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Moderate expression of CD39 in GPC3-CAR-T cells shows high efficacy against hepatocellular carcinoma

FRONTIERS OF MEDICINE 2024年第4期18卷 708-720页

作者： Zou, Fan Wei, Jialiang Zhuang, Jialang Liu, Yafang Tan, Jizhou huang, xianzhang Liu, Ting Guangdong Acad Med Sci Guangdong Prov Peoples Hosp Guangdong Cardiovasc Inst Guangzhou 510080 Peoples R China Southern Med Univ Guangdong Prov Peoples Hosp Med Res Inst Guangdong Acad Med Sci Guangzhou 510080 Peoples R China Guangzhou Univ Chinese Med Guangdong Prov Hosp Chinese Med State Key Lab Tradit Chinese Med Syndrome Dept Lab MedClin Med Coll 2 Guangzhou 510120 Peoples R China Guangxi Med Univ Affiliated Hosp 1 Dept Med Oncol Nanning 530021 Peoples R China Sun Yat Sen Univ Affiliated Hosp 1 Dept Stomatol Guangzhou 510080 Peoples R China Shenzhen Polytech Univ Sch Food & Drug Shenzhen 518055 Peoples R China Shenzhen Univ Affiliated Hosp 1 Shenzhen Peoples Hosp 2 Shenzhen 518055 Peoples R China

CD39 serves as a crucial biomarker for neoantigen-specific CD8+ T cells and is associated with antitumor activity and exhaustion. However, the relationship between CD39 expression levels and the function of chimeric antigen receptor T (CAR-T) cells remains controversial. This study aimed to investigate the role of CD39 in the functional performance of CAR-T cells against hepatocellular carcinoma (HCC) and explore the therapeutic potential of CD39 modulators, such as mitochondrial division inhibitor-1 (mdivi-1), or knockdown CD39 through short hairpin RNA. Our findings demonstrated that glypican-3-CAR-T cells with moderate CD39 expression exhibited a strong antitumor activity, while high and low levels of CD39 led to an impaired cellular function. Methods modulating the proportion of CD39 intermediate (CD39int)-phenotype CAR-T cells such as mdivi-1 and CD39 knockdown enhanced and impaired T cell function, respectively. The combination of mdivi-1 and CD39 knockdown in CAR-T cells yielded the highest proportion of infiltrated CD39int CAR-T cells and demonstrated a robust antitumor activity in vivo. In conclusion, this study revealed the crucial role of CD39 in CAR-T cell function, demonstrated the potential therapeutic efficacy of combining mdivi-1 with CD39 knockdown in HCC, and provided a novel treatment strategy for HCC patients in the field of cellular immunotherapy.

关键词： CD39 CAR-T cells mdivi-1 hepatocellular carcinoma antitumor activity CD73

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南阳艾内生菌与关键次生代谢产物的相关性探究

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世界科学技术-中医药现代化 2024年第5期26卷 1202-1212页

作者：李孟芝李超崔占虎韦艳朱琳黄显章南阳理工学院张仲景国医国药学院河南省张仲景方药与免疫调节重点实验室河南大学附属南阳市第一人民医院

目的通过分析南阳艾不同部位内生菌菌群结构多样性及其与关键次生代谢产物含量之间的关系，探究南阳艾内生菌对其药材品质的影响。方法本研究采用高通量测序技术分析南阳艾不同组织内生菌群落的多样性和组成；利用高效液相色谱技术检... 详细信息

目的通过分析南阳艾不同部位内生菌菌群结构多样性及其与关键次生代谢产物含量之间的关系，探究南阳艾内生菌对其药材品质的影响。方法本研究采用高通量测序技术分析南阳艾不同组织内生菌群落的多样性和组成；利用高效液相色谱技术检测南阳艾不同组织中关键代谢产物的含量；进而通过皮尔逊相关性分析，筛选与南阳艾关键次生代谢产物显著相关的内生菌群落。结果南阳艾内生细菌和真菌多样性和组成具有显著组织差异，根中细菌和真菌多样性指数（Chao和Ace）均显著高于茎和叶。通过LEfSe分析，确定根瘤菌属、链霉菌属、黄单胞菌科、子囊菌纲等为南阳艾生物标记物。相关性分析的结果表明，根瘤菌属、假单胞菌属、黄杆菌属、链霉菌属、曲霉属、油壶菌属等属的丰度与部分苯丙素类和黄酮类代谢物的含量呈现显著正相关（P<0.05）。结论本研究筛选了一些南阳艾次生代谢物显著相关的内生菌群落，为进一步分离南阳艾关键次生代谢产物相关的内生菌株，提升南阳艾的品质提供了科学依据。

关键词：南阳艾内生菌多样性组成次生代谢产物

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无机元素与计量学模型结合的半夏产地溯源研究

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中国无机分析化学 2024年第5期14卷 652-661页

作者：李超申国玺徐铮锐宗子怡张超云黄显章南阳理工学院/河南省张仲景方药与免疫调节重点实验室河南南阳473000 河南金方源药业有限公司河南南阳473000

为建立不同产地半夏无机元素的分析方法和溯源体系,为半夏药材的质量控制和道地性评价提供技术支持。采用电感耦合等离子体质谱法(ICP-MS)和电感耦合等离子体原子发射光谱法(ICP-AES)对我国6个主产区72份半夏样品中K、Ca、Na、Mg、Al等3... 详细信息

为建立不同产地半夏无机元素的分析方法和溯源体系,为半夏药材的质量控制和道地性评价提供技术支持。采用电感耦合等离子体质谱法(ICP-MS)和电感耦合等离子体原子发射光谱法(ICP-AES)对我国6个主产区72份半夏样品中K、Ca、Na、Mg、Al等37种无机元素的含量进行测定,并采用方差分析、主成分分析、因子分析等计量学方法进行统计与评价。通过对比BP-神经网络算法、K-最近邻算法、最小二乘支持向量机等多种模式识别方法,探索适合半夏产地溯源的最佳模型。结果表明:不同产地半夏中无机元素的构成各具特征,各无机元素含量在产地间差异显著(P<0.05),其中La、Pb、As、Na、Bi、Hg、Sn、Cd、Ag 9种元素在不同产区间的差异最为明显;3D-plots图显示不同产地半夏样品分布相对集中,具备产地分类的可行性;KNN分类模型(曼哈顿距离)是半夏产地溯源的最佳方法,测试集的正确率达到100%。无机元素分析技术结合适当的计量学模型可以实现半夏的产地溯源。

关键词：半夏无机元素模式识别产地溯源计量学模型

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基于无机元素指纹分析的桔梗产地溯源

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中国无机分析化学 2024年第7期14卷 1006-1014页

作者：张超云费娜李孟芝李丹霞黄显章李超南阳理工学院/河南省张仲景方药与免疫调节重点实验室河南南阳473000 河南医药健康技师学院河南开封475000

为比较四川梓潼(SCZT)、云南玉龙(YNYL)、安徽太和(AHTH)、湖北英山(HBYS)、河南桐柏(HNTB)无机元素含量差异,结合计量学方法,探讨桔梗产地溯源应用的可行性,为桔梗产地溯源提供新方法。利用电感耦合等离子体质谱法(ICP-MS)和电感耦合... 详细信息

为比较四川梓潼(SCZT)、云南玉龙(YNYL)、安徽太和(AHTH)、湖北英山(HBYS)、河南桐柏(HNTB)无机元素含量差异,结合计量学方法,探讨桔梗产地溯源应用的可行性,为桔梗产地溯源提供新方法。利用电感耦合等离子体质谱法(ICP-MS)和电感耦合等离子体原子发射光谱法(ICP-AES)测定四川、云南、安徽、湖北、河南5个主产区共75份桔梗样品中K、P、Fe、Mn、B等37种元素的含量,通过主成分分析对5大产区桔梗进行聚类,运用KNN、Bayes、SVM-ga、BP-NN、LS-SVM、SVM-grid算法,建立桔梗产地溯源模型。结果表明:五大产区桔梗中无机元素含量差异显著(P<0.05),其中Sb、Sn、Ge、Nb、Ag 5种元素,在不同产区间差异最为明显;由主成分分析发现不同产地桔梗样品分布集中且相对独立,SVM-grid桔梗溯源模型能够100%将五大产区桔梗进行区分;Sb、Sn、Ge、Nb、Ag 5种元素含量分布具有明显的地域特征。以无机元素结合计量学方法可以对桔梗进行有效的产区判别,且准确率高,是产地溯源的有效方法。

关键词：桔梗无机元素模式识别产地溯源

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Dermcidin Enhances the Migration, Invasion, and Metastasis of Hepatocellular Carcinoma Cells In Vitro and In Vivo

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Journal of Clinical and Translational Hepatology 2022年第3期10卷 429-438页

作者： Fanghua Qiu Huajing Long Lu Zhang Jieyuan Liu Zetian Yang xianzhang huang Department of Hospital Acquired Infection Control Affiliated TCM Hospital of Guangzhou Medical UniversityGuangzhouChina Guangzhou University of Chinese Medicine GuangzhouChina University of California San DiegoWarren CollegeSan DiegoCAUSA Department of Clinical Laboratory Second Affiliated HospitalGuangzhou University of Chinese MedicineGuangzhouChina

Background and Aims:Hepatocellular carcinoma(HCC)is a common primary liver neoplasm with high ***(DCD),an antimicrobial peptide,has been reported to participate in *** study assessed the effects and underlying molecular events of DCD overexpression and knockdown on the regulation of HCC progression in vitro and in ***:The serum DCD level was detected using enzyme-linked immunosorbent *** overexpression,knockdown,and Ras-related C3 botulinum toxin substrate 1(Rac1)rescue were performed in SK-HEP-1 cells using *** staining,quantitative PCR,and Western blotting were used to detect the expression of different genes and *** in HCC cell migration and invasion were detected by Transwell migration and invasion assays.A nude mouse HCC cell orthotopic model was employed to verify the in vitro ***:The level of serum DCD was higher in patients with HCC and in SK-HEP-1 *** overexpression caused upregulation of DCD,fibronectin,Rac1,and cell division control protein 42 homologue(Cdc42)mRNA and proteins as well as actin-related protein 2/3(Arp2/3)protein(but reduced Arp2/3 mRNA levels)and activated Rac1 and ***,DCD overexpression induced HCC cell migration and invasion in vitro,whereas knockout of DCD expression had the opposite effects.A Rac1 rescue experiment in DCD-knockdown HCC cells increased HCC cell migration and invasion and increased the levels of active Rac1/total Rac1,Wiskott-Aldrich syndrome family protein(WASP),Arp2/3,and *** overexpression induced HCC cell metastasis to the abdomen and liver in ***:DCD promotes HCC cell migration,invasion,and metastasis through upregulation of noncatalytic region of tyrosine kinase adaptor protein 1(Nck1),Rac1,Cdc42,WASP,and Arp2/3,which induce actin cytoskeletal remodeling and fibronectin-mediated cell adhesion in HCC cells.

关键词： Hepatocellular carcinoma Dermcidin Metastasis Gene regulation Cell adhesion

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液相色谱-串联质谱临床推广与应用面临挑战

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中华检验医学杂志 2021年第8期44卷 661-663页

作者：黄宪章广东省中医院(广州中医药大学第二附属医院)检验医学部广州510120

液相色谱-串联质谱技术在检验医学领域正在快速应用与发展,从高分辨质谱促进生物标志物的高效筛选,到三重四极杆质谱助力验证生物标志物对疾病的诊断与疗效监测,其应用贯穿于组学研究到实验诊断的不同领域与环节,逐渐成为疾病研究与诊... 详细信息

液相色谱-串联质谱技术在检验医学领域正在快速应用与发展,从高分辨质谱促进生物标志物的高效筛选,到三重四极杆质谱助力验证生物标志物对疾病的诊断与疗效监测,其应用贯穿于组学研究到实验诊断的不同领域与环节,逐渐成为疾病研究与诊断的一种不可或缺的技术手段。目前大部分液相色谱串联质谱平台处于医学研究阶段,临床推广与应用还存在一些挑战。

关键词：液相色谱串联质谱组学定量检测临床应用

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Seismic response and correlation analysis of a pile-supported wharf to near-fault pulse-like ground motions

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Earthquake Engineering and Engineering Vibration 2024年第4期23卷 883-897页

作者： Wang, Jianfeng Su, Lei Xie, Libo Ling, xianzhang Ju, Peng School of Civil Engineering Qingdao University of Technology Qingdao China School of Civil Engineering Harbin Institute of Technology Harbin China No.2 Engineering Company Ltd. of CCCC First Harbor Engineering Company Ltd Qingdao China

Earthquake investigations have shown that near-fault pulse-like (NF-P) ground motions have unique characteristics compared to near-fault non-pulse-like (NF-NP) and far-field (FF) ground motions. It is necessary to study the seismic response of pile-supported wharf (PSW) structures under NF-P ground motions. In this study, a three-dimensional finite element numerical model is created to simulate a PSW. By imparting three types of ground motion, the engineering demand parameters (EDPs) of PSW under NF-P ground motions were analyzed and compared, in which EDPs are the maximum displacement and bending moment of the piles. Twenty intensity measures (IMs) were selected to characterize the properties of ground motions. The correlation between IMs and EDPs was explored. The results show that the piles present larger displacement and bending moment under NF-P ground motions compared to NF-NP and FF ground motions. None of the IMs have a high correlation with EDPs under NF-P ground motions, and these IMs are more applicable to FF ground motions. The correlation coefficients between EDPs and IMs under three types of ground motion were obtained, which will provide a valuable reference for the seismic design of PSWs.

关键词： pile-supported wharf correlation analysis near-fault pulse-like ground motion intensity measure seismic response

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Evolution and Application of Sealing Ability of Gypsum Caprocks under Temperature-Pressure Coupling:An Example of the ZS5 Well in the Tazhong Area of the Tarim Basin

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Acta Geologica Sinica(English Edition) 2024年第1期98卷 168-184页

作者： LIU Hua ZHAO Shan YANG xianzhang ZHU Yongfeng WANG Shen ZHANG Ke National Key Laboratory of Deep Oil and Gas China University of Petroleum(East China)QingdaoShandong 266580China School of Geosciences China University of Petroleum(East China)QingdaoShandong 266580China Laboratory for Marine Mineral Resources National Laboratory for Marine Science and TechnologyQingdaoShandong 266071China PetroChina Tarim Oil Field Company KorlaXinjiang 841001China

Gypsum caprocks'sealing ability is affected by temperature-pressure *** to the limitations of experimental conditions,there is still a lack of triaxial stress-strain experiments that simultaneously consider changes in temperature and pressure conditions,which limits the accuracy of the comprehensive evaluation of the brittle plastic evolution and sealing ability of gypsum rocks using temperature pressure *** stress-strain tests were utilized to investigate the differences in the evolution of the confinement capacity of gypsum rocks under coupled temperaturepressure action and isothermal-variable pressure action on the basis of sample feasibility *** to research,the gypsum rock's peak and residual strengths decrease under simultaneous increases in temperature and pressure over isothermal pressurization experimental conditions,and it becomes more *** reduces the amount of time it takes for the rock to transition from brittle to *** temperature is taken into account,both the brittle–plastic transformation's depth limit and the lithological transformation of gypsum rocks become shallower,and the evolution of gypsum rocks under variable temperature and pressure conditions is more complicated than that under isothermal *** sealing ability under the temperature-pressure coupling is more in line with the actual geological context when the application results of the Well#ZS5 are *** provides a theoretical basis for precisely determining the process of hydrocarbon accumulation and explains why the early hydrocarbon were not well preserved.

关键词： temperature-pressure coupling gypsum caprocks brittle-plastic evolution sealing capacity Tarim Basin

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Relationship between Natural Fracture and Structural Style and its Implication for Tight Gas Enrichment:A Case Study of Deep Ahe Formation in the Dibei–Tuzi Area,Kuqa Depression

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Acta Geologica Sinica(English Edition) 2024年第4期98卷 1086-1110页

作者： XIA Lu XI Kelai YANG xianzhang HAN Zhanghua XU Zhenping ZHOU Lu YU Guoding WANG Daoshen WANG Weiyu School of Petroleum Engineering Shandong Institute of Petroleum and Chemical TechnologyDongyingShandong 257061China National Key Laboratory of Deep Oil and Gas China University of Petroleum(East China)QingdaoShandong 266580China Research Institute of Petroleum Exploration and Development PetroChina Tarim Oilfield CompanyKorlaXinjiang 841000China

The deep Lower Jurassic Ahe Formation(J_(1a))in the Dibei–Tuzi area of the Kuqa Depression has not been extensively explored because of the complex distribution of fractures.A study was conducted to investigate the relationship between the natural fracture distribution and structural *** J_(1a)fractures in this area were mainly high-angle shear fractures.A backward thrust structure(BTS)is favorable for gas migration and accumulation,probably because natural fractures are more developed in the middle and upper parts of a thick competent *** opposing thrust structure(OTS)was strongly compressed,and the natural fractures in the middle and lower parts of the thick competent layer around the fault were more *** vertical fracture distribution in the thick competent layers of an imbricate-thrust structure(ITS)differs from that of BTS and *** intensity of the fractures in the ITS anticline is similar to that in the *** density in monoclinic strata in a ITS is controlled by ***,the structural style controls the configuration of faults and anticlines,and the stress on the competent layers,which significantly affects deep gas reservoir *** enrichment of deep tight sandstone gas is likely controlled by two closely spaced faults and a fault-related anticline.

关键词： fracture distribution structural style deep tight sandstone electrical image logging Kuqa Depression Tarim Basin

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宫颈病变患者人乳头瘤病毒16亚型E2基因多态性检测

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南方医科大学学报 2012年第10期32卷 1503-1506页

作者：邱峰袁丽娜黄宪章广东省中医院检验科广东广州510120 广东省中医院病理科广东广州510120

目的分析宫颈病变中人乳头瘤病毒（HPV）16亚型E2基因的多态与宫颈病变的关系,了解E2基因变异情况及其与宫颈病变的相关性。方法应用PCR和高分辨率熔解曲线方法针对379例HPV高危亚型阳性宫颈脱落细胞样本进行HPV16感染情况及HPV16亚型E... 详细信息

目的分析宫颈病变中人乳头瘤病毒（HPV）16亚型E2基因的多态与宫颈病变的关系,了解E2基因变异情况及其与宫颈病变的相关性。方法应用PCR和高分辨率熔解曲线方法针对379例HPV高危亚型阳性宫颈脱落细胞样本进行HPV16感染情况及HPV16亚型E2基因68位点和133位点多态分布情况进行检测。结果 379例HPV高危亚型阳性宫颈标本共检出78例HPV 16亚型阳性,其在宫颈癌、CINⅡ-Ⅲ、CINⅠ、炎症患者中的检出率分别为44.8%、31.5%、24.1%和9.6%;HPV16 E2基因68C和133G的频率在中重度宫颈内瘤样病变和宫颈癌中明显高于轻度上皮内瘤样病变和炎症患者（P〈0.05）。结论 HPV16是导致宫颈恶性病变的重要致病因素;随着病理类型的进展,HPV16感染率也逐渐增加;同时基因位点改变说明HPV 16 E2基因单核苷酸变异可能使致癌能力发生改变。

关键词：宫颈癌宫颈内瘤样病变人乳头瘤病毒 E2基因多态性

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