药物相互作用研究在新药研发和审评决策中的应用

药物相互作用改变了剂量效应关系，可能会降低疗效或增加毒性，是临床应用中合并用药治疗时重要的考虑因素。预测具有临床意义的药物相互作用是药物研发过程中获益风险评估的重要环节。本文概述了药物研发过程中药物相互作用研究的目的和意义，体内和体外研究的主要内容；梳理分析了2020年国家药品监督管理局（National Medical Products Administration, NMPA）和美国食品药品监督管理局（Food and Drug Administration, FDA）批准上市的新药药物相互作用研究情况，旨在为我国药物研发过程中药物相互作用研究及其监管审评提供参考。     

Synthesis of nanopowders with low agglomeration by elaborating Φ values for producing Gd2O3-MgO nanocomposites with extremely fine grain sizes and high mid-infrared transparency

Refining ceramic microstructures to the nanometric range to minimize light scattering provides an interesting methodology for developing novel optical ceramic materials. In this work, we reported the fabrication and properties of a new nanocomposite optical ceramic of Gd₂O₃-MgO. The citric acid sol-gel combustion method was adopted to fabricate Gd₂O₃-MgO nanocomposites with fine-grain sizes, dense microstructures and homogeneous phase domains. Nanopowders with low agglomeration and improved sinterability can be obtained by elaborating Φ values. Further refining of the microstructure of the nanocomposites was achieved by elaborating the hot-pressing conditions. The sample sintered at 65 MPa and 1300 °C showed a quite high hardness value of 14.3 ± 0.2 GPa, a high transmittance of 80.3 %–84.7 % over the 3?6 μm wavelength range, due mainly to its extremely fine-grain size of Gd₂O₃ and MgO (93 and 78 nm, respectively) and high density.     

基于IEC 60870-5-104协议的调度命令发送方法研究

对IEC 60870-5-104协议的调度命令进行了研究，提出了一种基于现有IEC 60870-5-104协议的调度命令发送新方法。此技术充分利用了IEC 60870-5-104协议的文件发送功能，通过远程终端单元（RTU）向电厂发送包含调度命令的文本文件。考虑到调度命令在电力系统和电力市场结算系统安全方面的重要性，将该方法应用在电网调度自动化 SCADA 系统中，可以实现交换数据的更高可用性。     

煤矿罗茨鼓风机的安装使用与故障分析

对罗茨鼓风机的特点、结构和工作原理进行了论述,对其安装使用与故障维修进行了归纳总结.在新型罗茨鼓风机的设计中,提出了一种由偏心孤和圆线曲线组合的三叶转子齿剖面,其在对新齿轮廓进行几何模型的基础上,提出了螺旋齿轮廓,并对啮合螺旋三叶进行了比较研究.结果 表明,新的螺旋齿轮廓可以创造更大的气流,降低鼓风机压力的峰值.     

Colossal dielectric response and relaxation behavior in novel system of Zr4+ and Nb5+ co-substituted CaCu3Ti4O12 ceramics

In this work, we developed a novel system of isovalent Zr⁴⁺ and donor Nb⁵⁺ co-doped CaCu₃Ti₄O₁₂ (CCTO) ceramics to enhance dielectric response. The influences of Zr⁴⁺ and Nb⁵⁺ co-substituting on the colossal dielectric response and relaxation behavior of the CCTO ceramics fabricated by a conventional solid-phase synthesis method were investigated methodically. Co-doping of Zr⁴⁺ and Nb⁵⁺ ions leads to a significant reduction in grain size for the CCTO ceramics sintered at 1060 °C for 10 h. XRD and Raman results of the CaCu₃Ti_3.8-xZr_xNb_0.2O₁₂ (CCTZNO) ceramics show a cubic perovskite structure with space group Im-3. The first principle calculation result exhibits a better thermodynamic stability of the CCTO structure co-doped with Zr⁴⁺ and Nb⁵⁺ ions than that of single-doped with Zr⁴⁺ or Nb⁵⁺ ion. Interestingly, the CCTZNO ceramics exhibit greatly improved dielectric constant (~10⁵) at a frequency range of 10²–10⁵ Hz and at a temperature range of 20–210 °C, indicating a giant dielectric response within broader frequency and temperature ranges. The dielectric properties of CCTZNO ceramics were analyzed from the viewpoints of defect-dipole effect and internal barrier layer capacitance (IBLC) model. Accordingly, the immensely enhanced dielectric response is primarily ascribed to the complex defect dipoles associated with oxygen vacancies by co-doping Zr⁴⁺ and Nb⁵⁺ ions into CCTO structure. In addition, the obvious dielectric relaxation behavior has been found in CCTZNO ceramics, and the relaxation process in middle frequency regions is attributed to the grain boundary response confirmed by complex impedance spectroscopy and electric modulus.     

Microstructure and electric properties of Pr-doped Pb(Zr0.52Ti0.48)O3 ceramics

Improving the piezoelectric activity of lead zirconate titanate (PZT) ceramics is of great importance for practical applications. In this study, the influence of Pr³⁺ doping on the ferroelectric phase composition, microstructure, and electric properties on the A-site of (Pb_1-1.5xPr_x)(Zr_0.52Ti_0.48)O₃ is extensively investigated. A dense and fine microstructural sample is obtained with the introduction of Pr³⁺. The results show that the morphotropic phase boundary (MPB) moves to the rhombohedral phase region. The rhombohedral and tetragonal phases exhibit an ideal coexistence in the 4 mol.% Pr³⁺ doped (PPZT4) samples. Lead vacancy and the reduction of the potential energy barrier are considered to be the key mechanisms for donor doping, which is upheld by the Pr³⁺ doping. Combining the I-E hysteresis loops with the P-E hysteresis loops, it becomes apparent that both contribution maximums of the domain switching and residual polarisation are in PPZT4. Moreover, the thermal aging resistance of PZT is improved by doping, and the temperature stability is optimised from 83% in PZT to 96% in PPZT4. Hence, an appropriate amount of Pr³⁺ doping can effectively improve the piezoelectric activity of PZT ceramics in the MPB area and optimise the performance stability of the material under application temperatures.     

Toughness and R-curve behaviour of laminated Si3N4/SiCw ceramics

Laminated Si₃N₄/SiC_w ceramics were successfully prepared by tape casting and hot-pressing. Its mechanical properties were measured and the impact resistance was discussed. The toughness of the laminated Si₃N₄/SiC_w ceramics was 13.5 MPa m^1/2, which was almost 1.6 times that of Si₃N₄/SiC_w composite ceramics, namely 8.5 MPa m^1/2. Moreover, the indentation strength of laminated Si₃N₄/SiC_w ceramics was not sensitive to increasing indentation loads and exhibited a rising R-curve behaviour, indicating that the laminated Si₃N₄/SiC_w ceramics had excellent impact resistance. The improved toughness and impact resistance of laminated Si₃N₄/SiC_w ceramics was attributed to the residual stress caused by a thermal expansion coefficient mismatch between the different layers, resulting in crack deflection and bridging of SiC whiskers in the interface layer, thus consuming a large amount of fracture work.     

Synthesis of succinic acid-based polyamide through direct solid-state polymerization method: Avoiding cyclization of succinic acid

Succinic acid is an important synthetic monomer but it is difficult to use it as a precursor for synthesizing high molecular weight polyamide, due to its tendency to perform intra-cyclization reaction at high temperature. In order to solve this problem, in this paper, the direct solid-state polymerization (DSSP) method with the initial reactant, nylon salt which was composed of 1, 5-diaminopentane, succinic acid, and terephthalic acid, was applied to synthesize the bio-based copolyamide PA 5T/54. In comparison with the conventional melting polymerization method, the DSSP method can prevent the cyclization reaction of succinic acid effectively due to the lower reacting temperature as well as the restriction effect of the nylon salt. As a result, the product fabricated by DSSP method has higher molecular weight and much lighter color from red to white. Therefore, the DSSP method is advantageous for the synthesis of the polymers or copolymers composed of the succinic acid as the monomer. Furthermore, the polymerization mechanism proposed in this work can serve as a guidance for the design of the molecular structure and control of the polymerization process.     

Performance of Al2O3 particle reinforced glass-based seals in planar solid oxide fuel cells

Glass-based materials are usually considered as excellent seals for jointing adjacent components in planar solid oxide fuel cells, but the uncontrollable crystallization in the glass may cause delamination and micro-cracks in such seals. To solve this problem, Al2O3 ceramic particles were added to a BaO–CaO–Al2O3–B2O3–SiO2 glass system to reduce negative effects caused by crystalline phase on the gas tightness and the joint strength in the seals. At an operating temperature of 750 °C, the glass-based seals with 20 wt% Al2O3 addition (GA80) exhibited extremely low leakage rates (~0.002 sccm/cm under an input gas pressure of 13.6 kPa) and higher shear strength (3.31 MPa). The Al2O3 ceramic addition and the crystalline phase BaAl2Si2O8 reinforced the glass matrix. Further thermal cycle analyses indicated that leakage rates for the GA80 seals remained at around 0.0025 sccm/cm after 10 thermal cycles, which was consistent with minor microstructural change and good interface bonding. Single cell testing with of GA80 seals was performed and the results demonstrated stable electrochemical performance through 6 thermal cycles at an open circuit voltage of 1.16–1.18 V, as well as a power density above 546 mW/cm2 at a current density of 925 mA/cm2. These results showed the high thermal cycle stability of the glass/Al2O3 composite seals in intermediate temperature planar solid oxide fuel cells.     

Enhanced thermal shrinkage behavior of phenolic-derived carbon aerogel-reinforced by HNTs with superior compressive strength performance

A novel carbon/m-HNTs composite aerogel was synthesized by introducing the modified halloysite nanotubes (m-HNTs) into phenolic (PR) aerogels through chemical grafting, followed with carbonization treatment. In order to explore the best proportion of HNTs to phenolic, the micromorphology of PR/m-HNTs were investigated by SEM before carbonization, confirming 10 wt% of m-HNTs is most beneficial to the porous network of aerogels. The interaction between PR and HNTs was studied by FTIR spectra, and microstructure evolution of the target product-carbon/m-HNTs composite aerogel were illustrated by SEM and TEM techniques. SEM patterns indicated that the carbon/m-HNTs aerogels maintain a stable porous structure at 1000 °C (carbonization temperature), while a ~20 nm carbon layer was formed around m-HNTs generating an integral unit through TEM analysis. Specific surface area and pore size distribution of composite aerogels were analyzed based on mercury intrusion porosimetry and N₂ adsorption–desorption method, the obtained results stayed around 500 m²g^?1 and 1.00 cm³g^?1 (pore volume) without significant discrepancy, compared with pure aerogel, showing the uniformity of pore size. The weight loss rate (26.76%) decreased greatly compared with pure aerogel, at the same time, the best volumetric shrinkage rate was only 30.83%, contributed by the existence of HNTs supporting the neighbor structure to avoid over-shrinking. The highest compressive strength reached to 4.43 MPa, while the data of pure aerogel was only 1.52 MPa, demonstrating the excellent mechanical property of carbon/m-HNTs aerogels.