-CL-20 (hexanitrohexaazaisowurtzi- tane), the most important high energy density compound (HEDC), and five polymer binders (Estane 5703, GAP, HTPB, PEG, and F2314) were constructed. Molecular dynamics (MD) method was employed to investigate their binding energies (Ebind), compatibility, safety, mechanical properties, and energetic properties. The information and rules were reported for choosing better binders and guiding formula- tion design of high energy density material (HEDM). According to the calculated binding energies, the ordering of compatibility and stability of the five PBXs was predicted as ε-CL-20/PEG > ε-CL-20/ Estane5703 ≈ε-CL-20/GAP > ε-CL-20/HTPB > ε-CL-20/F2314. By pair correlation function g(r) analyses, hydrogen bonds and vdw are found to be the main interactions between the two components. The elasticity and isotropy of PBXs based ε-CL-20 can be obviously improved more than pure ε-CL-20 crystal. It is not by changing the molecular structures of ε-CL-20 for each binder to affect the sensitivity. The safety and energetic properties of these PBXs are mainly influenced by the thermal capability (C°p) and density (ρ) of binders, respectively.     

血压指标的聚类分析

利用353人的血压数据,运用2种不同的聚类分析方法对15个血压指标分类并挑选典型指标:一是利用SAS软件包中提供的变量聚类过程(VARCLUS过程)对指标进行裂类聚类分析;一是利用SAS中提供的样品聚类过程(CLUSTER过程)对指标进行系统聚类分析.2种方法得到了相同的结果:15个指标分成了4类,得到4个典型指标:BPR(收缩压与舒张压比值),BPP(收缩压与舒张压乘积),MAPPr(平均动脉压与脉率乘积),BPRPr(BPR与脉率乘积).     

微控制器系统PCB的EMC问题和抗干扰设计

本文介绍了微控制器系统PCB的EMC问题、抗干扰设计的具体方法和经验。     

Endoscopic Observation of Tissue by Narrowband Illumination

We propose a new illumination method for a medical endoscope: narrow band imaging (NBI), in which the spectral bandwidth of the filtered light is narrowed. To confirm how the spectral specifications of the filtered light influence a reproduced image, an experiment was conducted observing the endoscopic images of the back mucosa of a human tongue. In addition, the effect of NBI on endoscopic images was investigated through preliminary clinical tests in colonoscopy and upper gastrointestinal endoscopy. It has been shown that NBI can enhance the capillary pattern and the crypt pattern on the mucosa. These patterns are useful features for diagnosing an early cancer.     

分层有限元及其数学特性研究

提出了三维问题的分层有限元迭代算法，对算法的数学特性进行了初步探讨。理论分析表明，该算法适应于一些椭圆型问题，且其工作量小，方便可靠。最后，给出具体的算例。     

家兔膀胱动脉的解剖学研究

用血管铸型和透明方法观察了家兔膀胱的血供情况。膀胱动脉主要起自脐动脉，沿膀胱侧缘行向膀胱顶，沿途发出１～４支基本对称的分支分布于膀胱前面，两侧膀胱动脉的分支在其表面有吻合现象。膀胱动脉及其分支均呈不同程度的弯曲或弹簧状，可能是适应膀胱生理性增大的结构基础。