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The unique genomic landscape and prognostic mutational signature of Chinese clear cell renal cell carcinoma

Journal of the National Cancer Center 2022年第3期2卷 162-170页

作者： Wenhao Xu Aihetaimujiang Anwaier wangrui liu Xi Tian Jiaqi Su Guohai Shi Yuanyuan Qu Hailiang Zhang Dingwei Ye Department of Urology Fudan University Shanghai Cancer CenterShanghai Medical CollegeFudan UniversityShanghaiChina Department of Interventional Oncology Renji HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Background:The genomic background affects the occurrence and metastasis of cancers,including clear cell renal cell carcinoma(ccRCC).However,reports focusing on the prognostic mutational signature of Chinese ccRCC are ***:Overall,929 patients,including a training cohort with Chinese patients(n=201),a testing cohort with Caucasian patients(n=274),and a validation cohort(n=454)were analyzed for the genomic landscape of ***,machine-learning algorithms were used to identify and evaluate the genomic mutational signature(GMS)in *** for prognosis,immune microenvironment,association with independent clinicopathological features,and predictive responses for immune checkpoint therapies(ICTs)were ***:The DNA variation data of 929 patients with ccRCC suggested markedly differential genomic mutational frequency of the most frequent genes,such as VHL,PBRM1,BAP1,SETD2,and KDM5C between the Chinese and Caucasian ***1 showed significant co-occurrence with VHL and *** then successfully iden-tified a seven-gene mutational signature(GMS^(Mut))that included mutations in FBN1,SHPRH,CELSR1,COL6A6,DST,ABCA13,and *** GMS^(Mut)significantly predicted progressive progression(P<0.0001,HR=2.81)and poor prognosis(P<0.0001,HR=3.89)in the Chinese training ***,ccRCC patients with the GMS^(Mut)had poor survival rates in the testing cohort(P=0.020)and poor outcomes were predicted for those treated with ICTs in the validation cohort(P=0.036).Interestingly,a favorable clinical response to ICTs,ele-vated expression of immune checkpoints,and increased abundance of tumor-infiltrated lymphocytes,specifically CD8^(+)T cells,Tregs,and macrophages,were observed in the GMS^(Mut)***:This study described the pro-tumorigenic GMS^(Mut)cluster that improved the prognostic accuracy in Chinese patients with *** discovery of the novel independent prognostic signature highlights the relationship between tumor phenotype a

关键词： Clear cell renal cell carcinoma Genomic mutation Immune checkpoint therapies Prognosis Tumor microenvironment

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Tumor microenvironment-based signatures distinguish intratumoral heterogeneity, prognosis, and immunogenomic features of clear cell renal cell carcinoma

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Journal of the National Cancer Center 2023年第3期3卷 236-249页

作者： Aihetaimujiang Anwaier Wenhao Xu wangrui liu Shiyin Wei Xi Tian Yuanyuan Qu Jianfeng Yang Hailiang Zhang Dingwei Ye Department of Urology Fudan University Shanghai Cancer Center/Department of OncologyShanghai Medical CollegeFudan UniversityShanghaiChina Shanghai Genitourinary Cancer Institute ShanghaiChina Department of Interventional Oncology Renji HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Affiliated Hospital of Youjiang Medical University for Nationalities BaiseChina Department of Surgery ShangNan Branch of Longhua HospitalShanghai University of Traditional Chinese MedicineShanghaiChina

Background:The tumor microenvironment(TME)performs a crucial function in the tumorigenesis and response to immunotherapies of clear cell renal cell carcinoma(ccRCC).However,a lack of recognized pre-clinical TME-based risk models poses a great challenge to investigating the risk factors correlated with prognosis and treatment responses for patients with ***:Stromal and immune contexture were assessed to calculate the TMErisk score of a large sample of patients with ccRCC from public and real-world cohorts using machine-learning ***,analyses for prognostic efficacy,correlations with clinicopathological features,functional enrichment,immune cell distribu-tions,DNA variations,immune response,and heterogeneity were performed and ***:Clinical hub genes,including INAFM2,SRPX,DPYSL3,VSIG4,APLNR,FHL5,A2M,SLFN11,ADAMTS4,IFITM1,NOD2,CCR4,HLA-DQB2,and PLAUR,were identified and incorporated to develop the TMErisk *** in the TME high risk group(category)exhibited a considerably grim prognosis,and the TMErisk model was shown to independently function as a risk indicator for the overall survival(OS)of ccRCC *** levels of immune checkpoint genes were substantially increased in TME high risk group,while those of the human leukocyte antigen(HLA)family genes were prominently *** addition,tumors in the TME high group showed significantly high infiltration levels of tumor-infiltrated lymphocytes,including M2 macrophages,CD8+T cells,B cells,and CD4+T *** heterogeneity analysis,more frequent somatic mutations,including pro-tumorigenic BAP1 and PBRM1,were observed in the TME high ***,19.3%of patients receiving immunotherapies in the TME high group achieved complete or partial response compared with those with immune tolerance in the TME low group,suggesting that TMErisk prominently differentiates prognosis and responses to immunotherapy for patients with ***:We first established the

关键词： Clear cell renal cell carcinoma Tumor microenvironment Risk group Immunogenomic feature

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Systematic Genome-Wide Profiles Reveal Alternative Splicing Landscape and Implications of Splicing Regulator DExD-Box Helicase 21 in Aggressive Progression of Adrenocortical Carcinoma

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Phenomics 2021年第6期1卷 243-256页

作者： Wenhao Xu Aihetaimujiang Anwaier wangrui liu Xi Tian Wen-Kai Zhu Jian Wang Yuanyuan Qu Hailiang Zhang Dingwei Ye Department of Urology Fudan University Shanghai Cancer CenterNo.270 Dong’an RoadShanghai 200032People’s Republic of China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032People’s Republic of China Department of Transplantation Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092People’s Republic of China

Alternative splicing(AS)in the tumor biological process has provided a novel perspective on ***,the clinical significance of individual AS patterns of adrenocortical carcinoma(ACC)has been underestimated,and in-depth investigations are *** selected 76 ACC samples from the Cancer Genome Atlas(TCGA)SpliceSeq and SpliceAid2 databases,and 39 ACC samples from Fudan University Shanghai Cancer Center(FUSCC).Prognosis-related AS events(PASEs)and survival analysis were evaluated based on prediction models constructed by machine-learning *** total,23,984 AS events and 3,614 PASEs were detected in the patients with *** predicted risk score of each patient suggested that eight PASEs groups were significantly correlated with the clinical outcomes of these patients(p<0.001).Prognostic models produced AUC values of 0.907 in all PASEs’*** splicing factors(SFs),including BAG2,CXorf56,DExD-Box Helicase 21(DDX21),HSPB1,MBNL3,MSI1,RBMXL2,and SEC31B,were identified in regulatory networks of ***21 was identified and validated as a novel clinical promoter and therapeutic target in 115 patients with ACC from TCGA and FUSCC *** conclusion,the strict standards used in this study ensured the systematic discovery of profiles of AS events using genome-wide *** findings contribute to a comprehensive understanding of the landscape and underlying mechanism of AS,providing valuable insights into the potential usages of DDX21 for predict-ing prognosis for patients with ACC.

关键词： Adrenocortical carcinoma Genome-wide analysis Prognosis Alternative splicing Bioinformatics DExD-Box Helicase 21(DDX21)

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Comprehensive characterization of alternative splicing in in hepatocellular carcinoma

Comprehensive characterization of alternative splicing in in...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： Shuai Zhao wangrui liu Jun Li Jian Wang Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine 上海交通大学医学院附属仁济医院(东院) 上海第十人民医院

In hepatocellular carcinoma(HCC),alternative splicing(AS) is related to tumor invasion and *** used HCC data from a public database to identify AS subtypes by unsupervised *** feature analysis of different splicing subtypes and acquisition of the differential alternative splicing events(DASEs) combined with enrichment analysis,the differences in several subtypes were ***,in keeping with the differences between these subtypes,DASEs identified survival-related AS times,and were used to construct risk proportional regression *** this study,AS was found to be useful for the classification of HCC subtypes,which changed the activity of tumor-related pathways through differential splicing effects,affected the tumor microenvironment,and participated in immune *** summary,we described the clinical and molecular characteristics of HCC splicing subtypes,and constructed an extremely effective prognostic model,providing a new approach for the personalized treatment of HCC patients.

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Integrated Machine Learning and Bioinformatic Analyses Constructed a Tumor immune microenvironment-Related Classifier to Predict Prognosis and Immunotherapy Responses for Hepatocellular Carcinoma Patients

Integrated Machine Learning and Bioinformatic Analyses Const...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： wangrui liu Tao Wang Jianfeng Xiang Jun Li Bo Zhai Affiliated Hospital of Youjiang Medical College for Nationalities 上海第十人民医院

Background:The occurrence and development of hepatocellular carcinoma(HCC) is a complex biologic process,and the influence of tumor immune microenvironment(TIME) and malignant tumor phenotypes remains ***:Based on the immune-related indicators from ImmPort and InnateDB,we first clustered the samples and analyzed the differentially expressed genes among immune subtype using machine-learning methods.A total of 790 HCC samples from TCGA,LIRI-JP,GSE76427 were enrolled as discovering,testing and validation *** score was constructed based on Boruta algorithm and used to evaluate independent prognostic and predictive immunotherapy response *** also conducted clinical cohort verification at our center to prove the predictive effect of ICIscore on ***:First,according to the immune gene expression level,immune cell abundance,immunescore and stromalscore,we obtained three independent immune subtypes with significance in survival and heterogeneity differences of ***,differentially expressed genes(DEGs) among 1022 immune subtypes divide HCC samples into three immune genotyping with significant difference in prognosis and ***,the ICI score,novel immunophenotyping of HCC,was established and significantly differs gender,stage,progression and DNA variation profiles of HCC(p<0.05).Additionally,ICI score could markedly predict responses to immunotherapies via chemokine signaling,focal adhesion and JAK/STAT signaling ***:This study first describes that tumor microenvironment and immunophenotyping clusters improve the accuracy of the prognosis of HCC *** new independent prognostic indicators discovered in HCC highlight the relationship between tumor phenotype and the immune environment.

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Role of the globus pallidus in motor and non-motor symptoms of Parkinson's disease

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Neural Regeneration Research 2025年第6期20卷 1628-1643页

作者： Yimiao Jiang Zengxin Qi Huixian Zhu Kangli Shen Ruiqi liu Chenxin Fang Weiwei Lou Yifan Jiang wangrui Yuan Xin Cao Liang Chen Qianxing Zhuang Department of Physiology School of MedicineNantong UniversityNantongJiangsu ProvinceChina Department of Neurosurgery Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiChina National Center for Neurological Disorders ShanghaiChina Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration ShanghaiChina State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institute of Brain ScienceFudan UniversityShanghaiChina

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the comp

关键词： anxiety basal ganglia bradykinesia deep brain stimulation depression globus pallidus externus globus pallidus internus lateral globus pallidus medial globus pallidus neural circuit Parkinson's disease

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miR-485-5p在前列腺癌组织中表达的临床意义及对前列腺癌细胞生物学行为的影响

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医学分子生物学杂志 2019年第6期16卷 537-541,546页

作者：韦高猛黄勇平刘王睿唐毓金右江民族医学院附属医院泌尿外科广西壮族自治区百色市533000

目的探讨miR-485-5p在前列腺癌组织中表达的临床意义及对前列腺癌细胞生物学行为的影响.方法收集42例来自2016年6月至2018年6月在右江民族医学院附属医院行前列腺癌手术患者的前列腺癌组织, 及其病理分级和临床分期, 以同期正常前列... 详细信息

目的探讨miR-485-5p在前列腺癌组织中表达的临床意义及对前列腺癌细胞生物学行为的影响.方法收集42例来自2016年6月至2018年6月在右江民族医学院附属医院行前列腺癌手术患者的前列腺癌组织, 及其病理分级和临床分期, 以同期正常前列腺组织为对照, 采用实时定量PCR检测两组组织中miR-485-5p的表达量.将正常培养LNCaP细胞分为对照组和miR-485-5p组, 采用细胞转染, 将miR-485-5pmimic转染于miR-485-5p组细胞.采用RT-PCR检测转染效率, 采用MTT法检测各组细胞增殖, Tran-swell检测各组细胞侵袭能力, 划痕实验检测各组细胞迁移能力, TUNEL法检测各组细胞的凋亡情况.结果与正常前列腺组织相比, 前列腺癌组织中miR-485-5p的mRNA表达量显著下调 (P<0.05);根据病理分级, G3期患者前列腺癌组织中miR-485-5p表达量显著低于G1~G2期患者 (P<0.05);根据临床分期, Ⅲ~Ⅳ期患者前列腺癌组织中miR-485-5p表达量显著低于Ⅰ~Ⅱ期 (P<0.05);细胞转染后, miR-485-5p组LNCaP细胞miR-485-5p的表达量显著升高 (P<0.05);与对照组相比, miR-485-5p组各时间点的LNCaP细胞数量显著降低 (P<0.05), 侵袭和迁移率显著下降 (P<0.05), 细胞凋亡率明显升高.结论 miR-485-5p可以抑制前列腺癌细胞LNCaP的增殖、侵袭和迁移, 促进其凋亡, 与前列腺癌的发生发展密切相关.

关键词： miR-485-5p 前列腺癌细胞生物学行为

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跨域水体生态修复全周期一体化项目管理实践——长三角生态绿色一体化发展示范区元荡示范段案例

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景观设计学（中英文） 2022年第6期10卷 68-89页

作者：毛永青刘王瑞王加伟刘安迪张杰龙启迪设计集团股份有限公司苏州215000 长三角生态绿色一体化发展示范区执委会生态和规划建设部上海201713 南京农业大学公共管理学院南京210014

区域城市一体发展是国家战略。在尊重现有行政区划的前提下实现一体化模式创新是长三角生态绿色一体化发展示范区重要示范和实践任务之一。本文首先分析了国内外跨域项目一体化实践案例,并总结了其模式及面临的关键问题,继而以跨越江苏... 详细信息

区域城市一体发展是国家战略。在尊重现有行政区划的前提下实现一体化模式创新是长三角生态绿色一体化发展示范区重要示范和实践任务之一。本文首先分析了国内外跨域项目一体化实践案例,并总结了其模式及面临的关键问题,继而以跨越江苏省和上海市的长三角生态绿色一体化发展示范区元荡示范段项目为例,在详述了一体化实施过程中各个阶段面临的具体问题和解决方式的基础上,提出了跨界水体修复全周期一体化管理的“3P3S”模式框架。实践表明,该框架摆脱传统依靠行政命令或者权威机构主导的一体化模式,是一种自发性、主动性相对较高的一体化模式的探索,可为常规的跨域项目的一体化实施提供参考。

关键词：长三角一体化长三角生态绿色一体化示范区跨域项目一体化跨域生态治理一体化模式创新

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Heterogeneous lamella design to tune the mechanical behaviour of a new cost-effective compositionally complicated alloy

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Journal of Materials Science & Technology 2022年第1期96卷 113-125页

作者： Yu Yin Qiyang Tan Qiang Sun wangrui Ren Jingqi Zhang Shiyang liu Yingang liu Michael Bermingham Houwen Chen Ming-Xing Zhang School of Mechanical and Mining Engineering University of QueenslandQLD 4072Australia College of Materials Science and Engineering Chongqing UniversityChongqing 400044China

A heterogeneous lamella(HL)design strategy was applied to manipulate mechanical properties of a new cost-effective Fe_(35)Ni_(35)Cr_(25)Mo_(5)compositionally complicated alloy(CCA).The HL structure was produced by single-step heat treatment(800℃for 1 h)after cold *** HL structure consists of alternative lamellae regions of coarse-grained FCC matrix(5-20μm),and regions containing ultra-fine grains or subgrains(200-500 nm)together with nanoprecipitates(20-500 nm)and annealing *** compared with other cost-effective CCAs,the 800℃annealed sample with HL structure demonstrated a comparable tensile property,with yield strength over 1.0 GPa and total elongation of~13%.Formation of the annealing twins and nanoprecipitates decorated HL structure was a result of the concurrent partial recrystallization and precipitation ofσphase at the shear bands with a high density of lattice defects(***-density dislocation walls and deformation twins).The latter restricted the growth of recrystallized grains,leading to the formation of ultrafine subgrains within the HL *** high yield strength resulted from the multistage hetero-deformation induced(HDI)strengthening and precipitation strengthening associated with heterogeneous lamella structures containing *** ductility was originated from the coexistence of multiple deformation mechanisms,which started with dislocation slip and formation of stacking faults at the initial stage,followed by nano-twinning at the higher strain *** HL design strategy,comprising composition and thermomechanical process designs,and the resultant microstructure tuning,open a broader window for the development of cost-effective CCAs with enhanced performance.

关键词： High entropy alloys Compositionally complicated alloys Heterogeneous lamella structure Nanoprecipitates Recrystallization Mechanical properties

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Fe^(3+)诱导聚多巴胺-聚乙烯亚胺电沉积制备单价选择性膜

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化工进展 2023年第3期42卷 1508-1514页

作者：赵王瑞刘燕张伟邓会宁河北工业大学化工学院天津300130

仿生黏合剂聚多巴胺(polydopamine,PDA)与聚乙烯亚胺(polyethyleneimine,PEI)共沉积是构建单价选择性分离层的有效方法。本实验通过浸泡预处理将Fe^(3+)引入阳离子交换膜,并利用电场作用和Fe^(3+)诱导PDA-PEI在膜面沉积改性。结果表明,... 详细信息

仿生黏合剂聚多巴胺(polydopamine,PDA)与聚乙烯亚胺(polyethyleneimine,PEI)共沉积是构建单价选择性分离层的有效方法。本实验通过浸泡预处理将Fe^(3+)引入阳离子交换膜,并利用电场作用和Fe^(3+)诱导PDA-PEI在膜面沉积改性。结果表明,该方法大大缩短了单价选择性膜的改性时间,制备了单价选择性阳离子交换膜。利用扫描电子显微镜、紫外可见分光光度计、红外光谱仪、zeta电位对制得的膜进行表征和性能测试,探讨了Fe^(3+)浓度对改性膜性能的影响。表明随着Fe^(3+)浓度的增加改性膜的膜电阻呈上升趋势,而表面荷正电性和选择性均呈先增加后降低的趋势。由于电场和Fe^(3+)对多巴胺聚合过程的共同影响,当Fe^(3+)的浓度为0.001mol/L时,改性膜Na^(+)/Mg^(2+)选择性高达12.8,并且具有较低的膜电阻和优异的稳定性。

关键词：离子交换膜聚合电沉积单价离子选择性

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