Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were establi...Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.展开更多
Background The pathological diagnosis is of critical importance to the subsequent treatment for the pathients with superior vena cava syndrome （SVCS）.The aim of this study is to report our experience in the diagnosi...Background The pathological diagnosis is of critical importance to the subsequent treatment for the pathients with superior vena cava syndrome （SVCS）.The aim of this study is to report our experience in the diagnosis of SVCS by endobronchial ultrasound guided transbronchial needle aspiration （EBUS-TBNA）.Methods The data of 520 patients who underwent EBUS-TBNA from September 2009 to May 2012 at our institution were reviewed.Of these,there were 14 males and 6 females （mean age of 59.1 years） with SVCS who received EBUS-TBNA that were included in the analysis.Results The mean short axis diameter of the paratracheal lesions was （3.32±1.79） cm （range,1.69 to 9.50 cm） and 6 cases also had subcarinal lymph node enlargement with a mean short axis diameter of （2.14±0.49） cm （range,1.73 to 3.01 cm）.An average of 4.3 punctures was performed per lesion.Malignancy was confirmed in 16 cases （10 small cell carcinomas,4 adenocarcinomas,1 squamous cell carcinoma and 1 Hodgkin lymphoma）.In two patients,pathological examination of tissue revealed no evidence of malignancy and for 13 to 24 months of follow-up.One patient from whom adequate tissue was not obtained refused further surgical biopsy since he had undergone endovascular stenting of the SVC.One patient in whom a diagnosis was not obtained by EBUS-TBNA underwent thoracoscopic biopsy and the final diagnosis was B cell non-Hodgkin＇s lymphoma.The diagnosis accuracy of EBUS-TBNA in SVCS was 18/20 patients.Conclusion EBUS-TBNA is a highly effective and safe procedure for the diagnosis of SVCS.展开更多
基金supported by the National Natural Science Foundation of China(81971875,82300661)Natural Science Foundation of Anhui province(2308085QH246)+3 种基金Natural Science Foundation of the Anhui Higher Education Institutions(KJ2021A0205)Basic and Clinical Cooperative Research Program of Anhui Medical University(2019xkjT002,2019xkjT022,2022xkjT013)Talent Training Program,School of Basic Medical Sciences,Anhui Medical University(2022YPJH102)National College Students Innovation and Entrepreneurship Training Program of China(202210366024)。
文摘Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.
文摘Background The pathological diagnosis is of critical importance to the subsequent treatment for the pathients with superior vena cava syndrome （SVCS）.The aim of this study is to report our experience in the diagnosis of SVCS by endobronchial ultrasound guided transbronchial needle aspiration （EBUS-TBNA）.Methods The data of 520 patients who underwent EBUS-TBNA from September 2009 to May 2012 at our institution were reviewed.Of these,there were 14 males and 6 females （mean age of 59.1 years） with SVCS who received EBUS-TBNA that were included in the analysis.Results The mean short axis diameter of the paratracheal lesions was （3.32±1.79） cm （range,1.69 to 9.50 cm） and 6 cases also had subcarinal lymph node enlargement with a mean short axis diameter of （2.14±0.49） cm （range,1.73 to 3.01 cm）.An average of 4.3 punctures was performed per lesion.Malignancy was confirmed in 16 cases （10 small cell carcinomas,4 adenocarcinomas,1 squamous cell carcinoma and 1 Hodgkin lymphoma）.In two patients,pathological examination of tissue revealed no evidence of malignancy and for 13 to 24 months of follow-up.One patient from whom adequate tissue was not obtained refused further surgical biopsy since he had undergone endovascular stenting of the SVC.One patient in whom a diagnosis was not obtained by EBUS-TBNA underwent thoracoscopic biopsy and the final diagnosis was B cell non-Hodgkin＇s lymphoma.The diagnosis accuracy of EBUS-TBNA in SVCS was 18/20 patients.Conclusion EBUS-TBNA is a highly effective and safe procedure for the diagnosis of SVCS.
