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Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C

Journal of Pharmaceutical Analysis 2023年第6期13卷 616-624页

作者： Ping Zhu Shi-You li Jin Ding Zhou Fei Sheng-Nan Sun Zhao-Hui Zheng Ding Wei Jun Jiang Jin-lin Miao san-zhong li Xing Luo Kui Zhang Bin Wang Kun Zhang Su Pu Qian-Ting Wang Xin-Yue Zhang Gao-liu Wen Jun Oliu John Thomas August Huijie Bian Zhi-Nan Chen You-Wen He Department of Clinical Immunology Xijing HospitalDepartment of Cell BiologyNational Translational Science Center for Molecular MedicineFourth Military Medical UniversityXi'an710032China Beijing Tricision Biotherapeutics Inc. Beijing100176China Department of Neurosurgery Xijing HospitalFourth Military Medical UniversityXi'an710032China Zhuhai Tricision Biotherapuetics Inc. ZhuhaiGuangdong519040China Department of Pharmacology and Molecular Sciences Johns Hopkins University School of MedicineBaltimoreMD21205USA

Glioblastoma(GBM)is a lethal cancer with limited therapeutic *** cell(DC)-based cancer vaccines provide a promising approach for GBM *** studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor ***,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 *** patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor ***,mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex(MHC)class I and II antigen *** treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC *** patient also received 28 doses of cyclophosphamide for depletion of regulatory T *** immunotherapy-related adverse events were observed during the *** antitumor CD4t and CD8t T-cell responses were *** patient remains free of disease *** is the first case report on the combination of the above three agents to treat glioblastoma *** results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

关键词： Glioblastoma multiforme DC vaccine Tumor-associated antigens Neoantigens

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Monitored anesthesia care and asleep-awake-asleep techniques combined with multiple monitoring for resection of gliomas in eloquent brain areas:a retrospective analysis of 225 patients

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Chinese Neurosurgical Journal 2023年第2期9卷 88-97页

作者： san-zhong li Ning Su Shuang Wu Xiao-Wei Fei Xin He Jiu-Xiang Zhang Xiao-Hui Wang Hao-Peng Zhang Xiao-Guang Bai Guang Cheng Zhou Fei Department of Neurosurgery Xijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Radiotherapy Xijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Anesthesiology Xijing HospitalFourth Military Medical UniversityXi’an 710032China

Background:Awake craniotomy(AC)has become gold standard in surgical resection of gliomas located in eloquent *** conscious sedation techniques in AC include both monitored anesthesia care(MAC)and asleep-awake-asleep(AAA).The choice of optimal anesthetic method depends on the preferences of the surgical team(mainly anesthesiologist and neurosurgeon).The aim of this study was to compare the difference in physiological and blood gas data,dosage of different drugs,the probability of switching to endotracheal intubation,and extent of tumor resection and dysfunction after operation between AAA and MAC anesthetic management for resection of gliomas in eloquent brain ***:Two-hundred and twenty-five patients with super-tentorial tumor located in eloquent areas underwent AC from 2009 to 2021 in Xijing ***-one patients underwent AAA technique,and the rest one-hundred eighty-four patients underwent MAC *** management,dosage of different drugs,intraoperative complications,postoperative outcomes,adverse events,extent of resection and motor,and sensory and language dysfunction after operation were compared between MAC and ***:There was no significant difference in gender,KPS score,MMSE score,glioma grade,type,and growth site between the patients in the two groups,except the older age of patients in MAC group than that in AAA *** the whole process of operation,there were greater pulse pressure difference(P=0.046),shorter operation time(P=0.039),less dosage of remifentanil(P=0.000),more dosage of dexmedetomidine(P=0.013),more use of antiemetics(81%,P=0.0067),lower use of vasoactive agent(45.1%,P=0.010),and lower probability of conversion to general anesthesia(GA,P=0.027)in MAC group than that in AAA *** gas analysis showed that PetCO2(P=0.000),Glu concentration(P=0.000),and PaCO2(P=0.000)were higher,but SPO2(P=0.002)and PaO2(P=0.000)were lower in MAC group than that in AAA *** the postoperative recovery stage,c

关键词： Monitored anesthesia care(MAC) Asleep-awake-asleep(AAA) Retrospective analysis Eloquent areas Gliomas

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High‑Entropy Electrode Materials:Synthesis,Properties and Outlook

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Nano-Micro Letters 2025年第1期17卷 472-506页

作者： Dongxiao li Chang liu Shusheng Tao Jieming Cai Biao zhong Jie li Wentao Deng Hongshuai Hou Guoqiang Zou Xiaobo Ji College of Chemistry and Chemical Engineering Central South UniversityChangsha 410083People’s Republic of China School of Chemistry and Chemical Engineering Hunan Institute of EngineeringXiangtan 411104People’s Republic of China

High-entropy materials represent a new category of high-performance materials,first proposed in 2004 and extensively investigated by researchers over the past two *** definition of high-entropy materials has continuously *** the last ten years,the discovery of an increasing number of high-entropy materials has led to significant advancements in their utilization in energy storage,electrocatalysis,and related domains,accompanied by a rise in techniques for fabricating high-entropy electrode ***,the research emphasis has shifted from solely improving the performance of high-entropy materials toward exploring their reaction mechanisms and adopting cleaner preparation ***,the current definition of high-entropy materials remains relatively vague,and the preparation method of high-entropy materials is based on the preparation method of single metal/low-or medium-entropy *** should be noted that not all methods applicable to single metal/low-or medium-entropy materials can be directly applied to high-entropy *** this review,the definition and development of high-entropy materials are briefly ***,the classification of high-entropy electrode materials is presented,followed by a discussion of their applications in energy storage and catalysis from the perspective of synthesis ***,an evaluation of the advantages and disadvantages of various synthesis methods in the production process of different high-entropy materials is provided,along with a proposal for potential future development directions for high-entropy materials.

关键词： High-entropy Energy storage Electrode materials

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The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury

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Neural Regeneration Research 2025年第11期20卷 3233-3244页

作者： Xiaoling zhong Wenjiao Tai Meng-Lu liu Shuaipeng Ma Tianjin Shen Yuhua Zou Chun-li Zhang Department of Molecular Biology University of Texas Southwestern Medical CenterDallasTXUSA Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical CenterDallasTXUSA Peter O’Donnell Jr.Brain Institute University of Texas Southwestern Medical CenterDallasTXUSA

The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following *** targeting this pathway is beneficial to brain injury remains *** this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral *** inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology ***,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin *** findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.

关键词： adeno-associated virus Citron homology Citron homology domain gene therapy mitogen-activated protein kinase kinase kinase kinases traumatic brain injury

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500 m水深张力腿平台总体运动性能分析

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船海工程 2018年第5期47卷 110-114页

作者：刘祥建刘文民伞立忠石强大连船舶重工集团设计研究院有限公司辽宁大连116005

为了验证张力腿平台在中国南海500 m水深下的环境适应性,采用时域耦合分析的方法分析500 m水深下张力腿平台的总体运动性能,重点分析张力腿平台关键运动参数,如平台水平位移、升沉运动、气隙和筋腱张力等,基于模型试验修正的数值分析,... 详细信息

为了验证张力腿平台在中国南海500 m水深下的环境适应性,采用时域耦合分析的方法分析500 m水深下张力腿平台的总体运动性能,重点分析张力腿平台关键运动参数,如平台水平位移、升沉运动、气隙和筋腱张力等,基于模型试验修正的数值分析,结果表明,张力腿平台在南海500 m水深下具有良好的运动性能,可以满足作业要求。

关键词：张力腿平台总体运动性能数值分析模型试验

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Ultralight and superelastic MXene/reduced graphene oxide aerogels for electromagnetic interference shielding

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Nano Research 2025年第1期18卷 1-9页

作者： Xinfeng Zhou Yang Dai Guoyao Yue Yiman Zhang Lulu li zhong-Zhen Yu Peng Min Hao-Bin Zhang 21 State Key Laboratory of Organic-Inorganic Composites College of Materials Science and EngineeringBeijing University of Chemical TechnologyBeijing 100029China Beijing Key Laboratory of Advanced Functional Polymer Composites College of Materials Science and EngineeringBeijing University of Chemical TechnologyBeijing 100029China Present address:BOE Technology Innovation Center BOE Technology Group Co.Ltd.Beijing 100176China Xi’an Modern Chemistry Research Institute Xi’an 710065China

lightweight aerogels feature multifunctionality and a high porosity,yet accompanied with poor structure recovery under large strain *** this work,we develop an air bubble-ice crystal dual template and annealing strategy to integrate low density and high resilience for the conductive transition metal carbides/nitrides(MXene)composite *** air bubbles and ice crystals synergistically exclude the nanosheets to the gas-liquid interfaces,thereby constructing unique Y-shaped junctions and robust *** annealing process greatly enhances the interlayer *** external load,the Yshaped structures prevent the stress concentration at the junctions by transferring the forces to the skeleton for maintaining structural *** addition,the wrinkled and thick cell walls,together with the enhanced interlayer interactions,endow the aerogel with exceptional structural stability and *** a result,the MXene/reduced graphene oxide(RGO)composite aerogels exhibit superelasticity with reversible compressive strains of up to 95%.In addition,the electron bridging effect of the RGO sheets affords the aerogel to deliver excellent electromagnetic interference shielding performance,as high as 46.3 dB at 2.5 ***,the remarkable reshapeability of the aerogels allows for precise regulation of structure and performance(33.5-75.1 dB)by a simple wetting compression *** summary,this work offers helpful inspirations for developing lightweight and superelasticity aerogels for extensive applications.

关键词： lightweight superelasticity MXene aerogel electromagnetic interference shielding reshapeability

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Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis

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Neural Regeneration Research 2025年第2期20卷 518-532页

作者： Conglin Wang Fangyuan Cheng Zhaoli Han Bo Yan Pan liao Zhenyu Yin Xintong Ge Dai li Rongrong zhong Qiang liu Fanglian Chen Ping Lei Department of Geriatrics Tianjin Medical University General HospitalTianjinChina School of Medicine Nankai UniversityTianjinChina Tianjin Neurological Institute TianjinChina

Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor ***-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system *** this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying *** results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral ***,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory *** sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier *** with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these *** summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

关键词： AKT astrocyte blood-brain barrier cerebral edema exosomes human-induced pluripotent stem cells intracerebral hemorrhage neural stem cells neuroinflammation PI3K

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“大、小、重、慢”疾病定义与全科医生“4善”定位的探讨

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中国全科医学 2025年第1期28卷 125-128页

作者：李敏王仲清华大学附属北京清华长庚医院临床医学院全科医学系北京市102218 北京清华长庚医院全科与健康医学部北京市102218

随着我国医药卫生体制的深度改革,特别是分级诊疗制度的推进,全科医生在基层医疗保健体系中的角色日益重要。全科医生不仅是居民健康的第一道防线,更是常见疾病预防、诊断、治疗及健康教育的关键执行者。国家对全科医生提出了“小病善... 详细信息

随着我国医药卫生体制的深度改革,特别是分级诊疗制度的推进,全科医生在基层医疗保健体系中的角色日益重要。全科医生不仅是居民健康的第一道防线,更是常见疾病预防、诊断、治疗及健康教育的关键执行者。国家对全科医生提出了“小病善治、大病善识、重病善转、慢病善管”的临床定位。本文通过问答形式,分析“小、大、重、慢”疾病的分类与全科医生的“4善”定位,探讨全科医生在新医改时代下的重要职能及挑战。访谈者认为虽然分级诊疗制度旨在优化医疗资源配置,但在实践中仍面临“大、小、重、慢”疾病分类的模糊性和基层医疗资源的不均衡分配等问题。全科医生在这个体系中扮演着至关重要的角色,其需要具备综合的临床诊疗能力,并与专科医生共同制定临床判断标准和诊疗标准。为了应对这些挑战并充分发挥全科医生在现代医疗体系中的作用,迫切需要对全科医学教育和实践进行进一步改革与优化,同时强化全科医生的角色定位,以确保在提升医疗服务质量和效率的同时,实现公平和可持续的健康保障体系。

关键词：全科医学全科医生分级诊疗医疗体系改革疾病分类医疗资源优化

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Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

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Neural Regeneration Research 2025年第10期20卷 2838-2854页

作者： Lu Guan Mengting Qiu Na li Zhengxiang Zhou Ru Ye liyan zhong Yashuang Xu Junhui Ren Yi liang Xiaomei Shao Jianqiao Fang Junfan Fang Junying Du Department of Neurobiology and Acupuncture Research Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Key Laboratory for Research of Acupuncture Treatment and Transformation of Emotional Diseases Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Fuchun Community Health Service Center of Fuyang District HangzhouZhejiang ProvinceChina

Pain is often comorbid with emotional disorders such as anxiety and *** of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid *** review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain *** understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these ***,the mechanisms that regulate gamma-aminobutyric acidergic systems remain *** is also unclear as to whether the mechanisms are presynaptic or *** exploration of the complexities of this system may reveal new pathways for research and drug development.

关键词： anterior cingulate cortex anxiety chronic pain circuit communication comorbidity depression gamma-aminobutyric acidergic neurons parvalbumin neurons synaptic transmission

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Physicochemical Properties and Evaluation of Microemulsion Systems for Transdermal Delivery of Meloxicam

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Chemical Research in Chinese Universities 2007年第1期23卷 81-86页

作者： YUAN Yue li san-ruing YU li-min DENG Pan zhong Da-fang School of Pharmacy Shenyang Pharmaceutical University Shenyang 110016 P. R. China Center for Drug Metabolism and Pharmacokinetics Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 P. R. China

Microemulsion systems, composed of water, isopropyl myristate （IPM）, polyoxyethylene sorbitan trioleate （Tween 85 ）, and ethanol, were investigated as transdermal drug delivery vehicles for a lipophilic model drug（ meloxicam）. The purpose of this study was to investigate the physicochemieal properties of the tested microemulsion and to find the correlation between the physicoehemical properties and the skin permeation rate of the microemulsion. Pseudo-ternary phase diagram of the investigated system at a constant surfactant/cosurfactant mass ratio （ Km = 1 ： 1 ） was constructed by titration at 20℃, and the five fommlations were selected for further research in the o/w microemulsion domains. The values of electrical conductivity and viscosity showed that the selected systems were bicontinuous or non-spherical o/w microemulsion, and the electrical conductivity and viscosity were increased with increasing the content of water. These results suggest that the optimum formulation of microemulsion, containing 0. 375 meloxicam, 5% isopropyl myristate, 25% Tween 85. 25% ethanol, and water, showed the maximum permeation rate. It had a high electrical conductivity, small droplet size, and proper viscocity.

关键词： Microemulsion Physicochemical property Transdermal delivery Meloxicam Polyoxyethylene sorbitan triolcate

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