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Improving gene transfection efficiency of highly branched poly(β-amino ester)s through the in-situ conversion of inactive terminal groups

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Chinese Chemical Letters 2024年第8期35卷 304-308页

作者： Zhili Li Qijun Wo Dongdong Huang Dezhong Zhou Lei Guo Yeqing Mao Department of urology The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310000China School of Chemical Engineering and Technology Xi’an Jiaotong UniversityXi’an 710049China urology&Nephrology Center Department of UrologyZhejiang Provincial People’s Hospital(Affiliated People’s Hospital)Hangzhou Medical CollegeHangzhou 310014China Key Laboratory of Endocrine Gland Diseases of Zhejiang Province Hangzhou 310014China Pooling institute of Translational Medicine Hangzhou 311100China

Highly branched poly(β-amino ester)s(HPAEs)have emerged as a safe and efficient type of non-viral gene delivery ***,the presence of inactive terminal secondary amine groups compromises their gene transfection *** this study,HPAEs with similar topological structures and chemical compositions but varying numbers of terminal secondary 4-amino-1-butanol(S4)and secondary/tertiary 3-morpholinopropylamine(MPA)groups were *** results demonstrate that an increased number of secondary/tertiary MPA groups in-situ significantly enhances the DNA binding capability of HPAEs,leading to the formation of smaller HPAE/DNA polyplexes with higher zeta potential,ultimately resulting in superior gene transfection efficiency in bladder epithelial *** study establishes a sim-ple yet effective strategy to maximize the gene transfection potency of HPAEs by converting the inactive terminal groups in-situ without the need for complex modifications to their topological structure and chemical composition.

关键词： Gene therapy Gene delivery vector Highly branched poly(β-amino ester)s Terminal groups Epithelial cells

Management of ruptured renal angiomyolipoma with bilateral staghorn calculi

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Asian Journal of urology 2024年第3期11卷 509-510页

作者： Amit Sharma Deepak Biswal Kishor Roy R.T.Raghavendra Department of urology AIIMSRaipurCGIndia

Dear Editor,We present a case of ruptured renal angiomyolipoma(AML)and bilateral renal staghorn *** discuss about the management of this patient by angioembolization,partial nephrectomy,and pyelolithotomy,followed by contralateral interval percutaneous nephrolithotomy(PCNL).Our case is a 40-year-old male who presented with history of dull aching and dragging sensation in bilateral flanks of 6-month *** was admitted and evaluated at other hospital for dizziness,sweating,and loss of *** was found to have bilateral staghorn calculi and left AML and was referred to our institute for further management after initial *** proper written and informed consent was taken from the patient for management as well as publication of the report and images,maintaining the patient’s anonymity.

关键词： admitted sensation renal

Integrated bulk and single-cell transcriptome data identify clinically relevant cell populations in clear cell renal cell carcinoma

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Genes & Diseases 2024年第1期11卷 42-45页

作者： Pingbao Zhang Pu Zhang Jun Gao Xiaosong Li Chengcheng Wei Weihui Liu QingLiu He Yuan Zhang Department of urology Zhongshan HospitalFudan UniversityShanghai 200032China Department of urology Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghai 200032China Clinical Molecular Medicine Testing Center The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of urology The Second Affiliated Hospital of Fujian Medical UniversityQuanzhouFujian 362000China Department of Nephrology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China

Renal cell carcinoma,which consists of three main histological subtypes,namely,clear cell renal cell carcinoma(ccRCC),papillary RCC(pRCC),and chromophobe RCC(chRCC),accounts for most kidney cancer *** accounts for approximately 85%of all RcC cases,1 and it is a malignant tumor with multiple molecular features and a poor *** have shown that ccRCC is one of the most immune and vaso-invasive cancer types.2 Considering that ccRCC is not sensitive to either radiotherapy or chemotherapy,targeted therapies.

关键词： chemotherapy cancer cases

Trogocytosis of CAR molecule regulates CAR-T cell dysfunction and tumor antigen escape

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Signal Transduction and Targeted Therapy 2024年第1期9卷 326-337页

作者： You Zhai Yicong Du Guanzhang Li Mingchen Yu Huimin Hu Changqing Pan Di Wang Zhongfang Shi Xu Yan Xuesong Li Tao Jiang Wei Zhang Department of Molecular Neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingPR China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingPR China Department of urology Peking University First HospitalInstitute of UrologyPeking UniversityNational Urological Cancer CenterBeijingPR China Department of Pathophysiology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingPR China China National Clinical Research Center for Neurological Diseases BeijingPR China Center of Brain Tumor Beijing Institute for Brain DisordersBeijingPR China Research Unit of Accurate Diagnosis Treatmentand Translational Medicine of Brain TumorsChinese Academy of Medical SciencesBeijingPR China Chinese Glioma Genome Atlas Network(CGGA)and Asian Glioma Genome Atlas Network(AGGA) BeijingPR China

Chimeric antigen receptor(CAR)T-cell therapy has demonstrated clinical response in treating both hematologic malignancies and solid *** instances of rapid tumor remissions have been observed in animal models and clinical trials,tumor relapses occur with multiple therapeutic resistance ***,while the mechanisms underlying the long-term therapeutic resistance are well-known,short-term adaptation remains less ***,more views shed light on short-term adaptation and hold that it provides an opportunity window for long-term *** this study,we explore a previously unreported mechanism in which tumor cells employ trogocytosis to acquire CAR molecules from CAR-T cells,a reversal of previously documented *** mechanism results in the depletion of CAR molecules and subsequent CAR-T cell dysfunction,also leading to short-term antigen loss and antigen *** type of intercellular communication is independent of CAR downstream signaling,CAR-T cell condition,target antigen,and tumor cell ***,it is mainly dependent on antigen density and CAR sensitivity,and is associated with tumor cell cholesterol *** mitigation of this trogocytosis-induced CAR molecule transfer can be achieved by adaptively administering CAR-T cells with antigen density-individualized CAR ***,our study reveals a dynamic process of CAR molecule transfer and refining the framework of clinical CAR-T therapy for solid tumors.

关键词： Together instance depletion

Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China:A nationwide,multi-center,population-based cross-sectional study

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Chinese Medical Journal 2024年第11期137卷 1324-1331页

作者： Weiyu Zhang Huixin Liu Ming Liu Shi Ying Renbin Yuan Hao Zeng Zhenting Zhang Sujun Han Zhannan Si Bin Hu Simeng Wen Pengcheng Xu Weimin Yu Hui Chen Liang Wang Zhitao Lin Tao Dai Yunzhi Lin Tao Xu Department of urology Peking University People’s HospitalBeijing 100044China Department of Clinical Epidemiology and Biostatistics Peking University People’s HospitalBeijing 100044China Department of urology Beijing HospitalNational Center of GerontologyBeijing 100005China institute of Geriatric Medicine Chinese Academy of Medical SciencesBeijing 100005China Department of urology Wuhan Union HospitalHuazhong University of Science&TechnologyWuhanHubei 430022China Department of urology The Third People’s Hospital of ChengduChengduSichuan 610014China Department of urology West China Hospital of Sichuan UniversityChengduSichuan 610041China Department of Urologic Oncology Tianjin Medical University Cancer Institute&HospitalTianjin 300060China Department of urology Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China National Cancer Center Beijing 100021China National Clinical Research Center for Cancer Beijing 100021China Department of urology Liaoning Cancer HospitalShenyangLiaoning 110801China Department of urology The Second Hospital of Tianjin Medical UniversityTianjin 300141China Tianjin institute of urology Tianjin Medical UniversityTianjin 300141China Department of urology Lu’an Affiliated Hospital of Anhui Medical UniversityLu’anAnhui 237322China Department of urology Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of urology Harbin Medical University Affiliated Cancer HospitalHarbinHeilongjiang 150081China Department of urology The Second Hospital of Dalian Medical UniversityDalianLiaoning 116023China Department of urology Surgery Fujian Cancer HospitalFuzhouFujian 350014China Department of urology Surgery Hunan Cancer HospitalChangshaHunan 410031China Department of urology Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350004China

Background:Cardiovascular disease(CVD)has emerged as the leading cause of death from prostate cancer(PCa)in recent decades,bringing a great disease burden *** with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy(ADT).The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in ***:Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience *** was defined as myocardial infarction,arrhythmia,heart failure,stroke,ischemic heart disease,and *** risk was estimated by calculating Framingham risk scores(FRS).Patients were accordingly divided into low-,medium-,and high-risk groups.χ2 or Fisher’s exact test was used for comparison of categorical ***:A total of 4253 patients were enrolled in the present study.A total of 27.0%(1147/4253)of patients had comorbid PCa and CVD,and 7.2%(307/4253)had two or more *** enrolled population was distributed in six regions of China,and approximately 71.0%(3019/4253)of patients lived in urban *** imaging and pathological evaluation,most PCa patients were diagnosed at an advanced stage,with 20.5%(871/4253)locally progressing and 20.5%(871/4253)showing *** of them initiated prostatectomy(46.6%,1983/4253)or regimens involving ADT therapy(45.7%,1944/4253)for prostate *** the present PCa cohort,43.1%(1832/4253)of patients had hypertension,and half of them had poorly controlled blood *** FRS stratification,as expected,a higher risk of CVD was related to aging and metabolic ***,we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without *** was in accordance with clinical practice,i.e.,aged patients or patients at advanced oncological stages were inclined to accept sys

关键词： Prostate cancer Castration Cardiovascular disease Prevalence Cardiovascular risk

AZGP1P2/UBA1/RBM15 Cascade Mediates the Fate Determinations of Prostate Cancer Stem Cells and Promotes Therapeutic Effect of Docetaxel in Castration-Resistant Prostate Cancer via TPM1 m6A Modification

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Research 2024年第3期6卷 151-167页

作者： Hong Wang Jj Liu Xiaojun Zhu Bin Yang Zuping He Xudong Yao Department of urology Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghaiChina Urologic Cancer institute School of MedicineTongji UniversityShanghaiChina. Department of urology Surgery The Affiliated Hospital of Inner Mongolia Medical UniversityHohhotChina. The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province School of MedicineHunan Normal UniversityThe Engineering Research Center of Reproduction and Translational Medicine of Hunan ProvinceChangshaChina Shanghai Key Laboratory of Reproductive Medicine Shanghai Jiao Tong University School of MedicineShanghaiChina.

Prostate cancer(PCa)is a common malignant tumor with high morbidity and mortality *** prostate cancer stem cell(PCSC)model provides novel insights into the pathogenesis of PCa and its therapeutic ***,the roles and molecular mechanisms of specific genes in mediating fate decisions of PCSCs and carcinogenesis of PCa remain to be *** this study,we have explored the expression,function,and mechanism of AZGP1P2,a pseudogene of AZGP1,in regulating the stemness and apoptosis of PCSCs and treatment resistance of docetaxel in castration-resistant prostate cancer(CRPC).We revealed that AZGP1P2 was downregulated in CRPC cell lines and PCSCs,while it was positively associated with progression-free *** of the AZGP1P2 enhanced the sensitivity of docetaxel treatment in CRPCs via inhibiting their *** pull-down associated with mass spectrometry analysis,co-immunoprecipitation assay,and RNA immunoprecipitation assay demonstrated that AZGP1P2 could bind to UBA1 and RBM15 as a“writer”of methyltransferase to form a ***1,an E1 ubiquitin-activating enzyme,contributed to RBM15 protein degradation via ubiquitination *** RNA immunoprecipitation assay displayed that RBM15 controlled the mRNA decay of TPM1 in m6A ***,a xenograft mouse model and patient-derived organoids showed that the therapeutic effect of docetaxel in CRPC was increased by AZGP1P2 in ***,these results imply that AZGP1P2 mediates the stemness and apoptosis of PCSCs and promotes docetaxel therapeutic effect by suppressing tumor growth and metastasis via UBA1/RBM15-mediated TPM1 mRNA decay in CRPC.

关键词： Prostate TPM1 m6A

A multicenter uroflowmetry study of healthy women in China

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Chinese Medical Journal 2024年第10期137卷 1225-1227页

作者： Xiaodong Liu Lingfeng Meng Jiawen Wang Tianming Ma Benkang Shi Hai Huang Qingwei Wang Min Chen Limin Liao Hong Shen Zhongqing Wei Yuansong Xiao Tiejun Pan Jian Ren Peng Zhang Xiaojun Tian Yaoguang Zhang Department of urology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Graduate School of Peking Union Medical College Beijing 100730China Department of urology Qilu HospitalShandong UniversityJinanShandong 250013China Department of urology SUN YAT-SEN Memorial HospitalGuangzhouGuangdong 510235China Department of urology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450003China Department of urology Tongji HospitalTongji Medical College of Huazhong University of Science and TechnologyWuhanHubei 430030China Department of urology China Rehabilitation Research CenterBeijing 100068China Department of urology West China HospitalChengduSichuan 610041China Department of urology The Second Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210011China Department of urology General Hospital of Southern Theatre CommandGuangzhouGuangdong 510010China Department of urology General Hospital of Central Theatre CommandWuhanHubei 430071China Department of urology China-Japan Friendship HospitalBeijing 100029China Department of urology Beijing Chao-Yang HospitalBeijing 100027China Department of urology Peking University Third HospitalBeijing 100191China

Uroflowmetry is an uroflow measurement technique used to record the voided volume(VV)and flow rate,which can help clinicians objectively evaluate lower urinary tract ***,few uroflowmetry studies have focused on the female population,[1]especially on the uroflow curve standard ***,we sought to establish dependable uroflow reference values and nomograms for Chinese women and to evaluate the relationship between uroflow patterns and demographic data.

关键词： function. flowmetry analysis.

Changes in the terminology and diagnostic criteria of non-alcoholic fatty liver disease:Implications and opportunities

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World Journal of Gastrointestinal Pathophysiology 2024年第1期15卷 1-8页

作者： Muhammed Mubarak Javed I.Kazi Department of Histopathology Sindh Institute of Urology and TransplantationKarachi 74200Pakistan

Fatty liver disease(FLD)is a highly prevalent pathological liver *** has many and varied etiologies and has heterogeneous clinical course and *** proper nomenclature and classification have been problematic since its initial ***,it was divided into two main categories:Alcoholassociated liver disease and nonalcoholic FLD(NAFLD).Among these,the latter condition has been plagued with nomenclature and classification *** two main objections to its use have been the use of negative(non-alcoholic)and stigmatizing(fatty)terms in its *** attempts were made to address these issues but none achieved universal *** recently,NAFLD has received a new nomenclature from an international collaborative effort based on a rigorous scientific *** has been renamed steatotic liver disease(SLD),and NAFLD as metabolic dysfunction-associated *** dysfunction-associated steatohepatitis was chosen as the replacement terminology for non-alcoholic *** is a significant positive change in the nomenclature and categorization of FLD and will likely have a major impact on research,diagnosis,treatment,and prognosis of the disease in the future.

关键词： Fatty liver disease Metabolic syndrome Non-alcoholic fatty liver disease Steatotic liver disease Steatohepatitis

Lipid nanoparticle-mediated base-editing of the Hao1 gene achieves sustainable primary hyperoxaluria type 1 therapy in rats

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Science China Life Sciences 2024年

作者： Dexin Zhang Rui Zheng Zhoutong Chen Liren Wang Xi Chen Lei Yang Yanan Huo Shuming Yin Dan Zhang Jiaxin Huang Xingang Cui Dali Li Hongquan Geng Department of urology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Department of urology Children's Hospital of Fudan University Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University

Primary hyperoxaluria type 1(PH1) is a severe hereditary disease, leading to the accumulation of oxalate in multiple organs, particularly the kidney. Hydroxyacid oxidase 1(HAO1), a pivotal gene involved in oxalate production, is an approved target for the treatment of PH1. In this study, we demonstrated the discovery of several novel therapeutic sites of the Hao1 gene and the efficient editing of Hao1 c.290-2 A in vivo with lipid nanoparticles(LNP) delivered adenine base editing(ABE) mR NA. A single infusion of LNP-ABE resulted in a near-complete knockout of Hao1 in the liver, leading to the sustainable normalization of urinary oxalate(for at least 6 months) and complete rescue of the pathophysiology in PH1 rats. Additionally, a significant correlation between Hao1 editing efficiency and urinary oxalate levels was observed and over60% Hao1 editing efficiency was required to achieve the normalization of urinary oxalate in PH1 rats. These findings suggest that the LNPmediated base-editing of Hao1 c.290-2 A is an efficient and safe approach to PH1 therapy, highlighting its potential utility in clinical settings.

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