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Cardiovascular toxicity in antitumor therapy: biological and therapeutic insights

TRENDS IN CANCER 2024年第10期10卷 920-934页

作者： lin, xuwen Ma, Xidong Zhao, Sheng Yao, Jie Han, Leng Jing, Ying Xue, Xinying Capital Med Univ Beijing Shijitan Hosp Emergency & Crit Care Med Ctr Dept Resp & Crit Care Beijing Peoples R China Chinese Acad Med Sci & Peking Union Med Coll Fuwai Hosp Natl Ctr Cardiovasc Dis State Key Lab Cardiovasc DisDept Cardiol Beijing Peoples R China Shandong Second Med Univ Dept Resp & Crit Care Weifang Peoples R China Indiana Univ Brown Ctr Immunotherapy Sch Med Indianapolis IN 46202 USA Indiana Univ Sch Med Dept Biostat & Hlth Data Sci Indianapolis IN 46202 USA Fudan Univ Greater Bay Area Inst Precis Med Guangzhou Ctr Intelligent Med Res Sch Life Sci Guangzhou Peoples R China

The evolution of antitumor therapies has significantly improved cancer prognosis but has concurrently resulted in cardiovascular toxicities. Understanding the biological mechanisms behind these toxicities is crucial for effective management. Immunotherapy-related cardiovascular toxicities are primarily mediated by immune cells and secreted cytokines. Chemotherapy may cause cardiovascular damage through autophagy disruption and mitochondrial dysfunction. Targeted therapies can induce toxicity through endothelin-1 (ET-1) production and cardiac signaling disruption. Radiotherapy may lead to cardiomyopathy and myocardial fibrosis by affecting endothelial cells, triggering inflammatory responses and accelerating atherosclerosis. This review provides insights into these mechanisms and strategies, aiming to enhance the clinical prevention and treatment of cardiovascular toxicities.

关键词： cardiovascular toxicities immunotherapy chemotherapy radiotherapy targeted therapy biological mechanisms

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Tertiary Lymphoid Structure in Tumor Microenvironment and Immunotherapy of Lung Cancer

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ARCHIVOS DE BRONCONEUMOLOGIA 2024年 60卷 S77-S85页

作者： Xie, Mei lin, xuwen Bao, Xinyu Liang, Yiran Deng, Hui Song, Jialin Ma, Xidong Zhang, Xin Yao, Jie Pan, Lei Xue, Xinying Capital Med Univ Beijing Shijitan Hosp Dept Resp & Crit Care Emergency & Crit Care Med Ctr Beijing 100038 Peoples R China Shandong Second Med Univ Sch Clin Med Dept Resp & Crit Care Weifang Shandong Peoples R China

Immune checkpoint inhibitors have opened an era of lung cancer therapy. However, a notable disparity exists in the efficacy of immunotherapy among individual patients. The tertiary lymphoid structure (TLS) is an ectopic lymphocyte aggregation that appears under pathological conditions and is the primary site of action for anti-tumor immunity. It is commonly reported that the presence of TLS within the tumor microenvironment (TME) relates to a favorable clinical prognosis and an excellent response to immunotherapy in lung cancer patients. A thorough understanding of TLS and its dynamic changes in TME has become an attractive focus for optimizing immunotherapy strategies for lung cancer. In this review, we comprehensively generalize the composition, formation, mechanism, detection methods of TLS, and summarize the role of TLS in lung cancer immunotherapy. Finally, induction of TLS is also discussed, which may provide more effective therapeutic strategies for lung cancer therapy. (c) 2024 The Authors. Published by Elsevier Espana, S.L.U. on behalf of SEPAR.

关键词： Tertiary lymphoid structures Lung cancer Immunotherapy Prognosis

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Latex microspheres lateral flow immunoassay with smartphone-based device for rapid detection of Cryptococcus

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TALANTA 2025年 284卷 127254页

作者： Zang, Xuelei Zhou, Yangyu Li, Shuming Shi, Gang Deng, Hengyu Zang, Xuefeng Cao, Jingrong Yang, Ruonan lin, xuwen Deng, Hui Huang, Yemei Yang, Chen Wu, Ningxin Song, Chao Wu, Lidong Xue, Xinying Capital Med Univ Beijing Shijitan Hosp Emergency & Crit Care Med Ctr Dept Resp & Crit Care Beijing 100038 Peoples R China Shandong Second Med Univ Weifang 261053 Peoples R China Datang Telecom Convergence Commun Technol Co Ltd Beijing 100094 Peoples R China Chinese Acad Fishery Sci Beijing 100141 Peoples R China Capital Med Univ Xuanwu Hosp Dept Clin Lab Beijing 100053 Peoples R China Nanjing Normal Univ Sch Food Sci & Pharmaceut Engn Nanjing 210023 Peoples R China Chinese Peoples Liberat Army Gen Hosp Med Lab Ctr Med Ctr 1 Beijing 1000853 Peoples R China 971 Hosp Chinese Peoples Liberat Army Navy Dept Cadres Qingdao 266000 Peoples R China Chinese Acad Fishery Sci Freshwater Fisheries Res Ctr Wuxi 214081 Peoples R China

Cryptococcus is a pathogenic fungus that poses a threat to human health. Conventional detection methods have limited the rapid and accurate qualitative and quantitative analysis of Cryptococcus, affecting early diagnosis and treatment. In this study, we developed a Point-of-Care Testing (POCT) platform that integrates lateral flow immunoassay (LFIA) with smartphones, enabling both rapid qualitative and quantitative detection of Cryptococcus. The LFIA strip utilizes latex microspheres (LMs) as labeling probes, achieving a detection limit of 3000 CFU/mL and presenting higher sensitivity than the Colloidal Gold Nanoparticles Lateral Flow Immunoassay (AuNPs-LFIA) strip, and approximately eight times that of the AuNPs-LFIA strip. Additionally, it exhibiting no cross-reactivity with over 24 common pathogens and validated in clinical samples. For quantitative analysis, artificial intelligence algorithms were employed to convert smartphone-captured images into grayscale values. Eleven feature values were utilized as a dataset for machine learning to construct a linear regression model, with Mean Squared Error (MSE) and R2 reaching 0.45 and 0.91, respectively. Moreover, the recovery rates in the serum samples ranged from 90.0 % to 108 %, indicating a good practicability. This research presents a rapid diagnostic technology for Cryptococcus and lays the theoretical and technical groundwork for detecting other pathogens.

关键词： Gold nanoparticles

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New biomarkers exploration and nomogram construction of prognostic and immune-related adverse events of advanced non-small cell lung cancer patients receiving immune checkpoint inhibitors

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RESPIRATORY RESEARCH 2023年第1期24卷 64-64页

作者： lin, xuwen Chen, Xi Long, Xiang Zeng, Chao Zhang, Zhihan Fang, Weiyi Xu, Ping Peking Univ Dept Pulm & Crit Care Med Shenzhen Hosp Shenzhen 518034 Guangdong Peoples R China Shantou Univ Med Coll Shantou 515041 Guangdong Peoples R China Southern Med Univ Canc Res Inst Sch Basic Med Sci Guangzhou 510515 Guangdong Peoples R China Southern Med Univ Integrated Hosp Tradit Chinese Med Canc Ctr Guangzhou 510315 Peoples R China

BackgroundImmune checkpoint inhibitors (ICIs) are regarded as the most promising treatment for advanced-stage non-small cell lung cancer (aNSCLC). Unfortunately, there has been no unified accuracy biomarkers and systematic model specifically identified for prognostic and severe immune-related adverse events (irAEs). Our goal was to discover new biomarkers and develop a publicly accessible method of identifying patients who may maximize benefit from *** retrospective study enrolled 138 aNSCLC patients receiving ICIs treatment. Progression-free survival (PFS) and severe irAEs were end-points. Data of demographic features, severe irAEs, and peripheral blood inflammatory-nutritional and immune indices before and after 1 or 2 cycles of ICIs were collected. Independent factors were selected by least absolute shrinkage and selection operator (LASSO) combined with multivariate analysis, and incorporated into nomogram construction. Internal validation was performed by applying area under curve (AUC), calibration plots, and decision *** nomograms with great predictive accuracy and discriminatory power were constructed in this study. Among them, two nomograms based on combined inflammatory-nutritional biomarkers were constructed for PFS (1 year-PFS and 2 year-PFS) and severe irAEs respectively, and one nomogram was constructed for 1 year-PFS based on immune indices. ESCLL nomogram (based on ECOG PS, preSII, changeCAR, changeLYM and postLDH) was constructed to assess PFS (1-, 2-year-AUC = 0.893 [95% CI 0.837-0.950], 0.828 [95% CI 0.721-0.935]). AdNLA nomogram (based on age, change-dNLR, changeLMR and postALI) was constructed to predict the risk of severe irAEs (AUC = 0.762 [95% CI 0.670-0.854]). NKT-B nomogram (based on change-CD3+CD56+CD16+NKT-like cells and change-B cells) was constructed to assess PFS (1-year-AUC = 0.872 [95% CI 0.764-0.965]). Although immune indices could not be modeled for severe irAEs prediction due to limited data, we were the

关键词： Immune Adverse events Lung cancer Biomarkers Nomogram

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Progresses in biomarkers for cancer immunotherapy

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MEDCOMM 2023年第5期4卷 e387页

作者： lin, xuwen Zong, Chenyu Zhang, Zhihan Fang, Weiyi Xu, Ping Peking Univ Shenzhen Hosp Dept Pulm & Crit Care Med Shenzhen Guangdong Peoples R China Shantou Univ Med Coll Dept Internal Med Shantou Guangdong Peoples R China Zunyi Med Univ Dept Internal Med Zunyi Guizhou Peoples R China Southern Med Univ Canc Res Inst Sch Basic Med Sci Guangzhou Guangdong Peoples R China Southern Med Univ Integrated Hosp Tradit Chinese Med Canc Ctr Guangzhou Guangdong Peoples R China Peking Univ Shenzhen Hosp Dept Pulm & Crit Care Med Shenzhen 518034 Guangdong Peoples R China Southern Med Univ Canc Res Inst Sch Basic Med Sci Guangzhou 510515 Guangdong Peoples R China

Currently, checkpoint inhibitor-based immunotherapy has emerged as prevailing treatment modality for diverse cancers. However, immunotherapy as a first-line therapy has not consistently yielded durable responses. Moreover, the risk of immune-related adverse events increases with combination regimens. Thus, the development of predictive biomarkers is needed to optimize individuals benefit, minimize risk of toxicities, and guide combination approaches. The greatest focus has been on tumor programmed cell death-ligand 1 (PD-L1), microsatellite instability (MSI), and tumor mutational burden (TMB). However, there remains a subject of debate due to thresholds variability and significant heterogeneity. Major unmet challenges in immunotherapy are the discovery and validation of predictive biomarkers. Here, we show the status of tumor PD-L1, MSI, TMB, and emerging data on novel biomarker strategies with oncogenic signaling and epigenetic regulation. Considering the exploration of peripheral and intestinal immunity has served as noninvasive alternative in predicting immunotherapy, this review also summarizes current data in systemic immunity, encompassing solute PD-L1 and TMB, circulating tumor DNA and infiltrating lymphocytes, routine emerging inflammatory markers and cytokines, as well as gut microbiota. This review provides up-to-date information on the evolving field of currently available biomarkers in predicting immunotherapy. Future exploration of novel biomarkers is warranted. Although immunotherapy has dramatically changed the clinical therapeutic landscape of various cancer patients, predictive biomarkers should therefore be early identified to discriminate patients who are most likely to benefit from *** review mainly focused on recent clinical trials presenting biomarkers derived from tissue, peripheral blood as well as gut microbiome that encompass tumor cells, immune cells, solute inflammation markers, and commensal *** prospective clini

关键词： biomarker immunity immunotherapy liquid biopsy tumor

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Optimization of car-sharing scheduling based on genetic combined with simulated annealing strategy 3

Optimization of car-sharing scheduling based on genetic comb...

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3rd International Academic Exchange Conference on Science and Technology Innovation, IAECST 2021

作者： Zhou, Chao Guo, Danyang Li, Jiaqi Rong, Aiqiong Liang, Sihua lin, xuwen Guangzhou City University of Technology College of Mechanical Engineering Guang Zhou510800 China

ISBN: (纸本)9781665402675

This paper conducts scientific research on the joint scheduling of vehicles and personnel based on the distribution of car-sharing use[1], so as to propose an optimal control scheduling scheme that improves car utilization while making customers more satisfied and maximizing corporate profits. To begin with, we used the partitioning method to pre-processing the shared vehicle location data set, and use Excel software to disassemble the coordinate information. We need to divide the data according to the parking points, count the data according to different parking points, make descriptive statistics on the total number of parked vehicles at the parking points, and then analyze the use distribution of car-sharing[2]. Additionally, a joint car-sharing scheduling optimization model is built and the model is improved, which is then transformed into a two-layer mTSP model[3]. The upper model is an mTSP model with uncertain number of vehicles with time windows, while the lower model is an mTSP model with uncertain number of persons with time windows. At the same time, the genetic algorithm is used to solve the model, and after the operation of selection, cross over and variation combined with the simulated annealing strategy[4] to achieve better optimization results and construct the most beneficial scheduling solution for the enterprise. © 2021 IEEE.

关键词： Genetic algorithms

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Bronchoalveolar Lavage as Potential Diagnostic Specimens to Genetic Testing in Advanced Nonsmall Cell Lung Cancer

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TECHNOLOGY IN CANCER RESEARCH & TREATMENT 2023年 22卷

作者： lin, xuwen Cai, Yazhou Zong, Chenyu Chen, Binbin Shao, Di Cui, Hao Li, Zheng Xu, Ping Peking Univ Resp Dept Shenzhen Hosp 1120 Lianhua Rd Shenzhen 518034 Peoples R China BGI Shenzhen BGI Genom Shenzhen Peoples R China Zhuhai Maternal & Child Hlth Hosp Zhuhai Peoples R China Cent South Univ Hunan Canc Hosp NHC Key Lab Carcinogenesis 88 Xiangya Rd Changsha 410005 Hunan Peoples R China Cent South Univ Xiangya Sch Med Affiliated Canc Hosp 88 Xiangya Rd Changsha 410005 Peoples R China

Background: There is limited knowledge on the yield of performing capture-based targeted ultradeep sequencing on bronchoalveolar lavage (BAL) specimens from advanced nonsmall cell lung cancer (NSCLC) patients. This study aimed to evaluate gene variations and performance characteristics in BAL and tissue specimens using targeted sequencing. Methods: This cohort study retrospectively enrolled 20 patients with advanced NSCLC. The variant detection percentage, correlation of tumor mutation burden (TMB), and allele frequency heterogeneity (AFH) were compared between paired BAL and tissue samples. A three-tiered system was also applied for the interpretation of gene variants according to the guidelines. Results: No statistical difference was observed in variant detection between BAL and tissue samples (P = .591 for variant tier and P = .409 for variant type). In general, BAL achieved higher detection rates in tier I variants (96.2% vs 84.6%) and gene fusions (75% vs 50%) compared with tissue samples;tissue samples had better variants detection rates for other variants, such as tier II (89.6% vs 76.0%), tier III (87.1% vs 72.6%), single nucleotide variant (SNV, 89.6% vs 76.5%), insertion/deletion/duplication (InDel, 74.6% vs 69.8%) and copy number variation (CNV, 93.8% vs 43.8%). Besides, there were significant correlations of TMB (R-2 = 0.96, P < .001) and AFH (R-2 = 0.87, P < .001) between BALs and paired tissues. Conclusions: The findings demonstrate that BAL may serve as a supplement in liquid biopsy for mutation detection and for routine utilization in clinical settings.

关键词： bronchoalveolar lavage capture-based targeted sequencing tumor mutation burden allele frequency heterogeneity advanced nonsmall cell lung cancer

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烧蚀炭化热防护材料热导率的贝叶斯辨识方法

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空天技术 2022年第3期2022卷 18-30+70页

作者：林旭文高博易法军杨强疏浩哈尔滨工业大学特种环境复合材料技术国家级重点实验室

烧蚀炭化材料热导率对热防护结构的温度分布、进入材料内部的净热流以及热应力分布具有重要影响，提出了一种基于动态贝叶斯网络（DBNs）的炭化材料热解过程热导率的辨识方法。在该方法中，利用全局敏感性分析方法获取各参数在整个升温... 详细信息

烧蚀炭化材料热导率对热防护结构的温度分布、进入材料内部的净热流以及热应力分布具有重要影响，提出了一种基于动态贝叶斯网络（DBNs）的炭化材料热解过程热导率的辨识方法。在该方法中，利用全局敏感性分析方法获取各参数在整个升温过程的主要影响区间，在各区间内仅求解相应敏感参数，减少同时辨识的参数个数。将该方法用于TACOT材料热导率辨识，数值算例结果表明，稀疏化后的DBNs使最大辨识误差降低为5.68%，温度复现的均方根误差降低了45.01%，且算法具有较好的稳定性，在考虑观测温度0.8%的高斯噪声下，变异系数仅为0.16。该方法可以进一步应用于求解烧蚀炭化热防护材料的其他参数、辨识结构边界所受气动热环境。

关键词：烧蚀炭化材料参数辨识动态贝叶斯网络全局敏感性分析热导率热解过程

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Arbidol/IFN-a2b therapy for patients with corona virus disease 2019: a retrospective multicenter cohort study

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MICROBES AND INFECTION 2020年第4-5期22卷 200-205页

作者： Xu, Ping Huang, Jianping Fan, Zhao Huang, Wendi Qi, Minghua lin, xuwen Song, Weidong Yi, Li Peking Univ Shenzhen Hosp Dept Resp & Crit Care Med Shenzhen 518036 Guangdong Peoples R China Hubei Jianli People Hosp Dept Infect Dis Jingzhou 433300 Hubei Peoples R China Peking Univ Dept Emergency Shenzhen Hosp Shenzhen Guangdong Peoples R China Peking Univ Dept Neurol Shenzhen Hosp 1120 Lianhua Rd Futian Area Shenzhen 518036 Guangdong Peoples R China

The spread of COVID-19 is accelerating. At present, there is no specific antiviral drugs for COVID-19 outbreak. This is a multicenter retrospective cohort study of patients with laboratory-confirmed COVID-19 infection pneumonia from 3 hospitals in Hubei and Guangdong province, 141 adults (aged ≥18 years) without ventilation were included. Combined group patients were given Arbidol and IFN-α2b, monotherapy group patients inhaled IFN-α2b for 10-14 days. Of 141 COVID-19 patients, baseline clinical and laboratory characteristics were similar between combined group and monotherapy group, that 30% of the patients leucocytes counts were below the normal range and 36.4% of the patients experienced lymphocytopenia. The duration of viral RNA of respiratory tract in the monotherapy group was not longer than that in the combined therapy group. There was no significant differences between two groups. The absorption of pneumonia in the combined group was faster than that in the monotherapy group. We inferred that Arbidol/IFN - 2 b therapy can be used as an effective method to improve the COVID-19 pneumonia of mild patients, although it helpless with accelerating the virus clearance. These results should be verified in a larger prospective randomized environment.

关键词： COVID-19 2019-nCoV Pneumonia Arbidol IFN-α2b Treatment RNA

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ClinICAL AND TRANSLATIONAL MEDICINE 2024年第3期14卷 e1613页

作者： lin, xuwen Xie, Mei Yao, Jie Ma, Xidong Qin, lin Zhang, Xu-Mei Song, Jialin Bao, Xinyu Zhang, Xin Zhang, Yinguang Liu, Yiming Han, Wenya Liang, Yiran Jing, Ying Xue, Xinying Capital Med Univ Beijing Shijitan Hosp Emergency & Crit Care Med Ctr Dept Resp & Crit Care Beijing Peoples R China Chinese Peoples Liberat Army Gen Hosp Dept Resp & Crit Care Beijing Peoples R China Capital Med Univ Beijing Chest Hosp TB & Thorac Tumor Inst Dept Endoscop Diag & Treatment Beijing Peoples R China Weifang Med Univ Dept Pathol Affiliated Hosp Weifang Shandong Peoples R China Weifang Med Coll Dept Resp & Crit Care Weifang Shandong Peoples R China Capital Med Univ Beijing Tiantan Hosp Dept Thorac Surg Beijing Peoples R China Chinese Peoples Liberat Army Gen Hosp Dept Thorac Surg Beijing Peoples R China Hubei Univ Med Taihe Hosp Dept Resp & Crit Care Shiyan Peoples R China Fudan Univ Ctr Intelligent Med Greater Bay Area Inst Precis Med Guangzhou Sch Life Sci Guangzhou Guangdong Peoples R China Fudan Univ Greater Bay Area Inst Precis Med Guangzhou Ctr Intelligent Med Sch Life Sci Guangzhou 511462 Guangdong Peoples R China Capital Med Univ Beijing Shijitan Hosp Emergency & Crit Care Med Ctr Dept Resp & Crit Care Beijing 100038 Peoples R China

The emergence of immune checkpoint inhibitors (ICIs) has heralded a transformative era in the therapeutic landscape of non-small cell lung cancer (NSCLC). While ICIs have demonstrated clinical efficacy in a portion of patients with NSCLC, these treatments concurrently precipitate a spectrum of immune-related adverse events (irAEs), encompassing mild to severe manifestations, collectively posing a risk of significant organ damage. Consequently, there exists an imperative to augment our comprehension of the pathophysiological underpinnings of irAEs and to formulate more efficacious preventive and ameliorative strategies. In this comprehensive review, we delineate the clinical presentation of organ-specific irAEs in patients with NSCLC and provide an in-depth analysis of recent advancements in understanding the mechanisms driving ICI-induced toxicity. Furthermore, we discuss potential strategies and targets for ameliorating these irAEs. Ultimately, this review aims to furnish valuable insights to guide further research endeavours in the context of irAEs in NSCLC patients. Immunotherapy not only revolutionises lung cancer treatment but also poses serious toxicity risks. Elucidating irAE mechanisms in NSCLC: T/B-cell dysregulation, cytokine imbalances, autoantibody production, genetic predispositions and gut microbiome alterations. Highlighting precise irAE interventions in NSCLC: corticosteroids, targeted immunosuppressants, monoclonal antibodies targeting lymphocytes, cytokine inhibitors and signalling pathway modulators. image

关键词： immune checkpoint inhibitors immune-related adverse events mechanism non-small cell lung cancer

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