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Frontiers of Medicine 2013年第3期7卷 389-394页

作者： Xiaohong Duan Thomas Markello David Adams Camilo Toro Cynthia Tifft William A. Gahl Cornelius F. Boerkoel Department of Oral Biology Clinic of Oral Rare Diseases and Genetic Diseases School of Stomatology the Fourth Military Medical University nih undiagnosed diseases program NIH Offce of Rare Diseases Research and NHGRI

Despite the current acceleration and increasing leadership of Chinese genetics research,genetics and its clinical application have largely been imported to China from the *** genetics nor the scientifc reductionism underpinning its clinical application is integral to the traditional Chinese *** that disease concepts and their incumbent diagnoses are historically derived and culturally meaningful,we hypothesize that the cultural expectations of genetic diagnoses and medical genetics practice differ between the Occident and ***,we suggest that an undiagnosed diseases program in China will differ from the recently established undiagnosed diseases program at the United States National Institutes of Health;a culturally sensitive concept will integrate traditional Chinese understanding of disease with the scientifc reductionism of Occidental medicine.

关键词： genetics cultural differences undiagnosed diseases program

Hepatitis B core-related antigen as a promising serological marker for monitoring hepatitis B virus cure

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World Journal of Hepatology 2025年第1期17卷 18-28页

作者： Yue Qiu Qiao Tang Xiao-Qing Liu Yun-Ling Xue Yi Zeng Peng Hu Department of Infectious diseases Institute for Viral HepatitisThe Key Laboratory of Molecular Biology for Infectious DiseasesChinese Ministry of EducationThe Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Hepatitis B virus(HBV)infection is a global health *** current sequen-tial endpoints for the treatment of HBV infection include viral suppression,hepatitis B e antigen(HBeAg)seroconversion,functional cure,and covalently closed circular DNA(cccDNA)*** hepatitis B core-related antigen(HBcrAg)is an emerging HBV marker comprising three components:HBeAg,hepatitis B core antigen,and *** responds well to the transcriptional activity of cccDNA in the patient's liver and is a promising alternative marker for serolo-gical *** is a strong correlation,and a decrease in its level corresponds to sustained viral *** patients with chronic hepatitis B(CHB),serum HBcrAg levels are good predictors of HBeAg seroconversion(both spontaneous and after antiviral therapy),particularly in HBeAg-positive *** low baseline HBcrAg levels and decreasing levels early in antiviral therapy favored HBsAg seroconversion,which may serve as a good surrogate option for treatment *** this review,we summarize the role of serum HBcrAg in the treat-ment of ***,long-term continuous monitoring of serum HBcrAg levels contributes to the clinical management of patients with CHB and optimizes the choice of treatment regimen,making it a promising marker for monitoring HBV cure.

关键词： Hepatitis B Hepatitis B core-related antigen Hepatitis B surface antigen Hepatitis B virus DNA Covalently closed circular DNA Hepatitis B virus cure

IL-17A mediates inflammation-related retinal pigment epithelial cells injury via ERK signaling pathway

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International Journal of Ophthalmology(English edition) 2025年第1期18卷 15-27页

作者： Hui-Min Zhong Bing-Qiao Shen Yu-Hong Chen Xiao-Huan Zhao Xiao-Xu Huang Min-Wen Zhou Xiao-Dong Sun Department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong UniversitySchool of MedicineShanghai 200080China National Clinical Research Center for Ophthalmic diseases Shanghai 200080China National Clinical Research Center for Eye diseases Shanghai 200080China Shanghai Key Laboratory of Fundus diseases Shanghai 200080China Shanghai Engineering Center for Visual Science and Photomedicine Shanghai 200080China

AIM:To investigate whether interleukin-17A(IL-17A)gets involved in the mechanisms of inflammation-related retinal pigment epithelium(RPE)cells injury and its significance in age-related macular degeneration(AMD).MRTHODS:A sodium iodate(NaIO3)mouse model as well as IL-17A-/-mice were *** effects of inflammatory cytokines in RPE cells and retinal microglia before and after NaIO3 modeling in vivo and in vitro,were investigated using immunofluorescence,immunoprotein blotting,and quantitative real-time fluorescence polymerase chain reaction(qRT-PCR),*** using recombinant IL-17A protein(rIL-17A)or IL-17A neutralizing antibody(IL-17A NAb)were used to observe the subsequent differences in fundus,fundus photography and optical coherence tomography(OCT),cell viability,and expression of oxidative stress-related markers before and after modeling,and to screen for key signaling ***:In the scenario of NaIO3 stimulation,RPE cells obviously tended to *** proliferation and activation of retinal microglia was confirmed in NaIO3-stimulated mice,whereas such effects induced by NaIO3 were significantly ameliorated with IL-17A NAb intervention or in IL-17A-/-*** addition,IL-17A promoted the proliferation and activation of microglia as well as oxidative damage and the secretion of inflammatory cytokines alongside NaIO3-induced damage in RPE cells in vivo and ex ***,the extracellular signalregulated kinase(ERK)signaling pathway was shown to be participated in the regulation of NaIO3-induced RPE cells injury mediated by IL-17A in vivo and ex vivo,as IL-17A induced inflammatory cytokines release in the NaIO3 model was alleviated after blocking the ERK ***:IL-17A probably promotes the NaIO3-induced RPE cells injury through exacerbating inflammation in terms of retinal microglia activation and inflammatory cytokines release via ERK signaling *** of IL-17A may be a new potential ta

关键词： age-related macular degeneration retinal pigment epithelium NaIO3 microglia IL-17A

C-X-C chemokine receptor type 5+CD8+T cells as immune regulators in hepatitis Be antigen-positive chronic hepatitis B under interferonalpha treatment

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World Journal of Gastroenterology 2025年第3期31卷 73-83页

作者： Zhen-Yu Xu Zhong-Shang Dai Guo-Zhong Gong Min Zhang Department of Infectious diseases Second Xiangya HospitalCentral South UniversityChangsha 410011Hunan ProvinceChina Institute of Hepatology and Department of Infectious diseases The Second Xiangya HospitalCentral South UniversityChangsha 410011Hunan ProvinceChina

BACKGROUND C-X-C chemokine receptor type 5(CXCR5)^(+)CD8^(+)T cells represent a unique immune subset with dual roles,functioning as cytotoxic cells in persistent viral infections while promoting B cell *** their importance,the specific role of CXCR5^(+)CD8^(+)T cells in chronic hepatitis B(CHB),particularly during interferon-alpha(IFN-α)treatment,is not fully *** study aims to elucidate the relationship between CXCR5^(+)CD8^(+)T cells and sustained serologic response(SR)in patients undergoing 48 weeks of pegylated IFN-α(peg-IFN-α)treatment for *** To elucidate the relationship between CXCR5^(+)CD8^(+)T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-αtreatment for *** This study enrolled 60 patients with hepatitis Be antigen(HBeAg)-positive CHB undergoing 48 weeks of peg-IFN-α*** were assessed for eligibility based on criteria such as persistent HBsAg-positive status for at least six months,HBeAb-negative,hepatitis B virus DNA levels exceeding 2×10^(4) copies/mL,and alanine aminotransferase(ALT)levels between 2 and 10 times the upper limit of *** samples were collected at baseline and at weeks 12,24,48,and a 24-week treatment-free follow-up(week 72)to measure serum interleukin(IL)-21 concentration via ELISA and to analyze CXCR5 and programmed death-ligand 1(PD-L1)expression on CD8^(+)T cells by flow cytometry,CXCR5 is a chemokine receptor that directs immune cells to specific tissues,while PD-L1 is a protein that regulates immune responses by inhibiting T cell *** Patients with CHB exhibited significantly lower levels of circulating CXCR5^(+)CD8^(+)T cells compared to healthy controls(P<0.01).Notably,CXCR5^(+)CD8^(+)T cells were prominently expressed in patients who achieved sustained SR compared to non-SR(NSR).A significant correlation was observed between CXCR5 and PD-L1 expression(r=-0.189,P=0.002).However,there was no significant correlation between serum IL-21 level

关键词： C-X-C chemokine receptor type 5 programmed death-ligand 1 Interleukin-21 Pegylated interferon-alpha Chronic hepatitis B

Timing of biomarker changes preceding Alzheimer's disease:for diagnosis,treatment or prevention?

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Science China(Life Sciences) 2025年第2期68卷 575-577页

作者： Meina Quan Innovation Center for Neurological Disorders and Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China National Medical Center for Neurological diseases and National Clinical Research Center for Geriatric diseases Beijing 100053China Center of Alzheimer’s Disease Beijing Institute of Brain DisordersCollaborative Innovation Center for Brain DisordersBeijing 100053China

The pathophysiological and behavioural features of Alzheimer’s disease(AD)have been extensively investigated in transgenic mouse models,including the temporal sequence of each pathophysiological change and behavioural abnormality,a summary of which was recently presented by our team in this Journal(Li et al.,2023).Nevertheless,studying such features and timings directly in human patients before symptoms occur is challenging.

关键词： prevention Alzheimer diagnosis

Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

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Neural Regeneration Research 2025年第2期20卷 378-393页

作者： Jingxiang Zhang Xia Sheng Quanju Ding Yujun Wang Jiwei Zhao Jingfa Zhang Department of Ophthalmology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina Department of Urology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina Department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong University School of MedicineShanghaiChina National Clinical Research Center for Eye diseases Shanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghaiChina

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular *** causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular *** pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely ***,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential *** current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/*** review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

关键词： choroidal neovascularization epithelial-mesenchymal transition mesenchymal transition myofibroblast neovascular age-related macular degeneration submacular fibrosis subretinal fibrosis therapeutic targets transforming growth factor-β vascular endothelial growth factor

Efficacy and safety of combined Kahook Dual Blade goniotomy with phacoemulsification in Chinese patients with primary open angle glaucoma

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International Journal of Ophthalmology(English edition) 2025年第2期18卷 268-274页

作者： Lin Fu Jiang-Tao Lou Yue Guo Pei-Juan Wang Rong-Rong Le Shu-Xia Xu Guo-Xing Li Yuan-Bo Liang National Clinical Research Center for Ocular diseases Eye HospitalWenzhou Medical UniversityWenzhou 325003Zhejiang ProvinceChina

AIM:To report the one-year surgical outcome Kahook Dual Blade goniotomy combined with phacoemulsification(KDB-Phaco)in Chinese patients with primary open angle glaucoma(POAG).METHODS:This is a retrospective study included 43 eyes of 28 Chinese POAG patients with cataract who accepted KDB-Phaco and followed-up for *** pressure(IOP),glaucoma medications and surgical complications were *** 1 and success 2 was defined as 5-21 mm Hg and 5-18 mm Hg,and success plus was determined if additional criteria of IOP reduction≥20%from baseline was reached.A corrected IOP by adding 3 mm Hg for each medication was used to do correlation ***’s proportional hazards regression model was used to test the hazard ratio for factors associated with surgical ***:After a 12-month follow up,the IOP decreased from 28.1±6.3 to 13.8±3.0 mm Hg(47.92%reduction,P<0.001),and the medications used decreased from 2.0(1.0)to 0.0(0.0)(95%reduction,P<0.001).The mean IOP of all postoperative visits were lower than preoperative IOP(all P<0.001),so as the number of glaucoma medications(all P<0.001).Complete success 1 and qualified success 1 were 87.80%and 100.00%*** complete success 1 plus and qualified success 1 plus were 85.37%and 97.56%,*** 82.93%and 90.24%of patients got complete success 2 and qualified success 2 while 80.49%and 87.80%of patients satisfied complete success 2 plus and qualified success 2 ***(r=-0.511,P=0.001)and visual acuity(VA;r=-0.321,P=0.041)were negatively correlated with postoperative corrected IOP at 12mo,while anterior chamber depth(r=0.432,P=0.005),mean deviation(r=0.617,P<0.001)and visual field index(r=0.524,P<0.001)were positively correlated with *** VA(OR=33.092,P=0.004)and MD(OR=1.481,P=0.018)were hazard factors associated with failure based on qualified success as 18 mm *** main complications of KDB were hyphema(9.30%),IOP spike(11.63%)and peripheral anterior synechia(6.98%).CONCLUSI

关键词： Kahook Dual Blade goniotomy primary open angle glaucoma success rate risk factors

The gut microbiome modulate response to immunotherapy in cancer

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Science China(Life Sciences) 2025年第2期68卷 381-396页

作者： Shan-Shan Jiang Zi-Ran Kang Ying-Xuan Chen Jing-Yuan Fang Division of Gastroenterologyand Hepatology Shanghai Instituteof Digestive DiseaseNHC KeyLaboratoryof Digestive DiseasesState KeyLaboratoryfor Oncogenesand Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200001China

Gut microbiota have been reported to play an important role in the occurrence and development of malignant ***,clinical studies have identified specific gut microbiota and its metabolites associated with efficacy of immunotherapy in multiple types of *** investigations have elucidated that gut microbiota modulate the antitumor immunity and affect the efficacy of cancer *** microbiota and its metabolites may favorably remodel the tumor microenvironment by engaging innate and/or adaptive immune *** how the gut microbiome interacts with cancer immunotherapy opens new avenues for improving treatment *** microbial transplants,probiotics,dietary interventions,and other strategies targeting the microbiota have shown promise in preclinical studies to enhance the *** clinical trials are evaluating these *** review presents the recent advancements in understanding the dynamic interplay among the host immunity,the microbiome,and cancer immunotherapy,as well as strategies for modulating the microbiome,with a view to translating into clinical applications.

关键词： cancer immunotherapy gut microbiota intratumoral microbiota microbiota-derived metabolites innate and adaptive immunity

Role of lysosomal trafficking regulator in autophagic lysosome reformation in neurons:a disease perspective

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Neural Regeneration Research 2024年第5期19卷 957-958页

作者： Prashant Sharma Jenny Serra-Vinardell Wendy J.Introne May Christine V.Malicdan nih undiagnosed diseases program Common FundOffice of the DirectorNational Institutes of HealthBethesdaMDUSA Human Biochemical Genetics Section Medical Genetics BranchNational Human Genome Research InstituteNational Institutes of HealthBethesdaMDUSA(Serra-Vinardell JIntrone)

Lysosomes are discrete organelles that act as recycling centers for extracellular and intracellular materials,playing a pivotal role in maintaining cellular *** acidic environment,maintained by numerous hydrolytic enzymes,facilitates substrate *** in lysosomal processes can lead to abnormal substrate degradation,significantly impacting cellular *** energy-demanding cells,such as post-mitotic neurons,are especially vulnerable to these changes,often resulting in neurological ***,a conserved catabolic process,requires extensive lysosomal *** plays a key role in removing unnecessary intracellular components,ensuring cellular homeostasis,and promoting cell survival during stress conditions such as starvation,infection,or cellular damage.

关键词： homeostasis lysosomal removing

Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

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Neural Regeneration Research 2025年第9期20卷 2667-2681页

作者： Liwen Zhou Karthik Venkudusamy Emily A.Hibbard Yessenia Montoya Alexa Olivarez Cathy Z.Yang Adelaide Leung Varun Gokhale Guhan Periyasamy Zeal Pathak Dale R.Sengelaub George D.Bittner Department of Neuroscience University of TexasAustinTXUSA program in Neuroscience Indiana UniversityBloomingtonINUSA Department of Molecular Biosciences University of TexasAustinTXUSA

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary *** preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion *** the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis *** nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the *** von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve *** withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not *** thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated *** sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the ***,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative

关键词： autophagia axotomy collateral sprouting neuropathic pain peripheral nerve repair polyethylene glycol fusion(PEG-fusion) saphenous nerve sensory neurons sex and strain Wallerian degeneration