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Innovative treatments for congenital heart defects

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World Journal of Pediatrics 2023年第1期19卷 1-6页

作者： Antonio F.Corno Taylor S.Koerner Jorge D.Salazar McGovern medical school Children's Heart InstituteMemorial Hermann Children's HospitalUniversity of Texas Health Science Center in Houston6410 Fannin StreetMSB 6.274HoustonTX 77030USA

The past few decades have witnessed substantial advances in the treatment of complex congenital heart defects,with most significant advances in surgical treatment strategies and improved outcomes dependent upon well-educated and calculated risk-taking *** the present surgical era,doing nothing for complex congenital heart defects is unacceptable,and pioneering surgeons are willing to under-take and accept the substantial risks of innovative pediatric cardiac surgery[1].

关键词： congenital treatment defects

Ferroptosis as an important driver of lupus

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Protein & Cell 2022年第5期13卷 313-315页

作者： Chao Mao Guang Lei Li Zhuang Boyi Gan Department of Experimental Radiation Oncology The University of Texas MD Anderson Cancer CenterHoustonTXUSA The university of texas MD Anderson UTHealth Graduate school of Biomedical Sciences HoustonTXUSA

Systemic lupus erythematosus(SLE),the most common form of lupus,is a chronic autoimmune disorder characterized by a global loss of self-tolerance and hyper-activation of both innate and adaptive immune systems(Kaul et al.,2016).Neutrophils,the most abundant leukocytes in human blood,have a critical role in maintaining immune surveillance and tissue homeostasis,and its dysregulation is of high relevance to SLE(Ricklin et al.,2010).In patients with SLE,accelerated neutrophil death and the deficiency in clearing dying neutrophils cause nuclear and cytoplasmic antigen exposure,excessive production of type I interferon(IFN),and neutrophil extracellular trap(NET)release,subsequently inducing autoimmune responses(Garcia-Romo et al.,2011).Dysregulated neutrophil death is believed to be a major cause of SLE;however,the underlying mechanism of neutrophil death in SLE is not well-defined.

关键词： al. lupus autoimmune

Enhanced CD19 activity in B cells contributes to immunodeficiency in mice deficient in the ICF syndrome gene Zbtb24

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Cellular & Molecular Immunology 2023年第12期20卷 1487-1498页

作者： Zhengzhou Ying Swanand Hardikar Joshua B.Plummer Tewfik Hamidi Bin Liu Yueping Chen Jianjun Shen Yunxiang Mu Kevin M.McBride Taiping Chen Department of Epigenetics and Molecular Carcinogenesis The University of Texas MD Anderson Cancer CenterHoustonTX77030USA Program in Genetics and Epigenetics The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical SciencesHoustonTX77030USA

Immunodeficiency,centromeric instability,and facial anomalies(ICF)syndrome is a rare autosomal recessive disorder characterized by DNA hypomethylation and antibody *** is caused by mutations in DNMT3B,ZBTB24,CDCA7,or *** progress has been made in elucidating the roles of these genes in regulating DNA methylation,little is known about the pathogenesis of the life-threatening hypogammaglobulinemia ***,we show that mice deficient in Zbtb24 in the hematopoietic lineage recapitulate the major clinical features of patients with ICF ***,Vav-Cre-mediated ablation of Zbtb24 does not affect lymphocyte development but results in reduced plasma cells and low levels of IgM,IgG1,and ***24-deficient mice are hyper and hypo-responsive to T-dependent and T-independent type 2 antigens,respectively,and marginal zone B-cell activation is ***,Zbtb24-deficient B cells show severe loss of DNA methylation in the promoter region of Il5ra(interleukin-5 receptor subunit alpha),and Il5ra derepression leads to elevated CD19 *** disruption of Cd19 can revert the hypogammaglobulinemia phenotype of Zbtb24-deficient *** results suggest the potential role of enhanced CD19 activity in immunodeficiency in ICF syndrome.

关键词： ICF syndrome ZBTB24 CD19 IL-5Ra hypogammaglobulinemia

Violence study of healthcare workers and systems in the Caribbean:ViSHWaS-Caribbean study

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World Journal of Methodology 2024年第3期14卷 106-118页

作者： Reshon Hadmon Daniella Myriam Pierre Akshat Banga Jacques W Clerville Hans Mautong Precious Akinsanya Rajat Das Gupta Sama Soliman Tolupe M Hunjah Bamidele A Hunjah Hafeez Hamza Ruman Khurshid Qasba Faisal A Nawaz Salim Surani Rahul Kashyap Department of Medicine St.George University School of MedicineGrenada FZ818West Indies Department of Research Global Remote Research Scholar ProgramSt PaulMN 55101United States Department of Public Health Cuny Graduate School of Public Health and Health PolicyNew YorkNY 10027United States Department of Internal Medicine Sawai Man Singh Medical CollegeJaipur 302004India school of Public Health Georgia State UniversityAtlantaGA 30302United States Department of Sociology and Demography School of HealthUniversidad de Especialidades Espiritu SantoSamborondon 092301Ecuador Department of Medicine Holy Name Medical CenterTeaneckNJ 07666United States Department of Epidemiology and Biostatistics University of South CarolinaColumbiaSC 29208United States Department of Medicine Pavlov First State Medical University of St PetersburgSankt-Peterburg 197022Russia Department of Medicine University of SuffolkIpswich IP41QJUnited Kingdom Department of Medicine Unicaf University of ZambiaLusaka 20842Zambia Department of Pharmacy School of PharmacyGirne 99428Cyprus Department of Medicine Sher-i-KashmirInstitute of Medical ScienceSrinagar 190011India Department of Psychiatry Al Amal Psychiatric HospitalEmirates Health ServicesDubaiUnited Arab Emirates Department of Medicine and Pharmacology Texas A and M UniversityCollege StationTX 77843United States Anesthesiology and Critical Care Mayo ClinicRochesterMN 55905United States Department of Research Wellspan HealthYorkPA 17403United States

BACKGROUND Violence against healthcare workers(HCWs)in the Caribbean continues to prevail yet remains *** aim is to determine the cause,traits,and consequences of violence on HCWs in the *** To determine the cause,traits,and consequences of violence on HCWs in the *** This research adopted an online cross-sectional survey approach,spanning over eight weeks(between June 6th and August 9th,2022).The survey was generated using Research Electronic Data Capture forms and followed a snowballing strategy to contact individuals using emails,social media,text messages,*** regression analysis was performed to evaluate the variables that influence violence,including gender,age,years of experience,institution type,and night shift *** The survey was completed by 225 *** comprised 61%.Over 51%of respondents belonged to the 21 to 35 age ***(n=61),Haiti(n=50),and Grenada(n=31)had the most *** HCWs(49%)worked for government academic institutions,followed by community hospitals(23%).medical students(32%),followed by attending physicians(22%),and others(16%)comprised the most common cadre of *** 39%of the participants reported experiencing violence themselves,and 18%reported violence against colleague(s).Verbal violence(48%),emotional abuse(24%),and physical misconduct(14%)were the most common types of *** 63%of respondents identified patients or their relatives as the most frequent *** logistic regression analyses demonstrated that female gender(OR=2.08;95%CI:1.16-3.76,P=0.014)and higher frequency of night shifts(OR=2.22;95%CI:1.08-4.58,P=0.030)were associated with significantly higher odds of experiencing *** than 50%of HCWs felt less motivated and had decreased job satisfaction post-violent *** A large proportion of HCWS in the Caribbean are exposed to violence,yet the phenomenon remains *** a result,HCWs’job s

关键词： ViSHWaS Healthcare workers Violence Survey Workplace violence Caribbean Cross-sectional study

DNA Damage Response Inhibitor and Anti-PD-L1 Therapy for Prostate Cancer: Development of Predictive Biomarkers

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Engineering 2022年第5期8卷 12-15页

作者： Chuandong Geng Timothy C.Thompson Department of Genitourinary medical Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA

*** Although androgen receptor biosynthesis and signaling inhibi-tors have significantly improved outcomes in patients with castra-tion-resistant prostate cancer(CRPC),there is still a dearth of effective treatment op... 详细信息

关键词： Cancer Therapy patients

Expression and functions of transient receptor potential channels in liver diseases

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Acta Pharmaceutica Sinica B 2023年第2期13卷 445-459页

作者： Wenhui Wang Pengyu Liu Yalin Zhang Li Yan Michael X.Zhu Jin Wang Ye Yu Department of Pharmacology School of PharmacyChina Pharmaceutical UniversityNanjing 210009China Department of medical Genetics and Developmental Biology School of Medicinethe Key Laboratory of Developmental Genes and Human DiseasesMinistry of EducationSoutheast UniversityNanjing 210009China school of Basic Medicine and Clinical Pharmacy and State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Department of Integrative Biology and Pharmacology McGovern Medical Schoolthe University of Texas Health Science Center at HoustonHoustonTX 77030USA

Liver diseases constitute a major healthcare burden globally,including acute hepatic injury resulted from acetaminophen overdose,ischemia-reperfusion or hepatotropic viral infection and chronic hepatitis,alcoholic liver disease(ALD),non-alcoholic fatty liver disease(NAFLD)and hepatocellular carcinoma(HCC).Attainable treatment strategies for most liver diseases remain inadequate,highlighting the importance of substantial *** transient receptor potential(TRP)channels represent a versatile signalling mechanism regulating fundamental physiological processes in the *** is not surprising that liver diseases become a newly explored field to enrich our knowledge of TRP ***,we discuss recent findings revealing TRP functions across the fundamental pathological course from early hepatocellular injury caused by various insults,to inflammation,subsequent fibrosis and *** also explore expression levels of TRPs in liver tissues of ALD,NAFLD and HCC patients from Gene Expression Omnibus(GEO)or The Cancer Genome Atlas(TCGA)database and survival analysis estimated by Kaplan-Meier *** last,we address the therapeutical potential and challenges by pharmacologically targeting TRPs to treat liver *** aim is to provide a better understanding of the implications of TRP channels in liver diseases,contributing to the discovery of novel therapeutic targets and efficient drugs.

关键词： TRP Liver disease Liver injury ALD NAFLD Fibrosis Inflammation HCC

deCS:A Tool for Systematic Cell Type Annotations of Single-cell RNA Sequencing Data among Human Tissues

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Genomics, Proteomics & Bioinformatics 2023年第2期21卷 370-384页

作者： Guangsheng Pei Fangfang Yan Lukas M.Simon Yulin Dai Peilin Jia Zhongming Zhao Center for Precision Health School of Biomedical InformaticsThe University of Texas Health Science Center at HoustonHoustonTX 77030USA Therapeutic Innovation Center Baylor College of MedicineHoustonTX 77030USA Human Genetics Center School of Public HealthThe University of Texas Health Science Center at HoustonHoustonTX 77030USA MD Anderson Cancer Center UTHealth Graduate school of Biomedical Sciences HoustonTX 77030USA Department of Biomedical Informatics Vanderbilt University Medical CenterNashvilleTN 37203USA CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China

Single-cell RNA sequencing(scRNA-seq)is revolutionizing the study of complex and dynamic cellular ***,cell type annotation remains a main challenge as it largely relies on a priori knowledge and manual curation,which is cumbersome and *** increasing number of scRNA-seq datasets,as well as numerous published genetic studies,has motivated us to build a comprehensive human cell type reference ***,we present decoding Cell type Specificity(deCS),an automatic cell type annotation method augmented by a comprehensive collection of human cell type expression profiles and marker *** used deCS to annotate scRNAseq data from various tissue types and systematically evaluated the annotation accuracy under different conditions,including reference panels,sequencing depth,and feature selection *** results demonstrate that expanding the references is critical for improving annotation *** to many existing state-of-the-art annotation tools,deCS significantly reduced computation time and increased *** can be integrated into the standard scRNA-seq analytical pipeline to enhance cell type ***,we demonstrated the broad utility of deCS to identify trait-cell type associations in 51 human complex traits,providing deep insights into the cellular mechanisms underlying disease pathogenesis.

关键词： Cell type-specific enrichment analysis scRNA-seq Cell type annotation Trait-cell type association Cell typemarkergene

Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2487-2503页

作者： Carlos A Castaneda Miluska Castillo Luis A Bernabe Joselyn Sanchez Matteo Fassan Katherine Tello Ignacio Ivan Wistuba Ivan Chavez Passiuri Eloy Ruiz Juvenal Sanchez Fernando Barreda Daniel Valdivia Yaqueline Bazan Milagros Abad-Licham Claudio Mengoa Hugo Fuentes Paola Montenegro Ebert Poquioma Raul Alatrista Claudio J Flores Luis Taxa Faculty of Health Sciences Universidad Cientifica del SurLima 15038Peru GECO PERU Grupo de Estudios Clinicos Oncologicos del PeruLima 15038Peru Department of Research Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Faculty of Human Medicine Universidad Ricardo PalmaLima 15039Peru Department of Medicine Surgical Pathology&Cytopathology UnitUniversity of PaduaPadua 35121Italy Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer CenterHoustonTX 77030United States Department of Abdominal Surgery Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of medical Specialties Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Regional de Enfermedades Neoplasicas del NorteTrujillo 13001Peru Faculty of Human Medicine Universidad Privada Antenor OrregoTrujillo 13008Peru Department of Surgery Instituto Regional de Enfermedades Neoplasicas del SurArequipa 04002Peru Department of medical Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Epidemiology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Unidad de Investigación Básica y Traslacional Oncosalud-AUNALima 15038Peru Faculty of Medicine Universidad San Martin de PorresLima 15008Peru

BACKGROUND The influence of Helicobacter-pylori(***)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively *** of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive *** To determine the rates of deficient mismatch-repair(dMMR),HER2-status and *** infection and their association with TIL levels in *** Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)*** density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).*** infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of *** dMMR was found in 34.4%,HER2+in 5%and ***-positive in 55.7%of *** IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)***2-was associated with high IT-CD8(P=0.009).*** was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and *** CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

关键词： Lymphocytes Macrophages Gastric cancer Helicobacter pylori HER2 Mismatch repair

Harnessing the synergy of perfusable muscle flap matrix and adipose-derived stem cells for prevascularization and macrophage polarization to reconstruct volumetric muscle loss

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Bioactive Materials 2023年第4期22卷 588-614页

作者： Qixu Zhang Yulun Chiu Youbai Chen Yewen Wu Lina W.Dunne Rene D.Largo Edward I.Chang David M.Adelman Mark V.Schaverien Charles E.Butler Department of Plastic Surgery The University of Texas MD Anderson Cancer CenterHoustonTX77030USA Department of Melanoma medical Oncology The University of Texas MD Anderson Cancer CenterHoustonTX77030USA Department of Plastic Surgery Chinese PLA General HospitalBeijing100853China

Muscle flaps must have a strong vascular network to support a large tissue volume and ensure successful *** developed porcine stomach musculofascial flap matrix(PDSF)comprising extracellular matrix(ECM)and intact *** had a dominant vascular pedicle,microcirculatory vessels,a nerve network,well-retained 3-dimensional(3D)nanofibrous ECM structures,and no allo-or ***-depth proteomic analysis demonstrated that PDSF was composed of core matrisome proteins(e.g.,collagens,glycoproteins,proteoglycans,and ECM regulators)that,as shown by Gene Ontology term enrichment analysis,are functionally related to musculofascial biological ***,PDSF􀀀human adipose-derived stem cell(hASC)synergy not only induced monocytes towards IL-10􀀀producing M2 macrophage polarization through the enhancement of hASCs’paracrine effect but also promoted the proliferation and interconnection of both human skeletal muscle myoblasts(HSMMs)and human umbilical vein endothelial cells(HUVECs)in static triculture ***,PDSF was successfully prevascularized through a dynamic perfusion coculture of hASCs and HUVECs,which integrated with PDSF and induced the maturation of vascular networks in *** a xenotransplantation model,PDSF demonstrated myoconductive and immunomodulatory properties associated with the predominance of M2 macrophages and regulatory T *** a volumetric muscle loss(VML)model,prevascularized PDSF augmented neovascularization and constructive remodeling,which was characterized by the predominant infiltration of M2 macrophages and significant musculofascial tissue *** results indicate that hASCs’integration with PDSF enhances the cells’dual function in immunomodulation and *** in part to this PDSF-hASC synergy,our platform shows promise for vascularized muscle flap engineering for VML reconstruction.

关键词： Muscle flap fabrication Extracellular matrix Decellularization Vascularization Macrophage polarization Volumetric muscle loss