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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 2×104 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 levels and CXCR5+CD8+lymphocytes(r=-0.03,P=0.62

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

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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

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Endocrine impact of Helicobacter pylori:Focus on ghrelin and ghrelin o-acyltransferase

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World Journal of Gastroenterology 2011年第10期17卷 1249-1260页

作者： Penny L Jeffery Michael A McGuckin Sara K Linden mucosal diseases program Mater Medical Research InstituteMater Health Services mucosal Immunobiology and Vaccine Center Sahlgrenska AcademyUniversity of Gothenburg

Ghrelin is predominantly produced by the gastric enteroendocrine cell compartment and is octanoylated by the recently discovered ghrelin o-acyltransferase （GOAT） before secretion into the bloodstream. This octanoylation is essential for many of the biological properties of ghrelin including appetite stimulation and anti-inflammatory properties as only the acylated form of ghrelin binds to the ghrelin receptor, the growth hormone secretagogue receptor （GHS-R）. Given the gastric location of ghrelin production, it is perhaps not surprising that insult to the gastric mucosa affects circulating ghrelin levels in humans. Helicobacter pylori （H. pylon） infects more than fifty percent of the world＇s population and once established within the gastric mucosa, can persist for life. Infection is associated with chronic gastritis, gastric atrophy and ulceration, reduced appetite and a lower body mass index （BMI）. The large majority of studies investigating levels of circulating ghrelin and ghrelin expression in the stomach in patients with H. pylori infection indicate that the bacterium has a negative impact on ghrelin production and/or secretion. Eradication of infection restores ghrelin, improves appetite and increases BMI in some studies, however, a causative relationship between H. pylori-associated serum ghrelin decline and food intake and obesity has not been established. Most studies measure total ghrelin in the circulation although the measurement of the ratio of acyl/total ghrelin gives a clearer indication that the ghrelin acylation process is altered during infection and atrophy. GOAT is essential for the production of biologically-active, acyl ghrelin and the impact of H. pylori on GOAT expression and activity will be highly informative in the future.

关键词： Appetite Ghrelin Ghrelin o-acyltransferase Helicobacterpylori Infection Inflammation Obesity

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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration Research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Shanghai Engineering Research Center of Stem Cells Translational Medicine ShanghaiChina National Center for Healthcare Quality Management in Neurological diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for Neurological diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

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Silent battles:immune responses in asymptomatic SARS-CoV-2 infection

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Cellular & Molecular Immunology 2024年第2期21卷 159-170页

作者： Nina Le Bert Taraz Samandari program in Emerging Infectious diseases Duke-NUS Medical SchoolSingaporeSingapore

SARS-CoV-2 infections manifest with a broad spectrum of presentations,ranging from asymptomatic infections to severe pneumonia and fatal *** review centers on asymptomatic infections,a widely reported phenomenon that has substantially contributed to the rapid spread of the *** such asymptomatic infections,we focus on the role of innate,humoral,and cellular ***,asymptomatic infections are characterized by an early and robust innate immune response,particularly a swift type 1 IFN reaction,alongside a rapid and broad induction of SARS-CoV-2-specific T ***,antibody levels tend to be lower or undetectable after asymptomatic infections,suggesting that the rapid control of viral replication by innate and cellular responses might impede the full triggering of humoral *** if antibody levels are present in the early convalescent phase,they wane rapidly below serological detection limits,particularly following asymptomatic ***,prevalence studies reliant solely on serological assays likely underestimate the extent of community exposure to the virus.

关键词： COVID-19 asymptomatic cellular immunity antibody

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Cultural differences defne diagnosis and genomic medicine practice: implications for undiagnosed diseases program in China

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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

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The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration Research 2025年第5期20卷 1505-1512页

作者： Jieying Wu Shan Ye Xiangyi Liu Yingsheng Xu Dongsheng Fan Department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative diseases BeijingChina Key Laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

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SARS-CoV-2 immunity

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Cellular & Molecular Immunology 2024年第2期21卷 101-102页

作者： Antonio Bertoleti program in Emerging Infectious diseases Duke-NUS Medical SchoolSingaporeSingapore

Four years have swiftly passed since the identification of a novel coronavirus from patients with pneumonia that signs the start of the COVID-19 pandemic[1].The world's social and economic landscape has largely reverted to its prepandemic state,and different issues unrelated to the pandemic are currently impacting various regions *** scientific community,which quickly modified its research focus during the initial years of the pandemic to generate a wealth of scientific data that helped in understanding and controlling SARS-CoV-2 infection,is also facing a new phase in the study of virus-host interactions.

关键词： immunity globally landscape

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Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain

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Neural Regeneration Research 2025年第9期20卷 2682-2696页

作者： Xiaoyu Zhang Yuqi Liu Fangxia Xu Chengcheng Zhou Kaimei Lu Bin Fang Lijuan Wang Lina Huang Zifeng Xu Department of Anesthesiology International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Anesthesiology Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Key Laboratory of Embryo Original diseases ShanghaiChina

Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal ***,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this *** this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic *** results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer *** addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain ***,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 ***,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was ***,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ***,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 *** findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.

关键词： dorsal root ganglion heterogeneous nuclear ribonucleoprotein F neuropathic pain protein arginine methyltransferase-6 sensory neurons

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Kangfuxin solution alleviates esophageal stenosis after endoscopic submucosal dissection:A natural ingredient strategy

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World Journal of Gastroenterology 2025年第1期31卷 110-125页

作者： Xin Zhou Dan Ma Yi-Xiang He Jing Jin Hong-Lian Wang Yun-Feng Wang Fan Yang Jian-Qin Liu Jie Chen Zhi Li Department of Spleen and Stomach diseases the Affiliated Traditional Chinese Medicine HospitalSouthwest Medical UniversityLuzhou 646000Sichuan ProvinceChina The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System diseases of Luzhou City The Affiliated Traditional Medicine HospitalSouthwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Department of Gastroenterology Changhai HospitalNaval Medical UniversityShanghai 20082China Research Center of Integrated Chinese and Western Medicine The Affiliated Traditional Chinese Medicine HospitalSouthwest Medical UniversityLuzhou 646000Sichuan ProvinceChina School of Integrated Traditional Chinese and Western Clinical Medicine North Sichuan Medical CollegeNanchong637100Sichuan ProvinceChina

BACKGROUND Esophageal stricture ranks among the most significant complications following endoscopic submucosal dissection(ESD).Excessive fibrotic repair is a typical pathological feature leading to stenosis after *** To examine the effectiveness and underlying mechanism of Kangfuxin solution(KFX)in mitigating excessive fibrotic repair of the esophagus *** Pigs received KFX at 0.74 mL/kg/d for 21 days after esophageal full circumferential *** examinations occurred on days 7 and 21 *** vitro,recombinant transforming growth factor(TGF)-β1(5 ng/mL)induced a fibrotic microenvironment in primary esophageal fibroblasts(pEsF).After 24 hours of KFX treatment(at 1.5%,1%,and 0.5%),expression ofα-smooth muscle actin-2(ACTA2),fibronectin(FN),and type collagen I was *** signaling was analyzed,including TGF-β1,Smad2/3,and phosphor-smad2/3(p-Smad2/3).RESULTS Compared to the Control group,the groups treated with KFX and prednisolone exhibited reduced esophageal stenosis,lower weight loss rates,and improved food tolerance 21 d after *** treatment,Masson staining revealed thinner and less dense collagen fibers in the submucosal ***,the expression of fibrotic effector molecules was notably ***,KFX downregulated the transduction levels of fibrotic functional molecules such as TGF-β1,Smad2/3,and p-Smad2/*** vitro,pEsF exposed to TGF-β1-induced fibrotic microenvironment displayed increased fibrotic activity,which was reversed by KFX treatment,leading to reduced activation of ACTA2,FN,and collagen *** 1.5%KFX treatment group showed decreased expression of p-Smad 2/3 in TGF-β1-activated *** KFX showed promise as a therapeutic option for post-full circumferential esophageal ESD strictures,potentially by suppressing fibroblast fibrotic activity through modulation of the TGF-β1/Smads signaling pathway.

关键词： Kangfuxin solution Natural component Endoscopic submucosal dissection Esophagus stricture Fibrosis

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