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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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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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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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Expression profiles of genes and enzymes related to ascorbic acid metabolism in fruits of

Yingying CHEN,Zhihui ZHAO,Jin ZHAO,Mengjun LIU

《农业科学与工程前沿（英文）》 2016年 第3卷 第2期   页码 131-136 doi: 10.15302/J-FASE-2016096

摘要： The fruit of Chinese jujube ( ) possesses extremely high concentrations of ascorbic acid (AsA). The accumulation of AsA, the expression patterns of the nine genes related to AsA metabolism as well as the activities of five enzymes involved in AsA synthesis, oxidation and recycling were investigated during fruit development in Mill. ‘Jinsixiaozao’. The results showed that the high level of AsA accumulation in jujube fruit is due to a contribution from both AsA biosynthesis and AsA recycling. It is suggested that L-galactono-1,4-lactone dehydrogenase, ascorbate peroxidase and monodehydro-ascorbate reductase are the crucial genes/enzymes of jujube AsA synthesis, oxidization and recycling, respectively. These results provide useful new insights into the regulatory mechanisms of AsA accumulation in Chinese jujube.

关键词： Chinese jujube     ascorbic acid     metabolism     gene     enzyme    

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Changes in lncRNAs and related genes in β-thalassemia minor and β-thalassemia major

null

《医学前沿（英文）》 2017年 第11卷 第1期   页码 74-86 doi: 10.1007/s11684-017-0503-1

摘要：

β-thalassemia is caused by β-globin gene mutations. However, heterogeneous phenotypes were found in individuals with same genotype, and still undescribed mechanism underlies such variation. We collected blood samples from 30 β-thalassemia major, 30 β-thalassemia minor patients, and 30 matched normal controls. Human lncRNA Array v2.0 (8 × 60 K, Arraystar) was used to detect changes in long non-coding RNAs (lncRNAs) and mRNAs in three samples each from β-thalassemia major, β-thalassemia minor, and control groups. Compared with normal controls, 1424 and 2045 lncRNAs were up- and downregulated, respectively, in β-thalassemia major patients, whereas 623 and 349 lncRNAs were up- and downregulated, respectively, in β-thalassemia minor patients. Compared with β-thalassemia minor group, 1367 and 2356 lncRNAs were up- and downregulated, respectively, in β-thalassemia major group. We selected five lncRNAs that displayed altered expressions (DQ583499, X-inactive specific transcript (Xist), lincRNA-TPM1, MRFS16P, and lincRNA-RUNX2-2) and confirmed their expression levels in all samples using real-time polymerase chain reaction. Based on coding-non-coding gene co-expression network and gene ontology biological process analyses, several signaling pathways were associated with three common organ systems exhibiting β-thalassemia phenotypes: hematologic, skeletal, and hepatic systems. This study implicates that abnormal expression levels of lncRNAs and mRNA in β-thalassemia cases may be correlated with its various clinical phenotypes.

关键词： β-thalassemia     long non-coding RNA     mRNA     phenotypic heterogeneity     pathway    

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Superenhancers activate the autophagy-related genes Beclin1 and LC3B to drive metastasis and drug resistance

《医学前沿（英文）》 2022年 第16卷 第6期   页码 883-895 doi: 10.1007/s11684-022-0919-0

摘要： Metastasis and drug resistance are the leading causes of poor prognosis in patients with osteosarcoma. Identifying the relevant factors that drive metastasis and drug resistance is the key to improving the therapeutic outcome of osteosarcoma. Here, we reported that autophagy was highly activated in metastatic osteosarcoma. We found increased autophagolysosomes in metastatic osteosarcoma cell lines by using electron microscopy, Western blot, and immunofluorescence experiments. We further examined the expression of the autophagy-related genes Beclin1 and LC3B in 82 patients through immunohistochemistry and found that Beclin1 and LC3B were highly related to unfavorable prognosis of osteosarcoma. Knockdown of Beclin1 and LC3B reduced invasion, metastasis, and proliferation in metastatic osteosarcoma cells. In vitro and in vivo studies also demonstrated that inhibiting by 3-MA inhibited cell growth and metastasis. Moreover, we demonstrated that autophagy-related genes were activated by SEs and that the inhibition of SEs by JQ-1 decreased the metastasis of osteosarcoma. Overall, our findings highlighted the association of autophagy with osteosarcoma progression and shed new light on autophagy-targeting therapy for osteosarcoma.

关键词： osteosarcoma     autophagy     metastasis     drug resistance     Beclin1     LC3B    

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Metagenomic analysis on resistance genes in water and microplastics from a mariculture system

《环境科学与工程前沿（英文）》 2022年 第16卷 第1期   页码 4-4 doi: 10.1007/s11783-021-1438-y

摘要：

Microplastics existing widely in different matrices have been regarded as a reservoir for emerging contaminants. Mariculture systems have been observed to host microplastics and antibiotic resistance genes (ARGs). However, more information on proliferation of ARGs and metal resistance genes (MRGs) in mariculture system at the presence of microplastics is needed.

关键词： Antibiotic resistance genes     Metal resistance genes     Metagenomic analysis     Microplastics     Mariculture    

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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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hsa-miR-197在子宫肌瘤中的表达及生物信息学特征分析

徐青,付子毅,吴小莉,皇甫玉爽,凌静

《中国工程科学》 2014年 第16卷 第5期   页码 99-104

摘要：

应用实时定量聚合酶链式反应（PCR）技术检测子宫肌瘤组织中的hsa-miR-197 表达水平，并与配对正常子宫肌细胞对比。通过miRbase、UCSC、NCBI等在线数据库获取并分析hsa-miR-197 序列保守性及其基因组特征。选择miRanda、MirTarget2 及TargetScan 三个在线数据库预测hsa-miR-197 的靶基因并取交集以便后续分析。通过基因本体（GO）功能注释、GO富集分析和信号转导通路富集分析初步阐明，hsamiR-197 靶基因参与调控的细胞功能与信号通路。hsa-miR-197 的功能较广泛，参与肿瘤发生的多种生物学过程，提示hsa-miR-197 可能与子宫肌瘤的发病机制密切相关。

关键词： 子宫肌瘤     hsa-miR-197     生物信息学     靶基因    

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Distribution and removal of antibiotic resistance genes during anaerobic sludge digestion with alkaline

Mengli Wang, Ruying Li, Qing Zhao

《环境科学与工程前沿（英文）》 2019年 第13卷 第3期 doi: 10.1007/s11783-019-1127-2

摘要：

Sludge digestion is critical to control the spread of ARGs from wastewater to soil.

Fate of ARGs in three pretreatment-AD processes was investigated.

UP was more efficient for ARGs removal than AP and THP in pretreatment-AD process.

The total ARGs concentration showed significant correlation with 16S rRNA gene.

The bacteria carrying ARGs could be mainly affiliated with Proteobacteria.

关键词： Tetracycline resistance genes     Sulfonamide resistance genes     16S rRNA gene     Sludge pretreatment     Anaerobic sludge digestion    

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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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Environmental effects and risk control of antibiotic resistance genes in the organic solid waste aerobic

《环境科学与工程前沿（英文）》 2021年 第15卷 第6期 doi: 10.1007/s11783-021-1415-5

摘要：

• ARGs were detected in livestock manure, sludge, food waste and fermentation dregs.

关键词： Antibiotic resistance genes     Organic solid waste     Aerobic composting     Livestock manure     Sludge    

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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

FGF13 suppresses acute myeloid leukemia by regulating bone marrow niches

期刊论文

Multi-target combinatory strategy to overcome tumor immune escape

期刊论文

Expression profiles of genes and enzymes related to ascorbic acid metabolism in fruits of

Yingying CHEN,Zhihui ZHAO,Jin ZHAO,Mengjun LIU

期刊论文

Changes in lncRNAs and related genes in β-thalassemia minor and β-thalassemia major

null

期刊论文

Superenhancers activate the autophagy-related genes Beclin1 and LC3B to drive metastasis and drug resistance

期刊论文

Metagenomic analysis on resistance genes in water and microplastics from a mariculture system

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

hsa-miR-197在子宫肌瘤中的表达及生物信息学特征分析

徐青,付子毅,吴小莉,皇甫玉爽,凌静

期刊论文

Distribution and removal of antibiotic resistance genes during anaerobic sludge digestion with alkaline

Mengli Wang, Ruying Li, Qing Zhao

期刊论文

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

null

期刊论文

Environmental effects and risk control of antibiotic resistance genes in the organic solid waste aerobic

期刊论文