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Natural killer cells in liver diseases

null

《医学前沿（英文）》 2018年第12卷第3期页码 269-279 doi: 10.1007/s11684-018-0621-4

摘要：

The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals. In addition to the innate direct “killer” functions, NK cell activity contributes to regulate innate and adaptive immunity (helper or regulator). Under the setting of liver diseases, NK cells are of great importance for stimulating or inhibiting immune responses, leading to either immune activation or immune tolerance. Here, we focus on the relationship between NK cell biology, such as their phenotypic features and functional diversity, and liver diseases.

关键词： natural killer cell phenotype immune activation immune tolerance liver diseases

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免疫细胞在器官移植免疫排斥和免疫耐受中的不同作用 Review

干晓杰, 古鉴, 鞠峥, 吕凌

《工程（英文）》 2022年第10卷第3期页码 44-56 doi: 10.1016/j.eng.2021.03.029

摘要：

器官移植免疫排斥反应是由多种细胞参与的复杂的免疫应答过程，是决定移植成败和患者生存的关键因素。目前大多数器官移植患者采用免疫抑制剂和生物制剂的组合疗法来控制移植器官的免疫排斥反应，然而免疫抑制剂的使用会降低移植患者免疫系统功能，导致严重的并发症，如慢性感染、恶性肿瘤等。因
此，彻底了解器官移植免疫耐受和免疫排斥的相关机制对于开发更好的治疗方案和改善患者预后至关重要。本文对免疫细胞在器官移植免疫排斥和免疫耐受诱导过程中的作用，以及目前针对移植患者处于临床试验阶段的新型细胞治疗进行概述。

关键词：免疫细胞固有免疫细胞适应性免疫细胞器官移植免疫耐受

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Functional tolerance theory in incremental growth design

YANG Bo, ZE Xiangbo, YANG Tao

《机械工程前沿（英文）》 2007年第2卷第3期页码 336-343 doi: 10.1007/s11465-007-0059-x

摘要： The evolutionary tolerance design strategy and its characteristics are studied on the basis of automation technology in the product structure design. To guarantee a successful transformation from the functional requirement to geometry constraints between parts, and finally to dimension constraints, a functional tolerance design theory in the process of product growth design is put forward. A mathematical model with a correlated sensitivity function between cost and the tolerance is created, in which the design cost, the manufacturing cost, the usage cost, and the depreciation cost of the product are regarded as control constraints of the tolerance allocation. Considering these costs, a multifactor-cost function to express quality loss of the product is applied into the model. In the mathematical model, the minimum cost is used as the objective function; a reasonable process capability index, the assembly function, and assembly quality are taken as the constraints; and depreciation cost in the objective function is expressed as the discount rate terminology in economics. Thus, allocation of the dimension tolerance as the function and cost over the whole lifetime of the product is realized. Finally, a design example is used to demonstrate the successful application of the proposed functional tolerance theory in the incremental growth design of the product.

关键词： successful transformation mathematical automation technology tolerance allocation minimum

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Advances on immune-related adverse events associated with immune checkpoint inhibitors

Yong Fan, Yan Geng, Lin Shen, Zhuoli Zhang

《医学前沿（英文）》 2021年第15卷第1期页码 33-42 doi: 10.1007/s11684-019-0735-3

摘要： Immunotherapy has recently led to a paradigm shift in cancer therapy, in which immune checkpoint inhibitors (ICIs) are the most successful agents approved for multiple advanced malignancies. However, given the nature of the non-specific activation of effector T cells, ICIs are remarkably associated with a substantial risk of immune-related adverse events (irAEs) in almost all organs or systems. Up to 90% of patients who received ICIs combination therapy experienced irAEs, of which majority were low-grade toxicity. Cytotoxic lymphocyte antigen-4 and programmed cell death protein-1/programmed cell death ligand 1 inhibitors usually display distinct features of irAEs. In this review, the mechanisms of action of ICIs and how they may cause irAEs are described. Some unsolved challenges, however really engrossing issues, such as the association between irAEs and cancer treatment response, tumor response to irAEs therapy, and ICIs in challenging populations, are comprehensively summarized.

关键词： cancer immunotherapy immune checkpoint inhibitors immune-related adverse events review

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Persistence of humoral and cellular immune response after SARS-CoV-2 infection: opportunities and challenges

Tangchun Wu

《医学前沿（英文）》 2020年第14卷第6期页码 816-819 doi: 10.1007/s11684-020-0823-4

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Heterogeneity of the tumor immune microenvironment and clinical interventions

《医学前沿（英文）》 2023年第17卷第4期页码 617-648 doi: 10.1007/s11684-023-1015-9

摘要： Heterogeneity of the tumor immune microenvironment and clinical interventions

关键词： Heterogeneity tumor immune

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Molecular classification and precision therapy of cancer: immune checkpoint inhibitors

null

《医学前沿（英文）》 2018年第12卷第2期页码 229-235 doi: 10.1007/s11684-017-0581-0

摘要：

On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers. This approach is the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body. FDA previously approved Keytruda for treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma, all of which carry positive programmed death-1/programmed death-ligand 1 biomarkers. Therefore, indications of Keytruda significantly expanded. Several types of malignancies are disclosed by MSI-H status due to dMMR and characterized by increased neoantigen load, which elicits intense host immune response in tumor microenvironment, including portions of colorectal and gastric carcinomas. Currently, biomarker-based patient selection remains a challenge. Pathologists play important roles in evaluating histology and biomarker results and establishing detection methods. Taking gastric cancer as an example, its molecular classification is built on genome abnormalities, but it lacks acceptable clinical characteristics. Pathologists are expected to act as “genetic interpreters” or “genetic translators” and build a link between molecular subtypes with tumor histological features. Subsequently, by using their findings, oncologists will carry out targeted therapy based on molecular classification.

关键词： molecular classification precision medicine pembrolizumab PD-1/PD-L1 MSI-H

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TiO supported IrO for anode reversal tolerance in proton exchange membrane fuel cell

《能源前沿（英文）》 2022年第16卷第5期页码 852-861 doi: 10.1007/s11708-021-0811-7

摘要： Fuel starvation can occur and cause damage to the cell when proton exchange membrane fuel cells operate under complex working conditions. In this case, carbon corrosion occurs. Oxygen evolution reaction (OER) catalysts can alleviate carbon corrosion by introducing water electrolysis at a lower potential at the anode in fuel shortage. The mixture of hydrogen oxidation reaction (HOR) and unsupported OER catalyst not only reduces the electrolysis efficiency, but also influences the initial performance of the fuel cell. Herein, Ti₄O₇ supported IrO_x is synthesized by utilizing the surfactant-assistant method and serves as reversal tolerant components in the anode. When the cell reverse time is less than 100 min, the cell voltage of the MEA added with IrO_x/Ti₄O₇ has almost no attenuation. Besides, the MEA has a longer reversal time (530 min) than IrO_x (75 min), showing an excellent reversal tolerance. The results of electron microscopy spectroscopy show that IrO_x particles have a good dispersity on the surface of Ti₄O₇ and IrO_x/Ti₄O₇ particles are uniformly dispersed on the anode catalytic layer. After the stability test, the Ti₄O₇ support has little decay, demonstrating a high electrochemical stability. IrO_x/Ti₄O₇ with a high dispersity has a great potential to the application on the reversal tolerance anode of the fuel cell.

关键词： proton exchange membrane fuel cell (PEMFC) fuel starvation cell reverse reversal tolerance anode oxygen evolution reaction

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APPLE SUMO E3 LIGASE MDSIZ1 NEGATIVELY REGULATES DROUGHT TOLERANCE

《农业科学与工程前沿（英文）》 2021年第8卷第2期

摘要：

Drought stress typically causes heavy losses in apple production and uncovering the mechanisms by which apple tolerates drought stress is important in apple breeding. MdSIZ1 is a SUMO (small ubiquitin-like modifier) E3 ligase that promotes SUMO binding to substrate proteins. Here, we demonstrate that MdSIZ1 in apple has a negative relationship with drought tolerance. MdSIZ1 RNAi transgenic apple trees had a higher survival rate after drought stress. During drought stress they had higher leaf water potential, reduced ion leakage, lower H₂O₂ and malondialdehyde contents, and higher catalase activity. In addition, MdSIZ1 RNAi transgenic plants had a higher net photosynthetic rate during the latter period of drought stress. Finally, the transgenic apple trees also altered expression levels of some microRNAs in response to drought stress. Taken together, these results indicate that apple MdSIZ1 negatively regulates drought stress by enhancing leaf water-holding capacity and antioxidant enzyme activity.

关键词： apple / drought tolerance / gene expression / MdSIZ1

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Hyperthermia on skin immune system and its application in the treatment of human papillomavirus-infected

null

《医学前沿（英文）》 2014年第8卷第1期页码 1-5 doi: 10.1007/s11684-014-0309-3

摘要：

Hyperthermia is a condition characterized by increased body temperature as a consequence of failed thermoregulation. Hyperthermia occurs when a body produces or absorbs more heat than it dissipates. Hyperthermia also elicits various effects on the physiology of living cells. For instance, fever-range temperature (39β°C to 40β°C) can modulate the activities of immune cells, including antigen-presenting cells, T cells, and natural killer cells. Heat shock temperature (41β°C to 43β°C) can increase the immunogenicity of tumor cells. Cytotoxic temperature (>43β°C) can create an antigen source to induce an anti-tumor immune response. The immunomodulatory effect of hyperthermia has promoted an interest in hyperthermia-aided immunotherapy, particularly against tumors. Hyperthermia has also been used to treat deep fungal, bacterial, and viral skin infections. We conducted a series of open or controlled trials to treat skin human papillomavirus infection by inducing local hyperthermia. More than half of the patients were significantly cured compared with those in the control trial. A series of challenging clinical cases, such as large lesions in pregnant patients or patients with diabetes mellitus, were also successfully and safely managed using the proposed method. However, further studies should be conducted to clarify the underlying mechanisms and promote the clinical applications of hyperthermia.

关键词： hyperthermia HPV immune response virus tumor

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SARS-CoV-2 variants, immune escape, and countermeasures

《医学前沿（英文）》 2022年第16卷第2期页码 196-207 doi: 10.1007/s11684-021-0906-x

摘要： Coronavirus disease 2019 (COVID-19) has become a global pandemic disease. SARS-CoV-2 variants have aroused great concern and are expected to continue spreading. Although many countries have promoted roll-out vaccination, the immune barrier has not yet been fully established, indicating that populations remain susceptible to infection. In this review, we summarize the literature on variants of concern and focus on the changes in their transmissibility, pathogenicity, and resistance to the immunity constructed by current vaccines. Furthermore, we analyzed relationships between variants and breakthrough infections, as well as the paradigm of new variants in countries with high vaccination rates. Terminating transmission, continuing to strengthen variant surveillance, and combining nonpharmaceutical intervention measures and vaccines are necessary to control these variants.

关键词： SARS-CoV-2 COVID-19 vaccine immune escape breakthrough prevention

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Multi-target combinatory strategy to overcome tumor immune escape

《医学前沿（英文）》 2022年第16卷第2期页码 208-215 doi: 10.1007/s11684-022-0922-5

摘要： Immune therapy has become the fourth approach after surgery, chemotherapy, and radiotherapy in cancer treatment. Many immune checkpoints were identified in the last decade since ipilimumab, which is the first immune checkpoint inhibitor to cytotoxic T-lymphocyte associated protein 4, had been approved by the US Food and Drug Administration (FDA) for the treatment of unresectable or metastatic melanoma in 2011. The use of several antibody drugs that target PD1/PD-L1 for various cancer treatments has been approved by the FDA. However, fewer people are benefitting from immune checkpoint inhibitor treatment in solid cancers. Approximately 80% of patients do not respond appropriately because of primary or acquired therapeutic resistance. Along with the characterization of more immune checkpoints, the combinatory treatment of multi-immune checkpoint inhibitors becomes a new option when monotherapy could not receive a good response. In this work, the author focuses on the combination therapy of multiple immune checkpoints (does not include targeted therapy of oncogenes or chemotherapy), introduces the current progression of multiple immune checkpoints and their related inhibitors, and discusses the advantages of combination therapy, as well as the risk of immune-related adverse events.

关键词： immune checkpoints multi-target immune escape immune-related adverse events combination therapy

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Estimating the number of Chinese cancer patients eligible for and benefit from immune checkpoint inhibitors

《医学前沿（英文）》 2022年第16卷第5期页码 773-783 doi: 10.1007/s11684-021-0902-1

摘要： The total number of cancer patients who are eligible for and will benefit from immune checkpoint inhibitors (ICIs) in China has not been quantified. This cross-sectional study was conducted to estimate the number of Chinese cancer patients with eligibility and response to ICIs based on the 2015 Chinese cancer statistics and the immune checkpoint inhibitor clinical practice guideline of the Chinese Society of Clinical Oncology. A total of 11 ICIs were recommended for 17 cancer types. The estimated number of eligible patients annually was 1 290 156 (55.18%), which included 888 738 males (60.05%) and 400 468 females (46.67%). The estimated number of responders annually was 448 972 (19.20%), which included 309 023 males (20.88%) and 139 764 females (16.29%). Gastric cancer (n=291 000, 12.45%), non-small-cell lung cancer (n=289 629, 12.39%), and hepatocellular carcinoma (n=277 100, 11.85%) were the top three cancer types with the highest number of eligible patients. Non-small-cell lung cancer (n=180 022, 7.70%), hepatocellular carcinoma (n=75 648, 3.24%), and small-cell lung cancer (n=64 362, 2.75%) were the top three cancer types with the highest number of responders. In conclusion, ICIs provide considerable benefit in Chinese cancer patients under optimal estimation.

关键词： benefit China eligibility immune checkpoint inhibitor public health

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A Robust Tolerance Design Method Based on Fuzzy Quality Loss

CAO Yan-long, MAO Jian, YANG Jiang-xin, WU Zhao-tong, WU Li-qun

《机械工程前沿（英文）》 2006年第1卷第1期页码 101-105 doi: 10.1007/s11465-005-0010-y

摘要：

The traditional tolerance design model ignores the impact of noise factor, so that the design may be infeasible due to variations in design constraints. Based on the analysis of fuzzy factors in tolerance design and the limitations of the traditional Taguchi squared quality loss function, a fuzzy quality loss function model utilizing fuzzy theory was introduced. Concepts on fuzzy quality loss and fuzzy quality loss cost were proposed in the model. The characteristics of the new model and the advantages over the traditional Taguchi quality loss function were analyzed. A robust tolerance design model using a fuzzy quality loss function was proposed. An example was given to illustrate the proposed model. Results and comparisons show that the method is suitable and reliable, and makes the conclusions more objective and reasonable.

关键词： impact function robust tolerance suitable quality

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Innate immune responses in RNA viral infection

Qian Xu, Yuting Tang, Gang Huang

《医学前沿（英文）》 2021年第15卷第3期页码 333-346 doi: 10.1007/s11684-020-0776-7

摘要： RNA viruses cause a multitude of human diseases, including several pandemic events in the past century. Upon viral invasion, the innate immune system responds rapidly and plays a key role in activating the adaptive immune system. In the innate immune system, the interactions between pathogen-associated molecular patterns and host pattern recognition receptors activate multiple signaling pathways in immune cells and induce the production of pro-inflammatory cytokines and interferons to elicit antiviral responses. Macrophages, dendritic cells, and natural killer cells are the principal innate immune components that exert antiviral activities. In this review, the current understanding of innate immunity contributing to the restriction of RNA viral infections was briefly summarized. Besides the main role of immune cells in combating viral infection, the intercellular transfer of pathogen and host-derived materials and their epigenetic and metabolic interactions associated with innate immunity was discussed. This knowledge provides an enhanced understanding of the innate immune response to RNA viral infections in general and aids in the preparation for the existing and next emerging viral infections.

关键词： innate immune viral infection intercellular signaling metabolic changes epigenetic changes