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Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa

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Neural Regeneration Research 2024年第11期19卷 2543-2552页

作者： Sam Enayati Karen Chang Anton Lennikov Menglu Yang Cherin Lee Ajay Ashok Farris Elzaridi Christina Yen Kasim Gunes Jia Xie Kin-Sang Cho Tor Paaske Utheim Dong Feng Chen Schepens Eye Research institute of Massachusetts Eye and ear Department of OphthalmologyHarvard Medical SchoolBostonMAUSA institute of clinical medicine Faculty of MedicineUniversity of OsloOsloNorway Department of Medical Biochemistry Oslo University HospitalUniversity of OsloOsloNorway Department of Ophthalmology Drammen HospitalVestre Viken Hospital TrustDrammenNorway Department of Histology and Embryology School of MedicineMarmara UniversityIstanbulTurkiye

Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor *** research supports the beneficial effect of electrical stimulation on photoreceptor *** study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal ***,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem *** this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp *** investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with *** retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in *** density was evaluated by rhodopsin *** vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp *** function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),*** was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse *** recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest *** of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human *** tem

关键词： bipolar cells electrical stimulation neuroprotection photoreceptor degeneration retina retinal explants retinitis pigmentosa transcorneal electrical stimulation waveform

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Unlocking the versatile potential:Adipose-derived mesenchymal stem cells in ocular surface reconstruction and oculoplastics

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World Journal of Stem Cells 2024年第2期16卷 89-101页

作者： Pier Luigi Surico Anna Scarabosio Giovanni Miotti Martina Grando Carlo Salati Pier Camillo Parodi Leopoldo Spadea Marco Zeppieri Schepens Eye Research institute of Mass Eye and ear Harvard Medical SchoolBostonMA 02114United States Department of Ophthalmology Campus Bio-Medico UniversityRome 00128Italy Department of Plastic Surgery University Hospital of UdineUdine 33100Italy Department of Internal Medicine Azienda Sanitaria Friuli OccidentaleSan Vito al Tagliamento 33078Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Eye Clinic Policlinico Umberto I“Sapienza”University of RomeRome 00142Italy

This review comprehensively explores the versatile potential of mesenchymal stem cells(MSCs)with a specific focus on adipose-derived *** and oculoplastic surgery,encompassing diverse procedures for ocular and periocular enhancement,demands advanced solutions for tissue restoration,functional and aesthetic refinement,and *** immunomodulatory,regenerative,and healing capacities of MSCs,this review underscores the potential use of adipose-derived MSCs as a cost-effective alternative from bench to bedside,addressing common unmet needs in the field of reconstructive and regenerative surgery.

关键词： Stem cells Adipose stem cell Ocular therapy Oculoplastics Regenerative

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Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer

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World Journal of Clinical Oncology 2024年第4期15卷 531-539页

作者： De-Yi Geng Qing-Shan Chen Wan-Xian Chen Lin-Sa Zhou Xiao-Sha Han Qi-Hu Xie Geng-Hong Guo Xue-Fen Chen Jia-Sheng Chen Xiao-Ping Zhong Department of Plastic and Burns Surgery The Second Affiliated Hospital of Shantou University Medical CollegeShantou 515000Guangdong ProvinceChina Plastic Surgery Research institute Ear Deformities Treatment Center and Cleft Lip and Palate Treatment Center of Shantou University Medical CollegeShantou 515000Guangdong ProvinceChina

Metastasis remains a major challenge in the successful management of malignant *** liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,stomach,and pancreatic cancers,as well as melanoma,breast cancer,and *** an important factor that influences the development of metastatic liver cancer,alternative splicing drives the diversity of RNA transcripts and protein subtypes,which may provide potential to broaden the target *** particular,the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence,progression,aggressiveness,and drug resistance of cancers caused by the selective splicing of specific *** review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver *** will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes,abnormal splicing,and the contribution of hypoxia to these changes during metastasis.

关键词： Alternative splicing Carcinoma Hepatocellular Metastasic Liver neoplasms Prognosis

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Improved hearing in noise using new signal processing algorithms with the Cochlear^(TM) Nucleus~ 6 sound processor

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Journal of Otology 2015年第2期10卷 51-56页

作者： Jan Gilden Kristen Lewis Ginger Grant Jillian Crosson Houston ear Research Foundation Midwest ear institute Cochlear Americas

Objective： To demonstrate the performance benefit of the Automatic Scene Classifier （SCAN） algorithm available in the Nucleus 6 （CP900 series） sound processor over the default processing algorithms of the previous generation Nucleus 5 （CP810） and Freedom HybridTM sound processors. Methods： Eighty-two cochlear implant recipients （40 Nucleus 5 processor users and 42 Freedom Hybrid processor users） listened to and repeated AzBio sentences in noise with their current processor and with the Nucleus 6 processor. Results： The SCAN algorithm when enabled yielded statistically significant non-inferior and superior performance when compared to the Nucleus 5 and Freedom Hybrid sound processors programmed with ASC ＋ ADRO. Conclusion： The results of these studies demonstrate the superior performance and clinical utility of the SCAN algorithm in the Nucleus 6 processor over the Nucleus 5 and Freedom Hybrid processors.

关键词： Cochlear implant Speech perception Nucleus 6 Automatic scene classifier (SCAN) SmartSound iQ

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Influence of BPPV and Meniere's Disease on Cognitive Abilities: A Questionnaire-Based Study

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Journal of Otology 2024年第1期19卷 10-18页

作者： Rohit Bhattacharyya Animesh Barman Freddy Antony All India institute of Speech and Hearing MysoreMysuruIndia

The vestibular system connects the inner ear to the midbrain and subcortical structures and can affect cognition. Patients with vertigo often experience cognitive symptoms such as attention deficits, memory problems, and spatial perception difficulties. This study aimed to explore the cognitive impairments associated with Benign paroxysmal positional vertigo(BPPV) and Meniere's Disease(MD). A non-experimental group comparison design was used with 107 participants divided into three groups: Group I(clinically normal), Group II(BPPV), and Group III(MD). Participants completed a questionnaire with 10 cognition-related questions, and their responses were scored. The data were found to be non-normally distributed. The analysis revealed a significant difference in scores between Group I and both Group II and Group III. Chi-square tests showed that the responses to cognition-related questions varied among the groups, with Group II exhibiting more cognitive problems. Associated conditions like hypertension, diabetes, and hearing loss did not significantly influence the responses within each group. This study suggests a significant relationship between cognitive problems and patients with BPPV and MD. However, there was no association found between the cognitive problems experienced in BPPV and MD patients. These findings align with previous research indicating that vestibular disorders can lead to deficits in spatial memory, attention, and other cognitive functions. By understanding the link between cognition and vestibular disorders, we can improve diagnosis and rehabilitation services to enhance the quality of life for these patients.

关键词： BPPV Meniere's disease Cognition Questionnaire

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Adeno-associated virus as a delivery vector for gene therapy of human diseases

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1808-1840页

作者： Jiang-Hui Wang Dominic J.Gessler Wei Zhan Thomas L.Gallagher Guangping Gao Horae Gene Therapy Center University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Microbiology and Physiological Systems University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVIC3002Australia Ophthalmology Department of SurgeryUniversity of MelbourneEast MelbourneVIC3002Australia Department of Neurological Surgery University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Neurosurgery University of MinnesotaMinneapolisMN55455USA Department of Medicine University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Li Weibo institute for Rare Diseases Research University of Massachusetts Chan Medical SchoolWorcesterMA01605USA

Adeno-associated virus(AAV)has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different *** AAV(rAAV)has been engineered for enhanced specificity and developed as a tool for treating various ***,as rAAV is being more widely used as a therapy,the increased demand has created challenges for the existing manufacturing *** rAAV-based gene therapy products have received regulatory approval,but there continue to be concerns about safely using high-dose viral therapies in humans,including immune responses and adverse effects such as genotoxicity,hepatotoxicity,thrombotic microangiopathy,and *** this review,we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing *** discuss how rAAVs are being employed in ongoing clinical trials for ocular,neurological,metabolic,hematological,neuromuscular,and cardiovascular diseases as well as *** outline immune responses triggered by rAAV,address associated side effects,and discuss strategies to mitigate these *** hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of rAAV-based gene therapy.

关键词： diseases specificity approval

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Genetically modified pigs:Emerging animal models for hereditary hearing loss

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Zoological Research 2024年第2期45卷 284-291页

作者： Xiao Wang Tian-Xia Liu Ying Zhang Liang-Wei Xu Shuo-Long Yuan A-Long Cui Wei-Wei Guo Yan-Fang Wang Shi-Ming Yang Jian-Guo Zhao State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100049China institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing institute for Stem Cell and Regenerative Medicine Beijing 100101China Department of Otolaryngology-Head and Neck Surgery Institute of OtolaryngologyChinese PLA General HospitalBeijing 100853China Division of Life Sciences and Medicine University of Science and Technology of ChinaHefeiAnhui 230022China State Key Laboratory of Animal Biotech Breeding Institute of Animal ScienceChinese Academy of Agricultural SciencesBeijing100193China

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for *** investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are *** have been extensively used as valuable large animal models in biomedical *** this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing ***,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL ***,this review provides insights and perspectives for future studies on HHL using porcine models.

关键词： Pigs Animal models Hereditary hearing loss Genetic modification Inner ear

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Accurate prediction of myopic progression and high myopia by machine learning

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Precision Clinical Medicine 2024年第1期7卷 14-20页

作者： Jiahui Li Simiao Zeng Zhihuan Li Jie Xu Zhuo Sun Jing Zhao Meiyan Li Zixing Zou Taihua Guan Jin Zeng Zhuang Liu Wenchao Xiao Ran Wei Hanpei Miao Ian Ziyar Junxiong Huang Yuanxu Gao Yangfa Zeng Xing-Tao Zhou Kang Zhang Guangzhou Women and Children's Medical Center Guangzhou Medical UniversityGuangzhou 510120China Guangzhou National Laboratory Guangzhou 510o0oChina Zhuhai International Eye Center of the First Affiliated Hospital of Faculty of Medicine Macao University of Science and TechnologyZhuhai 519000China Beijing institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing 100069China Key Laboratory of Myopia Ministry of HealthShanghai Key Laboratory of Visual Impairment and RestorationDepartment of OphthalmologyEye InstituteEye and EarNoseand Throat HospitalFudan UniversityShanghai 200031China DongguanPeople's Hospital The First School of Clinical MedicinelSouthern Medical UniversityDongguan 523059China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China Wenzhou Eye Hospital and institute for Advanced Study on Eye Health and Diseases Wenzhou Medical UniversityWenzhou 32500oChina

Background Myopia is a leading cause of visual impairment in Asia and ***,accurately predicting the progression of myopia and the high risk of myopia remains a *** study aims to develop a predictive model for the development of *** We first retrospectively gathered 612530 medical records from five independent cohorts,encompassing 227543 patients ranging from infants to young ***,we developed a multivariate linear regression algorithm model to predict the progression of myopia and the risk of high *** The model to predict the progression of myopia achieved an R^(2) value of 0.964 vs a mean absolute error(MAE)of 0.119D[95%confidence interval(CI):0.119,1.146]in the internal validation *** demonstrated strong generalizability,maintaining consistent performance across external validation sets:R^(2)=0.950 vs MAE=0.119D(95%CI:0.119,1.136)in validation study 1,R^(2)=0.950 vs MAE=0.121D(95%CI:0.121,1.144)in validation study 2,and R^(2)=0.806 vs MAE=−0.066D(95%CI:−0.066,0.569)in the Shanghai Children Myopia *** the Beijing Children Eye Study,the model achieved an R^(2) of 0.749 vs a MAE of 0.178D(95%CI:0.178,1.557).The model to predict the risk of high myopia achieved an area under the curve(AUC)of 0.99 in the internal validation set and consistently high area under the curve values of 0.99,0.99,0.96 and 0.99 in the respective external validation *** Our study demonstrates accurate prediction of myopia progression and risk of high myopia providing valuable insights for tailoring strategies to personalize and optimize the clinical management of myopia in children.

关键词： myopia progression machine learning prevention precision medicine

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Whole-eye transplantation: Current challenges and future perspectives

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World Journal of Transplantation 2024年第2期14卷 28-39页

作者： Anna Scarabosio Pier Luigi Surico Vlad Tereshenko Rohan Bir Singh Carlo Salati Leopoldo Spadea Glenda Caputo Pier Camillo Parodi Caterina Gagliano Jonathan M Winograd Marco Zeppieri Department of Plastic Surgery University Hospital of UdineUdine 33100Italy Department of Plastic Surgery Massachusetts General HospitalHarvard Medical SchoolBostonMA 02114United States Schepens Eye Research institute of Mass Eye and ear Harvard Medical SchoolBostonMA 02114United States Department of Ophthalmology University Hospital of UdineUdine 33100Italy Eye Clinic Policlinico Umberto I"Sapienza"University of RomeRome 00142Italy Department of Medicine and Surgery University of Enna"Kore"Enna 94100Italy Eye Clinic Catania University San Marco Hospital Viale Carlo Azeglio Ciampi 95121 CataniaItaly

Whole-eye transplantation emerges as a frontier in ophthalmology,promising a transformative approach to irreversible *** advancements,formidable challenges *** of donor eye viability post-enucleation necessitates meticulous surgical techniques to optimize retinal integrity and ganglion cell *** the inhibitory milieu of the central nervous system for successful optic nerve regeneration remains elusive,prompting the exploration of neurotrophic support and immunomodulatory *** tolerance,paramount for graft acceptance,confronts the distinc-tive immunogenicity of ocular tissues,driving research into targeted immunosup-pression *** and legal considerations underscore the necessity for stringent standards and ethical *** collaboration and ongoing research endeavors are imperative to navigate these ***,stem cell therapies,and precision immunomodulation represent promising avenues in this ***,the aim of this review is to critically assess the current landscape of whole-eye transplantation,elucidating the challenges and advancements while delineating future directions for research and clinical *** concerted efforts,whole-eye transplantation stands to revolu-tionize ophthalmic care,offering hope for restored vision and enhanced quality of life for those afflicted with blindness.

关键词： Eye Transplantation Optic nerve Nerve regeneration Immunological tolerance

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Bhlhe40 protects cochlear hair cell-like HEI-OC1 cells against H_(2)O_(2) ‑triggered oxidative injury

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BIOCELL 2024年第6期48卷 991-999页

作者： LITING WEN XIAOXIA ZENG PEIXIONG CHEN DAPENG ZHAO YANGYANG LI XIANHAI ZENG Department of Otorhinolaryngology Longgang Otorhinolaryngology Hospital and Shenzhen Key Laboratory of OtorhinolaryngologyShenzhen Institute of OtorhinolaryngologyShenzhenChina

Background:Cochlear hair cell injury is a common pathological feature of hearing *** basic helix-loop-helix family,member e40(Bhlhe40),a gene belonging to the basic helix-loop-helix(bHLH)family,exhibits strong transcriptional repression ***:Oxidative damage,in House ear institute-Organ of Corti 1(HEI-OC1)cells,was caused using hydrogen peroxide(H2O2).The Ad-Bhlhe40 particles were constructed to overexpress Bhlhe40 in HEI-OC1 *** assays including cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay(TUNEL),ﬂow cytometry,immunoﬂuorescence,and corresponding commercial kits were employed to investigate the impacts of Bhlhe40 on cell viability,apoptosis,oxidative stress levels,mitochondrial membrane potential and cellular ***,a dual-luciferase reporter assay was performed to conﬁrm the targeting of the histone deacetylases 2(Hdac2)by ***:The results revealed that Bhlhe40 was downregulated in H_(2)O_(2)-treated HEI-OC1 cells,but its overexpression improved cell viability and mitigated H_(2)O_(2)-induced oxidative injury in HEI-OC1 cells with increase of superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GPx)activities and decrease of reactive oxygen species(ROS)***,overexpression of Bhlhe40 suppressed H_(2)O_(2)-triggered cell senescence,as evidenced by the fact that the upregulation of P53,P21,and P16 in HEI-OC1 cells treated with H2O2 were all alleviated by Bhlhe40 *** we further veriﬁed that overexpression of Bhlhe40 could inhibit the expression of Hdac2,which may be related to the repression of Hdac2 ***:This study suggests that Bhlhe40 plays a protective role against senescence and oxidative damage in cochlear hair cells exposed to H2O2.

关键词： Bhlhe40 Oxidative injury Cochlear hair cell Histone deacetylases 2

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