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Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1236-1247页

作者： Kun-Peng Ma Jin-Xin Fu Feng Duan Mao-Qiang Wang Department of Interventional Radiology The Fifth Medical Center of Chinese People's Liberation Army General HospitalBeijing 100853China Chinese People's Liberation army Medical School Beijing 100853China

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to *** To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable *** This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April *** survival(OS)and progression-free survival(PFS)were *** objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid ***,the prognostic factors affecting the clinical outcome were *** One hundred and two patients were enrolled with a median follow-up duration of 12.63 *** median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,*** patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their *** This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable *** patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.

关键词： Transarterial chemoembolization Efficacy Lenvatinib Programmed cell death protein-1 inhibitors Unresectable hepatocellular carcinoma

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A Spleen Tyrosine Kinase’s Sky in Neuronal Degeneration

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Neuroscience Bulletin 2024年第2期40卷 273-276页

作者： Wan-Yun Zhang Sen Lin Department of Neurology Xinqiao HospitalThe Second Afliated HospitalArmy Medical UniversityChongqing 400042China Chongqing Institute for Brain and Intelligence Guangyang Bay LaboratoryChongqing 400064China

With the growing elderly population,neurodegenerative disorders like Alzheimer's disease(AD)are emerging as a significant public health *** is widely acknowledged in the scientific community that the accumulation of neurotoxic aggregates,such as amyloid beta(Aβ),within the central nervous system is a major factor in the development of these ***,human genome-wide association studies have identified mutations in microglial receptors that may be linked to a number of neurodegenerative diseases[1].

关键词： Aβ Spleen Alzheimer

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Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke

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Research 2024年第1期2023卷 369-387页

作者： Hongfei Ge Tengyuan Zhou Chao Zhang Yupeng Cun Weixiang Chen Yang Yang Qian Zhang Huanhuan Li Jun Zhong Xuyang Zhang Hua Feng Rong Hu Department of Neurosurgery and Key Laboratory of Neurotrauma Southwest HospitalThird Military Medical University(Army Medical University)400038 ChongqingChina Medical Research Center Southwest HospitalThird Military Medical University(Army Medical University)400038 ChongqingChina Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChildren’s Hospital of Chongqing Medical University400014 ChongqingChina

Cell replacement therapy using neural progenitor cells(NPCs)has been shown to be an effective treatment for ischemic ***,the therapeutic effect is unsatisfactory due to the imbalanced homeostasis of the local microenvironment after *** acidosis is a common imbalanced homeostasis in the penumbra and could activate acid-sensing ion channels 1a(ASIC1a),a subunit of proton-gated cation channels following ischemic ***,the role of ASIC1a in NPCs post-ischemia remains ***,our results indicated that ASIC1a was expressed in NPCs with channel functionality,which could be activated by extracellular *** evidence revealed that ASIC1a activation inhibited NPC migration and neurogenesis through RhoA signaling-mediated reorganization of filopodia formation,which could be primarily reversed by pharmacological or genetic disruption of *** vivo data showed that the knockout of the ASIC1a gene facilitated NPC migration and neurogenesis in the penumbra to improve behavioral recovery after stroke.

关键词： ASIC1a homeostasis inhibited

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Multifaceted roles and functions of SOX30 in human cancer

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Cancer Innovation 2024年第2期3卷 11-27页

作者： Na Sun Cheng Wang Pingping Gao Rui Wang Yi Zhang Xiaowei Qi Department of Breast and Thyroid Surgery The Southwest Hospital of Army Medical UniversityChongqingChina

SRY-box transcription factor 30(SOX30)participates in tumor cell apoptosis in lung *** occurrence of somatic SOX30 mutations,the expression signature of SOX30 in normal and cancer tissues,the correlation of SOX30 with immune cells and immune-related genes,and the clinical significance of SOX30 in various cancers have stimulated interest in SOX30 as a potential cancer ***30 influences drug sensitivity and tumor immunity in specific cancer *** this review,we have comprehensively summarized the latest research on the role of SOX30 in cancer by combining bioinformatics evidence and a literature *** summarize recent research on SOX30 in cancer regarding somatic mutations,trials,transcriptome analysis,clinical information,and SOX30-mediated regulation of malignant ***,we report on the diagnostic value of SOX30 mRNA expression levels across different cancer *** review on the role of SOX30 in cancer progression may provide insights into possible research directions for SOX30 in cancer and a theoretical basis for guiding future studies.

关键词： cancer progression prognosis SOX30

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The emerging tumor microbe microenvironment: From delineation to multidisciplinary approach-based interventions

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1560-1591页

作者： Yu Fu Jia Li Wenyun Cai Yulan Huang Xinlong Liu Zhongyi Ma Zhongjie Tang Xufei Bian Ji Zheng Jiayun Jiang Chong Li Medical Research Institute College of Pharmaceutical SciencesSouthwest UniversityChongqing 400715China Institute of Hepatobiliary Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Urology Urologic Surgery CenterXinqiao HospitalThird Military Medical University(Army Medical University)Chongqing 400037China

Intratumoral microbiota has become research hotspots,and emerges as a non-negligent new component of tumor microenvironments(TME),due to its powerful infuence on tumor initiation,metas-tasis,immunosurveillance and prognosis despite in *** accumulations of microbes,and their related components and metabolites within tumor tissues,endow TME with additional pluralistic features which are distinct from the conventional ***,it's definitely necessary to comprehen-sively delineate the sophisticated landscapes of tumor microbe microenvironment,as well as their func-tions and related underlying ***,in this review,we focused on the fields of tumor microbe microenvironment,including the heterogeneity of intratumor microbiota in different types of tu-mors,the controversial roles of intratumoral microbiota,the basic features of tumor microbe microenvi-ronment(i.e.,pathogen-associated molecular patterns(PAMPs),typical microbial metabolites,autophagy,infammation,multi-faceted immunomodulation and chemoresistance),as well as the multi-disciplinary approach-based intervention of tumor microbiome for cancer therapy by applying wild-type or engineered live microbes,microbiota metabolites,antibiotics,synthetic biology and rationally de-signed *** hope our work will provide valuable insight to deeply understand the interplay of cancer-immune-microbial,and facilitate the development of microbes-based tumor-specific treatments.

关键词： Tumor microbe microenvironment Microbiota metabolites Immunomodulation Chemoresistance Multidisciplinary approach Genetically engineered microbiota Autophagy Outer membrane vesicles

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Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing

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Current Medical Science 2024年第2期44卷 419-425页

作者： Jia-xun LI Ling-rui MENG Bao-ke HOU Xiao-lu HAO Da-jiang WANG Ling-hui QU Zhao-hui LI Lei ZHANG Xin JIN Department of Senior Ophthalmology the Third Medical Center of PLA General HospitalBeijing 100853China Department of Ophthalmology the 74th Army Group HospitalGuangzhou 510318China

Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on *** potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes Ca2+-activated Cl−channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and *** this study,the complete clinical characteristics of two Chinese ARB families were ***:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family ***:Two novel mutations,c.202T>C(chr11:61722628,p.Y68H)and c.867+97G>A,in the BEST1 gene were identified in the two Chinese ARB *** novel missense mutation BEST1 c.202T>C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of *** novel variant,BEST1 c.867+97G>A(chr11:61725867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional ***:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific *** novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.

关键词： autosomal recessive bestrophinopathy BEST1 gene third-generation sequencing mutation

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DAPK2 promotes autophagy to accelerate the progression of ossification of the posterior longitudinal ligament through the mTORC1 complex

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BIOCELL 2024年第9期48卷 1389-1400页

作者： LEI SHI JIANSHI YIN YU CHEN JIANGANG SHI JINHAO MIAO Department of Spine Surgery Shanghai Changzheng HospitalShanghai200003China Department of Orthopedics The 967th Hospital of Chinese People’s Liberation ArmyDalian116000China

Background:Ossification of the posterior longitudinal ligament(OPLL)is a prevalent condition in *** death-associated protein kinase 2(DAPK2)is known to play roles in cellular apoptosis and autophagy,its specific contributions to the advancement of OPLL are not well ***:Ligament fibroblasts were harvested from patients diagnosed with *** such as real-time reverse transcriptasepolymerase chain reaction(RT-qPCR)and Western blot analysis were employed to assess DAPK2 levels in both ligament tissues and cultured *** extent of osteogenic differentiation in these cells was evaluated using an alizarin red S(ARS)***,the expression of ossification markers and autophagy markers was *** autophagic activity was further analyzed through LC3 immunofluorescence and transmission electron microscopy(TEM).An in vivo heterotopic bone formation assay was conducted in mice to assess the role of DAPK2 in ***:Elevated DAPK2 expression was confirmed in both OPLL patient tissues and derived fibroblasts,in contrast to non-OPLL *** of DAPK2 significantly curtailed osteogenic differentiation and autophagy in these fibroblasts,evidenced by decreased levels of LC3,and Beclin1,and reduced autophagosome ***,DAPK2 was found to inhibit the mechanistic target of the rapamycin complex 1(mTORC1)complex’s *** vivo studies demonstrated that DAPK2 facilitates ossification,and this effect could be counteracted by the mTORC1 inhibitor ***:DAPK2 enhances autophagy and osteogenic processes in OPLL through modulation of the mTORC1 pathway.

关键词： Ossification of the posterior longitudinal ligament DAPK2 Autophagy mTORC1

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Chinese Expert Consensus on Microvascular Protection Strategy During Emergency Percutaneous Coronary Intervention Therapy in Patients With ST-elevation Myocardial Infarction

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Cardiology Discovery 2024年第1期4卷 5-14页

作者： Chinese Society of Cardiology,Chinese Medical Association Editorial Board of Chinese Journal of Cardiology Muwei Li Yabin Wang Yaling Han Yun Zhang Feng Cao 不详 Fuwai Central China Cardiovascular hospital Chinese People’s Liberation army General hospital General hospital of Northern Theater Command Qilu hospital of Shandong University

Microcirculatory dysfunction(CMD)typically occurs in patients with acute ST-segment elevation myocardial infarction during percutaneous coronary intervention,which is associated with more severe myocardial injury and a worse *** the advancement of intracoronary physiology and imaging technology,the prevention and therapeutic interventions of CMD have attracted more ***,relevant guidelines or consensus on CMD are lacking in *** current consensus summarizes the prevention and diagnostic strategies of emergency percutaneous coronary intervention-related CMD and gives suggestions to improve the prognosis of ST-segment elevation myocardial infarction patients based on evidence from recent clinical studies,guidelines,and consensus from international sources.

关键词： Myocardial infarction Microcirculation dysfunction Percutaneous coronary intervention

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IL13RA2 promotes progression of infantile haemangioma by activating glycolysis and the Wnt/β-catenin signaling pathway

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Oncology Research 2024年第9期32卷 1453-1465页

作者： ZIYONG LIU TAO MA JINFANG LI WEI REN ZHIXIN ZHANG Department of Cardiothoracic Surgery 970th Hospital of the People’s Liberation ArmyWeihai264209China Department of Cardiac Ultrasound Weihai Municipal HospitalWeihai264200China

Background:Interleukin 13 receptor subunit alpha 2(IL13RA2)plays an essential role in the progression of many ***,the role of IL13RA2 in infantile haemangioma(IH)is still *** and Methods:IL13RA2 expression in IH tissues was analyzed using western blot,qRT-PCR,and *** role of IL13RA2 in haemangioma-derived endothelial cells(HemECs)was determined following knockdown or overexpression of IL13RA2 using CCK-8,colony formation,apoptosis,wound healing,tubule formation,Transwell,and western ***:IL13RA2 expression was upregulated in IH ***13RA2 overexpression promoted proliferation,migration,and invasion of HemECs and induced glycolysis,which was confirmed with a glycolysis ***,IL13RA2 interacted withβ-catenin and activated the Wnt/β-catenin pathway in HemECs,which were involved in the above-mentioned effects of ***:These findings revealed that targeting IL13RA2 is a potential therapeutic approach for IH.

关键词： Infantile haemangioma IL13RA2 Glycolysis Wnt/β-catenin pathway

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Clinicopathological Features and Long-Term Prognostic Role of Human Epidermal Growth Factor Receptor-2 Low Expression in Chinese Patients with Early Breast Cancer:A Single-Institution Study

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Biomedical and Environmental Sciences 2024年第5期37卷 457-470页

作者： KONG Zi Qing LIU Li Qun HUANG De Qin WANG Yu Tong LI Jing Jie ZHANG Zheng WANG Xi Xi LIU Chuan Ling ZHANG Ya Di SHAO Jia Kang ZHU Yi Min CHEN Yi Meng LIU Mei ZHAO Wei Hong Medical School of Chinese PLA Beijing 100853China Department of Medical Oncology the First Medical CenterGeneral Hospital of the Chinese People’s Liberation ArmyBeijing 100853China Nankai University School of Medicine Tianjin 300071China Department of Medical Oncology the Fifth Medical CenterGeneral Hospital of the Chinese People’s Liberation ArmyBeijing 100039China Department of Medical Oncology Xi'an Jiaotong UniversityXi’an 710061ShaanxiChina Department of Pathology the Sixth Medical CenterGeneral Hospital of the Chinese People’s Liberation ArmyBeijing 100037China

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 *** Patients diagnosed with HER2-negative BC(N=999)at our institution between January2011 and December 2015 formed our study *** characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were ***-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low *** HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszelχ^(2)test,P<0.001,Pearson’s R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative *** were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%.Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

关键词： HER2 HER2-low Breast cancer Estrogen receptor Trastuzumab deruxtecan

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