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Magnetic resonance-guided focused ultrasound for essential tremor:a prospective,single center,single-arm study

Neural Regeneration Research 2024年第9期19卷 2075-2080页

作者： Rui Zong Xuemei Li Chunyu Yin Jianfeng He Dekang Zhang Xiangbing Bian Lichao Huang Jiayou Zhou Zhipei Ling Lin Ma Xin Lou Longsheng Pan Xinguang Yu Seniro department of Neurosurgery The First Medical Center of the PLA General HospitalBeijingChina clinics of Cadre Department of OutpatientThe First Medical Center of the PLA General HospitalBeijingChina department of Radiology The First Medical Center of the PLA General HospitalBeijingChina

The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential *** 2018,the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First medical Center of the PLA General *** prospective,single center,open-label,single-arm study was part of a worldwide prospective multicenter clinical trial(*** Identifier:NCT03253991)conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local *** 2019 to 2020,10 patients with medication refractory essential tremor were recruited into this open-label,single arm *** treatment efficacy was determined using the Clinical Rating Scale for *** was evaluated according to the incidence and severity of adverse *** of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate *** the baseline assessment,the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3±3.6,and this improved after treatment to 23.1±6.4 at a 12-month follow-up assessment.A total of 50 adverse events were recorded,and 2 were defined as *** most common intraoperative adverse events were nausea and *** most frequent postoperative adverse events were paresthesia and equilibrium *** of the adverse events were mild and usually disappeared within a few *** findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective,with a good safety profile,for patients in Chinese mainland.

关键词： efficacy essential tremor magnetic resonance-guided focused ultrasound(MRgFUS) movement disorder safety stereotactic therapy thalamotomy ventral intermediate nucleus

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New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： Xiao-Peng Duan Bao-Dong Qin Xiao-Dong Jiao Ke Liu Zhan Wang Yuan-Sheng Zang department of medical Oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each *** to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol *** recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous *** the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains *** majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial ***,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision ***,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive

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Microsurgical management of radicular cyst using guided tissue regeneration technique:A case report

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World Journal of Clinical Cases 2024年第7期12卷 1346-1355页

作者： Juan Carlos Gómez Mireles Eugenia Karina Martínez Carrillo Katia Alcalá Barbosa Evangelina Gutiérrez Cortés Javier González Ramos Luis Antonio González Gómez Rubén Alberto Bayardo González Sarah Monserrat Lomelí Martínez Periodontics Specialty Department of Integral Dentistry ClinicsCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340Mexico Endodontics Specialty Department of Integral Dentistry ClinicsCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340Mexico Endodontics Specialty Department of ClinicsCentro Universitario de Los AltosUniversidad de GuadalajaraTepatitlán de Morelos 47620Mexico Specialty in Oral Pathology Surgical-Stomatological DepartmentAutonomous University of GuadalajaraZapopan 45129Mexico Independent Researcher Guadalajara 44340Mexico department of Integral Dentistry clinics Centro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340Mexico department of medical and Life Sciences Centro Universitario de la CiénegaUniversidad de GuadalajaraOcotlán 47810Mexico Master of Public Health Department of Well-being and Sustainable DevelopmentCentro Universitario del NorteUniversidad de GuadalajaraColotlán 46200Mexico

BACKGROUND Radicular cyst is a lesion of odontogenic origin that arises from epithelial remains due to periapical periodontitis caused by inflammatory reactions generated at the apex of affected teeth with infected or necrotic *** therapeutic mana gement of radicular cysts is *** is only one case report of enucleation of a radicular cyst managed with microsurgery and apicoectomy,but without the use of the guided tissue regeneration(GTR)technique in the same surgical *** present clinical case describes the management of a radicular cyst with microsurgical approach,performance of an apicoectomy of the tooth associated with the entity,application of GTR technique,use of a resorbable membrane of type I bovine collagen,and bovine *** SUMMARY A 68-year-old patient presented with a radicular cyst from an upper lateral *** microsurgical management used was aimed at enucleating the chemical membrane,performing apicoectomy of the tooth along with careful and precise retrograde filling,and implementing GTR technique using a resorbable collagen membrane and bovine *** diagnosis of radicular cyst was confirmed using histopathological *** patient underwent follow-up evaluations at 10 and 30 d *** 4 months postoperative evaluation,she remained asymptomatic,and radiographs showed significant periapical healing with adequate bone *** These results suggest that microsurgical management using the GTR technique with collagen membrane and xenograft,contributes to bone regeneration.

关键词： Odontogenic cysts Apical periodontal cyst Dental root end cyst Case report

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Progress in the generation of spinal cord organoids over the past decade and future perspectives

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Neural Regeneration Research 2024年第5期19卷 1013-1019页

作者： Gang Zhou Siyuan Pang Yongning Li Jun Gao department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina department of International medical Service Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in *** emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past *** literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal ***,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional *** qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue *** utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord ***,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational *** of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

关键词： development organoid-on-a-chip pluripotent stem cells progress spinal cord diseases spinal cord organoids vascularization

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Leveraging diverse cell-death patterns to predict the clinical outcome of immune checkpoint therapy in lung adenocarcinoma:Based on muti-omics analysis and vitro assay

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Oncology Research 2024年第2期32卷 393-407页

作者： HONGYUAN LIANG YANQIU LI YONGGANG QU LINGYUN ZHANG department of Radiology Shengjing Hospital of China Medical UniversityShenyangChina department of Nephrology The First Affiliated Hospital of China Medical UniversityShenyangChina department of Clinical Medicine China Medical UniversityShenyangChina department of medical Oncology The First Hospital of China Medical UniversityShenyangChina

Advanced LUAD shows limited response to treatment including immune *** the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response *** GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R *** constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression *** calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier *** also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model *** addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment *** also used the TIDE algorithm to predict immunotherapy responses in the CDI ***,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture *** study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with *** KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological *** study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk *** comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS *** addition,the study used unsupervised cluster analysis to d

关键词： Lung adenocarcinoma Programmed cell death Iron-death Drug sensitivity Cancer therapy

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Baicalein suppresses Coxsackievirus B3 replication by inhibiting caspase-1 and viral protease 2A

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Virologica Sinica 2024年第4期39卷 685-693页

作者： Yanyan Dong Enze Shao Siwei Li Ruiqi Wang Dan Wang Lixin Wang Hong Yang Yingxia He Tian Luan Yang Chen Yao Wang Lexun Lin Yan Wang Zhaohua Zhong Wenran Zhao department of Cell Biology Harbin Medical UniversityHarbin 150081China department of Microbiology Harbin Medical UniversityHarbin 150081China

Myocarditis is an inflammatory disease of the cardiac muscle and one of the primary causes of dilated *** B coxsackievirus(CVB)is one of the leading causative pathogens of viral myocarditis,which primarily affects children and young *** to the lack of vaccines,the development of antiviral medicines is crucial to controlling CVB infection and the progression of *** this study,we investigated the antiviral effect of baicalein,a flavonoid extracted from Scutellaria *** results demonstrated that baicalein treatment significantly reduced cytopathic effect and increased cell viability in CVB3-infected *** addition,significant reductions in viral protein 3D,viral RNA,and viral particles were observed in CVB3-infected cells treated with *** found that baicalein exerted its inhibitory effect in the early stages of CVB3 *** also suppressed viral replication in the myocardium and effectively alleviated myocarditis induced by CVB3 *** study revealed that baicalein exerts its antiviral effect by inhibiting the activity of caspase-1 and viral protease *** together,our findings demonstrate that baicalein has antiviral activity against CVB3 infection and may serve as a potential therapeutic option for the myocarditis caused by enterovirus infection.

关键词： Baicalein Coxsackievirus B(CVB) Myocarditis 2A protease Caspase-1

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Effect of cytochrome P4502C19(CYP2C19)gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI

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Journal of Geriatric Cardiology 2024年第1期21卷 90-103页

作者： Cheng-Yan HU Yan-Ling WANG Zhen-Xing FAN Xi-Peng SUN Shuai WANG Zhi LIU department of Geriatrics Fu Xing HospitalCapital Medical UniversityBeijingChina department of Cardiology Xuanwu Hospital Capital Medical UniversityBeijingChina Emergency department of Xuanwu Hospital Capital Medical UniversityBeijingChina

Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease(CHD)undergoing percutaneous coronary intervention(PCI).Methods In total,675 patients were *** on the platelet inhibition rate,patients were categorized into two groups:clopidogrel low responsiveness(CLR)and normal clopidogrel responsiveness(NCR).The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up *** were classified into three groups(normal metabolizer,intermediate metabolizer,and poor metabolizer)based on the CYP2C19 *** aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel *** cumulative rates of 12-month all-cause deaths,major adverse cardiovascular events(MACCEs),and bleeding events were *** CLR was observed in 44.4%of the overall *** differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes(P0.05).Conclusions Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene ***2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI,which is better than either test alone.

关键词： CYP2C19 drugs PCI

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Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways

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Military medical Research 2024年第4期11卷 500-520页

作者： Kun Zhang Meng-Xia Zhang Xiao-Xiang Meng Jing Zhu Jia-Jun Wang Yi-Fan He Ye-Hua Li Si-Cong Zhao Zhe-Min Shi Li-Na Zheng Tao Han Wei Hong department of Histology and Embryology School of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China department of Hepatology and Gastroenterology Tianjin Union Medical CenterTianjin Medical UniversityTianjin Union Medical Center Affiliated to Nankai UniversityTianjin 300000China

Background:G-protein coupled receptors(GPCRs)are recognized as attractive targets for drug ***,it remains poorly understood how GPCRs,except for a few chemokine receptors,regulate the progression of liver ***,we aimed to reveal the role of GPR65,a proton-sensing receptor,in liver fibrosis and to elucidate the underlying ***:The expression level of GPR65 was evaluated in both human and mouse fibrotic ***,Gpr65-deficient mice were treated with either bile duct ligation(BDL)for 21 d or carbon tetrachloride(CCl4)for 8 weeks to investigate the role of GPR65 in liver fibrosis.A combination of experimental approaches,including Western blotting,quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR),and enzyme-linked immunosorbent assay(ELISA),confocal microscopy and rescue studies,were used to explore the underlying mechanisms of GPR65’s action in liver ***,the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was ***:We found that hepatic macrophage(HM)-enriched GPR65 was upregulated in both human and mouse fibrotic ***,knockout of Gpr65 significantly alleviated BDL-and CCl4-induced liver inflammation,injury and fibrosis in vivo,and mouse bone marrow transplantation(BMT)experiments further demonstrated that the protective effect of Gpr65knockout is primarily mediated by bone marrow-derived macrophages(BMMs).Additionally,in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited,while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and transforming growth factor-β(TGF-β),all of which subsequently promoted the activation of hepatic stellate cells(HSCs)and the damage of hepatocytes(HCs).Mechanistically,GPR65 overexpression,the acidic pH and GPR65 exogenous agonist induced up-regulation of

关键词： GPR65 Hepatic fibrosis Hepatic macrophages Inflammation c-Jun N-terminal kinase Nuclear factorκB

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Single-cell RNA sequencing to understand host-virus interactions

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Virologica Sinica 2024年第1期39卷 1-8页

作者： Jia-Tong Chang Li-Bo Liu Pei-Gang Wang Jing An department of Microbiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Single-cell RNA sequencing(scRNA-seq)has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell *** review summarizes the existing scRNA-seq technologies together with their strengths and *** applications of scRNA-seq in various virological studies are discussed in depth,which broaden the understanding of the immune atlas,host-virus interactions,and immune ***-seq can be widely used for virology in the near future to better understand the pathogenic mechanisms and discover more effective therapeutic strategies.

关键词： Single-cell RNA sequencing(scRNA-seq) Host-virus interaction COVID-19 Flavivirus

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CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands department of medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands department of Otorhinolaryngology Leiden University medical Center LeidenThe Netherlands department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

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