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Acta Pharmaceutica Sinica B 2024年第2期14卷 517-532页

作者： Shuang Xiang xiaoyun lu International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education(MOE) Guangdong Provincial Key Laboratory of New Drug Design and EvaluationGuangzhou City Key Laboratory of Precision Chemical Drug DevelopmentSchool of PharmacyJinan UniversityGuangzhou 510632China

Neurotrophic receptor kinase(NTRK) fusions are actionable oncogenic drivers of multiple pediatric and adult solid tumors,and tropomyosin receptor kinase(TRK) has been considered as an attractive therapeutic target for "pan-cancer" harboring these ***,two generations TRK inhibitors have been *** representative second-generation inhibitors selitrectinib and repotrectinib were designed to overcome clinic acquired resistance of the first-generation inhibitors larotrectinib or entrectinib resulted from solvent-front and gatekeeper on-target ***,xDFG(TRKAG667C/A/S,homologous TRKCG696C/A/S) and some double mutations still confer resistance to selitrectinib and repotrectinib,and overcoming these resistances represents a major unmet clinical *** this review,we summarize the acquired resistance mechanism of the first-and second-generation TRK inhibitors,and firstly put forward the emerging selective type Ⅱ TRK inhibitors to overcome xDFG mutations mediated ***,we concluded our perspectives on new challenges and future directions in this field.

关键词： NTRK fusions TRK kinase Clinical resistance xDFG mutations Selective type II inhibitors

Cyclization mechanism of monoterpenes catalyzed by monoterpene synthases in dipterocarpaceae

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Synthetic and Systems Biotechnology 2024年第1期9卷 11-18页

作者： xiaoyun lu Jie Bai Zunzhe Tian Congyu Li Nida Ahmed Xiaonan Liu Jian Cheng Lina lu Jing Cai Huifeng Jiang Wen Wang School of Ecology and Environment Northwestern Polytechnical UniversityXi’anShanxi710072China Key Laboratory of Engineering Biology for Low-Carbon Manufacturing Tianjin Institute of Industrial BiotechnologyChinese Academy of SciencesTianjin300308China

Monoterpenoids are typically present in the secretory tissues of higher plants,and their biosynthesis is catalyzed by the action of monoterpene synthases(MTSs).However,the knowledge about these enzymes is restricted in a few plant *** are responsible for the complex cyclization of monoterpene precursors,resulting in the production of diverse monoterpene *** enzymatic reactions are considered exceptionally complex in ***,it is crucial to understand the catalytic mechanism of MTSs to elucidate their ability to produce diverse or specific monoterpenoid *** our study,we analyzed thirteen genomes of Dipterocarpaceae and identified 38 MTSs that generate a variety of monoterpene *** focusing on four MTSs with different product spectra and analyzing the formation mechanism of acyclic,monocyclic and bicyclic products in MTSs,we observed that even a single amino acid mutation can change the specificity and diversity of MTS products,which is due to the synergistic effect between the shape of the active cavity and the stabilization of carbon-positive intermediates that the mutation ***,residues N340,I448,and phosphoric acid groups were found to be significant contributors to the stabilization of intermediate terpinyl and pinene *** in these residues,either directly or indirectly,can impact the synthesis of single monoterpenes or their *** revealing the role of key residues in the catalytic process and establishing the interaction model between specific residues and complex monoterpenes in MTSs,it will be possible to reasonably design and engineer different catalytic activities into existing MTSs,laying a foundation for the artificial design and industrial application of MTSs.

关键词： Cyclization Monoterpene synthases Intermediate stabilization

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热连轧低温微量润滑优化及现场测试分析

锻压装备与制造技术 2024年第5期59卷 147-149页

作者：路晓云杨光新乡职业技术学院数控技术学院河南新乡453000 新乡职业技术学院智能制造学院河南新乡453000

为了降低轧辊磨损消耗和提高节能效果,建立了低温微量润滑优化工艺,并在由七个机架组成的2160 mm热连轧机上开展轧辊消耗试验。通过现场测试分析了工艺润滑下辊间压力横向分布,并开展低温微量润滑优化前后指标参数对比。研究结果表明:... 详细信息

为了降低轧辊磨损消耗和提高节能效果,建立了低温微量润滑优化工艺,并在由七个机架组成的2160 mm热连轧机上开展轧辊消耗试验。通过现场测试分析了工艺润滑下辊间压力横向分布,并开展低温微量润滑优化前后指标参数对比。研究结果表明:相比较润滑优化前,增加低温微量润滑工艺后,热滑伤指数减小了约15%;打滑因子减小了约13%;轧辊消耗减小了约18%。采用本文的低温微量润滑优化方法有效减小轧辊消耗,进而有效避免打滑现象,最终优化了带钢出口板形,实现了节能效果和热轧质量的大幅提升。

关键词：热连轧轧辊消耗工低温微量润滑辊间压力

CNC机床丝杠热误差实时补偿设计及自动补偿试验

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机械管理开发 2024年第5期39卷 43-44,49页

作者：杨光路晓云新乡职业技术学院智能制造学院河南新乡453000 新乡职业技术学院数控技术学院河南新乡453000

为了降低数控机床丝杠传动系统因热误差引起的定位误差,完成机床工作台各运行阶段的实时补偿。用非接触模式为丝杠非电机连接端安装位移检测器,以电涡流传感器时间监测丝杠端面位置数据,获得丝杠产生的总热误差,通过热补偿得到每段丝杠... 详细信息

为了降低数控机床丝杠传动系统因热误差引起的定位误差,完成机床工作台各运行阶段的实时补偿。用非接触模式为丝杠非电机连接端安装位移检测器,以电涡流传感器时间监测丝杠端面位置数据,获得丝杠产生的总热误差,通过热补偿得到每段丝杠的热误差程度,确定每段坐标系原点发生的偏移,完成自主补偿机床丝杠热误差的效果。研究结果表明:采用分段补偿方法可以获得比其他热误差补偿模型更优的丝杠全段补偿性能。分别检测丝杠各段发生的热误差再对其实施补偿,可以根据丝杠各部位热误差程度实施补偿。

关键词：数控机床热误差丝杠传动实时补偿

杆驱工业机械臂双缸RBF优化模糊PID同步控制研究

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现代工业经济和信息化 2024年第9期14卷 113-114,119页

作者：杨光路晓云新乡职业技术学院智能制造学院河南新乡453000 新乡职业技术学院数控技术学院河南新乡453000

为了提高杆驱工业机械臂双液压缸同步控制精度,设计了一种RBF优化模糊PID控制方法,并在Simulink平台完成性能仿真。研究结果表明:速度信号发生了先加速,之后进入稳定速度,最后再减速。低速下,以RBF优化模糊PID控制的双液压缸最大同步误... 详细信息

为了提高杆驱工业机械臂双液压缸同步控制精度,设计了一种RBF优化模糊PID控制方法,并在Simulink平台完成性能仿真。研究结果表明:速度信号发生了先加速,之后进入稳定速度,最后再减速。低速下,以RBF优化模糊PID控制的双液压缸最大同步误差约为0.08 mm,稳定状态下的误差约为0.01 mm;高速下,以RBF优化模糊PID控制的双液压缸最大同步误差降低至0.11 mm,在稳定状态下的误差减小为0.02 mm。该研究有助于提供工业机器人控制精度,提高双臂协作效率。

关键词：双液压缸同步 RBF优化模糊PID控制精度误差调节

New antituberculosis drugs targeting the respiratory chain

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Chinese Chemical Letters 2020年第6期31卷 1357-1365,F0003页

作者： Qian Li xiaoyun lu International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) School of PharmacyJi'nan UniversityGuangzhou 510632China

With the emergence of multidrug-resistant tuberculosis and extensive drug-resistant tuberculosis strains,there is an urgent need to develop novel drugs for the treatment of *** respiratory chain is a promising target for the development of newantimycobacterial agents,and a growing number of compounds have been reported and some have entered clinical *** this review,we summarize the main features and the electron transfer process of the mycobacterial respiratory chain,and the recent progress in the search for new small molecule inhibitors to rgeting the three main potential targets in the respiratory chain of Mycrobacterium *** emphasis is on the optimization strategy of QcrB inhibitors and the challenges of developing QcrB inhibitors as antituberculosis drugs due to the alternate bd-type oxidase oxidative compensation pathway are discussed.

关键词： Respiratory chain Antituberculosis drug QcrB NADH-2 ATP synthase

数控机床工作台DSP定位误差系统设计及分析

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机械管理开发 2024年第3期39卷 187-188,191页

作者：路晓云杨光新乡职业技术学院数控技术学院河南新乡453000 新乡职业技术学院智能制造学院河南新乡453000

为进一步优化数控机床对于测试误差的补偿功能,开发通过DSP硬件系统对误差进行准确预测并设置补偿措施。建立的定位误差模型预测补偿系统包含数控系统进给轴反馈结构、DSP建模预测系统以及数控系统。研究结果表明,采用Matlab软件运行得... 详细信息

为进一步优化数控机床对于测试误差的补偿功能,开发通过DSP硬件系统对误差进行准确预测并设置补偿措施。建立的定位误差模型预测补偿系统包含数控系统进给轴反馈结构、DSP建模预测系统以及数控系统。研究结果表明,采用Matlab软件运行得到的优化权值与阈值建立的GA-BP网络进行误差预测共需251μs;采用GA-BP网络构建的模型进行预测时达到了更高精度。该研究有助于提高数控机床加工精度,对提高加工参数的优化起到很好的指导意义以及控制效果。

关键词：数控机床定位误差数字信号处理器遗传算法反向传播网络

Group Decision-Making Method with Incomplete Intuitionistic Fuzzy Preference Relations Based on a Generalized Multiplicative Consistent Concept

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Computer Modeling in Engineering & Sciences 2022年第9期132卷 881-907页

作者： xiaoyun lu Jiuying Dong Hecheng Li Shuping Wan School of Computer Science Qinghai Normal UniversityXining810008China School of Science Shanghai Institute of TechnologyShanghai201418China School of Statistics Jiangxi University of Finance and EconomicsNanchang330013China School of Information Technology Jiangxi University of Finance and EconomicsNanchang330013China

Based on the analyses of existing preference group decision-making(PGDM)methods with intuitionistic fuzzy preference relations(IFPRs),we present a new PGDM framework with incomplete IFPRs.A generalized multiplicative consistent for IFPRs is defined,and a mathematical programming model is constructed to supplement the missing values in incomplete ***,in this study,another mathematical programming model is constructed to improve the consistency level of unacceptably multiplicative consistent *** group decisionmaking(GDM)with incomplete IFPRs,three reliable sources influencing the weights of experts are ***,a method for determining the weights of experts is developed by simultaneously considering three reliable ***,a targeted consensus process(CPR)is developed in this study with reference to the actual situation of the consensus level of each ***,in response to the proposed multiplicative consistency definition,a novel method for determining the optimal priority weights of alternatives is ***,based on the above theory,a novel GDM method with incomplete IFPRs is developed,and the comparative and sensitivity analysis results demonstrate the utility and superiority of this work.

关键词： Intuitionistic fuzzy preference relations multiplicative consistency consensus optimization model group decision-making

头孢哌酮/舒巴坦致神经外科患者凝血功能异常的特征及其风险因素

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武警医学 2024年第6期35卷 511-515页

作者：金星路晓芸李亚美空军军医大学西京医院疾病预防控制科西安市第一医院药学部

目的探讨神经外科患者发生头孢哌酮/舒巴坦相关性凝血功能异常的特征及其风险因素。方法回顾性分析2020-01至2023-02空军军医大学西京医院神经外科使用头孢哌酮/舒巴坦的病例资料，根据用药后是否发生凝血功能异常分为正常组与异常组... 详细信息

目的探讨神经外科患者发生头孢哌酮/舒巴坦相关性凝血功能异常的特征及其风险因素。方法回顾性分析2020-01至2023-02空军军医大学西京医院神经外科使用头孢哌酮/舒巴坦的病例资料，根据用药后是否发生凝血功能异常分为正常组与异常组。通过LASSO回归筛选凝血功能异常的风险因素，构建预测模型。结果共入选病例108例，其中用药后凝血功能异常43例(39.81%),凝血功能正常65例(60.19%)。头孢哌酮/舒巴坦相关性凝血功能异常，表现为凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)延长，凝血酶原活动度(PTA)降低，国际标准化比值(INR)升高的特征性变化，其中PT、PTA、INR易受影响，变化幅度大，可作为风险识别的敏感指标。用药后凝血功能异常风险与APACHEⅡ评分(OR=1.133, 95%CI:1.039～1.234)、年龄(OR=1.024, 95%CI:0.993～1.054)正相关，与PTA(OR=0.959, 95%CI:0.929～0.989)负相关。结论利用诺模图进行风险评估识别高危人群，加强PT、PTA及APTT等特征性指标的监测，可减少风险事件发生。

关键词：头孢哌酮/舒巴坦凝血功能异常风险因素 LASSO回归诺模图

单腔内镜双弯式用于胃困难部位内镜黏膜下剥离术的安全性及有效性初探(含视频)

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中华消化内镜杂志 2024年第8期41卷 658-662页

作者：吴泽宇毛丽娟张婷金甜卢晓云陆宏娜刘昌恩胡晓张其德南京中医药大学附属医院江苏省中医院消化内镜中心南京210029 宁波市医疗中心李惠利医院消化内科宁波315040 天津市第三中心医院消化内科天津300170 四川省人民医院消化内科成都610072

胃底穹窿部和胃体上部等属于内镜黏膜下剥离术(endoscopic submucosal dissection,ESD)操作困难的部位,这些部位的病变ESD及其衍生技术的切除效果不满意,主要原因在于内镜前端难以抵近操作。笔者在软式肠镜进镜过弯形成α袢和双腔双弯... 详细信息

胃底穹窿部和胃体上部等属于内镜黏膜下剥离术(endoscopic submucosal dissection,ESD)操作困难的部位,这些部位的病变ESD及其衍生技术的切除效果不满意,主要原因在于内镜前端难以抵近操作。笔者在软式肠镜进镜过弯形成α袢和双腔双弯曲内镜的启发下,通过单腔治疗型内镜形成双弯形态——单腔内镜双弯式,并于2021年6—12月间对南京中医药大学附属医院消化内镜中心收治的3例胃底穹窿部、2例胃体上部大弯侧和1例胃底贲门下后壁病变患者进行了单腔内镜双弯式辅助下切除治疗。术中尝试2~3次后,6例均成功建立单腔内镜双弯式,用时60~120 s。6例均顺利完成内镜下切除治疗,包括4例ESD和2例内镜全层切除术,总体手术耗时20~80 min,均无明显并发症发生。初步结果显示,对于胃ESD操作困难部位的病变,ESD及其衍生技术治疗过程中采用单腔内镜双弯式辅助安全、有效,术中内镜前端易于靠近病变,剥离视野暴露良好,剥离平面稳定。

关键词：胃肿瘤内镜黏膜下剥离术内镜全层切除术操作困难部位单腔内镜双弯式