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Development of a radiomics model to discriminate ammonium urate stones from uric acid stones in vivo:A remedy for the diagnostic pitfall of dual-energy computed tomography

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Chinese Medical Journal 2024年第9期137卷 1095-1104页

作者： Junjiong Zheng Jie Zhang Jinhua Cai Yuhui Yao Sihong Lu Zhuo Wu Zhaoxi Cai Aierken Tuerxun Jesur Batur Jian Huang Jianqiu Kong Tianxin Lin Department of Urology Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene RegulationGuangdong Provincial Clinical Research Center for Urological DiseasesGuangzhouGuangdong 510120China Department of Neurology Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510120China Department of Radiology Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510120China Department of Urology The First People’s Hospital of Kashgar PrefectureKashgarXinjiang 844000China

Background:Dual-energy computed tomography(DECT)is purported to accurately distinguish uric acid stones from non-uric acid ***,whether DECT can accurately discriminate ammonium urate stones from uric acid stones remains ***,we aimed to explore whether they can be accurately identified by DECT and to develop a radiomics model to assist in distinguishing ***:This research included two *** the first purpose to evaluate the accuracy of DECT in the diagnosis of uric acid stones,178 urolithiasis patients who underwent preoperative DECT between September 2016 and December 2019 were *** model construction,93,40,and 109 eligible urolithiasis patients treated between February 2013 and October 2022 were assigned to the training,internal validation,and external validation sets,*** features were extracted from non-contrast CT images,and the least absolute shrinkage and selection operator(LASSO)algorithm was used to develop a radiomics ***,a radiomics model incorporating the radiomics signature and clinical predictors was *** performance of the model(discrimination,calibration,and clinical usefulness)was ***:When patients with ammonium urate stones were included in the analysis,the accuracy of DECT in the diagnosis of uric acid stones was significantly ***-two percent of ammonium urate stones were mistakenly diagnosed as uric acid stones by DECT.A radiomics model incorporating the radiomics signature,urine pH value,and urine white blood cell count was *** model achieved good calibration and discrimination{area under the receiver operating characteristic curve(AUC;95%confidence interval[CI]),0.944(0.899-0.989)},which was internally and externally validated with AUCs of 0.895(95%CI,0.796-0.995)and 0.870(95%CI,0.769-0.972),*** curve analysis revealed the clinical usefulness of the ***:DECT cannot accurately differentiate amm

关键词： Ammonium urate Dual-energy scanned projection radiography Radiomics Uric acid Urolithiasis

Transcription factor EHF interacting with coactivator AJUBA aggravates malignancy and acts as a therapeutic target for gastroesophageal adenocarcinoma

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2119-2136页

作者： Li Peng Yanyi Jiang Hengxing Chen Yongqiang Wang Qiusheng Lan Shuiqin Chen Zhanwang Huang Jingyuan Zhang Duanqing Tian Yuntan Qiu Diankui Cai Jiangyun Peng Daning Lu Xiaoqing Yuan Xianzhu Yang Dong Yin Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Medical Research Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Hefei Institutes of Physical Science Chinese Academy of SciencesHefei 230031China Department of Gastrointestinal Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Hepatobiliary Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou International CampusGuangzhou 511442China

Transcriptional dysregulation of genes is a hallmark of tumors and can serve as targets for cancer drug ***,it is extremely challenging to develop small-molecule inhibitors to target abnormally expressed transcription factors(TFs)except for the nuclear receptor family of *** is known about the interaction between TFs and transcription cofactors in gastroesophageal adenocarcinoma(GEA)or the therapeutic effects of targeting TF and transcription cofactor *** this study,we found that ETS homologous factor(EHF)expression is promoted by a core transcriptional regulatory circuitry(CRC),specifically ELF3-KLF5-GATA6,and interference with its expression suppressed the malignant biological behavior of GEA ***,we identified Ajuba LIM protein(AJUBA)as a new coactivator of EHF that cooperatively orchestrates transcriptional network activity in ***,we identified KRAS signaling as a common pathway downstream of EHF and ***,dual targeting of EHF and AJUBA by lipid nanoparticles cooperatively attenuated the malignant biological behaviors of GEA in vitro and in *** conclusion,EHF is upregulated by the CRC and promotes GEA malignancy by interacting with AJUBA through the KRAS *** of both EHF and its coactivator AJUBA through lipid nanoparticles is a novel potential therapeutic strategy.

关键词： EHF AJUBA KRAS pathway Enhancer Core transcriptional regulatory circuitry Gastroesophageal adenocarcinoma Gastric adenocarcinoma Esophageal adenocarcinoma Transcription factor Coactivator Lipid nanoparticles

Nanomedicine targeting ferroptosis to overcome anticancer therapeutic resistance

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Science China(Life Sciences) 2024年第1期67卷 19-40页

作者： Jing Cai Xiaoding Xu Phei Er Saw Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineMedical Research CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Nanhai Translational Innovation Center of Precision Immunology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityFoshan 528200China

A potential reason for the failure of tumor therapies is treatment *** to chemotherapy,radiotherapy,and immunotherapy continues to be a major obstacle in clinic,resulting in tumor recurrence and *** major mechanisms of therapy resistance are inhibitions of cell deaths,like apoptosis and necrosis,through drug inactivation and excretion,repair of DNA damage,tumor heterogeneity,or changes in tumor microenvironment,*** studies have shown that ferroptosis play a major role in therapies resistance by inducing phospholipid peroxidation and iron-dependent cell *** ferroptosis inducers in combination with clinical treatment techniques have been used to enhance the effect in tumor ***,versatile ferroptosis nanoinducers exhibit an extensive range of functions in reversing therapy resistance,including directly triggering ferroptosis and feedback ***,we provide a detailed description of the design,mechanism,and therapeutic application of ferroptosis-mediated synergistic tumor *** also discuss the prospect and challenge of nanomedicine in tumor therapy resistance by regulating ferroptosis and combination therapy.

关键词： ferroptosis cancer therapy therapy resistance nanoinducers

LncRNA ZFPM2-AS1 promotes phyllodes tumor progression by binding to CDC42 and inhibiting STAT1 activation

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2942-2958页

作者： Shishi He Guowei Huang Rong Lei Rurong Jia Zhanghai He Jiewen Chen Hongyan Huang Zixian Huang Ailifeire Yilihamu Xun Li Zilin Zhuang Mengjia Han Xueman Chen Di Huang Yan Nie Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineMedical Research CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Breast Tumor Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Pathology Shantou University Medical CollegeShantou 515041China School of Basic Medical Science Southern Medical UniversityGuangzhou 510515China Department of Pathology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Breast Medicine Affiliated Foshan Maternity and Child Healthcare HospitalSouthern Medical UniversityFoshan 528000China Department of Breast Surgery Zhujiang HospitalSouthern Medical UniversityGuangzhou 510282China Department of Oral and Maxillofacial Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China

Breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant *** non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involvement in breast PT remains largely *** this study,microarray was leveraged for the first time to investigate the role of lncRNA in *** identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT,and its overexpression endowed PT with high tumor grade and adverse ***,we elucidated that ZFPM2-AS1 promotes the proliferation,migration,and invasion of malignant PT in *** ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft(PDX)model could effectively inhibit tumor progression in ***,our findings showed that ZFPM2-AS1 is competitively bound to CDC42,inhibiting ACK1 and STAT1 activation,thereby launching the transcription of *** conclusion,our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT,and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.

关键词： LncRNA Phyllodes tumor ZFPM2-AS1 Cell division cycle 42 Activated cdc42 kinase 1 Signal transducer and activator of transcription 1 TNF receptor superfamily member 19 Nano particles

Restoring cosmological concordance with axion-like early dark energy and dark matter characterized by a constant equation of state?

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Communications in Theoretical Physics 2024年第7期76卷 74-82页

作者： Yan-Hong Yao Xin-He Meng School of Physics and Astronomy Sun Yatsen University 2 Daxue RoadTangjiaZhuhaiChina School of Physics Nankai University 94 Weijin RoadNankaiTianjinChina

The Hubble tension persists as a challenge in *** early dark energy(EDE)models,initially considered the most promising for alleviating the Hubble tension,fall short of addressing the issue without exacerbating other tensions,such as the S_(8)*** that a negative dark matter(DM)equation of state(EoS)parameter is conducive to reduce the value of the σ_(8)parameter,we extend the axion-like EDE model in this paper by replacing the cold dark matter(CDM)with DM characterized by a constant EoS w_(dm)(referred to as WDM hereafter).We then impose constraints on this axion-like EDE extension model,along with three other models:the axion-like EDE model,ΛWDM,and Λ*** constraints are derived from a comprehensive analysis incorporating data from the Planck 2018 cosmic microwave background,baryon acoustic oscillations,and the Pantheon compilation,as well as a prior on H_(0)(i.e.H_(0)=73.04±1.04,based on the latest local measurement by Riess et al)and a Gaussianized prior on S_(8)(i.e.S_(8)=0.766±0.017,determined through the joint analysis of KID1000+BOSS+2dLenS).We find that although the new model maintains the ability to alleviate the Hubble tension to~1.4σ,it still exacerbates the S_(8)tension to a level similar to that of the axion-like EDE model.

关键词： Hubble tension early dark energy noncold dark matter S8 tension

TP53-specific mutations serve as a potential biomarker for homologous recombination deficiency in breast cancer:a clinical next-generation sequencing study

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Precision Clinical Medicine 2024年第2期7卷 122-131页

作者： Yongsheng Huang Shuwei Ren Linxiaoxiao Ding Yuanling jiang Jiahuan Luo Jjinghua Huang Xinke Yin Jianli Zhao Sha Fu Jianwei Liao Cellular&Molecular Diagnostics Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Clinical Laboratory The Sixth Affliated HospitalSun Yat-sen UniversityGuangzhou 510655China Breast Tumor Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Guangzhou Regenerative Medicine and Health Guangdong LaboratorySun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China

Background:TP53 mutations and homologous recombination deficiency(HRD)occur frequently in breast ***,the characteristics of TP53 pathogenic mutations in breast cancer patients with/without HRD are not ***:Clinical next-generation sequencing(NGS)of both tumor and paired blood DNA from 119 breast cancer patients(BRCA-119 cohort)was performed with a 520-gene ***,tumor mutation burden(TMB),and genomic HRD scores were assessed from NGS *** data from 47 breast cancer patients in the HRD test cohort were analyzed for further ***:All TP53 pathogenic mutations in patients had somatic origin,which was associated with the protein expression of estrogen receptor and progestogen *** to patients without TP53 pathologic mutations,patients with TP53 pathologic mutations had higher levels of HRD scores and different genomic *** frequency of TP53 pathologic mutation was higher in the HRDhigh group(HRD score≥42)relative to that in the HRD-low group(HRD score<42).TP53 has different mutational characteristics between the HRD-low and HRD-high ***53-specific mutation subgroups had diverse genomic features and ***,TP53 pathogenic mutations predicted the HRD status of breast cancer patients with an area under the curve(AUC)of ***53-specific mutations,namely HRD-low mutation,HRD-high mutation,and HRD common mutation,predicted the HRD status of breast cancer patients with AUC values of 0.32,0.72,and 0.58,***,TP53 HRD-high mutation and HRD common mutation combinations showed the highest AUC values(0.80)in predicting HRD ***:TP53-specific mutation combinations predict the HRD status of patients,indicating that TP53 pathogenic mutations could serve as a potential biomarker for poly-ADP-ribose polymerase(PARP)inhibitors in breast cancer patients.

关键词： next-generation sequencing homologous recombination deficiency TP53 breast cancer

Roles of cancer-associated fibroblast functional heterogeneity in shaping the lymphatic metastatic landscape:new insights and therapeutic strategies

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Cancer Biology & Medicine 2024年第6期21卷 445-450页

作者： Hanhao Zheng Daiyin Liu Zhicong Liu Mingjie An Yuming Luo Changhao Chen Tianxin Lin Department of Urology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510003China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalState Key Laboratory of Oncology in South ChinaGuangzhou 510003China Department of General Surgery Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510003China

Lymph node (LN) metastasis is a process in which cancer cells travel from primary tumors to LNs via the lymphatic system,then proliferate and spread within the LNs. In most cancers,LN metastasis is a major mode of cancer dissemination,and a critical indicator of cancer progression and worsening prognosis1. The occurrence of LN metastasis indicates that the tumor has invaded the lymphatic system.

关键词： metastasis lymphatic landscape

Redox responsive polymeric nanoparticles enhance the efficacy of cyclin dependent kinase 7 inhibitor for enhanced treatment of prostate cancer

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Chinese Chemical Letters 2024年第8期35卷 443-448页

作者： Yiran Tao Chunlei Dai Zhaoxiang Xie Xinru You Kaiwen Li Jun Wu Hai Huang Department of Urology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Urology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510120China Biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510120China School of Biomedical Engineering Sun Yat-sen UniversityShenzhen 518107China Center for Nanomedicine and Department of Anesthesiology Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115United States Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalSun Yat-Sen UniversityGuangzhou 510120China Department of Urology The Sixth Affiliated Hospital of Guangzhou Medical UniversityQingyuan People’s HospitalQingyuan 511518China Bioscience and Biomedical Engineering Thrust The Hong Kong University of Science and Technology(Guangzhou)Guangzhou 511400China Division of Life Science The Hong Kong University of Science and TechnologyHong KongChina Guangdong Provincial Clinical Research Center for Urological Diseases Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China

Traditional therapies such as surgery and endocrine therapy no longer meet the clinical needs in prostate cancer treatment,and more effective treatments are urgently *** studies have reported that targeted inhibition of the transcription factor cyclin dependent kinase 7(CDK7)could effectively suppress prostate cancer ***,the toxicity of CDK7 inhibitors such as THZ1 is the main limitation of the clinical *** this work,we synthesized Cys8E(C8E)nanoparticles(NPs)loaded with THZ1(C8E@THZ1),a novel GSH-targeting and stimuli-responsive nano-delivery platform,and investigated its anti-tumor potential and biosafety *** vitro,C8E@THZ1 potently inhibited the proliferation and promoted the apoptosis of prostate cancer *** tumor-bearing mice,C8E@THZ1 inhibited tumors by up to 85%,while the damage of THZ1 to liver function was effectively *** results confirmed that inhibition of CDK7 can effectively block the progression of prostate cancer,and that Cys8E NPs is a highly prospective delivery platform to promote the clinical application of CDK7 inhibitors.

关键词： Prostate cancer Nanoparticles CDK7 THZ1 THZ1@Cys8E NPs

Protective Effects of Phellodendron Species on Bone Health: A Novel Perspective on Their Potentials in Treating Osteoporosis and Osteoarthritis

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Chinese Journal of Integrative Medicine 2024年第4期30卷 379-384页

作者： XIN Li TAN Guo-yao ZHANG Qiang ZHANG Qun Good Clinical Practice Development Guangdong Provincial Key Laboratory of Bone and Joint Degeneration DiseasesThe Third Affiliated Hospital of Southern Medical UniversityGuangzhou(510630)China Department of Pharmacy Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou(510120)China

Phellodendron(PN)species,traditionally used in Chinese medicine for centuries,hold promise as a potential treatment for osteoporosis(OP)and osteoarthritis(OA)due to their bioactive *** bioactive compounds,including berberine and palmatine,exhibit anti-inflammatory,antioxidant,and bone-protective properties,contributing to their potential therapeutic benefits in promoting bone health and preventing bone ***,challenges such as the need for standardized preparation and dosing,limited clinical studies,and potential interactions with other medications hinder their clinical ***,the rich history of PN species in Chinese medicine provides a promising foundation for future investigation into their potential as alternative treatments for OP and *** research is needed to fully understand the underlying mechanisms of action and explore the clinical implications of PN for bone health.

关键词： Phellodendron species bone health osteoporosis osteoarthritis review