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MYC in T-cell acute lymphoblastic leukemia: functional implications and targeted strategies

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Blood Science 2021年第3期3卷 65-70页

作者： Qilong Li Sa Pan Ting Xie hudan liu Department of Hematology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Frontier Science Center for Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan 430071China

T-cell acute lymphoblastic leukemia(T-ALL)is an aggressive hematological cancer that frequently occurs in children and adolescents,which results from the transformation of immature T-cell progenitors.Aberrant cell growth and proliferation of T-ALL lymphoblasts are sustained by activation of strong oncogenic drivers.Mounting evidence highlights the critical role of the NOTCH1-MYC highway toward the initiation and progression of T-ALL.MYC has been emphasized as a primary NOTCH1 transcriptional target impinging in leukemia-initiating cell activity particularly responsible for disease onset and relapse.These findings lay a foundation of T-ALL as an ideal disease model for studying MYC-mediated cancer.The biology of MYC deregulation in T-ALL supports innovative strategies for therapeutic targeting of MYC.To summarize the relevant literature and data in recent years,we here provide a comprehensive overview of the functional importance of MYC in T-ALL development,and the molecular mechanisms underlying MYC deregulation in T-ALL.Finally,we illustrate the innovative MYC-targeted approaches that have been evaluated in pre-clinical models and shown significant efficacy.Given the complexity of T-ALL molecular pathogenesis,we propose that a combination of anti-MYC strategies with conventional chemotherapies or other targeted/immunotherapies may provide the most durable response,especially for those patients with relapsed and refractory T-ALL.

关键词： MYC T-ALL Targeted therapy

Targeting oncogenic Myc as a strategy for cancer treatment

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Signal Transduction and Targeted Therapy 2018年第1期3卷 284-290页

作者： Hui Chen hudan liu Guoliang Qing Zhongnan Hospital of Wuhan University WuhanPeople’s Republic of China Medical Research Institute Wuhan UniversityWuhanPeople’s Republic of China

The MYC family oncogene is deregulated in>50%of human cancers,and this deregulation is frequently associated with poor prognosis and unfavorable patient survival.Myc has a central role in almost every aspect of the oncogenic process,orchestrating proliferation,apoptosis,differentiation,and metabolism.Although Myc inhibition would be a powerful approach for the treatment of many types of cancers,direct targeting of Myc has been a challenge for decades owing to its“undruggable”protein structure.Hence,alternatives to Myc blockade have been widely explored to achieve desirable anti-tumor effects,including Myc/Max complex disruption,MYC transcription and/or translation inhibition,and Myc destabilization as well as the synthetic lethality associated with Myc overexpression.In this review,we summarize the latest advances in targeting oncogenic Myc,particularly for cancer therapeutic purposes.

关键词： structure. cancer treatment

新时代我国体文旅产业融合发展:逻辑、模式、问题与路径

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山东体育学院学报 2024年第1期40卷 70-79页

作者：潘怡曹胡丹封慧广西师范大学体育与健康学院广西桂林541006 长江大学教育与体育学院湖北荆州434023 国防科技大学研究生院湖南长沙410073

体文旅产业融合发展对助力中国式现代化体育产业体系构建具有一定的现实意义。该研究运用文献资料、逻辑分析等方法,以体文旅产业融合发展的现实逻辑、政策逻辑和理论逻辑为基础,梳理并厘清了新时代我国体文旅产业融合发展的模式机制、... 详细信息

体文旅产业融合发展对助力中国式现代化体育产业体系构建具有一定的现实意义。该研究运用文献资料、逻辑分析等方法,以体文旅产业融合发展的现实逻辑、政策逻辑和理论逻辑为基础,梳理并厘清了新时代我国体文旅产业融合发展的模式机制、现实问题及提升路径。研究认为,新时代我国体文旅产业融合发展模式主要包括交叉渗透模式、互动延伸模式、分解重组模式;其互动机制主要包括资源共享机制、内容技术机制、业态聚集机制及多元协同机制。新时代我国体文旅产业融合发展面临政策合力缺乏,关联互补不强;模式存在缺陷,融合效益较低;内容技术受阻,多元协同失位等问题。基于此,该研究建议加强顶层制度设计,保障体文旅产业政策落地;优化产业融合模式,提升体文旅产业融合效益;创新产业内容技术,推进体文旅产业多元协同。

关键词：体育产业文化产业旅游产业体文旅产业产业融合高质量发展

Animal models of T-cell acute lymphoblastic leukemia: mimicking the human disease

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Journal of Bio-X Research 2018年第1期1卷 32-40页

作者： Qin You Hexiu Su Jingchao Wang Jue Jiang Guoliang Qing hudan liu Medical Research Institute Wuhan University Institute of Hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

T-cell acute lymphoblastic leukemia(T-ALL)is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic abnormalities.In the past decade,large-scale genomic analysis has shed new light on providing potentially important oncogenic or tumor suppressive candidates involved in the disease progression.Following in silico analysis,functional studies are usually performed to vigorously investigate the biological roles of candidate genes.For this purpose,animal models faithfully recapitulating the human disease are widely applied to decipher the mechanism underlying T-cell transformation.Conversely,an increased understanding of T-ALL biology,including identification of oncogene NOTCH1,TAL1 and MYC as well as tumor suppressor phosphatase and tensin homolog(PTEN),has significantly improved the development of T-ALL animal models.These progresses have opened opportunities for development of new therapeutic strategy to benefit T-ALL patients.In this review,we particularly summarize the mouse and zebrafish models used in T-ALL research and also the most recent advances from these in vivo studies.

关键词： hematopoietic stem cell transplant T-cell acute lymphoblastic leukemia transgenetic mice transgenic zebrafish xenograft

Whether Probiotic Supplementation Benefits Rheumatoid Arthritis Patients： A Systematic Review and Meta-Analysis

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Engineering 2017年第1期3卷 115-121页

作者： hudan Pan Runze Li Ting Li Jun Wang Liang liu State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and Technology Macao China Macao Institute for Applied Research in Medidne and Health Macao University of Science and Technology Macao China

Gut and oral microflora are important factors in the pathogenesis and development of rheumatoid arthritis(RA). Recent studies have shown that probiotic supplements have beneficial consequences on experimental arthritis in rats. However, results from randomized clinical trials on the effects of probiotics have not been consistent. The aim of this study was to systematically review the existing evidence for the effects of probiotic intervention in RA. We included randomized controlled trials(RCTs) of RA patients receiving stable treatment with disease-modifying anti-rheumatic drugs(DMARDs) that:(1) were combined with additional probiotic supplements or(2) were combined with either no additional supplements or only a placebo treatment. Statistical analysis was performed using Review Manager 5.3.3.Six randomized clinical trials were eligible for inclusion in the meta-analysis, with 249 participants in total. The results showed that the probiotic intervention treatment has not yet achieved significant improvement in the American College of Rheumatology 20% improvement criteria(ACR20) score and the disease activity score in 28 joints(DAS28). The laboratory index C-reactive protein(CRP)(mg·L–1) was significantly reduced in the intervention group. The expression of inflammatory cytokines tumor necrosis factor(TNF)-α and interleukine(IL)-1β was also significantly reduced, while IL-10 expression increased in the probiotic intervention groups. This article is the first systematic review and meta-analysis providing a comprehensive assessment of the benefits of treating RA with probiotics. We found that probiotic supplementation may show a limited improvement in RA therapy in existing reports because of a lack of sufficiently high-quality work on the part of clinicians. More multi-centered, large-sample RCTs are needed in order to evaluate the benefits of probiotics in RA treatment.

关键词：类风湿关节炎临床试验益生菌辅助系统综述荟萃分析

Deciphering the pharmacological mechanism of Guan-Jie-Kang in treating rat adjuvant-induced arthritis using omics analysis

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Frontiers of Medicine 2019年第5期13卷 564-574页

作者： hudan Pan Yanfang Zheng Zhongqiu liu Zhongwen Yuan Rutong Ren Hua Zhou Ying Xie Liang liu tate Key Laboratory of Quality Research in Chinese Medicine/Macao Institute for Applied Research in Medicine and Health Macao University of Science and TechnologyMacaoChina Fujian University of Traditional Chinese Medicine Fuzhou 350122China International Institute for Translational Research of Traditional Chinese Medicine of Guangzhou University of Chinese Medicine Guangzhou 510006China

Traditional Chinese medicine (TCM) formulas have attracted increasing attention worldwide in the past few years for treating complex disease including rheumatoid arthritis. However, their mechanisms are complex and remain unclear. Guan-Jie-Kang (GJK), a prescription modified from “Wu Tou Decoction,” was found to significantly relieve arthritis symptoms in rats with adjuvant-induced arthritis after 30-day treatment, especially in the 24 g/kg/day group. By analyzing 1749 targets related to 358 compounds in the five herbs of GJK, we identified the possible anti-arthritis pathways of GJK, including the calcium signaling and metabolic pathways. Bone damage levels were assessed by micro-computed tomography, and greater bone protective effect was observed with GJK treatment than with methotrexate. Receptor activator of nuclear factor kB ligand (RANKL)-RANK signaling, which is related to calcium signaling, was significantly regulated by GJK. Moreover, a target metabolomics assay of serum was conducted;17 metabolic biomarkers showed significant correlations with treatment. An integrated pathway analysis revealed that pyruvate metabolism, purine metabolism, and glycolysis metabolism were significantly associated with the effects of GJK in arthritis treatment. Thus, this study establishes a new omics analytical method integrated with bioinformatics analysis for elucidating the multi-pathway mechanisms of TCM.

关键词： rheumatoid arthritis traditional Chinese medicine pharmacological mechanism metabolism adjuvant-induced arthritis omics analysis

Ecological service assessment of human-dominated freshwater ecosystem with a case study in Yangzhou Prefecture, China

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Journal of Environmental Sciences 2004年第5期16卷 755-761页

作者： YEYa-ping WANGRu-song RENJing-ming hudan YUANShao-jun WANGMin ResearchCenterforEco-EnvironmentalSciences ChineseAcademyofSciencesBeijing100085China

Freshwater ecosystems provide a host of services to humanity. These services are now rapidly being lost, not least because of the inability of making the impacts measurable. To overcome this obstacle, assessment frameworks for freshwater ecosystem services are needed. A simple water equivalent framework to assess the ecological services provided by freshwater ecosystems was developed in this study. It translated the occupation of freshwater ecosystem services into biologically freshwater volumes and then compares this consumption to the freshwater throughput, that is, the ecological capacity available in this region. In this way, we use the example of Yangzhou Prefecture, to account the main categories of human occupation of water ecosystem services. The result showed that there is a huge gap between the consumption and the supply of freshwater ecosystem services. This must encourage local government to make land-use and water management decisions both economically rational and environmentally sound.

关键词： freshwater ecosystems services human impacts assessment water equivalent Yangzhou Prefecture

Inter-femtocell interference coordination in 3D in-building scenario

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The Journal of China Universities of Posts and Telecommunications 2012年第2期19卷 36-42,66页

作者： hudan LIHong-jia XUXiao-dong TAOXiao-feng WirelessTechnologyInnovationInstitute KeyLaboratoryofUniversalWirelessCommunicationMinistryofEducationBeltingUniversityofPostsandTelecommunicationsBeijingl00876China HighPerformanceNetworkLaboratory InstituteofAcousticsChineseAcademyofSciencesBeijingl00190China

With rapid development of femtocell, dense deployment of femtocells in buildings will become an important study scenario. In this scenario, there exists severe inter-femtocell interference in the same building, which is revealed by our simulations in the 3-dimention （3D） scenario. If this type of interference is not well controlled, services to indoor users are bound to be deteriorated, especially for the femtocell edge users. Motivated by this problem, femto users＇ received interference model is constructed based on the scenario of 3D femtocell deployment. Then, a graph theory based in-building inter-femtocell coordination scheme is proposed, which includes three phases： establishment of femtocell interference graph, femtocell clustering and frequency resources allocation based on the proposed cluster influence circle. Finally, the simulation results confirm that the proposed scheme improves the femtocell average throughput by 22.4% and 26.2% in comparison with frequency universal reuse scheme and channel demodulation reliability of cell edge femto users. frequency hopping scheme respectively, and ensures the

关键词： femtocell interference management resource management graph

Effects of emitter discharge rates on soil salinity distribution and cotton(Gossypium hirsutum L.) yield under drip irrigation with plastic mulch in an arid region of Northwest China

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Journal of Arid Land 2013年第1期5卷 51-59页

作者： Sulitan DANIERHAN Abudu SHALAMU hudan TUMAERBAI DongHai GUAN State Key Laboratory of Desert and Oasis Ecology Xinjiang Institute of Ecology and Geography Chinese Academy of Sciences Urumqi 830011 China Xinjiang Institute of Water Resources and Hydroelectric Sciences Urumqi 830049 China College of Water Conservancy and Civil Engineering Xinjiang Agricultural University Urumqi 830052 China

A field experiment was carried out to investigate the effects of different emitter discharge rates under drip irrigation on soil salinity distribution and cotton yield in an extreme arid region of Tarim River catchment in Northwest China. Four treatments of emitter discharge rates, i.e. 1.8, 2.2, 2.6 and 3.2 L/h, were designed under drip irrigation with plastic mulch in this paper. The salt distribution in the range of 70-cm horizontal distance and 100-cm vertical distance from the emitter was measured and analyzed during the cotton growing season. The soil salinity is expressed in terms of electrical conductivity （dS/m） of the saturated soil extract （ECe）, which was measured using Time Domain Reflector （TDR） 20 times a year, including 5 irrigation events and 4 measured times before/after an irrigation event. All the treatments were repeated 3 times. The groundwater depth was observed by SEBA MDS Dipper 3 automatically at three experimental sites. The results showed that the order of reduction in averaged soil salinity was 2.6 L/h 〉 2.2 L/h 〉 1.8 L/h 〉 3.2 L/h after the completion of irrigation for the 3-year cotton growing season. Therefore, the choice of emitter discharge rate is considerably important in arid silt loam. Usually, the ideal emitter discharge rate is 2.4-3.0 L/h for soil desalinization with plastic mulch, which is advisable mainly because of the favorable salt leaching of silt loam and the climatic conditions in the studied arid area. Maximum cotton yield was achieved at the emitter discharge rate of 2.6 L/h under drip irrigation with plastic mulch in silty soil at the study site. Hence, the emitter discharge rate of 2.6 L/h is recommended for drip irrigation with plastiic mulch applied in silty soil in arid regions.

关键词： drip irrigation soil salinity salt balance cotton yield emitter discharge rate