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Signal Transduction and Targeted Therapy 2024年第4期9卷 1706-1720页

作者： Jian Zhang Kejia Zhao Wenjing Zhou Ran Kang Shiyou Wei Yueli Shu Cheng Yu Yin Ku Yonghong Mao Hao Luo Juqin Yang jiandong mei Qiang Pu Senyi Deng Zhengyu Zha Gang Yuan Shensi Shen Yaohui Chen Lunxu Liu Department of Thoracic Surgery and Institute of Thoracic Oncology West China Hospital of Sichuan UniversityChengdu 610097China Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer Sichuan UniversityChengdu 610097China Biobank of West China Hospital Sichuan UniversityChengdu 610041China

Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiting clinical *** found that TET2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC *** perturbationof TET2 rendered parental cells more tolerant to TKI ***2 was stabilized by MEK1 phosphorylation at Ser 1107,while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7^(FBXW11),Loss of TET2 resulted in the upregulation of TNF/NF-kB signaling that confers the EGFR-TKI *** or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in *** findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2,and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 ***,combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.

关键词： TET2 TKI resistance

急性坏死性纵隔炎176例临床特征及转归的回顾性队列研究

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中国胸心血管外科临床杂志 2024年第2期31卷 243-248页

作者：梁林川彭智愚林华杭周柯梅建东四川大学华西医院胸外科成都610041

目的分析急性坏死性纵隔炎临床特征、诊断和治疗转归,为临床诊疗提供参考。方法回顾性分析四川大学华西医院2012年3月—2021年4月期间收治的急性坏死性纵隔炎患者的临床资料,包括病因、临床表现、影像学资料、病原学结果、手术方式及转... 详细信息

目的分析急性坏死性纵隔炎临床特征、诊断和治疗转归,为临床诊疗提供参考。方法回顾性分析四川大学华西医院2012年3月—2021年4月期间收治的急性坏死性纵隔炎患者的临床资料,包括病因、临床表现、影像学资料、病原学结果、手术方式及转归,分析其发病特点、临床诊疗方法及预后因素。结果共纳入176例患者,中位年龄60(0~84)岁,男124例、女52例。最常见的感染来自颈部(66例,37.5%),最常见的临床表现是发热(85例,48.3%),脓液培养中以星座链球菌最常见(23例,13.1%)。本组患者中119例(67.6%)接受手术治疗,单纯颈部入路54例(30.7%)、单纯胸部入路27例(15.3%)[开胸9例(5.1%)、胸腔镜18例(10.2%)]、颈部+胸部入路37例(21.0%)[开胸7例(4.0%)、胸腔镜30例(17.0%)]、剑突下入路1例(0.6%)。176例患者中治愈出院144例(81.8%),死亡32例(18.1%)。多因素分析显示年龄调整后Charlson合并症指数(OR=2.95,P=0.022)、围术期存在脓毒症(OR=2.84,P=0.024)、未行外科手术引流(OR=2.41,P=0.043)是患者死亡的独立预测因素。结论临床疑诊急性坏死性纵隔炎的患者应行影像学检查明确脓肿累及范围,以指导手术入路的选择,对于诊断明确的患者尽早行手术治疗,及时清除感染组织、充分引流。年龄调整后Charlson合并症指数、围术期存在脓毒症以及未行外科手术引流与患者的预后不良密切相关。

关键词：急性坏死性纵隔炎临床特征病原学手术转归

Decentralized direct adaptive neural network control for a class of interconnected systems

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Journal of Systems Engineering and Electronics 2006年第2期17卷 374-380页

作者： Zhang Tianping mei jiandong Dept. of Computer CoIL of Information Engineering Yangzhou Univ. Yangzhou 225009 P.R. China

The problem of direct adaptive neural network control for a class of large-scale systems with unknown function control gains and the high-order interconneetions is studied in this paper. Based on the principle of sliding mode control and the approximation capability of multilayer neural networks, a design scheme of decentralized di- rect adaptive sliding mode controller is proposed. The plant dynamic uncertainty and modeling errors are adaptively compensated by adjusted the weights and sliding mode gains on-line for each subsystem using only local informa- tion. According to the Lyapunov method, the closed-loop adaptive control system is proven to be globally stable, with tracking errors converging to a neighborhood of zero. Simulation results demonstrate the effectiveness of the proposed approach.

关键词： neural networks decentralized control sliding mode control adaptive control global stability.

Prediction of sepsis within 24 hours at the triage stage in emergency departments using machine learning

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World Journal of Emergency Medicine 2024年第5期15卷 379-385页

作者： Jingyuan Xie jiandong Gao Mutian Yang Ting Zhang Yecheng Liu Yutong Chen Zetong Liu Qimin mei Zhimao Li Huadong Zhu Ji Wu Department of Electronic Engineering Tsinghua UniversityBeijing 100084China Center for Big Data and Clinical Research Institute for Precision MedicineTsinghua UniversityBeijing 100084China Institute of Medical Technology Peking University Health Science CenterBeijing 100091China Emergency Department State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100005China Department of Health Care Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China

BACKGROUND:Sepsis is one of the main causes of mortality in intensive care units(ICUs).Early prediction is critical for reducing *** approximately 36%of sepsis occur within 24 h after emergency department(ED)admission in Medical Information Mart for Intensive Care(MIMIC-IV),a prediction system for the ED triage stage would be *** methods such as the quick Sequential Organ Failure Assessment(qSOFA)are more suitable for screening than for prediction in the ED,and we aimed to fi nd a light-weight,convenient prediction method through machine ***:We accessed the MIMIC-IV for sepsis patient data in the *** dataset comprised demographic information,vital signs,and synthetic *** Gradient Boosting(XGBoost)was used to predict the risk of developing sepsis within 24 h after ED ***,SHapley Additive exPlanations(SHAP)was employed to provide a comprehensive interpretation of the model's *** percent of the patients were randomly selected as the testing set,while the remaining patients were used for training with 10-fold ***:For 10-fold cross-validation on 14,957 samples,we reached an accuracy of 84.1%±0.3%and an area under the receiver operating characteristic(ROC)curve of 0.92±*** model achieved similar performance on the testing set of 1,662 *** values showed that the fi ve most important features were acuity,arrival transportation,age,shock index,and respiratory ***:Machine learning models such as XGBoost may be used for sepsis prediction using only a small amount of data conveniently collected in the ED triage *** may help reduce workload in the ED and warn medical workers against the risk of sepsis in advance.

关键词： Sepsis Machine learning Emergency department Triage Informatics

Chemical construction and anti-HCoV-OC43 evaluation of novel 10,12-disubstituted aloperine derivatives as dual cofactor inhibitors of TMPRSS2 and SR-B1

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Chinese Chemical Letters 2024年第5期35卷 201-206页

作者： Yulong Shi Fenbei Chen Mengyuan Wu Xin Zhang Runze Meng Kun Wang Yan Wang Yuheng mei Qionglu Duan Yinghong Li Rongmei Gao Yuhuan Li Hongbin Deng jiandong Jiang Yanxiang Wang Danqing Song Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Department of Pharmacy Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJining 272000China

Thirty-one new 10,12-disubstituted aloperine derivatives were subtly constructed through a selective oxidation on the 10-α-C-H induced by sulfonyl and a nucleophilic substitution with the stereoselectivity and *** them,compound 6b displayed a moderate anti-human coronavirus OC43(HCoV-OC43)potency and blocked the viral entry stage through a host mechanism of *** chemoproteomic techniques,both transmembrane serine protease 2(TMPRSS2)and scavenger receptor class B type 1(SR-B1)proteins,which act as host cofactors of viral entry,were identified to be the direct targets of 6b against ***,6b may deactivate the TMPRSS2 by inducing a change in protein conformation,rather than binding to its catalytic center,thus suppressing the viral membrane ***,our study provided key scientific data for the development of aloperine derivatives into a new class of antiviral candidates against humanβ-coronavirus,including severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).

关键词： Aloperine SARS-CoV-2 TMPRSS2 SR-B1 Synthesis

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单向式胸腔镜肺外科学技术体系构建与推广

中国科学：生命科学 2022年第11期52卷 1636-1643页

作者：蒲强刘成武梅建东刘伦旭四川大学华西医院胸外科成都610041

胸腔镜用于肺癌外科治疗已30年,尤以近15年是其高速发展期.经过前期的摸索和总结,本团队于2006年提出单向式胸腔镜肺癌切除术,经不断完善,建立了单向式胸腔镜肺外科学完整技术体系,涉及胸腔镜肺手术各个方面.通过建立和推广单向式胸腔... 详细信息

胸腔镜用于肺癌外科治疗已30年,尤以近15年是其高速发展期.经过前期的摸索和总结,本团队于2006年提出单向式胸腔镜肺癌切除术,经不断完善,建立了单向式胸腔镜肺外科学完整技术体系,涉及胸腔镜肺手术各个方面.通过建立和推广单向式胸腔镜肺外科学,推动微创胸外科的发展.

关键词：微创胸腔镜肺外科学单向式

白介素-17在肺癌发生及进展中的作用与机制研究进展

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中国肺癌杂志 2016年第1期19卷 46-51页

作者：梅建东刘伦旭四川大学华西医院胸外科中国西部肺癌早期诊断与综合治疗协同创新中心成都610041

白介素-17(interleukin 17,IL-17)是一个重要的炎症因子,参与介导了机体的抗感染免疫及自身免疫性疾病相关的病理性炎症;此外,IL-17还与多种炎症相关的肿瘤有着密切联系。吸烟是导致肺癌的重要危险因素之一,而吸烟等因素所致的肺部慢性... 详细信息

白介素-17(interleukin 17,IL-17)是一个重要的炎症因子,参与介导了机体的抗感染免疫及自身免疫性疾病相关的病理性炎症;此外,IL-17还与多种炎症相关的肿瘤有着密切联系。吸烟是导致肺癌的重要危险因素之一,而吸烟等因素所致的肺部慢性炎症反应伴有IL-17过表达,提示IL-17可能与肺癌的发生存在潜在联系;同时,IL-17还通过多种机制影响肺癌进展,本文对这一领域的相关研究进展进行了综述。

关键词：白介素-17 炎症肿瘤发生肿瘤进展肺肿瘤

胸腔镜解剖性肺切除手术常见意外情况及其处置

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中国肺癌杂志 2016年第6期19卷 382-388页

作者：梅建东刘伦旭四川大学华西医院胸外科中国西部肺癌早期诊断与综合治疗协同创新中心成都610041

现代意义上的胸腔镜肺外科始于20世纪90年代初,经过20余年发展,手术技术已臻成熟,同时也有了丰富的临床数据积累。以胸腔镜为代表的微创技术在早期非小细胞肺癌及肺部良性疾病的外科治疗、肺部疾病诊断等方面的应用均已得到公认,也是上... 详细信息

现代意义上的胸腔镜肺外科始于20世纪90年代初,经过20余年发展,手术技术已臻成熟,同时也有了丰富的临床数据积累。以胸腔镜为代表的微创技术在早期非小细胞肺癌及肺部良性疾病的外科治疗、肺部疾病诊断等方面的应用均已得到公认,也是上述情况的首选手术方法。随着胸腔镜解剖性肺切除手术的普及,文献中也逐渐有了一些临床实践中意外情形的报道,涉及解剖异常、病变自身相关因素、手术操作及技术等多方面,但目前少有对胸腔镜解剖性肺切除手术中意外情形的系统梳理,本文拟结合自身临床实践及文献报道,对这方面内容进行总结,为临床工作提供参考。

关键词：胸腔镜解剖性肺切除意外情形中转开胸出血

教学专职岗在临床教学医院中设定的作用及意义

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继续医学教育 2023年第3期37卷 137-140页

作者：沈诚梅建东车国卫四川大学华西医院胸外科四川成都610041

以医疗、教学、科研为一体的现代化大型综合医院,不仅承担着救死扶伤的使命,还肩负着培养优秀医学人才的重任,其科研水平的高低也将在很大程度上影响着医院科技的发展和综合竞争力。在临床教学过程中,由于学制较复杂、培训对象年资差别... 详细信息

以医疗、教学、科研为一体的现代化大型综合医院,不仅承担着救死扶伤的使命,还肩负着培养优秀医学人才的重任,其科研水平的高低也将在很大程度上影响着医院科技的发展和综合竞争力。在临床教学过程中,由于学制较复杂、培训对象年资差别大、水平良莠不齐、不同类别的学习者来科室学习目的不同等相关问题,也会给临床教学、培训带来很大难度。在此背景下,医院为各科室专门设立了教学专职岗,为各专业临床教学和医师培训提供了保障。文章就教学专职岗在临床教学医院中设定的作用及意义做一综述。

关键词：教学专职岗临床教学医院医师培养实习医生住培医生进修医生

MinerVa——一种用于实体瘤微小残留病灶检测的高性能检测算法

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生物医学工程学杂志 2023年第2期40卷 313-319页

作者：杨飘张亚晰夏粱梅建东范锐黄宇刘伦旭陈维之无锡臻和生物科技有限公司江苏无锡214000 四川大学华西医院胸外科成都610041

如何提高循环肿瘤DNA(ctDNA)信号的获取能力以及判定低频信号的真实性是肿瘤微小残留病灶(MRD)检测的难点问题。本研究开发了多变异联合置信概率分析的MRD生物信息学算法(MinerVa),并在ctDNA标准品和早期非小细胞肺癌患者血浆DNA样本中... 详细信息

如何提高循环肿瘤DNA(ctDNA)信号的获取能力以及判定低频信号的真实性是肿瘤微小残留病灶(MRD)检测的难点问题。本研究开发了多变异联合置信概率分析的MRD生物信息学算法(MinerVa),并在ctDNA标准品和早期非小细胞肺癌患者血浆DNA样本中对算法效能进行评估。结果显示,MinerVa算法对多变异共追踪的特异性稳定在99.62%~99.70%,当追踪30个变异时,可检测低至6.3×10^(-5)变异丰度的变异信号;进一步对27例非小细胞肺癌患者的数据进行分析,ctDNA-MRD动态监测复发的特异性为100%,灵敏度为78.6%。数据表明MinerVa算法可高效地捕获血液ctDNA信号,在MRD检测中具有较好的准确性。

关键词：循环肿瘤DNA 微小残留病灶多变异联合置信概率分析技术噪音基线单碱基分辨率