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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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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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FGF13 suppresses acute myeloid leukemia by regulating bone marrow niches

《医学前沿（英文）》 2022年 第16卷 第6期   页码 896-908 doi: 10.1007/s11684-022-0944-z

摘要： Fibroblast growth factor 13 (FGF13) is aberrantly expressed in multiple cancer types, suggesting its essential role in tumorigenesis. Hence, we aimed to explore its definite role in the development of acute myeloid leukemia (AML) and emphasize its associations with bone marrow niches. Results showed that FGF13 was lowly expressed in patients with AML and that its elevated expression was related to prolonged overall survival (OS). Univariate and multivariate Cox regression analyses identified FGF13 as an independent prognostic factor. A prognostic nomogram integrating FGF13 and clinicopathologic variables was constructed to predict 1-, 3-, and 5-year OS. Gene mutation and functional analyses indicated that FGF13 was not associated with AML driver mutations but was related to bone marrow niches. As for immunity, FGF13 was remarkably associated with T cell count, immune checkpoint genes, and cytokines. In addition, FGF13 overexpression substantially inhibited the growth and significantly induced the early apoptosis of AML cells. The xenograft study indicated that FGF13 overexpression prolonged the survival of recipient mice. Overall, FGF13 could serve as an independent prognostic factor for AML, and it was closely related to the bone marrow microenvironment.

关键词： acute myeloid leukemia     FGF13     prognosis     immune-related genes     bone marrow niches    

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surgical patients at high risk of OSAS using the Berlin Questionnaire to detect potential high risk of adverserespiratory events in post anesthesia care unit

null

《医学前沿（英文）》 2018年 第12卷 第2期   页码 189-195 doi: 10.1007/s11684-017-0533-8

摘要：

Obstructive sleep apnea syndrome (OSAS) increases the risk of post-surgery complications. This study uses Berlin Questionnaire (BQ) to identify Chinese adult surgical patients who are at a high risk of OSAS and to determine if the BQ could be used to detect potential high risk of adverse respiratory events in the post anesthesia care unit (PACU). Results indicated that only 11.4% of the patients were considered at a high risk of OSAS. Age and body mass index are the key factors for the risk of OSAS prevalence in China and also gender specific. Furthermore, the incidence of adverse respiratory events in the PACU was higher in patients with high risk of OSAS than others (6.8% vs. 0.9%, <0.001). They also stayed longer than others in the PACU (95±28 min vs. 62±19 min, <0.001). Age, high risk for OSAS, and smoking were independent risk factors for the occurrence of adverse respiratory events in the PACU. The BQ may be adopted as a screening tool for anesthesiologists in China to identify patients who are at high risk of OSAS and determine the potential risk of developing postoperative respiratory complications in the PACU.

关键词： obstructive sleep apnea     Berlin Questionnaire     Chinese surgical patients     adverse respiratory event    

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Detection of digestive malignancies and post-gastrectomy complications via gastrointestinal fluid examination

null

《医学前沿（英文）》 2017年 第11卷 第1期   页码 20-31 doi: 10.1007/s11684-016-0493-4

摘要：

To date, gastric carcinoma (GC) is one of the common and fatal digestive malignancies worldwide. The prognosis of GC is not always satisfactory because of late diagnosis. Scholars are keen on discovering novel accurate and economical biomarkers in body liquids for GC screening to detect and evaluate the lesion before the results of imaging techniques are obtained. While traditional serum assays have limited sensitivity and specificity, gastrointestinal juice may provide relevant specific biomarkers because of its close contact with the tumor. Herein, the current progress in the relationship between gastrointestinal fluid analyses and GC is systematically and comprehensively reviewed. The detection of gastric juice pH, fluorescence spectrum, cytology, Helicobacter pylori-associated markers, nitrosamines, conventional tumor markers, amino acids, proteomics, microRNAs, long noncoding RNAs, protein-coding genes, vitamin C, etc., and combination tests of different category markers could provide important diagnostic and prognostic clues for gastrointestinal diseases. Particularly, early GC may be efficiently screened using gastric juice. Gastrointestinal fluid examination could also predict the adverse effects of postgastrectomy, such as pancreatic leakage, fistula, and abscess. Gastric fluid markers should be further studied to reveal the early predicators of malignancy and complications. The methods for obtaining the samples of gastrointestinal juice with minimum incision should also be comprehensively investigated.

关键词： gastrointestinal fluid     gastric carcinoma     biomarker     diagnosis     prognosis     gastrectomy     adverse events    

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Smoothing ramp events in wind farm based on dynamic programming in energy internet

Jiang LI, Guodong LIU, Shuo ZHANG

《能源前沿（英文）》 2018年 第12卷 第4期   页码 550-559 doi: 10.1007/s11708-018-0593-8

摘要：

The concept of energy internet has been gradually accepted, which can optimize the consumption of fossil energy and renewable energy resources. When wind power is integrated into the main grid, ramp events caused by stochastic wind power fluctuation may threaten the security of power systems. This paper proposes a dynamic programming method in smoothing ramp events. First, the energy internet model of wind power, pumped storage power station, and gas power station is established. Then, the optimization problem in the energy internet is transformed into a multi-stage dynamic programming problem, and the dynamic programming method proposed is applied to solve the optimization problem. Finally, the evaluation functions are introduced to evaluate pollutant emissions. The results show that the dynamic programming method proposed is effective for smoothing wind power and reducing ramp events in energy internet.

关键词： energy internet     wind power     ramp events     dynamic programming    

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The most influential “Top 10 Events” in carbon neutrality and climate change in 2022

《能源前沿（英文）》 2023年 第17卷 第1期   页码 1-4 doi: 10.1007/s11708-023-0869-5

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逆压梯度下近壁湍流的喷射和扫掠

张强,陆利蓬

《中国工程科学》 2003年 第5卷 第11期   页码 47-50

摘要：

采用Fourier谱展开和紧致有限差分格式，选用两组共振三波为相干结构的初值，计算了其在零压和逆压梯度作用下的演化。对演化后期流场的2，4象限的运动进行了详细的分析。结果发现，在逆压梯度下，扫掠对雷诺应力的贡献要强于喷射。无论是在零压梯度还是逆压梯度下，uv和u2在法向的输运主要是靠Q2和Q4这两种运动来完成的。零压梯度下喷射部分对输运的贡献大于扫掠的部分。而在逆压梯度下喷射部分对输运的贡献明显减少，扫掠的作用要强于喷射。

关键词： 相干结构     湍流边界层     逆压梯度     直接数值模拟    

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design of novel proton-pump inhibitors with reduced adverse effects

Xiaoyi Li, Hong Kang, Wensheng Liu, Sarita Singhal, Na Jiao, Yong Wang, Lixin Zhu, Ruixin Zhu

《医学前沿（英文）》 2019年 第13卷 第2期   页码 277-284 doi: 10.1007/s11684-018-0630-3

摘要： The development of new proton-pump inhibitors (PPIs) with less adverse effects by lowering the pKa values of nitrogen atoms in pyrimidine rings has been previously suggested by our group. In this work, we proposed that new PPIs should have the following features: (1) number of ring II= number of ring I+ 1; (2) preferably five, six, or seven-membered heteroatomic ring for stability; and (3) 1

关键词： proton-pump inhibitor     adverse effect     pharmacological mechanism     toxicological mechanism     pKa calculation    

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The effects of festivals and special events on city image design

LIU Yuan, CHEN Chong

《结构与土木工程前沿（英文）》 2007年 第1卷 第2期   页码 255-259 doi: 10.1007/s11709-007-0032-0

摘要： City marketing provides a good vehicle to strengthen a city in competition. On the analysis of the important roles of events and city image in the context of city marketing, this paper suggests that holding festivals or special events is an effective approach to enhance city marketing. The positive impacts of festivals and special events, such as the identification of city image, the promotion of the transmission of city image, and the reversal of the negative image of the city, are discussed. The negative impacts of festivals and special events are also talked about. The unique image of the city could be identified by the City Mind Identity, the City Visual Identity and the City Behavior Identity concerned with festivals and special events.

关键词： Visual Identity     reversal     transmission     marketing     Behavior Identity    

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Characterization of bacterial communities during persistent fog and haze events in the Qingdao coastal

《环境科学与工程前沿（英文）》 2021年 第15卷 第3期 doi: 10.1007/s11783-020-1334-x

摘要：

• Light haze had little effect on bacterial communities.

关键词： Bacterial community     Persistent fog and haze     Particle size    

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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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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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标题 作者 时间 类型 操作

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

Yong Fan, Yan Geng, Lin Shen, Zhuoli Zhang

期刊论文

Multi-target combinatory strategy to overcome tumor immune escape

期刊论文

FGF13 suppresses acute myeloid leukemia by regulating bone marrow niches

期刊论文

surgical patients at high risk of OSAS using the Berlin Questionnaire to detect potential high risk of adverserespiratory events in post anesthesia care unit

null

期刊论文

Detection of digestive malignancies and post-gastrectomy complications via gastrointestinal fluid examination

null

期刊论文

Smoothing ramp events in wind farm based on dynamic programming in energy internet

Jiang LI, Guodong LIU, Shuo ZHANG

期刊论文

The most influential “Top 10 Events” in carbon neutrality and climate change in 2022

期刊论文

逆压梯度下近壁湍流的喷射和扫掠

张强,陆利蓬

期刊论文

design of novel proton-pump inhibitors with reduced adverse effects

Xiaoyi Li, Hong Kang, Wensheng Liu, Sarita Singhal, Na Jiao, Yong Wang, Lixin Zhu, Ruixin Zhu

期刊论文

The effects of festivals and special events on city image design

LIU Yuan, CHEN Chong

期刊论文

Characterization of bacterial communities during persistent fog and haze events in the Qingdao coastal

期刊论文

Natural killer cells in liver diseases

null

期刊论文

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

Tangchun Wu

期刊论文

Heterogeneity of the tumor immune microenvironment and clinical interventions

期刊论文

Molecular classification and precision therapy of cancer: immune checkpoint inhibitors

null

期刊论文