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基于网络药理学探究“葫芦巴-迷迭香”提取物治疗Ⅱ型糖尿病的潜在作用机制及实验验证

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云南化工 2024年第2期51卷 48-54页

作者：张彦昕柴贝贝石玉节李海利郑州赛科药业科技有限公司河南郑州450000 河南省农业科学院畜牧兽医研究所河南郑州450000

(目的)利用网络药理学相关技术,分析中药“葫芦巴-迷迭香”提取物治疗Ⅱ型糖尿病的潜在作用机制。(方法)构建活性物质、活性靶点和疾病相关靶点的网络药理图,通过网络分析阐释其作用机制。选取50只SD大鼠,随机分为空白组、Ⅱ型糖尿病模... 详细信息

(目的)利用网络药理学相关技术,分析中药“葫芦巴-迷迭香”提取物治疗Ⅱ型糖尿病的潜在作用机制。(方法)构建活性物质、活性靶点和疾病相关靶点的网络药理图,通过网络分析阐释其作用机制。选取50只SD大鼠,随机分为空白组、Ⅱ型糖尿病模型组及“葫芦巴-迷迭香”提取物高、中、低剂量治疗组,每组10只。试剂盒检测大鼠血清中总甘油三脂、总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇的含量,ELISA法检测各组大鼠血清中白细胞介素IL-6、IL-2、肿瘤坏死因子(TNF)-α、血管内皮生长因子(VEGF)和表皮细胞生长因子(EGF)表达情况。(结果)“葫芦巴-迷迭香”筛选得到56个活性成分及764个治疗Ⅱ型糖尿病潜在相关靶点。蛋白相互作用分析提示FGFR1、TNF、INSR、IL-6、MAPK14、JUN、PPARA、VEGFA、PTPN1、PTPN2、IGF1R、PTPN11为关键靶点。动物实验表明“葫芦巴-迷迭香”提取物给药中、高剂量组可显著降低血清中的甘油三酯和胆固醇,上调高密度脂蛋白胆固醇的含量,下调低密度脂蛋白胆固醇的含量,调节炎性因子TNF-α、IL-6、IL-2的含量,提高VEGF和EGF的表达。(结论)较为系统地解析了“葫芦巴-迷迭香”提取物治疗Ⅱ型糖尿病的作用机制,为中医药治疗Ⅱ型糖尿病和中药新药的研发奠定了基础。

关键词：网络药理学 Ⅱ型糖尿病葫芦巴迷迭香

非小细胞肺癌患者并发免疫检查点抑制剂肺炎的临床特征及预后分析

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中华结核和呼吸杂志 2024年第3期47卷 207-213页

作者：陈茹萱刘湘宁徐燕石钰洁王梦淇邵池黄慧徐凯王孟昭徐作军中国医学科学院北京协和医学院北京协和医院呼吸与危重症医学科北京100730 中国医学科学院北京协和医学院北京协和医院内科北京100730 中国医学科学院北京协和医学院北京协和医院放射科北京100730

目的分析接受抗肿瘤免疫治疗后发生免疫检查点抑制剂肺炎的非小细胞肺癌患者的临床特征,探索其预后相关因素。方法回顾性分析自2018年7月1日至2022年11月30日我院接受抗肿瘤免疫治疗后发生免疫检查点抑制剂肺炎的非小细胞肺癌患者的临床... 详细信息

目的分析接受抗肿瘤免疫治疗后发生免疫检查点抑制剂肺炎的非小细胞肺癌患者的临床特征,探索其预后相关因素。方法回顾性分析自2018年7月1日至2022年11月30日我院接受抗肿瘤免疫治疗后发生免疫检查点抑制剂肺炎的非小细胞肺癌患者的临床-影像学特征以及病情转归等资料。结果共纳入70例临床诊断免疫检查点抑制剂肺炎的非小细胞肺癌病例,其中男57例(57/70,81%),女13例(13/70,19%);70例患者年龄45~78(65.2±6.3)岁,46例(66%)有吸烟史,26例(37%)合并肺气肿,19例(27%)既往合并间质性肺疾病,26例(37%)既往有胸部放疗史。开始接受免疫检查点抑制剂治疗到出现免疫性肺炎的时间间距为(122.7±106.9)d(范围:2~458 d),胸部CT表现主要为非特异性间质性肺炎型(30例)、机化性肺炎型(26例)及混合型(11例),病情分级主要为2级及3级(分别为21例、34例),有17例合并其他免疫治疗相关不良反应(包括皮疹、肝炎、肠炎、甲状腺炎等)。半数(36例)患者存在发热,所有患者血沉升高,52例C反应蛋白升高,34例患者血乳酸脱氢酶升高。大部分(50例,71%)患者接受泼尼松[或糖皮质激素(简称激素)当量]≥1 mg·kg^(-1)·d^(-1)作为起始治疗方案。并发肺部感染(OR值为4.44,P=0.03)、使用抗真菌药物(OR值为5.10,P=0.03)或治疗量磺胺(OR值为4.86,P=0.04)、泼尼松(或激素当量)1 mg·kg^(-1)·d^(-1)应用时间越长(Z值为-2.33,P=0.02)可能是免疫性肺炎预后不良的相关因素。结论有吸烟史的、老年男性患者是本组非小细胞肺癌患者接受免疫检查点抑制剂后发生免疫检查点抑制剂肺炎的主要人群。胸部CT以非特异性间质性肺炎型、机化性肺炎型为主;并发肺部真菌感染或肺孢子菌感染、足量激素使用时间更长可能是免疫检查点抑制剂肺炎预后不良的相关因素。

关键词：癌非小细胞肺抗肿瘤免疫治疗免疫检查点抑制剂免疫检查点抑制剂肺炎预后

露水草中β-蜕皮甾酮提取工艺优化及其体外抗氧化能力研究

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云南化工 2024年第1期51卷 38-41页

作者：张彦昕柴贝贝石玉节李海利郑州赛科药业科技有限公司河南郑州450000 河南省农业科学院畜牧兽医研究所河南郑州450000

为探究露水草β-蜕皮甾酮的最佳提取工艺,分别考察提取方式和提取温度对β-蜕皮甾酮含量的影响;使用高效液相色谱法检测含量,利用DPPH和ABTS方法评价最佳提取工艺得到β-蜕皮甾酮的抗氧化能力。使用温浸提取和加热回流两种提取方式,分... 详细信息

为探究露水草β-蜕皮甾酮的最佳提取工艺,分别考察提取方式和提取温度对β-蜕皮甾酮含量的影响;使用高效液相色谱法检测含量,利用DPPH和ABTS方法评价最佳提取工艺得到β-蜕皮甾酮的抗氧化能力。使用温浸提取和加热回流两种提取方式,分别考察了60、80、100℃下溶剂为水的提取物中β-蜕皮甾酮的含量;选择最佳提取工艺进行提取,进行方法学考察;利用DPPH和ABTS体外自由基清除实验测定其抗氧化活性。结果表明,以水为溶剂,100℃加热回流的提取方式得到的β-蜕皮甾酮的含量最高;在该液相条件下,露水草样品可快速检出并且峰型良好,分离度高。通过自由基清除实验表明其具有体外抗氧化能力并呈一定浓度依赖型。

关键词：露水草 β-蜕皮甾酮高效液相色谱方法学验证抗氧化

快速循环刻意练习在助产士专业技能中的应用进展及启示

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护士进修杂志 2024年第14期39卷 1506-1511页

作者：石玉洁罗丽娟田文纯谢荣凯陆军军医大学第二附属医院重庆400037

快速循环刻意练习(rapid cycle deliberate practice,RCDP)是近年来医学模拟教学(simulation-based medical education,SBME)领域中非常重要的新型培训方式,该方式为让学员在一个心理安全的模拟情景下,不断进行刻意练习并给予其定向反馈... 详细信息

快速循环刻意练习(rapid cycle deliberate practice,RCDP)是近年来医学模拟教学(simulation-based medical education,SBME)领域中非常重要的新型培训方式,该方式为让学员在一个心理安全的模拟情景下,不断进行刻意练习并给予其定向反馈,以达到掌握专业技能的目的,具有良好的培训效果,在复杂技能培训中有独特优势。本综述总结了RCDP的诞生背景、概念,相关理论、核心成分及其与传统SBME的应用异同,优势、适用与不适用范围,实施原则、实施方法,相关研究及效果评价,旨在为我国助产士专业技能培训提供新方向。

关键词：助产士快速循环刻意练习模拟练习专业技能培训综述

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Local sustained release of PD-1 monoclonal antibody and lenvatinib by thermo-sensitive hydrogel for improving tumor immunotherapy

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中国化学快报:英文版 2023年第8期34卷 241-247页

作者： Lin Zhai yujie shi Yi Yan An Lu Xiaoyu Liu Lei Lei Yi Sun Linxia Jiang Xiangyu Wang Honggang Qian Jiancheng Wang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Pharmaceutical Analysis School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of Hepato-Pancreato-Biliary SurgeryPeking University Cancer Hospital&InstituteBeijing 100142China

In clinic,the combination of intravenous pembrolizumab(PD-1 monoclonal antibody)with oral Lenvatinib(LEN)exhibited an enhanced synergistic benefit for cancer ***,the clinical outcomes were always limited by the problems of inconsistent pharmacokinetic profiles of two drugs,lower drug accumulation in tumor and obvious side effects during the combination ***,in situ-forming thermosensitive hydrogels based on PLGA-PEG-PLGA triblock copolymers were prepared for local administration of anti-PD1 and LEN(P&L@Gel)to improve therapeutic efficacy and *** peritumoral or surgical resection site injection,the significant increased concentrations of both drugs in tumor were observed with the local sustained release of P&L@*** comparison with the group of intraperitoneal anti-PD1 plus oral LEN(P-ip&L-po),significantly higher tumor inhibition efficiency on CT26 tumor models could be obtained in P&L@Gel group,even at the dose of one-eighth of the former,same tumorinhibition effects could be *** enhanced antitumor efficacy of P&L@Gel group was probably associated with the 2.2 folds of increased level of CD8+T cells and the polarization of tumor associated macrophage from M2 to M1 along with the increased drug ***,compared with the obvious side effects of P-ip&L-po group,no significant changes of PLT,ALT and UA in blood,as well as IL-1αand IL-1βin mice paws were observed between P&L@Gel group and untreated *** results suggested that local administration of anti-PD1 and LEN with thermosensitive hydrogel could offer a potential strategy for tumors or tumor postoperative adjuvant treatment.

关键词： Lenvatinib PD-1 antibody Thermosensitive hydrogels Topical administration Tumor immunotherapy

Development of small molecule drugs targeting immune checkpoints

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Cancer Biology & Medicine 2024年第5期21卷 382-399页

作者： Luoyi Chen Xinchen Zhao Xiaowei Liu yujie Ouyang Chuan Xu Ying shi Department of Oncology Sichuan Academy of Medical SciencesSichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610054China Institute for Breast Health Medicine State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Acupuncture and Massage College Chengdu University of Traditional Chinese MedicineChengdu 611137China

Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune *** of small molecule drugs or biological materials,especially antibody-based ICIs,are actively being studied and antibodies are currently widely ***,such as anti-tumor efficacy,poor membrane permeability,and unneglected tolerance issues of antibody-based ICIs,remain evident but are thought to be overcome by small molecule *** structural studies have broadened the scope of candidate immune checkpoint molecules,as well as innovative chemical *** way of comparison,small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic *** ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions,including immune regulation,anti-angiogenesis,and cell cycle *** this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins,which will lay the foundation for further exploration.

关键词： Immune checkpoints small molecule drugs programmed death protein 1 CD47 signal-regulatory proteinα

Analysis and Optimization of Transient Mode Switching Behavior for Power Split Hybrid Electric Vehicle with Clutch Collaboration

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Automotive Innovation 2024年第1期7卷 150-165页

作者： Dehua shi Sheng Liu yujie Shen Shaohua Wang Chaochun Yuan Long Chen Automotive Engineering Research Institute Jiangsu UniversityZhenjiang 212013China Jiangsu Province Engineering Research Center of Electric Drive System and Intelligent Control for Alternative Vehicles Zhenjiang 212013China

The power split hybrid electric vehicle(HEV)adopts a power coupling configuration featuring dual planetary gearsets and multiple clutches,enabling diverse operational modes through clutch engagement and *** multi-clutch configuration usually involves the collaboration of two clutches during the transient mode switching process,thereby substantially elevating control *** study focuses on power split HEVs that integrate multi-clutch mechanisms and investigates how different clutch collaboration manners impact the characteristics of transient mode *** powertrain model for the power-split HEV is established utilizing matrix-based *** the formulation of clutch torque curves and clutch collaboration models,this research systematically explores the effects of clutch engagement timing and the duration of clutch slipping state on transient mode switching *** upon this analysis,an optimization problem for control parameters pertaining to the two collaborative clutches is *** simulated annealing algorithm is employed to optimize these control *** results demonstrate that the clutch collaboration manners have a great influence on the transient mode switching *** with the pre-calibrated benchmark and the optimal solution derived by the genetic algorithm,the maximal longitudinal jerk and clutch slipping work during the transient mode switching process is reduced obviously with the optimal control parameters derived by the simulated annealing *** study provides valuable insights for the dynamic coordinated control of the power-split HEVs featuring complex clutch collaboration mechanisms.

关键词： Power split hybrid electric vehicle Transient mode switching Clutch collaboration Simulated annealing Powertrain model

尿毒症维持性血液透析患者脑钠肽与干体重的相关性分析

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中国循证心血管医学杂志 2024年第1期16卷 93-95,99页

作者：张鑫石宇杰苏莉王慧田新利霍延红解放军总医院第一医学中心肾脏病医学部北京100010 解放军总医院第七医学中心肾脏病科北京100010 解放军总医院第七医学中心心脏内科北京100010

目的分析尿毒症维持性血液透析(MHD)患者血浆脑钠肽(BNP)与干体重(△OH值)的相关性。方法选定解放军总医院第七医学中心于2020年12月至2022年12月就诊的80例尿毒症MHD患者研究,根据△OH值将患者分为两组,干体重达标患者设为干体重达标组... 详细信息

目的分析尿毒症维持性血液透析(MHD)患者血浆脑钠肽(BNP)与干体重(△OH值)的相关性。方法选定解放军总医院第七医学中心于2020年12月至2022年12月就诊的80例尿毒症MHD患者研究,根据△OH值将患者分为两组,干体重达标患者设为干体重达标组(n=30),干体重未达标患者设为干体重未达标组(n=50),比较透析治疗前后血清BNP、△OH值,Pearson分析血清BNP与△OH值的相关性,使用受试者工作曲线(ROC)分析血清BNP对干体重达标的预测价值,统计MHD治疗相关并发症。结果患者透析后血清BNP、△OH值均低于透析前,差异有统计学意义(P<0.05)。干体重未达标组血清BNP水平高于干体重达标组,差异有统计学意义(P<0.05)。血清BNP与△OH值呈正相关性(r=0.359,P<0.05)。血清BNP对于干体重达标具有一定的预测价值(AUC=0.916,95%CI:0.848~0.955,P<0.05),灵敏度96.20%(95%CI:0.853~0.944,P<0.05)、特异度90.16%(95%CI:0.748~0.936,P<0.05)。治疗期间患者均病情平稳,无心血管事件发生,2例患者在透析中有血压偏低表现,予以停止超滤后自行好转,下机后无其他不适。结论尿毒症MHD患者血清BNP表达量与△OH值呈正相关性,临床可通过检测血清BNP表达量,提高对干体重达标的预测效能,从而指导临床针对性地展开治疗。

关键词：尿毒症维持性血液透析脑钠肽

Sustainable all-weather CO2 utilization by mimicking natural photosynthesis in a single material

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National Science Review 2024年第2期11卷 177-187页

作者： Xianjin shi Yu Huang Ran Long Zhenyu Wang Liqin Wang Junji Cao Gangqiang Zhu yujie Xiong State Key Laboratory of Loess and Quaternary Geology(SKLLQG) Key Laboratory of Aerosol Chemistry and Physics Institute of Earth EnvironmentChinese Academy of Sciences Center of Excellence in Quaternary Science and Global Change Chinese Academy of Sciences University of Chinese Academy of Sciences Hefei National Research Center for Physical Sciences at the Microscale School of Chemistry and Materials Science and National Synchrotron Radiation Laboratory University of Science and Technology of China Institute of Atmospheric Physics Chinese Academy of Sciences School of Physics and Information Technology Shaanxi Normal University

Solar-driven CO2conversion into hydrocarbon fuels is a sustainable approach to synchronously alleviating the energy crisis and achieving net ***,the dependence of the conversion process on solar illumination hinders its practical application due to the intermittent availability of sunlight at night and on cloudy or rainy ***,we report a model material of Pt-loaded hexagonal tungsten trioxide（Pt/h-WO3） for decoupling light and dark reaction processes,demonstrating the sustainable CO2conversion under dark conditions for the first *** such a material system,hydrogen atoms can be produced by photocatalytic water splitting under solar illumination,stored together with electrons in the h-WO3through the transition of W6+to W5+and spontaneously released to trigger catalytic CO2reduction under dark ***,we demonstrate using natural light that CH4production can persist at night and on rainy days,proving the accomplishment of all-weather CO2conversion via a sustainable way.

关键词： sustainable CO2 utilization artificial photosynthesis all-weather application charge storage