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Advances in immunopathogenesis of adult immune thrombocytopenia

null

《医学前沿（英文）》 2013年第7卷第4期页码 418-424 doi: 10.1007/s11684-013-0297-8

摘要：

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immune-mediated accelerated platelet destruction and/or suppressed platelet production. Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP, several abnormalities involving the cellular mechanisms of immune modulation have been identified, and the pathways behind the immune-mediated destruction of platelets have opened new avenues for the design of specific immunotherapies in an attempt to reduce the platelet destruction. This review is primarily focused on the recent literature with respect to immunopathological mechanisms in patients with ITP.

关键词： primary immune thrombocytopenia B lymphocytes T lymphocytes antigen-presenting cells cytokines

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A rare case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) translocation

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《医学前沿（英文）》 2018年第12卷第3期页码 324-329 doi: 10.1007/s11684-017-0558-z

摘要：

Splenic lymphoma with villous lymphocytes (SLVL) or splenic marginal zone lymphoma with circulating villous lymphocytes is rare, and prolymphocytic transformation of SLVL is rarer. At present, only one case of SLVL with t(8;14)(q24;q32) translocation has been reported. In this study, we report a case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) chromosome translocation that we inclined to SLVL with a prolymphocytic transformation. A 73-year-old female showed marked hepatosplenomegaly and high lymphocytosis (lymphocytes>200×10⁹/L). The abnormal lymphocytes had short coarse villi and round nuclei with prominent nucleoli. The immunophenotypes showed CD19⁺, CD20⁺, HLA-DR⁺, CD22⁺, CD5⁺, Kappa⁺, CD25^dim, CD71^dim, Lambda⁻, CD7⁻, CD10⁻, CD23⁻, CD34⁻, CD33⁻, CD13⁻, CD14⁻, CD117⁻, CD64⁻, CD103⁻, and CD11c⁻. The karyotype showed complex abnormality: 46XX,+3,−10, t(8;14)(q24;q32)[11]/46XX[⁹]. The cytoplasmic projection, immunological characteristics, and trisomy 3 chromosome abnormality supported the diagnosis of SLVL. However, the presence of prominent nucleoli and high lymphocytosis suggested prolymphocytic transformation, probably as a result of t(8,14) chromosome translocation. In this report, we described an unusual case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) translocation, which could provide help in the diagnosis and differential diagnosis of B-lymphocytic proliferative diseases.

关键词： splenic lymphoma with villous lymphocytes splenic marginal zone lymphoma transformation chromosome translocation

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Tim-3 mRNA expression in peripheral blood lymphocytes from asthmatic patients

Xiaoxia LU, Weikun HU, Shengdao XIONG, Guopeng XU, Fen LAN

《医学前沿（英文）》 2009年第3卷第2期页码 187-190 doi: 10.1007/s11684-009-0033-6

摘要： The study aimed to detect the expression of the Th1-specific cell surface protein T cell Ig and mucin domain-containing molecule-3 (Tim-3) mRNA in peripheral blood lymphocytes isolated from asthmatic patients and to examine the correlation among Tim-3 mRNA, interleukin-4 (IL-4), interferon-γ (IFN-γ) level, and FEV1/FVC (force expiratory volume in one second/forced vital capacity) to explore the role of Tim-3 in the development and progression of asthmatic inflammation. Tim-3 mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR). The IL-4 and IFN-γ levels were determined by using enzyme-linked immunosorbent assay (ELISA). The correlation among Tim-3 mRNA, IL-4, IFN-γ level, and pulmonary ventilatory capacity was analyzed. The expression of Tim-3 mRNA in patients with acute asthma exacerbation was 0.39±0.06, significantly higher than that in patients at the remission stage and controls (0.18±0.05 and 0.07±0.03, <0.05). The level of IL-4 in patients with acute asthma exacerbation was 68.42±10.54, significantly higher than that in the patients at the remission stage and controls (41.83±9.37 and 32.75±8.16, <0.05). The level of IL-4 in patients in remission was significantly higher than that in controls ( <0.05). The level of IFN-γ in patients with acute asthma exacerbation was 65.74±7.85, significantly lower than that in patients in remission and the control group (120.84±11.62 and 139.65±13.47, <0.05). The level of IFN-γ in patients in asthma remission was significantly lower than that in controls ( <0.05). Tim-3 mRNA expression was positively correlated with the level of IL-4 ( =0.68, <0.05) and negatively with the level of IFN-γ and pulmonary ventilatory capacity ( =-0.85, =-0.76, both <0.01). The increased expression of Tim-3 mRNA in peripheral blood lymphocytes might be involved in the development and progression of asthmatic inflammation.

关键词： asthma airway inflammation peripheral blood lymphocyte Tim-3

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供体来源的CD19靶向T细胞输注可以消除异基因造血干细胞移植后对供者淋巴细胞无反应的急性B淋巴细胞白血病微小残留病 Article

程翼飞, 陈育红, 闫晨华, 王昱, 赵翔宇, 陈瑶, 韩伟, 许兰平, 张晓辉, 刘开彦, 王莎莎, 张隆基, 肖磊, 黄晓军

《工程（英文）》 2019年第5卷第1期页码 150-155 doi: 10.1016/j.eng.2018.12.006

摘要：虽然供体来源的CD19 导向嵌合抗原受体（chimeric antigen receptor-modified，CAR）修饰T 细胞（CART19）可能治愈白血病，但输注此类细胞的效率与安全性尚未在经过在2014 年9 月至2018 年2 月期间，6 名患者均一次或多次输注了HSCT 供者提供的CD19 导向CAR 修饰T 细胞。其中有5 名患者（83.33%）的MRD 阴性得到缓解，而另1 名患者对CAR T 细胞并无反应。6 名患者中有3 名至今存活，白血病也并未复发。对于在allo-HSCT 后出现MRD 的B-ALL 患者且对DLI 并无反应的患者而言，供体来源的CAR T 细胞输注似乎是一种有效而安全的干预手段。

关键词：供体来源的CD19靶向T细胞输注造血干细胞移植急性B淋巴细胞白血病微小残留病

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Deubiquitinases as pivotal regulators of T cell functions

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《医学前沿（英文）》 2018年第12卷第4期页码 451-462 doi: 10.1007/s11684-018-0651-y

摘要：

T cells efficiently respond to foreign antigens to mediate immune responses against infections but are tolerant to self-tissues. Defect in T cell activation is associated with severe immune deficiencies, whereas aberrant T cell activation contributes to the pathogenesis of diverse autoimmune and inflammatory diseases. An emerging mechanism that regulates T cell activation and tolerance is ubiquitination, a reversible process of protein modification that is counter-regulated by ubiquitinating enzymes and deubiquitinases (DUBs). DUBs are isopeptidases that cleave polyubiquitin chains and remove ubiquitin from target proteins, thereby controlling the magnitude and duration of ubiquitin signaling. It is now well recognized that DUBs are crucial regulators of T cell responses and serve as potential therapeutic targets for manipulating immune responses in the treatment of immunological disorders and cancer. This review will discuss the recent progresses regarding the functions of DUBs in T cells.

关键词： deubiquitinase ubiquitination T cell activation T cell differentiation T cell tolerance

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Regulation of T cell immunity by cellular metabolism

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《医学前沿（英文）》 2018年第12卷第4期页码 463-472 doi: 10.1007/s11684-018-0668-2

摘要：

T cells are an important adaptive immune response arm that mediates cell-mediated immunity. T cell metabolism plays a central role in T cell activation, proliferation, differentiation, and effector function. Specific metabolic programs are tightly controlled to mediate T cell immune responses, and alterations in T cell metabolism may result in many immunological disorders. In this review, we will summarize the main T cell metabolic pathways and the important factors participating in T cell metabolic programming during T cell homeostasis, differentiation, and function.

关键词： T cell immunity metabolic pathways nutrient uptake metabolic checkpoints

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Separation and extraction of bridge dynamic strain data

Baijian WU, Zhaoxia LI, Ying WANG, T. H. T. CHAN,

《结构与土木工程前沿（英文）》 2009年第3卷第4期页码 395-400 doi: 10.1007/s11709-009-0049-7

摘要： Through comparing the measured data of dynamic strains due to loading and temperature by the stain gauge and temperature sensor at the same location, the information in the strain data was divided into three parts in the frequency domain by using the defined index named power spectral density (PSD)-ratio index. The three parts are dominated respectively by temperature varying, stresses, and noises and thus can be distinguished from the determined the separatrix frequencies. Also, a simple algorithm was developed to separate the three types of information and to extract the strain caused mainly by structural stresses. As an application of the proposed method, the effect of strain deformation and noises on the fatigue assessment was investigated based on the separated data. The results show that, the determined values of separatrix frequencies are valuable for the monitoring data from other bridges. The algorithm is a multiresolution and hierarchical method, which has been validated as a simple and effective method for data analyses, and is suitable for the compression and preprocessing of the great amount monitoring data and easy to be integrated into the structural health monitoring (SHM) soft system. The strain due to temperature varying attributes a little to the errors of fatigue assessment; however, the noises or random disturbance existed in the monitoring data have much responsibility for the errors, and the main reason is that the random disturbance shifts the real strain/stress amplitude picked up by real structural stress or strain.

关键词： dynamic valuable separatrix strain/stress amplitude frequency

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Carcinogens that induce the A:T>T:A nucleotide substitutions in the genome

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《医学前沿（英文）》 2018年第12卷第2期页码 236-238 doi: 10.1007/s11684-017-0611-y

摘要：

Recently, Ng . reported that the A:T>T:A substitutions, proposed to be a signature of aristolochic acid (AA) exposure, were detected in 76/98 (78%) of patients with hepatocellular carcinoma (HCC) from the Taiwan Province of China, and 47% to 1.7% of HCCs from the Chinese mainland and other countries harbored the nucleotide changes. However, other carcinogens, e.g., tobacco carcinogens 4-aminobiphenyl and 1,3-butadiene, air toxic vinyl chloride and its reactive metabolites chloroethylene oxide, melphalan and chlorambucil, also cause this signature in the genome. Since tobacco smoke is a worldwide public health threat and vinyl chloride distributes globally and is an air pollutant in Taiwan Province, the estimation of the patients’ exposure history is the key to determine the “culprit” of the A:T>T:A mutations. Apparently, without estimation of the patients’ exposure history, the conclusion of Ng is unpersuasive and misleading.

关键词： genomic signature carcinogen aristolochic acid tobacco smoke vinyl chloride hepatocellular carcinoma

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γδ T cells in liver diseases

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《医学前沿（英文）》 2018年第12卷第3期页码 262-268 doi: 10.1007/s11684-017-0584-x

摘要：

γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues. γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and liver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.

关键词： γδT cells liver infection non-alcoholic fatty liver disease autoimmune hepatitis liver fibrosis and cirrhosis liver cancer liver regeneration

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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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A case for assessing

Ian T. RILEY

《农业科学与工程前沿（英文）》 2021年第8卷第4期页码 568-582 doi: 10.15302/J-FASE-2019270

摘要： Agroecosystems in water-limited contexts— Mediterranean, semi-arid and arid climatic zones—are too frequently degraded systems that will not provide the needed ecosystem services to ensure a future of sustainable agricultural production. The processes that have created this situation continue and are being accelerated by anthropogenic climate change. Increasing arboreal vegetation in these areas through agroforestry is an important strategy to conserve and improve their agroecosystems. Actinorhizal trees and shrubs in the Casurinaceae have a unique set of adaptations for heat and water stress, and/or infertile to hostile soils. Central Anatolia, Turkey is particularly at risk of increasing aridity and further degradation. Therefore, species of and have been evaluated for their potential use in agroecosystem improvement in semi-arid areas with a focus on Central Anatolia. Based on a semiquantitative environmental tolerance index and reported plant stature, eight species were identified as being of high ( . and . ) to moderate ( . , . , . , . , . and . ) priority for assessment, with none of these species having been adequately evaluated for agroforestry deployment in semi-arid agroecosystems in any context.

关键词： actinorrhizal trees agroforestry climate change ecosystem restoration

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CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies

《医学前沿（英文）》 2021年第15卷第6期页码 783-804 doi: 10.1007/s11684-021-0904-z

摘要： The current standard of care in hematological malignancies has brought considerable clinical benefits to patients. However, important bottlenecks still limit optimal achievements following a current medical practice. The genetic complexity of the diseases and the heterogeneity of tumor clones cause difficulty in ensuring long-term efficacy of conventional treatments for most hematological disorders. Consequently, new treatment strategies are necessary to improve clinical outcomes. Chimeric antigen receptor T-cell (CAR T) immunotherapy opens a new path for targeted therapy of hematological malignancies. In this review, through a representative case study, we summarize the current experience of CAR T-cell therapy, the management of common side effects, the causative mechanisms of therapy resistance, and new strategies to improve the efficacy of CAR T-cell therapy.

关键词： CAR T cells hematological malignancies review

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Chimeric antigen receptor T cell therapies for acute myeloid leukemia

Bin Gu, Jianhong Chu, Depei Wu

《医学前沿（英文）》 2020年第14卷第6期页码 701-710 doi: 10.1007/s11684-020-0763-z

摘要： Abstract Chimeric antigen receptor T cell (CAR T) therapies have achieved unprecedented efficacy in B-cell tumors, prompting scientists and doctors to exploit this strategy to treat other tumor types. Acute myeloid leukemia (AML) is a group of heterogeneous myeloid malignancies. Relapse remains the main cause of treatment failure, especially for patients with intermediate or high risk stratification. Allogeneic hematopoietic stem cell transplantation could be an effective therapy because of the graft-versus-leukemia effect, which unfortunately puts the patient at risk of serious complications, such as graft-versus-host disease. Although the identification of an ideal target antigen for AML is challenging, CAR T therapy remains a highly promising strategy for AML patients, particularly for those who are ineligible to receive a transplantation or have positive minimal residual disease. In this review, we focus on the most recent and promising advances in CAR T therapies for AML.

关键词： acute myeloid leukemia CAR T immunotherapy

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Innate and adaptive T cells in influenza disease

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《医学前沿（英文）》 2018年第12卷第1期页码 34-47 doi: 10.1007/s11684-017-0606-8

摘要：

Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza-specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses (T cells and antibody-producing B cells) achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T-cells (MAIT cells, gd T cells, and NKT cells) in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and gd T cells as well as adaptive CD8⁺ and CD4⁺ T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.

关键词： influenza innate T cells CD4⁺ and CD8⁺ T cells vaccination

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Treating wastewater under zero waste principle using wetland mesocosms

Ezzat, Mohammed T. Mohammed T.

《环境科学与工程前沿（英文）》 2021年第15卷第4期 doi: 10.1007/s11783-020-1351-9

摘要： Abstract • Smart wetland was designed to treat wastewater according to zero waste principle. • The system included a dynamic roughing filter, Cyperus papyrus (L.) and zeolite. • It removed 98.8 and 99.8% of chemical and bacterial pollutants in 3 days. • The effluent reused to irrigate a landscape and the sludge recycled as fertilizer. • The plant biomass is a profitable resource for antibacterial and antioxidants. The present investigation demonstrates the synergistic action of using a sedimentation unit together with Cyperus papyrus (L.) wetland enriched with zeolite mineral in one-year round experiment for treating wastewater. The system was designed to support a horizontal surface flow pattern and showed satisfactory removal efficiencies for both physicochemical and bacteriological contaminants within 3 days of residence time. The removal efficiencies ranged between 76.3% and 98.8% for total suspended solids, turbidity, iron, biological oxygen demand, and ammonia. The bacterial indicators (total and fecal coliforms, as well as fecal streptococci) and the potential pathogens (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) showed removal efficiencies ranged between 96.9% and 99.8%. We expect the system to offer a smart management for every component according to zero waste principle. The treated effluent was reused to irrigate the landscape of pilot area, and the excess sludge was recycled as fertilizer and soil conditioner. The zeolite mineral did not require regeneration for almost 36 weeks of operation, and enhanced the density of shoots (14.11%) and the height of shoots (15.88%). The harvested plant biomass could be a profitable resource for potent antibacterial and antioxidant bioactive compounds. This could certainly offset part of the operation and maintenance costs and optimize the system implementation feasibility. Although the experiment was designed under local conditions, its results could provide insights to upgrade and optimize the performance of other analogous large-scale constructed wetlands.

关键词： Wastewater dynamic roughing filter Cyperus papyrus (L.) zeolite zero waste