EGFR突变非小细胞肺癌患者奥希替尼诱导间质性肺疾病后奥希替尼再挑战:病例报道

奥希替尼诱导的间质性肺疾病(interstitial lung disease,ILD)是一种罕见的、致命的肺毒性疾病。我们报道1例64岁男性IV期肺腺癌患者,伴有表皮生长因子受体(epidermal growth factor receptor,EGFR)外显子19缺失,使用奥希替尼80 mg/d作为一线靶向治疗。奥希替尼开始治疗后第60天患者出现ILD。立即停用奥希替尼,并开始口服泼尼松60 mg/d,ILD在13 d内得到改善。权衡风险和获益后,再次开始奥希替尼与泼尼松治疗。奥希替尼治疗16个月以上,患者既没有疾病进展,也没有ILD复发。根据我们的病例和既往文献,在仔细评估EGFR突变非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的风险及获益后,在类固醇激素辅助下再次使用奥希替尼可被视为一种有效的治疗选择。

70岁及以上临床晚期胃癌患者化疗相关不良反应的列线图预测模型的构建与验证

目的:本研究拟在≥70岁临床晚期胃癌患者中探索化疗相关毒性(chemotherapy related toxicities,CRT)相关危险因素并建立列线图预测CRT的风险。方法:选取2003年7月至2020年8月就诊于北京协和医院的≥70岁临床晚期胃癌患者,收集其临床资料,通过Logistic回归模型探索与CRT相关的危险因素,随后构建列线图模型来预测CRT发生的概率,通过自举重采样技术验证模型,采用校准曲线检验模型的一致性。结果:纳入研究的178例患者中CRT的发生率为41%。其中女性、ECOG≥1分、体质量减轻、化疗前血白蛋白<30 g/L、化疗前中性粒细胞与淋巴细胞比值(neutrophil and lymphocyte ratio,NLR)<4和化疗前血小板水平是CRT的独立危险因素。基于上述6个潜在危险因素构建列线图模型,该模型具有良好的诊断能力[曲线下面积(AUC)=0.716,95%CI:0.677~0.755]和良好的校准和拟合能力。结论:本研究构建了一个列线图模型预测≥70岁临床晚期胃癌患者CRT发生的概率。该模型可作为一种无创的、方便的模型早期预测这些患者CRT的发生。

Effect of supercritical water on the stability and activity of alkaline carbonate catalysts in coal gasification

The stability and activity of alkaline carbonate catalysts in supercritical water coal gasification has been investigated using density functional theory method. Our calculations present that the adsorption of Na2CO3 on coal are more stable than that of K2CO3, but the stability of Na2CO3 is strongly reduced as the cluster gets larger. In supercritical water system, the dispersion and stability of Na2CO3 catalyst on coal support is strongly improved. During coal gasification process, Na2CO3 transforms with supercritical water into NaOH and NaHCO3, which is beneficial for hydrogen production. The transformation process has been studied via thermodynamics and kinetics ways. The selectively catalytic mechanism of NaOH and the intermediate form of sodium-based catalyst in water-gas shift reaction for higher hydrogen production has also been investigated. Furthermore, NaOH can transform back to Na2CO3 after catalyzing the water-gas shift reaction. Thus, the cooperative effects between supercritical water and Na2CO3 catalyst form a benignant circle which greatly enhances the reaction rate of coal gasification and promotes the production of hydrogen.

Optimization of Fermentation Medium for Producing α-Hydroxyphenylacetic Acid by Using Plackett-Burman Design and Response Surface Methodology

Plackett-Burman design and response surface methodology were applied in order to optimize the fermentation medium of (R)-α-hydroxyphenylacetic acid ((R)-HPA) producing Bacillus sp. HZG-19. The factors playing important roles in the production of (R)-HPA were selected based on Plackett-Burman design. The path of steepest ascent was undertaken to optimize said fermentation medium. Finally, the optimal levels of the factors with the greatest change in regard to product yield were further optimized using Box-Behnken and response surface analysis. The optimal conditions were found to be as follows: casein peptone 30.49 (g × L-1), glycerol 14.09 (g × L-1), KH2PO4 0.1345 (g × L-1), K2HPO4 0.01 (g × L-1), CaCl2 0.1 (g × L-1), MnSO4 0.01 (g × L-1). Under the optimal conditions described above, the yield of (R)-HPA reached 63.30%, which indicated an increase of 14.9%, as compared to the yield obtained before optimization.

Enzymatic Hydrolysis of Hairtail Surimi in an Ultra-High Pressure Bioreactor

Amino acids have been extracted from Hairtail surimi using enzymes in an ultra-high pressure bioreactor. The extraction efficiency of different enzymes including papain, trypsin, and proteases (acid, neutral, alkaline) also has been evaluated, and it has been discovered that neutral protease behaved the best. The amino acids were analyzed using automatic amino acid analyzer, and the enzymatic digestion conditions were optimized. For neutral protease, the optimal condition was 50℃, 250 MPa, pH 7.0. Material to liquid ratio of enzyme is 6%. More than 29 amino acids were detected after 24 hours of hydrolysis;the enzymatic hydrolysis rate can reach 83.29%. The results show that enzymatic digestion under ultra-high-pressure provides a very promising approach to extract amino acids from Hairtail surimi.

Vibration characteristics analysis of tank gun barrel with nonuniform cross-section

The firing accuracy of a tank gun is affected significantly by the flexural motion of the barrel.For the purpose of satisfying the requirement of efficiently and accurately dynamic analysis and optimization of the tank gun barrel to ensure it has good dynamic characteristics and firing accuracy,the high-fidelity dynamic model of a tank gun barrel is developed according to the transfer matrix method for multibody system which has features of high degree of stylization and high computational speed.The transfer matrix of the non-uniform Euler-Bernoulli beam(NU-EB beam)is deduced from governing differential equations of motion utilizing the differential transform method.The orthogonality of augmented eigenvectors for the NU-EB beam is proven which can be used for its exact dynamics response analysis using the modal method.In allusion to the tank gun barrel with non-uniform cross-section,the barrel is modeled as a combination of several uniform and non-uniform transverse vibrating Euler-Bernoulli beams.The overall transfer equation and matrix of the tank gun barrel are established according to the automatic deduction theorem of the overall transfer equation of multibody system.The present method is proven to be effective by comparing the computational results to those in published literatures.The vibration characteristics of a tank gun barrel with a non-uniform cross-section are analyzed accurately and are verified by the modal test.

Development, applications and challenges of ReaxFF reactive force field in molecular simulations

As an advanced and new technology in molecular simulation fields, ReaxFF reactive force field has been developed and widely applied during the last two decades. ReaxFF bridges the gap between quantum chemistry （QC） and non-reactive empirical force field based molecular simulation methods, and aims to provide a transferable potential which can describe many chemical reactions with bond formation and breaking. This review presents an overview of the development and applications of ReaxFF reactive force field in the fields of reaction processes, biology and materials, including （1） the mechanism studies of organic reactions under extreme conditions （like high temperatures and pressures） related with high-energy materials, hydrocarbons and coals, （2） the structural properties ofnanomaterials such as graphene oxides, carbon nanotubes, silicon nanowires and metal nanoparticles, （3） interfacial interactions of solid-solid, solid-liquid and biological/inorganic surfaces, （4） the catalytic mechanisms of many types of metals and metal oxides, and （5） electrochemical mechanisms of fuel cells and lithium batteries. The limitations and challenges of ReaxFF reactive force field are also mentioned in this review, which will shed light on its future applications to a wider range of chemical environments.

Eigenvalue analysis of planar linear multibody system under conservative force based on the transfer matrix method

The linear multibody system transfer matrix method(LMSTMM)provides a powerful tool for analyzing the vibration characteristics of a mechanical system.However,the original LMSTMM cannot resolve the eigenvalues of the systems with ideal hinges(i.e.,revolute hinge,sliding hinge,spherical hinge,cylindrical hinge,etc.)or bodies under conservative forces due to the lack of the corresponding transfer matrices.This paper enables the LMSTMM to solve the eigenvalues of the planar multibody systems with ideal hinges or rigid bodies under conservative forces.For a rigid body,the transfer matrix can now consider coupling terms between forces and kinematic state perturbations.Also,conservative forces that contribute to the eigenvalues can be considered.Meanwhile,ideal hinges are introduced to LMSTMM,which enables the treatment of eigenvalues of general multibody systems using LMSTMM.Finally,the comparative analysis with ADAMS software and analytical solutions verifies the effectiveness of the proposed approach in this paper.

Generation mechanism and control of high-frequency vibration for tracked vehicles

A crawler system provides much larger ground contact,leading to excellent terrain adaptability.Due to its structural characteristics,high‐frequency vibration proportional to the vehicle speed is generated during the driving process.This is a result of the polygon and rolling effects between the track and the wheels.A field test of a tracked vehicle is performed to monitor movement signals of the chassis and a rocker arm.Their corresponding power spectral density distributions confirm the correctness of the frequency‐calculation equation.Then,a novel elastic track tensioning device with a damper is designed as a cushion between the idler and the chassis.Depending on its geometry,the equivalent damping coefficient for a dynamic model is evaluated.Subsequently,the damping is altered in response to different operating conditions by a hybrid damping fuzzy semiactive control system.The controller accounts for both chassis and track vibration.Based on the transfer matrix method for multibody systems,a dynamical model of the track system is developed.Control performances are evaluated using two numerical simulations of obstacle crossing and off‐road driving operations.Results indicate that the proposed semiactive tensioner is substantially better than the conventional one.This paper provides a novel feasible scheme for vibration reduction of tracked vehicles.