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Hernandezine promotes cancer cell apoptosis and disrupts the lysosomal acidic environment and cathepsin D maturation

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Chinese Journal of Natural Medicines 2024年第5期22卷 387-401页

作者： FENG Qianwen SUN Lu Muhammad Jibran Sualeh ZHAO Qingli ZHAO Songji CUI Zhengguo INADERA Hidekuni department of Public health Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-8501Japan department of Pediatric Cardiology Heart CenterGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510000China department of Basic Medical sciences College of MedicineUniversity of SharjahSharjah 57545United Arab Emirates department of radiology Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-8501Japan Advanced Clinical Research center Fukushima Global Medical Science CenterFukushima Medical UniversityFukushima CityFukushima 960-8074Japan department of Environmental health School of Medical SciencesUniversity of FukuiFukui 910-8580Japan

Hernandezine(Her),a bisbenzylisoquinoline alkaloid extracted from Thalictrum flavum,is recognized for its range of biological activities inherent to this herbal *** its notable properties,the anti-cancer effects of Her have remained largely *** this study,we elucidated that Her significantly induced cytotoxicity in cancer cells through the activation of apoptosis and necroptosis ***,Her triggered autophagosome formation by activating the AMPK and ATG5 conjugation systems,leading to LC3 *** findings revealed that Her caused damage to the mitochondrial membrane,with the damaged mitochondria undergoing mitophagy,as evidenced by the elevated expression of mitophagy ***,Her disrupted autophagic flux,demonstrated by the upregulation of p62 and accumulation of autolysosomes,as observed in the RFP-GFP-LC3 reporter ***,we determined that Her did not prevent the fusion of autophagosomes and ***,it inhibited the maturation of cathepsin D and increased lysosomal pH,indicating an impairment of lysosomal *** use of the early-stage autophagy inhibitor,3-methyladenine(3-MA),did not suppress LC3II,suggesting that Her also induces noncanonical autophagy in autophagosome *** application of Bafilomycin A1,an inhibitor of noncanonical autophagy,diminished the recruitment of ATG16L1 and the accumulation of LC3II by Her,thereby augmenting Her-induced cell *** observations imply that while autophagy initially plays a protective role,the disruption of the autophagic process by Her promotes programmed cell *** study provides the first evidence of Her’s dual role in inducing apoptosis and necroptosis while also initiating and subsequently impairing autophagy to promote apoptotic cell *** insights contribute to a deeper understanding of the mechanisms underlying programmed cell death,offering potential avenues for enhancing cancer prevention and therapeutic st

关键词： Hernandezine Apoptosis Mitophagy Autophagic flux Lysosome Noncanonical autophagy

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A machine learning model for diagnosing acute pulmonary embolism and comparison with Wells score,revised Geneva score,and Years algorithm

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Chinese Medical Journal 2024年第6期137卷 676-682页

作者： Linfeng Xi Han Kang Mei Deng Wenqing Xu Feiya Xu Qian Gao Wanmu Xie Rongguo Zhang Min Liu Zhenguo Zhai Chen Wang Capital Medical University Beijing 100069China National center for Respiratory Medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Pulmonary and Critical Care MedicineCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Institute of Advanced Research Infervision Medical Technology Co.Ltd.Beijing 100025China department of radiology China-Japan Friendship HospitalBeijing 100029China Chinese Academy of Medical sciences and Peking Union Medical College Beijing 100730China department of radiology Peking University China-Japan Friendship School of Clinical MedicineBeijing 100191China

Background:Acute pulmonary embolism(APE)is a fatal cardiovascular disease,yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs.A simple,objective technique will help clinicians make a quick and precise *** population studies,machine learning(ML)plays a critical role in characterizing cardiovascular risks,predicting outcomes,and identifying *** work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment ***:This is a single-center retrospective *** with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets.A total of 8 ML models,including random forest(RF),Naïve Bayes,decision tree,K-nearest neighbors,logistic regression,multi-layer perceptron,support vector machine,and gradient boosting decision tree were developed based on the training set to diagnose ***,the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies,including the Wells score,revised Geneva score,and Years ***,the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic(ROC)***:The ML models were constructed using eight clinical features,including D-dimer,cardiac troponin T(cTNT),arterial oxygen saturation,heart rate,chest pain,lower limb pain,hemoptysis,and chronic heart *** eight ML models,the RF model achieved the best performance with the highest area under the curve(AUC)(AUC=0.774).Compared to the current clinical assessment strategies,the RF model outperformed the Wells score(P=0.030)and was not inferior to any other clinical probability assessment *** AUC of the RF model for diagnosing APE onset in internal validation set was ***:Based on RF algorithm,a novel prediction model was finally constructed for AP

关键词： Acute pulmonary embolism Machine learning Wells score Revised Geneva score Years algorithm

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Engagement of N^(6)-methyladenisine methylation of Gng4 mRNA in astrocyte dysfunction regulated by CircHECW2

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1644-1660页

作者： Ying Bai Di Chang Hui Ren Minzi Ju Yu Wang Biling Chen Han Li Xue Liu Daxing Li Xinchen Huo Xiaofei Guo Mengze Tong Ying Tan Honghong Yao Bing Han department of Pharmacology Jiangsu Provincial Key Laboratory of Critical Care MedicineSchool of MedicineSoutheast UniversityNanjing 210009China department of radiology Zhongda HospitalJiangsu Key Laboratory of Molecular and Functional ImagingMedical School of Southeast UniversityNanjing 210009China Co-Innovation center of Neuroregeneration Nantong UniversityNantong 226001China Institute of Life sciences Key Laboratory of Developmental Genes and Human DiseaseSoutheast UniversityNanjing 210096China center for Global health School of Public HealthNanjing Medical UniversityNanjing 211166China

The N^(6)-methyladenosine(m^(6)A)modification is the most prevalent modification of eukaryotic mRNAs and plays a crucial role in various physiological processes by regulating the stability or function of target *** evidence has suggested that m6A methylation may be involved in the pathological process of major depressive disorder(MDD),a common neuropsychiatric disorder with an unclear ***,we found that the levels of the circular RNA HECW2(circHECW2)were significantly increased in the plasma of both MDD patients and the chronic unpredictable stress(CUS)mouse ***,the downregulation of circHECW2 attenuated astrocyte dysfunction and depression-like behaviors induced by ***,we demonstrated that the downregulation of circHECW2 increased the expression of the methylase WTAP,leading to an increase in Gng4 expression via m^(6)A *** findings provide functional insight into the correlation between circHECW2 and m^(6)A methylation,suggesting that circHECW2 may represent a potential target for MDD treatment.

关键词： N^(6)-Methyladenosine Depression circHECW2 Astrocyte WTAP Ubiquitination GNG4 Dysfunction

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Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

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Oncology Research 2024年第2期32卷 309-323页

作者： BEHROOZ JOHARI MILAD PARVINZAD LEILAN MAHMOUD GHARBAVI YOUSEF MORTAZAVI ALI SHARAFI HAMED REZAEEJAM department of Medical Biotechnology School of MedicineZanjan University of Medical SciencesZanjanIran Zanjan Pharmaceutical Biotechnology Research center Zanjan University of Medical SciencesZanjanIran Nanotechnology Research center Ahvaz Jundishapur University of Medical SciencesAhvazIran department of radiology Technology School of Allied Medical SciencesZanjan University of Medical SciencesZanjanIran

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell *** and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 *** nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical ***,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer *** anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized *** revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation *** can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

关键词： Combinational therapy Antisense therapy Myc signaling pathway Niosomes Radiation therapy SeNPs

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Congenital Disseminated Pyogenic Granuloma:A Case With Numerous Mucocutaneous and Visceral Lesions

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Maternal-Fetal Medicine 2024年第3期6卷 190-195页

作者： Siavash Ghaderi-Sohi Behnaz Moradi Mahboobeh Shirazi Rahil Rahimi Romina Ravanbakhsh Ariana Kariminejad Elham Feizabad Kariminejad-Najmabadi Pathology&Genetics center Tehran ***Iran department of radiology Advanced Diagnostic and Interventional Radiology Research Center(ADIR)Tehran University of Medical SciencesTehran ***Iran Yas Complex Hospital Tehran University of Medical SciencesTehran ***Iran Nikan Hospital Tehran ***Iran

Congenital disseminated pyogenic granuloma(CDPG)is characterized by eruptive disseminated or localized lesions,which may arise spontaneously or secondary to predisposing *** rarer is the occurrence of CDPG with numerous lesions affecting variable organs,which develop during the fetal *** report describes the case of a 32-week-old fetus presenting with severe hydrocephalus and vascular intracranial and right lung masses on magnetic resonance *** labor occurred at the 32^(nd)week due to preterm premature rupture of membranes,and the newborn died due to cardiac dysfunction within 2 hours *** subsequent autopsy revealed multiple violaceous to dark red papules,nodules,pedunculated and un-pedunculated mucocutaneous masses,as well as two brain lesions,a lung lesion,a thoracic wall intramuscular mass,and a pyloric *** examination and immunohistochemical evaluation for glucose transporter 1(GLUT1)confirmed the diagnosis of *** represents a rare condition with an elusive etiology and limited reports in the *** diagnosis from multifocal infantile hemangioma,based on GLUT1 negativity of CDPG,is imperative due to differing clinical course and treatment *** report underscores a severe case of CDPG characterized by preterm labor and demise shortly after delivery,notable for its extensive involvement across multiple organs,including the brain,lung,intestine,musculoskeletal system,mucosal,and numerous cutaneous sites.

关键词： Pyogenic Granuloma Congenital Hemangioma

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Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

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Oncology Research 2024年第1期32卷 101-125页

作者： ROGHAYEH GHORBANI MAHMOUD GHARBAVI ALI SHARAFI ELHAM RISMANI HAMED REZAEEJAM YOUSEF MORTAZAVI BEHROOZ JOHARI department of Medical Biotechnology School of MedicineZanjan University of Medical SciencesZanjanIran Nanotechnology Research center Ahvaz Jundishapur University of Medical SciencesAhvazIran Zanjan Pharmaceutical Biotechnology Research center Zanjan University of Medical SciencesZanjanIran department of Pharmaceutical Biotechnology School of PharmacyZanjan University of Medical SciencesZanjanIran Molecular Medicine department Biotechnology Research CenterPasteur Institute of IranPasteur AvenueTehranIran department of radiology Technology School of Allied Medical SciencesZanjan University of Medical SciencesZanjanIran

In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer *** decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics *** were loaded on the synthesized Se@BSA@Chi-MTX *** physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis ***,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell *** results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,*** results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of *** results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/*** ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic *** targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the *** results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP *** nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

关键词： Chemoradiotherapy Combination therapy Decoy oligodeoxynucleotides Myc transcription factor Selenium nanoparticle Prostate cancer

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Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1690-1705页

作者： Yan Fu Keyu Shen Hao Wang Shun Wang Xufeng Wang Le Zhu Yan Zheng Tiantian Zou Hongfei Ci Qiongzhu Dong Lun-Xiu Qin Hepatobiliary Surgery Department of General SurgeryHuashan Hospital&Cancer Metastasis InstituteFudan University200040 ShanghaiChina center of Interventional radiology and Vascular Surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast University87 Dingjiaqiao Road210009 NanjingChina institutes of Biomedical sciences Fudan University200032 ShanghaiChina Key Laboratory of Whole-period Monitoring and Precise Intervention of Digestive Cancer Shanghai Municipal Health CommissionMinhang HospitalFudan UniversityShanghaiChina

Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor *** cells could exhibit a"neural addiction"property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated *** the dysregulated nervous systems might represent a novel strategy for cancer ***,whether intrahepatic cholangiocarcinoma(ICC)could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely *** staining and Enzyme-linked immunosorbent assay suggested that IcC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes IcC metastasis by inducing epithelial-mesenchymal transition(EMT).Acetylcholine promoted iCC metastasis through interacting with its receptor,alpha 5 nicotine acetylcholine receptor subunits(CHRNA5).Furthermore,acetylcholine/CHRNA5 axis activated GSK3β/β-catenin signaling pathway partially through the influx of Ca^(2+)-mediated activation of Ca/calmodulin-dependent protein kinases(CAMKll).In addition,acetylcholine signaling activation also expanded nerve infiltration through increasing the expression of Brain-Derived Neurotrophic Factor(BDNF),which formed a feedforward acetylcholine-BDNF axis to promote ICC ***93,a small-molecule inhibitor of CAMKIll,significantly inhibited the migration and enhanced the sensitivity to gemcitabine of ICC *** all,Acetylcholine/CHRNA5 axis increased the expression ofβ-catenin to promote the metastasis and resistance to gemcitabine of ICC via CAMKIl/GSK3βsignaling,and the CAMKIl inhibitor KN93 may be an effective therapeutic strategy for combating ICC metastasis.

关键词： GSK3β metastasis Alpha

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Dendritic nanomedicine enhances chemoimmunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3680-3696页

作者： Yunkun Li Xiaoding Shen Haitao Ding Yuxin Zhang Dayi Pan Liping Su Yahui Wu Zaixiang Fang Jie Zhoua Qiyong Gong Kui Luo department of radiology Huaxi MR Research Center(HMRRC)Frontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China department of radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune ***,we constructed a PEGylated dendritic epirubicin(Epi)prodrug(Epi-P4D)to regulate the metabolism of cancer-associated fibroblasts(CAFs),thus enhancing Epi penetration into both multicellular tumor spheroids(MTSs)and tumor tissues in mouse colon cancer(CT26),mouse breast cancer(4T1)and human breast cancer(MDA-MB-231)*** cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin,α-SMA,and collagen ***,thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell(DC)maturation and subsequent immune activation,including elevating the CD4^(+)T cell population,reducing CD4^(+)and CD8^(+)T cell hyperactivation and exhaustion,and amplifying the natural killer(NK)cell proportion and effectively activating *** a result,this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.

关键词： Dendritic prodrug Enhanced penetration Metabolic intervention Cancer-associated fibroblasts Immunogenic cell death Chemotherapy Immunotherapy Immune microenvironment reconstitution

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Structural and functional connectivity of the whole brain and subnetworks in individuals with mild traumatic brain injury:predictors of patient prognosis

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Neural Regeneration Research 2024年第7期19卷 1553-1558页

作者： Sihong Huang Jungong Han Hairong Zheng Mengjun Li Chuxin Huang Xiaoyan Kui Jun Liu department of radiology The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina department of Computer Science Aberystwyth UniversityAberystwythCeredigionUK Shenzhen Institutes of Advanced Technology Chinese Academy of SciencesShenzhenGuangdong ProvinceChina School of Computer Science and Engineering Central South UniversityChangshaHunan ProvinceChina department of radiology Quality Control Center of Hunan ProvinceChangshaHunan ProvinceChina Clinical Research center for Medical Imaging of Hunan Province ChangshaHunan ProvinceChina

Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly *** resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain *** approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and ***,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional *** that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is *** the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain *** this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy ***-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network *** the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention *** than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 ***,better cognitive function was associated with more efficient ***,our data indicated that small-worldness in the acute sta

关键词： cognitive function cross-section follow-up functional connectivity graph theory longitudinal study mild traumatic brain injury prediction small-worldness structural connectivity subnetworks whole brain network

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Investigating the relationship between intracranial atherosclerotic plaque remodelling and diabetes using high-resolution vessel wall imaging

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World Journal of Diabetes 2024年第1期15卷 72-80页

作者： Yong-Qian Mo Hai-Yu Luo Han-Wen Zhang Yu-Feng Liu Kan Deng Xiao-Lei Liu Biao Huang Fan Lin department of radiology Peking University Shenzhen HospitalShenzhen 518000Guangdong ProvinceChina department of Ultrasound Peking University Shenzhen HospitalShenzhen 518000Guangdong ProvinceChina The Second School of Clinical Medicine Southern Medical UniversityGuangzhou 510282Guangdong ProvinceChina department of radiology The First Affiliated Hospital of Shenzhen UniversityHealth Science CenterShenzhen Second People’s HospitalShenzhen 518036Guangdong ProvinceChina Research department Philips HealthcareGuangzhou 518000Guangdong ProvinceChina department of radiology Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510000Guangdong ProvinceChina

BACKGROUND Intracranial atherosclerosis,a leading cause of stroke,involves arterial plaque *** study explores the link between plaque remodelling patterns and diabetes using high-resolution vessel wall imaging(HR-VWI).AIM To investigate the factors of intracranial atherosclerotic remodelling patterns and the relationship between intracranial atherosclerotic remodelling and diabetes mellitus using *** Ninety-four patients diagnosed with middle cerebral artery or basilar artery INTRODUCTION Intracranial atherosclerotic disease is one of the main causes of ischaemic stroke in the world,accounting for approx-imately 10%of transient ischaemic attacks and 30%-50%of ischaemic strokes[1].It is the most common factor among Asian people[2].The adaptive changes in the structure and function of blood vessels that can adapt to changes in the internal and external environment are called vascular remodelling,which is a common and important pathological mechanism in atherosclerotic diseases,and the remodelling mode of atherosclerotic plaques is closely related to the occurrence of *** remodelling(PR)is an outwards compensatory remodelling where the arterial wall grows outwards in an attempt to maintain a constant lumen *** a long time,it was believed that the degree of stenosis can accurately reflect the risk of ischaemic stroke[3-5].Previous studies have revealed that lesions without significant luminal stenosis can also lead to acute events[6,7],as summarized in a recent meta-analysis study in which approximately 50%of acute/subacute ischaemic events were due to this type of lesion[6].Research[8,9]has pointed out that the PR of plaques is more dangerous and more likely to cause acute ischaemic *** studies[10-13]have found that there are specific vascular remodelling phenomena in the coronary and carotid arteries of diabetic ***,due to the deep location and small lumen of intracranial arteries and limitations of i

关键词： High-resolution vessel wall imaging Intracranial atherosclerosis Vascular remodelling Magnetic resonance imaging

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