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Penpulimab,an anti-PD-1 antibody,for heavily pretreated metastatic nasopharyngeal carcinoma:a single-arm phase II study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3056-3062页

作者： xiaozhong Chen Wei Wang Qingfeng Zou xiaodong Zhu Qin lin Yi Jiang Yan Sun Liangfang Shen lin Wang Guorong Zou xiaoyan lin Shaojun lin Minying Li Ying Wang Ruilian Xu Rui Ao Rensheng Wang Haifeng lin Shuang Huang Tingting Xu Wenting Li Mengying xia Yu xia Zhongmin Wang Baiyong Li Jingao Li Chaosu Hu Department of Radiation Oncology Cancer Hospital of the University of ChineseAcademy of Sciences(Zhejiang Cancer Hospital)HangzhouChina Gastroenterology and Urology Department II Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina Clinical Research Center for Gastrointestinal Cancer in Hunan Province ChangshaChina Department of Medical Oncology Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhouChina Department of Radiation Oncology Guangxi Medical University Affiliated Tumor Hospital&Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University)Ministry of Education&Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency TumorGuangxi Medical UniversityNanningChina Department of Radiation Oncology Cancer CenterThe First Affiliated Hospital of Xiamen UniversityXiamenChina Department of Medical Oncology Cancer Hospital of Shantou University Medical CollegeShantouChina Department of Radiation Oncology Peking University Cancer Hospital&InstituteBeijingChina Department of Oncology Xiangya Hospital Central South UniversityChangshaChina Department of Medical Oncology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikouChina Department of Oncology The Affiliated Panyu Central Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Medical Oncology Fujian Medical University Union HospitalFuzhouChina Department of Radiation Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhouChina Department of Radiation Therapy for Thoracic Tumors Zhongshan City People’s HospitalZhongshanChina Tumor Radiotherapy Center Chongqing University Cancer HospitalChongqing Cancer HospitalChongqing Cancer InstituteChongqingChina Department of Oncology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSo

Penpulimab is an anti-programmed cell death-1(PD-1)IgG1 antibody with no Fc gamma receptor(FcγR)binding activity,and thus theoretically reduced immune-related adverse events(irAEs)while maintaining *** single-arm,phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma(NPC)who had failed two or more lines of previous systemic *** received 200-mg penpulimab intravenously every 2 weeks(4 weeks per cycle)until disease progression or intolerable *** primary endpoint was objective response rate(ORR)per RECIST(version 1.1),as assessed by an independent radiological review *** secondary endpoints included progression-free survival(PFS)and overall survival(OS).One hundred thirty patients were enrolled and 125 were efficacy *** the data cutoff date(September 28,2022),1 patient achieved complete response and 34 patients attained partial *** ORR was 28.0%(95%CI 20.3–36.7%).The response was durable,with 66.8%still in response at 9 ***-three patients(26.4%)were still on *** median PFS and OS were 3.6 months(95%CI=1.9–7.3 months)and 22.8 months(95%CI=17.1 months to not reached),***(7.6%)patients experienced grade 3 or higher *** has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients,supporting further clinical development as third-line treatment of metastatic NPC.

关键词： metastatic nasopharyngeal supporting

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Analysis on characteristics of extreme precipitation indices and atmospheric circulation in Northern Shanxi

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Research in Cold and Arid Regions 2024年第2期16卷 84-97页

作者： xia Cai Yan Song lin Cai Xin Su GuiHua Liang YanMing Xu Shuozhou Meteorological Bureau of Shanxi Province ShuozhouShanxi 036002China China Meteorological Administration Training Center Beijing 100081China Heze University of Shandong Province HezeShandong 274000China Huafeng Meteorological Media Group Beijing 100081China Shuocheng Meteorological Bureau ShuozhouShanxi 036002China

This article utilizes daily precipitation data from 28 national meteorological stations in northern Shanxi Province spanning from 1972 to 2020,and the US NCEP/NCAR monthly average reanalysis and ERA5 monthly average reanalysis *** study employs techniques such as empirical orthogonal function(EOF)decomposition,MannKendall mutation and other methods to investigate the spatiotemporal distribution of extreme precipitation index in northern Shanxi and their correlation with atmospheric *** research results show that:the absolute index,relative index,intensity index and sustained dry period index(CDD)in the continuous index appear from southwest to *** spatial distribution characteristics of the central region decrease,while the continuous wet period(CWD)decreases from the central to the east and *** three indices Rx1day,Rx5day,and CWD mutated in 1978,1975,and 1983 respectively,and other extreme precipitation indices all appeared in a sudden change from a low-value period to a high-value period occurred around *** the high-value years of the summer extreme precipitation index,there is a significant negative anomaly in the height field in the mid-high latitude regions of *** Shanxi is controlled by a broad low-pressure trough in the Lake Baikal *** vapor transported via the east,west,and south routes converges in the northern Shanxi region and encounters cold air from the *** is a strong upward motion anomaly at 500 hPa in the troposphere,and the dynamic conditions of upper-level divergence and lower-level convergence lead to more summer extreme precipitation in the northern Shanxi ***,in the low-value years of the summer extreme precipitation index,northern Shanxi is affected by a strong high-pressure ridge north of Lake *** is a downward motion anomaly at 500 hPa,and the northern Shanxi region lacks water *** cold and warm air cannot converge,and both the water vapor conditions

关键词： Northern Shanxi Extreme precipitation indices Spatio-temporal distribution and evolution Mutations Atmospheric circulation anomaly

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Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death

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Biomedical and Environmental Sciences 2024年第1期37卷 54-70页

作者： YU Jin Hai HU Guo Liang GUO xiao Quan CAO Hua Bin xia zhao Fei AMIN Buhe Jiangxi Provincial Key Laboratory for Animal Health Institute of Animal Population HealthCollege of Animal Science and TechnologyJiangxi Agricultural UniversityNanchang 330045JiangxiChina Internal Medicine Laboratory Department of Veterinary Clinical MedicineCollege of Veterinary MedicineChina Agricultural UniversityBeijing 100091China Department of Cancer Surgery Beijing Shijitan Hospital Affiliated with Capital Medical UniversityBeijing 100038China

Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac *** Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic *** embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western *** They demonstrated that the heart presented inflammatory responses after LPS *** LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three *** significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS *** significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS *** treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS *** significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS *** significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS *** significantly decreased protein expressions of AMPKα1,LC3-I,and *** significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or

关键词： Quercetin Lipopolysaccharide Inflammation Autophagy Programmed cell death Myocardiocytes permeability

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In patients who had a stroke or TIA, enlarged perivascular spaces in basal ganglia may cause future haemorrhagic strokes

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Stroke & Vascular Neurology 2024年第1期9卷 8-17,I0001-I0033页

作者： Yu Tian Mengxing Wang Yuesong Pan xia Meng Xingquan zhao Liping Liu Yongjun Wang Yilong Wang Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina National Center for Neurological Diseases BeijingChina Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina

Introduction It remains unclear whether enlarged perivascular spaces(EPVS)predict poor clinical outcomes in patients with acute ischaemic stroke(AIS)or transient ischaemic attack(TIA).Method Data were obtained from the Third China National Stroke Registry *** estimated EPVS in basal ganglia(BG)and centrum semiovale(CSO)using a semiquantified scale(Grade from 0 to 4).Using Cox and logistic regression analyses,the associations of EPVS with 3-month and 1-year adverse outcomes(including recurrent stroke,ischaemic stroke,haemorrhagic stroke,combined vascular event,disability and mortality)were *** analyses of any association of cerebral small vessel disease at baseline and development of a small arterial occlusion(SAO)were *** Among 12603 patients with AIS/TIA,median age was 61.7±11.6 years,and 68.2%were *** adjusting for all potential confounders,frequent-to-severe BG-EPVS was associated with a decreased risk of recurrent ischaemic stroke(HR 0.71,95%CI 0.55 to 0.92,p=0.01)but an increased risk of haemorrhagic stroke(HR 1.99,95%CI 1.11 to 3.58,p=0.02)at 1 year after AIS/TIA,compared with none-to-mild *** with frequent-to-severe CSO-EPVS had a decreased risk of disability(OR 0.76,95%CI 0.62 to 0.92,p=0.004)and all-cause death(HR 0.55,95%CI 0.31 to 0.98,p=0.04)within 3-month but not 1-year follow-ups,compared with those with none-to-mild *** analyses showed that both BG-EPVS(HR 0.43,95%CI 0.21 to 0.87,p=0.02)and CSO-EPVS(HR 0.58,95%CI 0.35 to 0.95,p=0.03)were associated with a decreased risk of subsequent ischaemic stroke in patients with SAO during 1-year *** BG-EPVS increased the risk of haemorrhagic stroke in patients already with AIS/TIA within 1 ***,caution is recommended when selecting antithrombotic agents for secondary stroke prevention in patients with AIS/TIA and more severe BG-EPVS.

关键词： patients haemorrhagic prevention

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Hexamerin and allergen are required for female reproduction in the American cockroach,Periplaneta americana

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Insect Science 2024年第1期31卷 186-200页

作者： Shiming Zhu xiaoyi Chen Sishi xia Qin Li Ziqi Ye Shaoting zhao Kexin Liu Fangfang Liu Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology Institute of Insect Science and TechnologyInstitute of Insect Science and Technology&School of Life SciencesSouth China Normal UniversityGuangzhouChina Guangmeiyuan R&D Center Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied TechnologySouth China Normal UniversityMeizhouGuangdong ProvinceChina Guangdong Laboratory for lingnan Modern Agriculture South China Agricultural UniversityGuangzhouChina

Reproduction is of great importance for the continuation of the *** insects,the fat body is the major tissue for nutrient storage and involved in vitellogenesis,which is essential for female ***,2 proteins,hexamerin and allergen,were separated from the fat bodies of adult female American cockroaches(Periplaneta americana)and identified as storage proteins,encoding for 733 amino acids with molecular weight of 87.88 kDa and 686 amino acids with molecular weight of 82.18 kDa,*** encoding genes of these 2 storage proteins are mainly expressed in the fat *** interference-mediated knockdown of Hexamerin and Allergen in the early stage of the first reproductive cycle in females suppressed vitellogenesis and ovarian maturation,indicating that these storage proteins are involved in controlling ***,the expression of Hexamerin and Allergen was repressed by knockdown of the juvenile hormone(JH)receptor gene Met and the primary response gene Kr-h1,and was induced by methoprene,a JH analog,in both in vivo and in vitro ***,we have determined that hexamerin and allergen are identified as storage proteins and play an important role in promoting female reproduction in the American *** expression of their encoding genes is induced by JH *** data reveal a novel mechanism by which hexamerin and allergen are necessary for JH-stimulated female reproduction.

关键词： fat body juvenile hormone ovary reproduction storage protein vitellogenesis

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A Fault-Tolerant Mobility-Aware Caching Method in Edge Computing

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Computer Modeling in Engineering & Sciences 2024年第7期140卷 907-927页

作者： Yong Ma Han zhao Kunyin Guo Yunni xia Xu Wang xianhua Niu Dongge Zhu Yumin Dong School of Computer Information Engineering Jiangxi Normal UniversityNanchang330000China School of Digital Industry Jiangxi Normal UniversityShangrao334000China The College of Computer Science Chongqing UniversityChongqing400044China College of Mechanical and Vehicle Engineering Chongqing UniversityChongqing400030China School of Computer and Software Engineering Xihua UniversityChengdu610039China Electric Power Research Institute of State Grid Ningxia Electric Power Company Ltd. Yinchuan750002China College of Computer and Information Science Chongqing Normal UniversityChongqing401331China

Mobile Edge Computing(MEC)is a technology designed for the on-demand provisioning of computing and storage services,strategically positioned close to *** the MEC environment,frequently accessed content can be deployed and cached on edge servers to optimize the efficiency of content delivery,ultimately enhancing the quality of the user ***,due to the typical placement of edge devices and nodes at the network’s periphery,these components may face various potential fault tolerance challenges,including network instability,device failures,and resource *** the dynamic nature ofMEC,making high-quality content caching decisions for real-time mobile applications,especially those sensitive to latency,by effectively utilizing mobility information,continues to be a significant *** response to this challenge,this paper introduces FT-MAACC,a mobility-aware caching solution grounded in multi-agent deep reinforcement learning and equipped with fault tolerance *** approach comprehensively integrates content adaptivity algorithms to evaluate the priority of highly user-adaptive cached ***,it relies on collaborative caching strategies based onmulti-agent deep reinforcement learningmodels and establishes a fault-tolerancemodel to ensure the system’s reliability,availability,and *** results unequivocally demonstrate that FTMAACC outperforms its peer methods in cache hit rates and transmission latency.

关键词： Mobile edge networks mobility fault tolerance cooperative caching multi-agent deep reinforcement learning content prediction

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Field test of high-power microwave-assisted mechanical excavation for deep hard iron ore

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第6期16卷 1922-1935页

作者： Feng lin xia-Ting Feng Shiping Li xiao Hai Jiuyu Zhang xiangxin Su Tianyang Tong Jianchun Song Key Laboratory of Ministry of Education on Safe Mining of Deep Metal Mines Northeastern UniversityShenyang110819China Benxi Longxin Mining Corporation Limited Benxi117000China

Microwave-assisted mechanical excavation has great application prospects in mines and tunnels,but there are few field experiments on microwave-assisted rock *** paper takes the Sishanling iron mine as the research object and adopts the self-developed high-power microwave-induced fracturing test system for hard rock to conduct field experiments of microwave-induced fracturing of iron *** heating and reflection evolution characteristics of ore under different microwave parameters(antenna type,power,and working distance)were studied,and the optimal microwave parameters were ***,the ore was irradiated with the optimal microwave parameters,and the cracking effect of the ore under the action of the high-power open microwave was *** results show that the reflection coefficient(standing wave ratio)can be rapidly(ling speed was increased by 56.2%and 66.5%,respectively,compared to the case when microwaves were not used.

关键词： Microwave parameters High power Field experiment Mechanical mining

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The BCL-2 inhibitor APG-2575 resets tumor-associated macrophages toward the M1 phenotype,promoting a favorable response to anti-PD-1 therapy via NLRP3 activation

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Cellular & Molecular Immunology 2024年第1期21卷 60-79页

作者： Fan Luo Han Li Wenjuan Ma Jiaxin Cao Qun Chen Feiteng Lu Miaozhen Qiu Penghui Zhou Zengfei xia Kangmei Zeng Jianhua Zhan Ting Zhou Qiuyun Luo Wentao Pan lin Zhang Chaozhuo lin Yan Huang Li Zhang Dajun Yang Hongyun zhao State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhouChina Ascentage Pharma(Suzhou)Co Ltd 218 Xinghu StreetSuzhouJiangsu ProvinceChina

The main challenges in the use of immune checkpoint inhibitors(ICIs)are ascribed to the immunosuppressive tumor microenvironment and the lack of sufficient infiltration of activated CD8+T *** the tumor microenvironment(TME)from“cold”to“hot”and thus more likely to potentiate the effects of ICIs is a promising strategy for cancer *** found that the selective BCL-2 inhibitor APG-2575 can enhance the antitumor efficacy of anti-PD-1 therapy in syngeneic and humanized CD34+mouse *** single-cell RNA sequencing,we found that APG-2575 polarized M2-like immunosuppressive macrophages toward the M1-like immunostimulatory phenotype with increased CCL5 and CXCL10 secretion,restoring T-cell function and promoting a favorable immunotherapy ***,we demonstrated that APG-2575 directly binds to NF-κB p65 to activate NLRP3 signaling,thereby mediating macrophage repolarization and the activation of proinflammatory caspases and subsequently increasing CCL5 and CXCL10 chemokine *** a result,APG-2575-induced macrophage repolarization could remodel the tumor immune microenvironment,thus improving tumor immunosuppression and further enhancing antitumor T-cell *** immunohistochemistry confirmed that patients with better immunotherapeutic efficacy had higher CD86,p-NF-κB p65 and NLRP3 levels,accompanied by lower CD206 expression on ***,these data provide evidence that further study on APG-2575 in combination with immunotherapy for tumor treatment is required.

关键词： BCL-2 APG-2575 ICIs Macrophages NLRP3

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Analytical Solutions for an Isotropic Elastic Half-Plane with Complete Surface Effects Subjected to a Concentrated/Uniform Surface Load

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Acta Mechanica Solida Sinica 2024年第3期37卷 371-384页

作者： xia-Hui Pan School of Civil Engineering Henan Polytechnic UniversityJiaozuo454003China

Within the context of Gurtin-Murdoch surface elasticity theory,closed-form analytical solutions are derived for an isotropic elastic half-plane subjected to a concentrated/uniform surface *** the effects of residual surface stress and surface elasticity are *** stress function method and Fourier integral transform technique are *** solutions are provided in a compact manner that can easily reduce to special situations that take into account either one surface effect or none at *** results indicate that surface effects generally lower the stress levels and smooth the deformation profiles in the *** elasticity plays a dominant role in the in-plane elastic fields for a tangentially loaded half-plane,while the effect of residual surface stress is fundamentally crucial for the out-of-plane stress and displacement when the half-plane is normally *** the remaining situations,combined effects of surface elasticity and residual surface stress should be *** results for a concentrated surface force serve essentially as fundamental solutions of the Flamant and the half-plane Cerruti problems with surface *** solutions presented in this work may be helpful for understanding the contact behaviors between solids at the nanoscale.

关键词： Surface effects Residual surface stress Surface elasticity Half-plane Analytical solutions

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Multi-omics integration reveals potential stage-specific druggable targets in T-cell acute lymphoblastic leukemia

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Genes & Diseases 2024年第5期11卷 374-389页

作者： Zijun Yan Jie xia Ziyang Cao Hongyang Zhang Jinxia Wang Tienan Feng Yi Shu lin Zou Clinical Research Unit Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China Institute of Pediatric Infection Immunityand Critical Care MedicineShanghai Jiao Tong University School of MedicineShanghai 200062China Center for Clinical Molecular Laboratory Medicine of Children’s Hospital of Chongqing Medical University Chongqing 400014China Clinical Research Institute Shanghai Jiao Tong University School of MedicineShanghai 200025China Bioinformatics and BioMedical Bigdata Mining Laboratory School of Big HealthGuizhou Medical UniversityGuiyangGuizhou 554300China

T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell *** development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this *** this study,we performed multi-omics integration analysis,which included mRNA expression,chromatin accessibility,and gene-dependency database analyses,to identify potential stage-specific druggable targets and repositioned drugs for this *** multi-omics integration helped identify 29 potential pathological genes for *** genes exhibited tissue-specific expression profiles and were enriched in the cell cycle,hematopoietic stem cell differentiation,and the AMPK signaling *** these,four known druggable targets(CDK6,TUBA1A,TUBB,and TYMS)showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in *** TUBA1A expression level was higher in the early T cell precursor(ETP)-ALL cells,while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive ***6 exhibited a U-shaped expression pattern in malignant T cells along the naıve to maturation ***,mebendazole and gemcitabine,which target TUBA1A and TYMS,respectively,exerted stage-specific inhibitory effects on T-ALL cell lines,indicating their potential stage-specific antileukemic role in ***,our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.

关键词： Multi-omics Stage-specific druggable targets Targeted therapeutic strategies T-cell acute lymphoblastic leukemia Drug repositioning

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