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Cytokine storm and translating IL-6 biology into effective treatments for COVID-19

《医学前沿（英文）》 doi: 10.1007/s11684-023-1044-4

摘要： As of May 3, 2023, the coronavirus disease 2019 (COVID-19) pandemic has resulted in more than 760 million confirmed cases and over 6.9 million deaths. Several patients have developed pneumonia, which can deteriorate into acute respiratory distress syndrome. The primary etiology may be attributed to cytokine storm, which is triggered by the excessive release of proinflammatory cytokines and subsequently leads to immune dysregulation. Considering that high levels of interleukin-6 (IL-6) have been detected in several highly pathogenic coronavirus-infected diseases, such as severe acute respiratory syndrome in 2002, the Middle East respiratory syndrome in 2012, and COVID-19, the IL-6 pathway has emerged as a key in the pathogenesis of this hyperinflammatory state. Thus, we review the history of cytokine storm and the process of targeting IL-6 signaling to elucidate the pivotal role played by tocilizumab in combating COVID-19.

关键词： SARS-CoV-2 COVID-19 cytokine storm interleukin-6 tocilizumab

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Beneficial metabolic activities of inflammatory cytokine interleukin 15 in obesity and type 2 diabetes

null

《医学前沿（英文）》 2015年第9卷第2期页码 139-145 doi: 10.1007/s11684-015-0377-z

摘要：

In obesity, chronic inflammation is believed to induce insulin resistance and impairs adipose tissue function. Although this view is supported by a large body of literature, it has been challenged by growing evidence that pro-inflammatory cytokines may favor insulin sensitivity through induction of energy expenditure. In this review article, interleukin 15 (IL-15) is used as a new example to explain the beneficial effects of the pro-inflammatory cytokines. IL-15 is secreted by multiple types of cells including macrophages, neutrophils and skeletal muscle cells. IL-15 expression is induced in immune cells by endotoxin and in muscle cells by physical exercise. Its transcription is induced by transcription factor NF-κB. IL-15 binds to its receptor that contains three different subunits (α, β and γ) to activate JAK/STAT, PI3K/Akt, IKK/NF-κB and JNK/AP1 pathways in cells. In the regulation of metabolism, IL-15 reduces weight gain without inhibiting food intake in rodents. IL-15 suppresses lipogenesis, stimulates brown fat function, improves insulin sensitivity through weight loss and energy expenditure. In human, circulating IL-15 is negatively associated with body weight. In the immune system, IL-15 stimulates proliferation and differentiation of T cells, NK cells, monocytes and neutrophils. In the anti-obesity effects of IL-15, T cells and NK cells are not required, but leptin receptor is required. In summary, evidence from human and rodents supports that the pro-inflammatory cytokine IL-15 may enhance energy expenditure to protect the body from obesity and type 2 diabetes. The mechanism of IL-15 action remains to be fully uncovered in the regulation of energy expenditure.

关键词： inflammation obesity cytokine energy expenditure insulin resistance

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人工肝血液净化系统——一种针对COVID-19细胞因子风暴的有效救治方法

章益民, 俞亮, 汤灵玲, 朱梦飞, 金燕琪, 王周晗, 李兰娟

《工程（英文）》 2021年第7卷第1期页码 11-13 doi: 10.1016/j.eng.2020.03.006

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宁夏的沙尘暴天气及防沙治沙的对策建议

高庆先,任阵海

《中国工程科学》 2002年第4卷第2期页码 16-21

摘要：

通过对宁夏地区气象台站沙尘天气历史记录的分析，给出了宁夏地区沙尘天气的空间分布规律和时间演变情况，并结合对宁夏荒漠化地区的实地考察内容，初步提出宁夏防沙治沙对策建议。

关键词：沙尘暴防沙治沙对策建议扬沙浮尘

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Integrating storm surge modeling with traffic data analysis to evaluate the effectiveness of hurricane

《结构与土木工程前沿（英文）》 2021年第15卷第6期页码 1301-1316 doi: 10.1007/s11709-021-0765-1

摘要： An integrated storm surge modeling and traffic analysis were conducted in this study to assess the effectiveness of hurricane evacuations through a case study of Hurricane Irma. The Category 5 hurricane in 2017 caused a record evacuation with an estimated 6.8 million people relocating statewide in Florida. The Advanced Circulation (ADCIRC) model was applied to simulate storm tides during the hurricane event. Model validations indicated that simulated pressures, winds, and storm surge compared well with observations. Model simulated storm tides and winds were used to estimate the area affected by Hurricane Irma. Results showed that the storm surge and strong wind mainly affected coastal counties in south-west Florida. Only moderate storm tides (maximum about 2.5 m) and maximum wind speed about 115 mph were shown in both model simulations and Federal Emergency Management Agency (FEMA) post-hurricane assessment near the area of hurricane landfall. Storm surges did not rise to the 100-year flood elevation level. The maximum wind was much below the design wind speed of 150–170 mph (Category 5) as defined in Florida Building Code (FBC) for south Florida coastal areas. Compared with the total population of about 2.25 million in the six coastal counties affected by storm surge and Category 1–3 wind, the statewide evacuation of approximately 6.8 million people was found to be an over-evacuation due mainly to the uncertainty of hurricane path, which shifted from south-east to south-west Florida. The uncertainty of hurricane tracks made it difficult to predict the appropriate storm surge inundation zone for evacuation. Traffic data were used to analyze the evacuation traffic patterns. In south-east Florida, evacuation traffic started 4 days before the hurricane’s arrival. However, the hurricane path shifted and eventually landed in south-west Florida, which caused a high level of evacuation traffic in south-west Florida. Over-evacuation caused Evacuation Traffic Index (ETI) to increase to 200% above normal conditions in some sections of highways, which reduced the effectiveness of evacuation. Results from this study show that evacuation efficiency can be improved in the future by more accurate hurricane forecasting, better public awareness of real-time storm surge and wind as well as integrated storm surge and evacuation modeling for quick response to the uncertainty of hurricane forecasting.

关键词： storm surge modeling traffic evacuation Hurricane Irma

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中药治疗新冠病毒肺炎的科学基础 Perspective

梁丽娴, 潘胡丹, 黄虞枫, 范星星, 王婉莹, 何芳, 蔡俊, 周华, 刘良

《工程（英文）》 2020年第6卷第10期页码 1099-1107 doi: 10.1016/j.eng.2020.08.009

摘要：

新近暴发的新冠病毒肺炎（COVID-19）已成为危害全球健康的紧急事件。现有证据表明，新冠病毒（SARS-CoV-2）与其他冠状病毒（如SARS-CoV和MERS-CoV）的基因序列具有相似性。因此，针对现存冠状病毒的引发疾病的机制研究和在治疗SARS时所取得的经验和教训，可咨今天对抗新冠病毒引发疾病的参考。COVID-19患者的临床病理特征提示患者在病情进展过程中通常会经历五个发展阶段：大量病毒感染、免疫系统抑制、细胞因子风暴、多器官损伤及后期的肺纤维化样改变，严重者常导致死亡。早期阻断疾病进展是取得治疗成功的关键。但是，目前尚无针对COVID-19的特效药物或疫苗，世界卫生组织（WHO）正敦促尽快建立新型预防和治疗策略。传统中医药（TCM）对于疫病的防治的实践已经积累了几千年的有用经验，它通过整体调节机体功能发挥疗效。在此次疫情中，中医药作为替代治疗或与西药联合使用，在疫情防控中发挥了重要的作用。本文总结了此次抗疫过程中中国国家和省级机构推荐使用的中药复方和中成药的潜在用途和治疗机制，以期发现其治疗COVID-19的潜在科学内涵。同时，整合应用多种组学及转化医学技术开展基础与临床研究有望进一步证实中药复方的治疗机制。

关键词： COVID-19 SARS-CoV-2 中药抗病毒细胞因子风暴肺纤维化

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Inflammation and liver tumorigenesis

null

《医学前沿（英文）》 2013年第7卷第2期页码 242-254 doi: 10.1007/s11684-013-0256-4

摘要：

Inflammation has been considered as one of the hallmarks of cancer, and chronic hepatitis is a major cause of liver cancer. This review will focus on the pathogenic role of inflammation in hepatocarcinogenesis and will discuss recent advances in understanding the chronic hepatitis-liver cancer link based on hot spots in liver cancer research, including cellular interaction, cytokines, microRNA and stem cells. All of these mechanisms should be taken into consideration because they are crucial for the development of more efficacious therapeutic strategies for preventing and treating human chronic hepatitis and hepatocellular carcinoma.

关键词： hepatocellular carcinoma hepatitis cytokine stem cell miRNA

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High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells

Synat Kang, Yanyan Li, Yifeng Bao, Yi Li

《医学前沿（英文）》 2019年第13卷第1期页码 69-82 doi: 10.1007/s11684-018-0677-1

摘要：

Cytokine-activated T cells (CATs) can be easily expanded and are widely applied to cancer immunotherapy. However, the good efficacy of CATs is rarely reported in clinical applications because CATs have no or very low antigen specificity. The low-efficacy problem can be resolved using T cell antigen receptor-engineered CAT (TCR-CAT). Herein, we demonstrate that NY-ESO-1_157–165 HLA-A*02:01-specific high-affinity TCR (HAT)-transduced CATs can specifically kill cancer cells with good efficacy. With low micromolar range dissociation equilibrium constants, HAT-transduced CATs showed good specificity with no off-target killing. Furthermore, the high-affinity TCR-CATs delivered significantly better activation and cytotoxicity than the equivalent TCR-engineered T cells (TCR-Ts) in terms of interferon-g and granzyme B production and in vitro cancer cell killing ability. TCR-CAT may be a very good alternative to the expensive TCR-T, which is considered an effective personalized cyto-immunotherapy.

关键词： cytokine-activated T cells high-affinity T cell receptor cancer immunotherapy TCR-CAT

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Molecular characterization of two suppressor of cytokine signaling 1 genes (

Xue XU,Jiannan ZHANG,Juan LI,Yajun WANG

《农业科学与工程前沿（英文）》 2015年第2卷第1期页码 73-83 doi: 10.15302/J-FASE-2015044

摘要： Suppressor of cytokine signaling 1 (SOCS1) protein can inhibit the signal transduction triggered by some cytokines or hormones and thus are important in many physiological/pathological processes, including innate and adaptive immunity, inflammation, and development in mammals. However, there is sparse information about their structure, tissue expression, in birds, where their biological functions remain unknown. In this study, we cloned and characterized two genes (named and ) from chickens. is predicted to encode a 207-amino acid protein, which shares high amino acid sequence identity (64%–67%) with human and mouse SOCS1. Besides , a novel gene was also identified in chickens and other non-mammalian vertebrates including . Chicken is predicted to encode a 212-amino acid protein, which shares only 30%–32% amino acid sequence identity with human SOCS1 and cSOCS1a. RT-PCR assay revealed that both and are widely expressed in all chicken tissues. Using a luciferase reporter assay system, we further demonstrated that transient expression of and can significantly inhibit chicken growth hormone (GH)- or prolactin (PRL)-induced luciferase activities of Hep G2 cells expressing cGH receptor (or cPRL receptor), indicating that SOCS1a and SOCS1b proteins can negatively regulate GH/PRL signaling. Taken together, these data suggest that both cSOCS1a and cSOCS1b may function as negative regulators of cytokine/hormone actions, such as modulation of GH/PRL actions in chickens.

关键词： chicken SOCS1a SOCS1b growth hormone prolactin

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Numerical simulations of morphological changes in barrier islands induced by storm surges and waves using

Soumendra Nath KUIRY, Yan DING, Sam S Y WANG

《结构与土木工程前沿（英文）》 2014年第8卷第1期页码 57-68 doi: 10.1007/s11709-014-0235-0

摘要： In this paper, an advanced explicit finite volume flow model in two-dimensions is presented for simulating supercritical coastal flows and morphological changes in a tidal/coastal inlet and barrier islands due to storm surges and waves. This flow model is coupled with existing wave-action model and sediment transport model. The resulting integrated coastal process model is capable of simulating flows induced by extreme conditions such as waves, surge tides, river flood flows, etc., and morphological changes induced by rapid coastal currents and waves. This developed supercritical flow model is based on the solution of the conservative form of the nonlinear shallow water equations with the effects of the Coriolis force, uneven bathymetry, wind stress, and wave radiation stresses. The forward Euler scheme is used for the unsteady term; and the convective term is discretized using the Godunov-type shock-capturing scheme along with the HLL Riemann solver on non-uniform rectilinear grids. The accuracy of the developed model is investigated by solving an experimental dam-break test case. Barrier island breaching, overflow and overwash due to severe storm attack are simulated and the predicted morphological changes associated to the events are analyzed to investigate the applicability of the model in a coast where all the physical forces are present.

关键词： coastal inlet coastal process modeling supercritical flow sediment transport barrier islands

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Critical flow-storm approach to total maximum daily load (TMDL) development: an analytical conceptual

Zhang Harry, Yu Shaw

《环境科学与工程前沿（英文）》 2008年第2卷第3期页码 267-273 doi: 10.1007/s11783-008-0058-0

摘要： One of the key challenges in the total maximum daily load (TMDL) development process is how to define the critical condition for a receiving waterbody. The main concern in using a continuous simulation approach is the absence of any guarantee that the most critical condition will be captured during the selected representative hydrologic period, given the scarcity of long-term continuous data. The objectives of this paper are to clearly address the critical condition in the TMDL development process and to compare continuous and event-based approaches in defining critical condition during TMDL development for a waterbody impacted by both point and nonpoint source pollution. A practical, event-based critical flow-storm (CFS) approach was developed to explicitly addresses the critical condition as a combination of a low stream flow and a storm event of a selected magnitude, both having certain frequencies of occurrence. This paper illustrated the CFS concept and provided its theoretical basis using a derived analytical conceptual model. The CFS approach clearly defined a critical condition, obtained reasonable results and could be considered as an alternative method in TMDL development.

关键词： representative hydrologic occurrence simulation approach scarcity alternative

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一场潜在的5G干扰风暴

Chris Palmer

《工程（英文）》 2019年第5卷第5期页码 815-816 doi: 10.1016/j.eng.2019.08.007

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Management of cytokine release syndrome related to CAR-T cell therapy

Hongli Chen, Fangxia Wang, Pengyu Zhang, Yilin Zhang, Yinxia Chen, Xiaohu Fan, Xingmei Cao, Jie Liu, Yun Yang, Baiyan Wang, Bo Lei, Liufang Gu, Ju Bai, Lili Wei, Ruili Zhang, Qiuchuan Zhuang, Wanggang Zhang, Wanhong Zhao, Aili He

《医学前沿（英文）》 2019年第13卷第5期页码 610-617 doi: 10.1007/s11684-019-0714-8

摘要： Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5–10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.

关键词： chimeric antigen receptor T cell cytokine release syndrome tocilizumab

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北京大气环境的区域特征与沙尘影响

任阵海,高庆先,苏福庆,王耀庭,张志刚,杨新兴

《中国工程科学》 2003年第5卷第2期页码 49-56

摘要：

讨论了北京大气环境的区域性特征。利用网络点集确定出大气输送通道，提出了汇聚带概念，同时分析了北京地区大气污染特征，使用激光技术探测了大气气溶胶的垂直分布。研究表明北京大气环境质量与周边地区的污染源有密切的关系，认为只有进行同步治理才能有效地改善首都大气环境的质量。通过卫星监测技术和对气象流场进行分析，对我国沙尘暴现象进行了研究。指出境外沙尘源和境内沙尘源，并以2002年3月20日北京一次特强沙尘暴为例，对原始沙尘源的分布进行了解析，分析指出原始沙尘源包括春季长江以北广大的裸露土地，显示出沙尘暴起始过程是以点源群出现，然后合并为沙尘带，最后出现大面积沙尘污染。并简述了我国现代环境理念。

关键词：沙尘暴输送通道环境污染中国

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沙尘暴监测预警服务系统一期工程建设及应注意的问题

王雪臣,程磊

《中国工程科学》 2004年第6卷第3期页码 64-67

摘要：

沙尘暴是一种灾害性天气，对我国国民经济和人民生活产生了严重影响。加强沙尘暴监测预警服务工作是利国利民之举，意义深远。目前的监测预报能力尚存在不足，不能满足对沙尘暴进行定量实时监测和预报的要求。通过沙尘暴监测预警服务系统一期工程建设可以明显增强对沙尘暴的监测预警服务能力。一期工程建设主要包括监测分系统、预警服务分系统、通信传输分系统等部分。为确保该项目建设效益的发挥，该项目的建设要充分发挥现有台站的监测能力，并考虑系统功能的整体性、可拓展性和资料格式的标准化等问题。

关键词：沙尘暴监测预警服务系统工程建设拓展问题