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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

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

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

Solid-state atomic hydrogen as a broad-spectrum RONS scavenger for accelerated diabetic wound healing

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National Science Review 2024年第2期11卷 196-206页

作者： Man Luo Qin Wang Gang Zhao Wei Jiang Cici Zeng Qingao Zhang Ruyu Yang Wang Dong Yunxi Zhao Guozhen Zhang Jun Jiang Yucai Wang Qing Zhu Key Laboratory of Precision and Intelligent Chemistry School of Chemistry and Materials Science University of Science and Technology of China department of radiology The First Affiliated Hospital of University of Science and Technology of China Division of Life Sciences and Medicine University of Science and Technology of China Shenzhen Senior High School Institute of Intelligent Innovation Henan Academy of Sciences

Hydrogen therapy shows great promise as a versatile treatment method for diseases associated with the overexpression of reactive oxygen and nitrogen species（RONS）. However, developing an advanced hydrogen therapy platform that integrates controllable hydrogen release, efficient RONS elimination, and biodegradability remains a giant technical challenge. In this study, we demonstrate for the first time that the tungsten bronze phase H0.53WO3（HWO） is an exceptionally ideal hydrogen carrier, with salient features including temperature-dependent highly-reductive atomic hydrogen release and broad-spectrum RONS scavenging capability distinct from that of molecular hydrogen. Moreover, its unique p H-responsive biodegradability ensures post-therapeutic clearance at pathological sites. Treatment with HWO of diabetic wounds in an animal model indicates that the solid-state atomic H promotes vascular formation by activating M2-type macrophage polarization and anti-inflammatory cytokine production, resulting in acceleration of chronic wound healing. Our findings significantly expand the basic categories of hydrogen therapeutic materials and pave the way for investigating more physical forms of hydrogen species as efficient RONS scavengers for clinical disease treatment.

关键词： atomic hydrogen RONS scavenger inflammatory regulation diabetic wound healing hydrogen therapy

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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Regulation of specific abnormal calcium signals in the hippocampal CA1 and primary cortex M1 alleviates the progression of temporal lobe epilepsy

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Neural Regeneration Research 2024年第2期19卷 425-433页

作者： Feng Chen Xi Dong Zhenhuan Wang Tongrui Wu Liangpeng Wei Yuanyuan Li Kai Zhang Zengguang Ma Chao Tian Jing Li Jingyu Zhao Wei Zhang Aili Liu Hui Shen Laboratory of Neurobiology School of Biomedical EngineeringTianjin Medical UniversityTianjinChina Institute for Translational Neuroscience the Second Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Institute for Translational Brain Research Fudan UniversityShanghaiChina department of radiology the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsu ProvinceChina Innovative Institute of Chinese Medicine and Pharmacy Shandong University of Traditional Chinese MedicineJinanChina department of Anesthesiology Tianjin Medical University General HospitalTianjinChina department of Orthopaedics Tianjin Medical University General HospitalTianjinChina Tianjin Eye Hospital Tianjin Eye InstituteTianjin Key Lab of Ophthalmology and Visual ScienceTianjinChina Laboratory of Neurobiology School of Basic Medical SciencesTianjin Medical UniversityTianjinChina

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence *** pathogenesis of temporal lobe epilepsy is complex and is not fully *** calcium dynamics have been implicated in temporal lobe ***,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving *** this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy *** found that calcium signals varied according to the grade of temporal lobe epilepsy *** particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor *** inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠ*** addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly ***,it was possible to rescue the altered intracellular calcium *** simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were *** results indicate that the calcium dynamic between CA1 and M1 may reflect sp

关键词： Ca^(2+) calcium signals chemogenetic methods hippocampus primary motor cortex pyramidal neurons temporal lobe epilepsy

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Integrative analysis of tumor stemness and immune microenvironment deciphers novel molecular subtypes in hepatocellular carcinoma

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Genes & Diseases 2024年第5期11卷 81-84页

作者： Zhiyi Wang Shuang Chen Dongxiao Li Hui Xu Siyuan Weng Yuyuan Zhang Yuqing Ren Chunguang Guo Xiuling Li Zaoqu Liu Xinwei Han department of Interventional radiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China department of Gastroenterology Henan Provincial People’s HospitalZhengzhou University People’s HospitalZhengzhouHenan 450004China Center of Reproductive Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China department of Endovascular Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China State Key Laboratory of medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical SciencesDepartment of PathophysiologyPeking Union Medical CollegeBeijing 100730China

Hepatocellular carcinoma(HCC)is a highly heterogeneous tumor,with dynamic equilibrium and complex interplay between its intricate tumor nature and ambient tumor immune microenvironment(TIME).1 Elegant research has indicated that cancer stem cells,a small subset of neoplastic cells confined within dedicated niches,display stem cell-like properties and interact with cells in TIME,thereby imparting an indelible impact on stemness regulation,tumor heterogeneity,and cancer cell plasticity.2 Previous taxonomies solely from the perspective of stemness or TIME may introduce some degree of bias in the comprehension of HCC carcinogenesis,3,4 and thus it is of paramount importance to systematically consider tumor stemness and TIME as a whole to truly portray the biological landscape of HCC.

关键词： thereby landscape stem

Immunotherapeutic hydrogel for co-delivery of STAT3 siRNA liposomes and lidocaine hydrochloride for postoperative comprehensive management of NSCLC in a single application

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Asian Journal of Pharmaceutical sciences 2024年第3期19卷 115-130页

作者： Xianglei Fu Yanbin Shi Zili Gu Hengchang Zang Lian Li Qingjie Wang Yongjun Wang Xiaogang Zhao Hang Wu Shengnan Qiu Yankun Zhang Jiamin Zhou Xiangqin Chen Hua Shen Guimei Lin department of Pharmaceutics School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China School of Mechanical and Automotive Engineering Qilu University of Technology(Shandong Academy of Sciences)Jinan 250353China department of radiology Leiden University Medical CenterAlbinusdreef 22333 ZA LeidenNetherlands NMPA Key Laboratory for Technology Research and Evaluation of Drug Products School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Laboratory of Basic medical sciences Qilu HospitalShandong UniversityJinan 250063China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China department of Thoracic Surgery The Second Hospital of Shandong UniversityJinan 250033China

Despite standard treatment for non-small cell lung cancer(NSCLC)being surgical resection,cancer recurrence and complications,such as induction of malignant pleural effusion(MPE)and significant postoperative pain,usually result in treatment *** this study,an alginate-based hybrid hydrogel(SOG)is developed that can be injected into the resection surface of the lungs during ***,endoplasmic reticulum-modified liposomes(MSLs)pre-loaded with the signal transducer and activator of transcription 3(STAT3)small interfering RNA and lidocaine hydrochloride are encapsulated in *** applied,MSLs strongly downregulated STAT3 expression in the tumor microenvironment,resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like ***,the release of lidocaine hydrochloride(LID)was beneficial for pain relief and natural killer cell *** data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life,including reduced MPE volume and pain relief in orthotopic NSCLC mouse models,even with a single ***@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC,and may alter the treatment paradigms for other cancers.

关键词： Liposome Hydrogel Signal transducer and activator of transcription 3 Non-small cell lung cancer Macrophage

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Revolutionizing palliative care:Electrocautery-enhanced lumenapposing metal stents in endoscopic-ultrasound-guided biliary drainage for malignant obstructions

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2358-2361页

作者： Nirmal Kumar Reddy Onteddu Naga Sai Rasagna Mareddy Sai Swarupa R Vulasala Jayabharath Onteddu Mayur Virarkar department of Internal Medicine University of Florida College of MedicineJacksonvilleFL 32209United States department of Diagnostic radiology University of AlabamaBirminghamAL 35294United States department of Diagnostic radiology University of Florida College of MedicineJacksonvilleFL 32209United States department of Public Health sciences University of FloridaGainesvilleFL 32611United States

Patients with malignant biliary obstruction,following endoscopic retrograde cholangiopancreatography(ERCP)failure could be referred for endoscopicultrasound-guided biliary drainage through electrocautery-enhanced(ECE)lumen-apposing metal stent(LAMS)***,the efficacy and safety of ECE-LAMS in this scenario have remained debatable due to minimal scientific *** current confirmed 91.0%clinical success,96.7%technical success,7.3%reintervention rate,and 17.5%adverse events,following the treatment of malignant biliary obstruction with ECE-LAMS ***,ECE-LAMS proved to be a generalizable strategy for managing biliary obstruction for patients who were excluded from ERCP.

关键词： Endoscopic retrograde cholangiopancreatography Electrocautery-enhancedlumen-apposing metal stent Biliary drainage Biliary stent Endoscopic ultrasound