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The multiple faces of cGAS-STING in antitumor immunity:prospects and challenges

Medical Review 2024年第3期4卷 173-191页

作者： Zheqi Zhou Sanling Huang Fangying Fan Yan Xu casey Moore Sirui Li Chuanhui Han Peking University International Cancer institute Peking University Cancer Hospital and InstituteHealth Science CenterPeking UniversityBeijingChina Department of Interventional Ultrasound Chinese PLA General HospitalBeijingChina Departments of Immunology PathologyUT Southwestern Medical CenterDallasTexasUSA Peking University International Cancer institute Peking University Cancer Hospital and InstituteHealth Science CenterPeking UniversityBeijing 100143China Department of Genetics Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel HillChapel HillNC 27599USA

As a key sensor of double-stranded DNA(dsDNA),cyclic GMP-AMP synthase(cGAS)detects cytosolic dsDNA and initiates the synthesis of 2′3′cyclic GMP-AMP(cGAMP)that activates the stimulator of interferon genes(STING).This finally promotes the production of type I interferons(IFN-I)that is crucial for bridging innate and adaptive im*** evidence show that several antitumor therapies,including radiotherapy(RT),chemotherapy,targeted therapies and immunotherapies,activate the cGAS-STING pathway to provoke the antitumor *** the last decade,the development of STING agonists has been a major focus in both basic research and the pharmaceutical in***,up to now,none of STING agonists have been approved for clinical *** the broad expression of STING in whole body and the direct lethal effect of STING agonists on immune cells in the draining lymph node(dLN),research on the optimal way to activate STING in tumor microenvironment(TME)appears to be a promising ***,besides enhancing IFN-I signaling,the cGAS-STING pathway also plays roles in senescence,autophagy,apoptosis,mitotic arrest,and DNA repair,contributing to tumor development and *** this review,we summarize the recent advances on cGAS-STING pathway’s response to antitumor therapies and the strategies involving this pathway for tumor treatment.

关键词： cGAS STING agonist IFN-I tumor

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Etiology,diagnosis, management and outcomes of epiphora referrals to an oculoplastic practice

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International Journal of Ophthalmology(English edition) 2016年第12期9卷 1751-1755页

作者： Guang-Lin Shen John D.Ng Xiao-Ping Ma Department of Ophthalmology Zhongshan Hospital of Fudan University casey Eye institute Oregon Health and Science University

AIM： To investigate the etiology, diagnosis, management and outcome of epiphora referrals to an oculoplastic ***： Retrospective chart review of patients referred for epiphora to an oculoplastic clinic between 2005 and 2009. Patient demographics, past history, ophthalmic examination, treatment and outcome were ***： There were 237 subjects with a primary complaint of epiphora. They included 130 （55%） females and 107 （45%） males with an average age of 55.9±25.9y. The most common cause of epiphora was lacrimal obstruction （46%）; followed by multifactorial epiphora （22%）, reflex tearing （22%） and eyelid malposition （11%）. Differences in prevalence of etiology were noted in terms of age and gender distribution. Of the 182 （77%） patients who returned for follow up, 41 （23%） reported a complete resolution and 102 （56%） reported a significant improvement in their ***： Epiphora is a common condition with many causes. A thorough history and examination are required to provide the appropriate treatment tailored to the underlying cause.

关键词： epiphora etiology lacrimal disease dry eye

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Exercise training improves long-term memory in obese mice

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Life Metabolism 2024年第1期3卷 37-50页

作者： Oliver K.Fuller casey L.Egan Tina L.Robinson Nimna Perera Heidy K.Latchman Lauren V.Terry Emma D.McLennan Carolina Chavez Emma L.Burrows John W.Scott Robyn M.Murphy Henriette van Praag Martin Whitham Mark A.Febbraio Monash institute of Pharmaceutical Sciences Monash UniversityMelbourneVictoria3052Australia La Trobe institute for Molecular Science La Trobe UniversityMelbourneVictoria3086Australia Florey institute of Neuroscience and Mental health University of MelbourneMelbourneVictoria3052Australia Department of Biomedical Sciences Charles E.Schmidt College of Medicineand Stiles-Nicholson Brain InstituteFlorida Atlantic UniversityJupiterFL 33458United States College of Life and Environmental Sciences University of BirminghamEdgbastonBirmingham B152TTUnited Kingdom

Obesity has been linked to a range of pathologies,including *** contrast,regular physical activity is associated with the prevention or reduced progression of ***,physical activity can improve memory and spatial cognition,reduce age-related cognitive decline,and preserve brain volume,but the mechanisms are not fully ***,we investigated whether any detrimental effects of high-fat diet(HFD)-induced obesity on cognition,motor behavior,adult hippocampal neurogenesis,and brain-derived neurotrophic factor(BDNF)could be mitigated by voluntary exercise training in male C57Bl/6 ***-induced impairment of motor function was not reversed by ***,voluntary wheel running improved long-term memory and increased hippocampal neurogenesis,suggesting that regular physical activity may prevent cognitive decline in obesity.

关键词： obesity exercise cognition

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Syringoid eccrine carcinoma of the eyelid presenting as cicatricial entropion

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International Journal of Ophthalmology(English edition) 2014年第5期7卷 912-913页

作者： Manjool M.Shah Eric A.Steele Kevin P.White David J.Wilson Department of Ophthalmology Casey Eye InstituteOregon Health&Science University Portland Veteran's Affairs Medical Center Department of Dermatology Oregon Health&Science University

Dear Sir,My name is Manjool ***,from the casey Eye institute at Oregon health&Science University in Portland,Oregon,USA.I wish to write to you with regards to an interesting presentation of a rare eyelid malignancy.A ... 详细信息

关键词： MICROCYSTIC ADNEXAL CARCINOMA SYRINGOMATOUS CARCINOMA ORBIT

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Cryotherapy in Ophthalmology

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Open Journal of Ophthalmology 2013年第4期3卷 103-117页

作者： Shandiz Tehrani Frederick W Fraunfelder casey Eye institute Oregon Health & Science University Portland USA casey Eye institute Oregon Health & Science University Portland USA.

Cryogens have been used to freeze living tissue for the purpose of treating benign and malignant lesions. Within the last century, ophthalmologists have found cryotherapy to be useful in treating a variety of ocular pathologies. Here, we review the history of cryotherapy, its introduction to the field of ophthalmology, its proposed mechanism of action, and its current applications in treating surface and intraocular eye disease.

关键词： Cryotherapy Cryosurgery Cryogenic Surgery Cryoprobe Cryospray Liquid Nitrogen Surface Eye Disease

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Optical coherence tomography angiography of non-exudative choroidal neovascularization

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眼科学报：英文版 2016年第4期31卷 243-245页

作者： Lee Kiang Steven T.Bailey Yali Jia David Huang casey Eye institute Department of Ophthalmology Oregon Health and Science University

Age-related macular degeneration(AMD)has been classified in two groups,neovascular and non-neovascular,which historically has been synonymous with exudative and non-exudative,*** AMD occurs when pathologic blood vesse... 详细信息

关键词：血管造影新生血管脉络膜渗出性断层扫描光学相干年龄相关 AMD

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Giving voice to adolescent mothers’ challenges

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Open Journal of Obstetrics and Gynecology 2013年第9期3卷 27-34页

作者： Amanda Skowron Crystal T. Clark Netta Sadovsky Katherine L. Wisner casey health institute Gaithersburg USA Northwestern University Chicago USA Washington University St. Louis USA

An estimated 32% to 60% of adolescent mothers experience postpartum depression. Young women who deal with the simultaneous developmental tasks of adolescence and parenting are vulnerable to depression, which affects the welfare of both the mother and child. The primary objective of this qualitative study was to appreciate the unique experiences of adolescent mothers. Seventeen postpartum adolescents participated in two focus groups and completed the Center for Epidemiologic Studies Depression Scale (CES-D). The qualitative data analysis identified 19 major conceptual themes in the data. The four most frequently discussed themes that emerged were: 1) social support, 2) differences between teen and adult mothers, 3) parenting ability, and 4) increased maturity. Six of the 17 participants (35.3%) had CES-D scores of 16 or above, which is indicative of a probable major depression. These findings highlight areas that could inform screening assessments, treatment, and prevention programs for adolescent mothers.

关键词： Postpartum Care Adolescents Pregnancy/Parenting

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Altering the intestinal microbiota for therapeutic benefit in uveitis

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Annals of Eye Science 2020年第3期5卷 50-55页

作者： Phoebe Lin casey Eye institute Oregon Health&Science UniversityPortlandORUSA

An intestinal dysbiosis is connected to a number of inflammatory diseases through various mechanisms relating to its effect on immune cell function and *** is a review of the literature summarizing our current understanding of intestinal microbial contributions to non-infectious uveitis and strategies to target the intestinal microbiome to treat *** groups have demonstrated an intestinal dysbiosis associated with certain types of non-infectious ***,approaches to treat uveitis by modifying the intestinal microbiota,such as oral antibiotics or administration of oral short chain fatty acids(SCFAs),which are intestinal bacterial metabolites produced by fermentation of dietary fiber,can successfully treat uveitis in mouse *** reduction in severity of ocular inflammation occurs via the following mechanisms:enhancement of regulatory T cells,decreasing intestinal permeability,and/or affecting T cell trafficking between the intestines and the *** strategies that are directed at the intestinal microbiota that might be effective to treat uveitis include dietary changes,probiotics,or fecal microbial *** commensal gut bacteria are influential in systemic and intestinal mucosal immunity and thus contribute to the development of extraintestinal inflammation like *** the intestinal microbiome thus has the potential to be a successful strategy to treat non-infectious uveitis.

关键词： Non-infectious uveitis microbiome short chain fatty acids(SCFAs)

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Program & faculty evaluation

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Annals of Eye Science 2017年第1期2卷 220-228页

作者： Andreas K.Lauer casey Eye institute Oregon Health and Science UniversityPortland OregonUSA

Graduate medical education(GME)has shifted its curricula from process-oriented approach to outcomes-oriented *** and faculty evaluation are methods by which educational curricula may adjust the teaching and learning environment to meet the needs and fills the gaps in *** measurement of educational outcomes is an essential for assessing teaching effectiveness in a shifting health care *** addition to trainee,program,and faculty evaluations,annual program review(APR)and evaluation and navigational changes made by the program education committee are essential to maintain effectiveness of an educational curriculum in a contemporary graduate medical training program.

关键词： Program evaluation faculty evaluation program evaluation committee(PEC) annual program review(APR) graduate medical education(GME)

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Biologics in non-infectious uveitis past,present and future

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Annals of Eye Science 2021年第2期6卷 89-99页

作者： Amr M.Zaki Eric B.Suhler casey Eye institute Oregon Health&Science UniversityPortlandORUSA VA Portland health Care System PortlandORUSA

Our increase in knowledge of the pathophysiology of non-infectious uveitis(NIU)and other immune-mediated diseases has been mirrored over the last two decades by the expansion of therapeutic options in the realm of immunosuppressive *** among these advances is the emergence of biologics,which offer the promise of targeted therapy and the hope of reduced toxicity when compared to corticosteroids and“standard”*** the biologics,monoclonal antibodies blocking tumor necrosis factor alpha(TNF-α)have been shown to be a very effective therapeutic target for uveitis and many associated systemic inflammatory *** TNF blockers have shown benefit for uveitis,and in 2016,adalimumab became the first biologic and non-corticosteroid immunosuppressive to obtain Food and Drug Administration(FDA)approval in the treatment of *** effective,TNF blockers are not universally so,and safety concerns such as infection and demyelinating disease must be carefully considered and ruled out prior to their use,especially in patients with intermediate uveitis with which multiple sclerosis is a known *** study has identified novel targets for regulation in the treatment of immune-mediated and inflammatory ***,interleukin and Janus kinase inhibitors in addition to antibodies targeting T cell and B cell activation highlight the expanding field of treatment modalities in *** study will be required to better determine the safety and efficacy of biologics in the armamentarium of immunosuppressive treatments for NIU.

关键词： Non-infectious uveitis biologics

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