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Advances in immunopathogenesis of adult immune thrombocytopenia

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《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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Understanding risk of thrombosis with thrombocytopenia syndrome after Ad26.COV2.S vaccination

《医学前沿（英文）》 2021年第15卷第6期页码 938-941 doi: 10.1007/s11684-021-0895-9

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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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Natural killer cells in liver diseases

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《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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Evaluation of power regeneration in primary suspension for a railway vehicle

Ruichen WANG, Zhiwei WANG

《机械工程前沿（英文）》 2020年第15卷第2期页码 265-278 doi: 10.1007/s11465-019-0571-9

摘要： To improve the fuel economy of rail vehicles, this study presents the feasibility of using power regenerating dampers (PRDs) in the primary suspension systems of railway vehicles and evaluates the potential and recoverable power that can be obtained. PRDs are configured as hydraulic electromagnetic-based railway primary vertical dampers and evaluated in parallel and series modes (with and without a viscous damper). Hydraulic configuration converts the linear behavior of the track into a unidirectional rotation of the generator, and the electromagnetic configuration provides a controllable damping force to the primary suspension system. In several case studies, generic railway vehicle primary suspension systems that are configured to include a PRD in the two configuration modes are modeled using computer simulations. The simulations are performed on measured tracks with typical irregularities for a generic UK passenger route. The performance of the modified vehicle is evaluated with respect to key performance indicators, including regenerated power, ride comfort, and running safety. Results indicate that PRDs can simultaneously replace conventional primary vertical dampers, regenerate power, and exhibit desirable dynamic performance. A peak power efficiency of 79.87% is theoretically obtained in series mode on a top-quality German Intercity Express track (Track 270) at a vehicle speed of 160 mile/h (~257 km/h).

关键词： railway vehicle primary damper power regeneration ride comfort running safety

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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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Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice

《医学前沿（英文）》页码 957-971 doi: 10.1007/s11684-023-0988-8

摘要： Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.

关键词： DNAH10 mice motile cilia mutation primary ciliary dyskinesia

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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

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《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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Approach for natural gas to be a primary energy source in China

Weihe HUANG, Jindian CHEN, Chuan FU, Yan HUANG

《工程管理前沿（英文）》 2019年第6卷第4期页码 467-476 doi: 10.1007/s42524-019-0068-6

摘要： This work reveals the positioning of natural gas in the evolution of world energy and the general law of its development. In the long-term adjustment of energy structure, natural gas has gradually become the primary energy source because of five factors: policy, resources, technology, facilities, and market. To expedite the revolution of energy production and consumption, China must urgently expand the use of natural gas toward a more positive role in complementing coal and renewable energy and prioritize its usage in three areas, namely, urban gas, power generation, and industrial fuel. Natural gas is expected to account for approximately 15% of China’s total energy consumption in the future. For natural gas to be the primary energy, the exploitation of gas resources must be expanded, resource access must be improved, a flexible trade system must be set up, infrastructure investment must be increased, and the security system must be enhanced.

关键词： natural gas energy revolution primary energy utilization areas approaching means

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Effect of traditional Chinese medicine combined with Western therapy on primary hepatic carcinoma: a

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《医学前沿（英文）》 2017年第11卷第2期页码 191-202 doi: 10.1007/s11684-017-0512-0

摘要：

Primary hepatic carcinoma (PHC) is a common malignant tumor in China. Cancer is comprehensively treated with various therapeutic regimes, including traditional Chinese medicine (TCM). TCM has been widely used to improve the quality of life, delay the time of cancer progression, and prolong the median survival time. This systematic review with meta-analysis aimed to assess the effect of TCM combined with Western therapy on primary hepatic carcinoma. A comprehensive literature search was conducted in six databases, including CNKI, VIP, Wan-Fang Database, CBM, PubMed, and Cochrane library. A total of 44 randomized controlled trials (RCTs) involving 3429 participants suffering from PHC were selected. Meta-analysis results indicated that the overall effect of TCM and Western integrative treatment on PHC was higher than that of Western intervention alone, which can postpone tumor recurrence and metastasis and prolong the overall survival time of patients with PHC. Although the obtained evidence remained weak because of the poor methodological quality of the included studies, this review provided relevant data supporting the efficacy and safety of TCM combined with Western therapies. In future research, individual RCT studies should incorporate accepted standards for trial design and reporting, proper outcome indicators according to international standards, blinding in allocation concealment, and valid follow-up periods.

关键词： traditional Chinese medicine primary hepatic carcinoma meta-analysis

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

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《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