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Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

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World Journal of Gastroenterology 2025年第1期31卷 126-145页

作者： Xing-Hui Yu Yan Xie Jian Yu Kun-Ning Zhang Zhou-Bo Guo Di Wang Zhao-Xian Li Wei-Qi Zhang Yu-Ying Tan Li Zhang Wen-Tao Jiang School of Medicine Nankai UniversityTianjin 300192China Tianjin Key Laboratory of Molecular diagnosis and Treatment of Liver Cancer Tianjin First Center HospitalTianjin 300192China department of Liver Transplantation Tianjin First Center HospitalTianjin 300192China First Central clinical School Tianjin Medical UniversityTianjin 300192China

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated *** therapeutic targets are beneficial to treat and predict the ***,the exact molecular mechanisms leading to the progression of HCC are still *** has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor *** this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between *** To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC *** In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC ***,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,*** statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank *** In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival ***1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated ***,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via *** the exploration mechanism,we found ASH1L may promote an immunosuppressive mi

关键词： Hepatocellular carcinoma MicroRNA-142-3p ASH1L Immune evasion Tumor immune microenvironment Apoptosis

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Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

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Neural Regeneration Research 2025年第1期20卷 41-53页

作者： Alessio Canovai Pete A.Williams department of Biology University of PisaPisaItaly department of clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/*** quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary *** quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many *** this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian *** the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and *** quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully ***,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological *** addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

关键词： metabolism mitochondria neurodegenerative disease neuroprotection pyrroloquinoline quinone retinal diseases

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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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clinical value of the emergency department in screening and diagnosis of COVID-19 in China

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2020年第5期21卷 388-393页

作者： Qin ZHANG Jian PAN Min-xing ZHAO Yuan-qiang LU department of Emergency Medicine the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China Key Laboratory for diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou S10003China

目的:通过对浙江大学医学院附属第一医院急诊科筛查出的4例新型冠状病毒肺炎(新冠肺炎)病例进行分析,探讨急诊科在新冠肺炎精准筛查和诊断中的作用。创新点:分析新型冠状病毒肺炎的致病机制、传播方式和临床特征;总结急诊科医护人员的... 详细信息

目的:通过对浙江大学医学院附属第一医院急诊科筛查出的4例新型冠状病毒肺炎(新冠肺炎)病例进行分析,探讨急诊科在新冠肺炎精准筛查和诊断中的作用。创新点:分析新型冠状病毒肺炎的致病机制、传播方式和临床特征;总结急诊科医护人员的自身防护和诊断策略。方法:回顾性分析我院急诊科筛查出的4例新型冠状病毒肺炎病例,总结急诊科的临床价值。结论:在新冠肺炎的筛查和诊断体系中,中国急诊科发挥了不可替代的作用。急诊科医护人员应充分做好自身防护,对患者进行细致、耐心、谨慎地病史采集和全面的体格检查,并关注患者的心理状态,有效应用肺部计算机断层扫描(CT)、核酸检测等检测方法,做好新冠肺炎筛查工作。

关键词：新型冠状病毒肺炎 SARS-CoV-2 急诊科

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Significance of a novel sucrose permeability test using serum in the diagnosis of early gastric cancer

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World Journal of Gastroenterology 2005年第44期11卷 6905-6909页

作者： Tadayuki Shishido Taketo Yamaguchi Takeo Odaka Masanori Seimiya Hiromitsu Saisho Fumio Nomura department of Medicine and clinical Oncology department of Molecular diagnosis

AIM： To investigate the usefulness of sucrose permeability test using serum in the diagnosis of gastric diseases, with special reference to early gastric cancer （EGC）. METHODS： A total of 63 subjects, including 11 patients with gastric ulcer, 20 patients with gastric cancer （13, early; 7, advanced） and 32 healthy controls, were studied. Blood and urine samples were collected repeatedly for 5 h before and after the sucrose loading. Sucrose levels were measured by a newly developed RESULTS： Serum sucrose levels started to increase 15 min after loading, and peaked at 60 min in the gastric disease groups. The levels for gastric ulcer, EGC and advanced gastric cancer （AGC） at 60 min were significantly higher than that in the healthy controls （26.9±2.4, 34.4±5.0, and 71.8±15.6 vs 7.9±0.7 mol/L, respectively, P〈0.01）. The cut-off level set at 15.4 mol/L （60 min） offered the best distinction between EGC patients and healthy controls; and the sensitivity and specificity were 92.3% and 93.8%, respectively, while those of the urine method were 76.9% and 93.8%, respectively. CONCLUSIONS： The gastric permeability test using serum is reliable for the detection of EGC, and this test can provide results much earlier than the conventional urine method. This test may offer a useful alternative to more invasive tests for EGC.

关键词： Sucrose test Gastric permeability Early gastric cancer Advanced gastric cancer Gastric ulcer

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Neuronal regulated cell death in aging-related neurodegenerative diseases:key pathways and therapeutic potentials

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Neural Regeneration Research 2025年第8期20卷 2245-2263页

作者： Run Song Shiyi Yin Jiannan Wu Junqiang Yan department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Neuromolecular Biology Laboratory The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and ***,excessive activation of regulated cell death may lead to the progression of aging-related *** review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related ***,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative *** forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein *** review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and *** instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis ***,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to *** insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death *** conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.

关键词： apoptosis autophagy cuproptosis disulfidptosis ferroptosis necroptosis neurodegenerative disease neurological aging diseases PANoptosis pyroptosis

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Non-coding RNAs in acute ischemic stroke:from brain to periphery

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Neural Regeneration Research 2025年第1期20卷 116-129页

作者： Shuo Li Zhaohan Xu Shiyao Zhang Huiling Sun Xiaodan Qin Lin Zhu Teng Jiang Junshan Zhou Fuling Yan Qiwen Deng department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina department of Neurology Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsu ProvinceChina General clinical Research Center Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and *** predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain *** innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental *** expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic ***,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and *** particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic *** this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and *** from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

关键词： acute ischemic stroke apoptosis blood–brain barrier damage circular RNAs excitatory toxicity long non-coding RNAs microRNAs neuroinflammation non-coding RNAs oxidative stress

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Insights into spinal muscular atrophy from molecular biomarkers

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Neural Regeneration Research 2025年第7期20卷 1849-1863页

作者： Xiaodong Xing Xinzhu Liu Xiandeng Li Mi Li Xian Wu Xiaohui Huang Ajing Xu Yan Liu Jian Zhang department of clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina College of Pharmacy Chongqing Medical UniversityChongqingChina

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle *** is one of the most common genetic causes of mortality among infants aged less than 2 *** research is currently receiving more attention,and new candidate biomarkers are constantly being *** review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and *** also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific *** review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future ***,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

关键词： biomarkers disease progression gene-targeting therapy neurofilaments Nusinersen spinal muscular atrophy(SMA) survival motor neuron therapeutic evaluation treatment outcomes

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Hemogram-derived ratios as prognostic markers for major adverse cardiovascular events in patients with non-ST-segment elevation myocardial infarction

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World Journal of Methodology 2025年第2期15卷 125-136页

作者： Emir Bećirović Minela Bećirović SabinaŠegalo Amir Bećirović Semir Hadžić Kenana Ljuca Emsel Papić Lamija Ferhatbegović Malik Ejubović Amira JagodićEjubović Amila Kovčić ArminŠljivo Emir Begagić department of Intensive Care University Clinical Center TuzlaTuzla 75000Bosnia and Herzegovina department of Nephrology University Clinical Center TuzlaTuzla 75000Bosnia and Herzegovina department of Laboratory Technologies Faculty of Health SciencesUniversity of SarajevoSarajevo 71000Bosnia and Herzegovina department of Endocrinology University Clinical Center TuzlaTuzla 75000Bosnia and Herzegovina School of Medicine University of TuzlaTuzla 75000Bosnia and Herzegovina department for Internal Diseases and Hemodialysis Canton Hospital ZenicaZenica 72000Bosnia and Herzegovina department of Internal Medicine Canton Hospital ZenicaZenica 72000Bosnia and Herzegovina department of Radiotherapy University Clinical Center TuzlaTuzla 75000Bosnia and Herzegovina department of Cardiology University Clinical Center SarajevoSarajevo 72000Bosnia and Herzegovina department of General Medicine University of ZenicaSchool of MedicineZenica 72000Bosnia and Herzegovina

BACKGROUND Non-ST segment elevation myocardial infarction(NSTEMI)poses significant challenges in clinical management due to its diverse *** the prognostic role of hematological parameters and derived ratios in NSTEMI patients could aid in risk stratification and improve patient *** To evaluate the predictive value of hemogram-derived ratios for major adverse cardiovascular events(MACE)in NSTEMI patients,potentially improving clinical *** A prospective,observational cohort study was conducted in 2021 at the Internal Medicine Clinic of the University Hospital in Tuzla,Bosnia and *** study included 170 patients with NSTEMI,who were divided into a group with MACE and a control group without ***,the MACE group was subdivided into lethal and non-lethal groups for prognostic *** hematological parameters,an additional 13 hematological-derived ratios(HDRs)were monitored,and their prognostic role was *** Hematological parameters did not significantly differ between non-ST segment elevation myocardial infarction(NSTEMI)patients with MACE and a control group at T1 and ***,significant disparities emerged in HDRs among NSTEMI patients with lethal and non-lethal outcomes ***,neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)were elevated in lethal ***,C-reactive protein-to-lymphocyte ratio(CRP/Ly)at T1(>4.737)demonstrated predictive value[odds ratio(OR):3.690,P=0.024].Both NLR at T1(>4.076)and T2(>4.667)emerged as significant predictors,with NLR at T2 exhibiting the highest diagnostic performance,as indicated by an area under the curve of 0.811(95%CI:0.727-0.859)and OR of 4.915(95%CI:1.917-12.602,P=0.001),emphasizing its important role as a prognostic *** This study highlights the significant prognostic value of hemogram-derived indexes in predicting MACE among NSTEMI *** follow-up,NLR,PLR,and CRP/Ly off

关键词： Hemogram-derived ratios Prognostic markers Neutrophil-to-lymphocyte ratio Myocardial infarction

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Nanomaterials-mediated lysosomal regulation:a robust protein-clearance approach for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第2期20卷 424-439页

作者： Mengqi Hao Jianjian Chu Tinglin Zhang Tong Yin Yuankai Gu Wendanqi Liang Wenbo Ji Jianhua Zhuang Yan Liu Jie Gao You Yin department of Neurology Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)ShanghaiChina School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina Changhai clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina department of clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina department of Neurology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the ***,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular *** studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s *** the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s ***,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and ***,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical *** review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s *** review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal *** conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s *** application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

关键词： Alzheimer’s disease autophagy dysfunction lysosomal acidification lysosomal system nanomaterials neurodegenerative diseases

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