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World Journal of Orthopedics 2024年第10期15卷 902-907页

作者： Bruce m Rothschild department of m.d.cine Indiana University Ball Memorial HospitalMuncieIN 47303United States

Recognizing the mechanical origin of enthesitis/enthesopathy and the avulsion-nature of what had previously been considered erosions,it seems inappropriate to attribute it to stresses related to a person’s normal ***,sudden or unconditioned repetitive stresses appears the more likely *** of enthesial reaction have lacked standardization as to findings present among individuals who appear to be *** evaluation by palpation and mani-pulation may be as effective as application of radiologic *** of the mechanical nature of the disease,including individuals with inflammatory arthritis suggests prescription of mechanical solutions that reduce stresses across the involved enthesis.

关键词： Enthesitis Epicondylitis Erosion Avulsion Clinical examination

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 m.d.cal 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 Biom.d.cal 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

Nanom.d.cine 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-m.d.ated synergistic tumor *** also discuss the prospect and challenge of nanom.d.cine in tumor therapy resistance by regulating ferroptosis and combination therapy.

关键词： ferroptosis cancer therapy therapy resistance nanoinducers

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 m.d.cine 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 m.d.cine 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 perform.d.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 scoredifferent 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

Sutured scleral fixation of existing subluxated/dislocated acrylic one-piece intraocular lenses

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 665-669页

作者： Wei-Yu Huang Yung-Jen Chen department of Ophthalmology Chi Mei Medical CenterTainan City 710TaiwanChina department of Ophthalmology Chang Gung Memorial HospitalKaohsiung City 833TaiwanChina

AIm:To evaluate the visual and refractive outcomes in cases after sutured scleral fixation of existing subluxated or dislocated acrylic one-piece intraocular lenses(IOLs).mETHOdS:This study retrospectively enrolled a consecutive series of patients who underwent a surgery of sutured existing subluxated or dislocated IOLs from October 2018 to June *** patients underwent comprehensive preoperative and postoperative ophthalmologic examination,and data were collected including age,sex,surgical indications,best-corrected visual acuity,refractive error,intraocular *** of intraoperative and postoperative surgical complications was ***:A total of 20 consecutive cases were enrolled for analysis with mean final follow-up period 9.8±*** acuity improved from a mean of 0.35(0.46±0.32 logmAR)preoperatively to 0.61(0.21±0.18 logmAR)at the 3-month follow-up(P=0.002).The mean amount of preoperative keratometric astigmatism and total postoperative refractive astigmatism was-1.24±0.80 diopters(d)and-1.42±0.97 d,*** was no statistically significant difference between preoperative and postoperative astigmatism(P=0.156).The mean IOL-induced astigmatism was-0.23±0.53 *** mean spherical equivalent at the 3-month follow-up was-0.1±0.94 *** major complications were noted during the follow-up ***:Surgical techniques using sutured scleral fixation of existing subluxated or dislocated acrylic one-piece IOLs result in favorable visual and refractive outcomes without major complications.

关键词： intraocular lens dislocation intraocular lens subluxation lens dislocation lens subluxation scleral fixation

diabetes and pulmonary infection:how hyperglycaemia shapes the immune system

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1245-1246页

作者： Christian Herder michael Roden Nicolas Venteclef Institute for Clinical diabetology German Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf40225DüsseldorfGermany German Center for diabetes Research(dZd) Partner Düsseldorf85764München-NeuherbergGermany department of Endocrinology and diabetology Medical Faculty and University Hospital DüsseldorfHeinrich Heine University Düsseldorf40225DüsseldorfGermany Institut Necker-Enfants malades(INEm) UniversitéParis CitéINSERM UMR-S1151CNRS UMR-S8253ParisFrance

In a recent study published in Nature,Nobs and colleagues aim.d.to identify novel mechanisms that may explain why diabetes is associated with an increased susceptibility to viral respiratory *** analyses revealed a central role of lung dendritic cells(dC)which exhibited several functional defects induced by hyperglycaemia and consequently result in impaired antiviral immune responses.

关键词： impaired lung respiratory

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 Biom.d.cal Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510120China School of Biom.d.cal Engineering Sun Yat-sen UniversityShenzhen 518107China Center for Nanom.d.cine 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 Biom.d.cal 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 confirm.d.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

dysfunction of the adhesion G protein-coupled receptor latrophilin 1(AdGRL1/LPHN1)increases the risk of obesity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2298-2311页

作者： Heba ZabriTorsten Schöneberg AndréNguyen dietzsch Hadi Al-Hasani Joachim Altschmied Katharina Bottermann Jana Brendler Judith Haendeler Susanne Horn Isabell Kaczmarek Antje Körner Kerstin Krause Kathrin Landgraf diana Le duc Laura Lehmann Stefan Lehr Stephanie Pick Albert Ricken Rene Schnorr Angela Schulz martina Strnadová Akhil Velluva Heba Zabri Torsten Schöneberg doreen Thor Simone Prömel Rudolf Schönheimer Institute of Biochemistry Medical FacultyLeipzig UniversityLeipzigGermany Institute for Clinical Biochemistry and Pathobiochemistry Medical FacultyGerman Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University DüsseldorfDüsseldorfGermany German Center for diabetes Research(dZd e.V.) Munich-NeuherbergGermany Cardiovascular degeneration Clinical Chemistry and Laboratory DiagnosticsMedical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Cardiovascular Research Institute(CARId) Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Pharmacology Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Anatomy Medical FacultyLeipzig UniversityLeipzigGermany Center for Pediatric Research Hospital for Children and AdolescentsMedical FacultyLeipzig UniversityLeipzigGermany Helmholtz Institute for metabolic Obesity and Vascular Research(HI-MAG)of the Helmholtz Zentrum München at the University of Leipzig and University Hospital LeipzigLeipzigGermany department of Endocrinology NephrologyRheumatologyLeipzig University Medical CenterLeipzigGermany Institute of Human Genetics Leipzig University Medical CenterLeipzigGermany Institute of Cell Biology Department of BiologyHeinrich Heine University DüsseldorfDüsseldorfGermany School of m.d.cine University of Global Health EquityKigaliRwanda

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide *** the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity.G protein-coupled receptors(GPCRs)are among the main m.d.lators of metabolism and energy ***,for instance,regulate appetite and satiety in certain hypothalamic neurons,as well as glucose and lipid metabolism and hormone secretion from *** in some GPCRs,such as the melanocortin receptor type 4(mC4R),have been associated with early-onset ***,we identified the adhesion GPCR latrophilin 1(AdGRL1/LPHN1)as a member of the regulating network governing food intake and the maintenance of energy *** of the highly conserved receptor in mice results in increased food consumption and severe obesity,accompanied by dysregulation of glucose ***,we identified a partially inactivating mutation in human AdGRL1/LPHN1 in a patient suffering from ***,we propose that LPHN1 dysfunction is a risk factor for obesity development.

关键词： obesity metabolism intake

Novel insights into d-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

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Neural Regeneration Research 2024年第2期19卷 289-295页

作者： dina m.d.na-Vera Antonio Jesús López-Gambero Juan Antonio Navarro Carlos Sanjuan Elena Baixeras Juan decara Fernando Rodríguez de Fonseca Instituto de Investigación Biom.d.ca de málaga y Plataforma en Nanom.d.cina-IBImA Plataforma BIONANd UGC Salud MentalMálagaSpain Facultad de Ciencias Universidad de MálagaMálagaSpain CIBER Enferm.d.des Cardiovasculares(CIBERCV) Hospital Universitario Virgen de la VictoriaUGC del CorazónMálagaSpain University of Bordeaux INSERMNeurocentre MagendieBordeauxFrance Euronutra S.L.Calle Johannes Kepler MálagaSpain departamento de Bioquímica y Biología molecular Facultad de MedicinaUniversidad de MálagaMálagaSpain

Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s *** pathogenesis of Alzheimer’s disease is mainly m.d.ated by the phosphorylation and aggregation of tau *** the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug *** present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease m.d.fiers capable of bringing hope to the millions of people affected by this devastating disease.

关键词： Alzheimer’s disease cyclin-dependent kinase 5 diabetes d-Pinitol inositols insulin resistance kinases phosphorylation PI3K/Akt tau

The dorsal root ganglion as a target for neurorestoration in neuropathic pain

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Neural Regeneration Research 2024年第2期19卷 296-301页

作者： Guillermo Estivill-Torrús Ana Belen martínez-Padilla Lourdes Sánchez-Salido Anne Baron-Van Evercooren Beatriz García-díaz Instituto de Investigación Biom.d.ca de málaga y Plataforma en Nanom.d.cina(IBImA Plataforma BIONANd) MálagaSpain Unidad Clínica de Neurociencias Hospital Regional Universitario de MálagaMálagaSpain departamento de Biología molecular y Bioquímica Universidad de MálagaSpain Sorbonne Université Institut du Cerveau-Paris Brain Institute-ICMINSERMCNRSAP-HPHôpital Pitié-SalpêtrièreParisFrance

Neuropathic pain is a severe and chronic condition widely found in the general *** reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in *** the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical ***,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative ***,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic *** importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

关键词： cytokines dorsal root ganglia genetic factors neuropathic pain neurotrophic factors pharmacologic and nonpharmacologic therapies satellite glial cells sensory neurons