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Initial COVID-19 severity influenced by SARS-CoV-2-specific T cells imprints T-cell memory and inversely affects reinfection

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2791-2803页

作者： Gang Yang Jinpeng Cao Jian Qin Xinyue Mei Shidong Deng Yingjiao Xia Jun Zhao Junxiang Wang Tao Luan Daxiang Chen Peiyu Huang Cheng Chen Xi Sun Qi Luo Jie Su Yunhui Zhang nanshan zhong zhongfang Wang The Affiliated Hospital of Kunming University of Science and Technology.Department of Respiratory and Critical Care Medicine The First People’s Hospital of Yunnan provinceKunmingYunnanChina Guangzhou National Laboratory BiolandGuangzhouGuangdongChina State Key Laboratory of Respiratory Disease&National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhouChina

The immunoprotective components control COVID-19 disease severity,as well as long-term adaptive immunity maintenance and subsequent reinfection risk discrepancies across initial COVID-19 severity,remain ***,we longitudinally analyzed SARS-CoV-2-specific immune effectors during the acute infection and convalescent phases of 165 patients with COVID-19 categorized by *** found that early and robust SARS-CoV-2-specific CD4^(+)and CD8^(+)T cell responses ameliorate disease progression and shortened hospital stay,while delayed and attenuated virus-specific CD8^(+)T cell responses are prominent severe COVID-19 *** antiviral antibody generation rather than titer level associates with severe ***,initial COVID-19 severity imprints the long-term maintenance of SARS-CoV-2-specific adaptive immunity,demonstrating that severe convalescents exhibited more sustained virus-specific antibodies and memory T cell responses compared to mild/moderate ***,initial COVID-19 severity inversely correlates with SARS-CoV-2 reinfection ***,our study unravels the complicated interaction between temporal characteristics of virus-specific T cell responses and COVID-19 severity to guide future SARS-CoV-2 wave management.

关键词： severity immunity infection

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双免疫治疗驱动基因和PD-L1双阴性晚期非小细胞肺癌患者的效果和安全性分析

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中华医学杂志 2024年第30期104卷 2797-2804页

作者：栾涛谢晓鸿林心情邓海怡李逸佳孙君璐杨罡张云辉王帅颖王长春钟南山周承志广州医科大学第一附属医院肿瘤内科国家医学呼吸中心呼吸疾病国家重点实验室广州昆明理工大学附属医学院呼吸内科云南省第一人民医院呼吸内科昆明浙江省肿瘤医院手术中心杭州

目的探讨纳武利尤单抗+伊匹木单抗双免疫治疗驱动基因和程序性细胞死亡配体1(PD-L1)双阴性晚期非小细胞肺癌(NSCLC)患者的效果和安全性。方法回顾性收集2019年1月至2023年6月就诊于广州医科大学第一附属医院接受纳武利尤单抗+伊匹木单... 详细信息

目的探讨纳武利尤单抗+伊匹木单抗双免疫治疗驱动基因和程序性细胞死亡配体1(PD-L1)双阴性晚期非小细胞肺癌(NSCLC)患者的效果和安全性。方法回顾性收集2019年1月至2023年6月就诊于广州医科大学第一附属医院接受纳武利尤单抗+伊匹木单抗双免疫治疗的61例驱动基因和PD-L1双阴性NSCLC患者的临床资料。根据治疗情况, 将患者分为一线和非一线双免疫治疗组。每月随访1次, 随访截至2023年10月1日。应用实体瘤疗效评价标准评价疗效, 不良反应评价参照美国国立癌症研究所制定的通用不良反应术语标准。以Kaplan-Meier法绘制生存曲线, 采用log-rank检验比较一线和非一线双免疫治疗患者无进展生存时间(PFS)和总生存时间(OS)的差异。采用多因素Cox风险回归模型分析PFS的影响因素。结果 61例NSCLC患者中, 男49例(80.3%);年龄23～88(65.3±7.4)岁;TNM分期为ⅢC期14例(23.0%), Ⅳ期47例(77.0%);非一线治疗40例(65.6%)。客观缓解率为24.6%(15/61), 疾病控制率为52.5%(32/61)。61例患者均获得随访, 中位随访时间为17.8个月, 中位PFS为6.0个月(95%CI:5.5～6.4个月), 中位OS为17.0个月(95%CI:14.8～19.2个月)。一线双免疫治疗患者的中位PFS长于非一线双免疫治疗患者[7.0个月(95%CI:6.0～7.9个月)比4.0个月(95%CI:3.3～4.6个月), P<0.001];一线双免疫治疗患者中位OS长于非一线双免疫治疗患者[19.0个月(95%CI:18.1～19.9个月)比13.0个月(95%CI:10.8～15.1个月), P<0.001]。多因素Cox风险回归模型分析结果显示, 肿瘤远处转移(HR=1.414, 95%CI:1.253～1.725)、非一线双免疫疗法(HR=1.412, 95%CI:1.184～1.652)、肿瘤突变负荷<10 mut/Mb(HR=1.328, 95%CI:1.151～1.546)是PFS的危险因素, 非鳞癌(HR=0.917, 95%CI:0.823～0.984)是PFS的保护因素。发生免疫治疗相关不良反应41例(67.2%), 其中3～4级不良反应21例(32.8%), 停药8例(13.1%), 无死亡病例。结论纳武利尤单抗+伊匹木单抗双免疫疗法可作为晚期驱动基因和PD-L1双阴性NSCLC患者的治疗选择。肿瘤远处转移、非一线双免疗法、肿瘤突变负荷<10 mut/Mb是影响患者PFS的危险因素, 非鳞癌是影响患者PFS的保护因素。

关键词：癌, 非小细胞肺双免疫疗法回顾性队列研究

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SYVN1介导FASN泛素化降解促进骨肉瘤细胞失巢凋亡

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实用癌症杂志 2024年第3期39卷 349-355页

作者：钟南山杨枫刘志礼南昌大学第一附属医院 330006 南昌大学脊柱脊髓研究所 330006

目的探讨FASN在骨肉瘤远处转移过程中受调控的机制。方法应用骨肉瘤失巢凋亡抵抗模型,通过在线预测、蛋白组学测序以及CO-IP实验等,筛选出与FASN相互作用的E3连接酶;Western blot、泛素化实验检测FASN蛋白的泛素化水平;应用流式细胞术,... 详细信息

目的探讨FASN在骨肉瘤远处转移过程中受调控的机制。方法应用骨肉瘤失巢凋亡抵抗模型,通过在线预测、蛋白组学测序以及CO-IP实验等,筛选出与FASN相互作用的E3连接酶;Western blot、泛素化实验检测FASN蛋白的泛素化水平;应用流式细胞术,肿瘤成球实验、裸鼠原位骨肉瘤肺转移模型等,探讨FASN泛素化在骨肉瘤远处转移中的调控机制。结果FASN在失巢凋亡抵抗细胞中泛素化水平降低而表达升高,预测结果提示SYVN1是FASN泛素化的E3连接酶;过表达SYVN1可以诱导骨肉瘤细胞失巢凋亡,并降低骨肉瘤原位成瘤和远处转移能力。结论E3连接酶SYVN1在骨肉瘤失巢凋亡抵抗过程中降低,导致FASN泛素化下降而表达升高,过表达SYVN1可抑制骨肉瘤进程。

关键词：骨肉瘤 FASN SYVN1 泛素化远处转移

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Role of let-7 family in the invasion and metastasis of osteosarcoma

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Chinese Medical Journal 2023年第1期136卷 120-122页

作者： Tong Xiao Xuan Yang nanshan zhong Zhiwen Luo Jiaming Liu Department of Orthopaedic Surgery The First Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China Medical College of Nanchang University NanchangJiangxi 330006China Institute of Spine and Spinal Cord Nanchang UniversityNanchangJiangxi 330006China

To the Editor:Osteosarcoma(OS),a disease seriously endangering the health of young people,is the eighth most common primary malignant bone tumor affecting children and *** occurring in the metaphysis of long tubular bone,OS develops from mesenchymal cells and accounts for 20%of primary bone *** 70%to 80%of patients are 8 to 9 years.

关键词： invasion metastasis osteosarcoma

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Translational medicine:What is in a name from the perspective of Chinese clinicians?

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Science China(Life Sciences) 2011年第12期54卷 1077-1080页

作者： ZENG GuangQiao zhong nanshan State Key Laboratory of Respiratory Disease First Affiliated Hospital of Guangzhou Medical College Guangzhou 510120 China

Translational medicine is an emerging medical practice that involves multidisciplinary collaborations to bridge between basic sciences and clinical use,aiming at enhancing patient care and preventive *** it suggests f... 详细信息

关键词：医学转化名称医生中国临床使用基础科学基础研究

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广州女性低剂量CT肺癌筛查结果及高危因素探索

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中国肺癌杂志 2024年第5期27卷 345-358页

作者：卢炫庄邱秋霞杨春玉黎才琛李坚福熊珊程博周楚静杜小芹张屹何建行梁文华钟南山广州医科大学附属第一医院广州510120 广州呼吸健康研究院广州510120 广州医科大学南山学院广州511436 广州市卫生健康委员会广州510080 南方医科大学广州510515

背景与目的肺癌高居中国恶性肿瘤发病率和死亡率之首。既往肺癌筛查试验大多为针对吸烟者等高危人群的选择性筛查,然而亚洲肺癌病例非吸烟女性占相当比例。本研究旨在评估广州市社区女性的肺癌患病率并探究肺癌高危因素。方法采用胸部... 详细信息

背景与目的肺癌高居中国恶性肿瘤发病率和死亡率之首。既往肺癌筛查试验大多为针对吸烟者等高危人群的选择性筛查,然而亚洲肺癌病例非吸烟女性占相当比例。本研究旨在评估广州市社区女性的肺癌患病率并探究肺癌高危因素。方法采用胸部低剂量计算机断层扫描(low-dose computed tomography,LDCT)对广州市40-74岁女性居民行肺癌筛查,并根据2018版《中国肺癌低剂量螺旋CT筛查指南》对肺结节进行分类管理及计算阳性结节和肺癌检出率。筛查对象在行检查前均须完成“肺癌危险因素调研问卷”,后对问卷危险因素进行最小绝对收缩和选择算子惩罚Logistic回归分析。结果分析共纳入6256名女性,发现阳性结节1228例(19.63%),确诊肺癌117例(1.87%),其中原位癌6例,I期103例(占肺癌比例88.03%)。根据问卷变量行最小绝对收缩和选择算子(Least absolute shrinkage and selection operator,LASSO)惩罚Logistic回归分析发现,年龄≥50岁(OR=1.07,95%CI:1.06-1.07)、个人恶性肿瘤史(OR=3.29,95%CI:3.22-3.37)、纺织职业(OR=1.10,95%CI:1.08-1.13)、小时候使用煤为燃料(OR=1.14,95%CI:1.13-1.16)以及食物过敏史(OR=1.10,95%CI:1.07-1.13)是该地区女性肺癌的高危因素。结论胸部LDCT可以发现大量早期肺癌,可用于女性肺癌筛查。年龄≥50岁、个人恶性肿瘤史、纺织职业、小时候使用煤为燃料和食物过敏史是该地区女性人群肺癌的高危因素,需提高该群体对肺癌早筛的重视程度。

关键词：肺肿瘤低剂量CT 早期筛查高危因素

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Induction of Th1-Type Immune Response by Chitosan Nanoparticles Containing Plasmid DNA Encoding House Dust Mite Allergen Der p2 for Oral Vaccination in Mice

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Cellular & Molecular Immunology 2009年第1期6卷 45-50页

作者： Guoping Li Zhigang Liu Bin Liao nanshan zhong Inflammation ＆ Allergic Disease Lab Affiliated Hospital of Luzhou Medical College Luzhou 646000 Sichuan China Medical College Shenzhen University Shenzhen 518060 GuangdongChina Guangzhou Institute of Respiratory Disease Guangzhou Medical College Guangzhou 510120 Guangdong China

This study was to prepare the chitosan-pDer p 2 nanoparticles and to investigate the effect of chitosan-DNA nanoparticles on immune response in mice by oral delivery of chitosan-DNA nanoparticles. The nanoparticles were synthesized by complexing chitosan with plasmid DNA. The DNA was fully complexed into chitosan-DNA nanoparticles, suggesting a 100% encapsulation efficiency. Chitosan-DNA complex renders a significant protection of the plasmid. No effect on cell viability was observed in both cell types and average cell viability over 100% was obtained. Oral gene delivery with chitosan-DNA nanoparticles can generate a higher level expression of gene in vivo. Oral chitosan-pDer p 2 nanoparticles in BALB/c mice can induce IFN-γ in serum and prevent subsequent sensitization of Th2 cell-regulated specific IgE responses. The data indicate that the oral administration of chitosan-pDer p 2 nanoparticles results in the expression of Der p 2 in the epithelial cells of both stomach and small intestine and the induction of Th1-type immune response. Cellular ＆ Molecular Immunology.

关键词： dermatophagoides pteronyssinus DNA vaccine chitosan nanoparticle

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Therapeutic Effects of DNA Vaccine on Allergen-Induced Allergic Airway Inflammation in Mouse Model

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Cellular & Molecular Immunology 2006年第5期3卷 379-384页

作者： Guoping Li Zhigang Liu nanshan zhong Bin Liao Ying Xiong Inflammafion ＆ Allergic Diseases Research Unit Affiliated Hospital of Luzhou Medical College Luzhou 646000 Sichuan China College of Life Sciences Shenzhen University Shenzhen 518060 China Guangzhou Institute of Respiratory Diseases Guangzhou Medical College Guangzhou 510120 China Department of Respiratory Disease Affiliated Hospital of Luzhou Medical College Luzhou 646000 China

Vaccination with DNA encoding Dermatophagoides pteronyssinus group 2 （Der p 2） allergen previously showed its effects of immunologic protection on Der p 2 allergen-induced allergic airway inflammation in mice. In present study, we investigated whether DNA vaccine encoding Der p 2 could exert therapeutic role on allergen-induced allergic airway inflammation in mouse model and explored the mechanism of DNA vaccination in asthma specific-allergen immunotherapy. After sensitized and challenged by Der p 2, the BALB/c mice were immunized with DNA vaccine. The degrees of cellular infiltration were scored. IgE levels in serum and IL-4/IL-13 levels in BALF were determined by ELISA. The lung tissues were assessed by histological examinations. Expressions of STAT6 and NF-kB in lung were determined by immunohistochemistry staining. Vaccination of mice with DNA vaccine inhibited the development of airway inflammation and the production of mucin induced by allergen, and reduced the level of Der p 2-specific IgE level. Significant reductions of eosinophil infiltration and levels of IL-4 and IL-13 in BALF were observed after vaccination. Further more, DNA vaccination inhibited STAT6 and NF-kB expression in lung tissue in Der p 2-immunized mice. These results indicated that DNA vaccine encoding Der p 2 allergen could be used for therapy of allergen-induced allergic airway inflammation in our mouse model. Cellular ＆ Molecular Immunology.

关键词： DNA vaccine Dermatophagoides pteronyssinus group 2 allergic airway inflammation

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Character of diaphragm compound muscle action potential and phrenic nerve conduction time in patients with obstructive sleep apnea-hypopnea syndrome

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Neural Regeneration Research 2008年第5期3卷 533-537页

作者： Yuhong HOU Rongchang Chen Jinbing Pan Yuanming Luo nanshan zhong Department of Emergency the First Affiliated Hospital Zhengzhou University Zhengzhou 450052 Henan Province China Guangzhou Institute of Respiratory Disease First Affiliated Hospital Guangzhou Medical College Guangzhou 510120 Guangdong Province China Department of Respiratory Medicine Henan Provincial Hospital Zhengzhou 450003 Henan Province China

BACKGROUND： Both hypoxia *** dioxide retention can damage phrenic nerve and muscle conduction, as well as diaphragm function. Diaphragm compound muscle action potential and phrenic nerve conduction time are reliable indicators for measuring phrenic nerve and diaphragm function. OBJECTIVES： To verify the hypothesis that changes of phrenic nerve conduction time （PNCT） and diaphragm compound muscle action potential （CMAP） in obstructive sleep apnea-hypopnea syndrome （OSAHS） patients might contribute to the decline of phrenic nerve and diaphragm function. PNCT and CMAP were measured with multipair esophageal electrodes combined with unilateral magnetic stimulation. DESIGN, TIME AND SETTING： Case controlled study. The experiment was carried out in Guangzhou Institute of Respiratory Disease, Guangzhou MediCal College, from June 2005 to April 2006. PARTICIPANTS： Twenty seven OSAHS patients and eight primary snoring subjects from Guangzhou Institute of Respiratory Disease, Guangzhou Medical College were recruited and all subjects were diagnosed by polysomnography （PSG）. Sixteen healthy, non-snoring subjects in the hospital for medical examination during the same time period were selected as the control group. METHODS： Esophageal electrodes, made by Guangzhou Institute of Respiratory Disease, combined with unilateral magnetic stimulation, were used to measure PNCT and CMAP of all subjects. PNCT was defined as the time from stimulation artifact to the onset of CMAP and diaphragm CMAP amplitude was measured from peak to peak. Oxygen desaturation index and apnea-hypopnea index were measured using PSG, and their relevance to PNCT and CMAP were analyzed. PNCT and CMAP in five OSAHS patients were repeatedly measured after effective nasal continuous positive airway pressure treatment for more than 2 months. MAIN OUTCOME MEASURES：（1） PNCT and diaphragm CMAP of subjects in each group. （2） Relevance of oxygen desaturation index and apnea-hypopnea index to PNCT and CMAP. （3） Ch

关键词： sleep apnea syndrome action potentials phrenic nerve

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SARS-CoV-2 spike protein receptor-binding domain perturbates intracellular calcium homeostasis and impairs pulmonary vascular endothelial cells

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3780-3793页

作者： Kai Yang Shiyun Liu Han Yan Wenju Lu Xiaoqian Shan Haixia Chen Changlei Bao Huazhuo Feng Jing Liao Shuxin Liang Lei Xu Haiyang Tang Jason X-J.Yuan nanshan zhong Jian Wang State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangdong Key Laboratory of Vascular DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Guangzhou National Laboratory Guangzhou International Bio IslandGuangzhouGuangdongChina Department of Pulmonary and Critical Care Medicine The Affiliated Hospital of Inner Mongolia Medical UniversityHohhotInner Mongolia Autonomous RegionChina Department of Pathology The Affiliated Cancer Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina School of Medicine Southern University of Science and TechnologyShenzhenGuangdongChina Section of Physiology Division of PulmonaryCritical Care and Sleep MedicineDepartment of MedicineUniversity of California San DiegoLa JollaCAUSA

Exposure to the spike protein or receptor-binding domain(S-RBD)of SARS-CoV-2 significantly influences endothelial cells and induces pulmonary vascular *** this study,angiotensin-converting enzyme 2 humanized inbred(hACE2 Tg)mice and cultured pulmonary vascular endothelial cells were used to investigate how spike protein/S-RBD impacts pulmonary vascular *** show that S-RBD leads to acute-to-prolonged induction of the intracellular free calcium concentration([Ca^(2+)]i)via acute activation of TRPV4,and prolonged upregulation of mechanosensitive channel Piezo1 and store-operated calcium channel(SOCC)key component Orai1 in cultured human pulmonary arterial endothelial cells(PAECs).In mechanism,S-RBD interacts with ACE2 to induce formation of clusters involving Orai1,Piezo1 and TRPC1,facilitate the channel activation of Piezo1 and SOCC,and lead to elevated *** effects are blocked by Kobophenol A,which inhibits the binding between S-RBD and ACE2,or intracellular calcium chelator,*** of Piezo1 and SOCC by GsMTx4 effectively protects the S-RBDinduced pulmonary microvascular endothelial damage in hACE2 Tg mice via normalizing the elevated[Ca^(2+)]*** to prototypic strain,Omicron variants(BA.5.2 and XBB)of S-RBD induces significantly less severe cell *** analysis indicates that prototypic S-RBD confers more severe acute impacts than Delta or Lambda *** summary,this study provides compelling evidence that S-RBD could induce persistent pulmonary vascular endothelial damage by binding to ACE2 and triggering[Ca^(2+)]i through upregulation of Piezo1 and *** inhibition of ACE2-Piezo1/SOCC-[Ca^(2+)]i axis proves a powerful strategy to treat S-RBD-induced pulmonary vascular diseases.

关键词： ACE2 elevated homeostasis

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