Regulatory T cells(Tregs) play a pivotal role in the pathological development of hypertension.Helios,a transcription factor from the Ikaros family,was recently reported to be a bona fide marker for natural Tregs or ...Regulatory T cells(Tregs) play a pivotal role in the pathological development of hypertension.Helios,a transcription factor from the Ikaros family,was recently reported to be a bona fide marker for natural Tregs or activated Tregs with suppression function,however,little has been known about its role in hypertension.This study was aimed to find whether Helios+ Tregs really play a vital role in hypertension.A total of 60 hypertension patients,and 46 normotension subjects were enrolled in this study.Frequencies of different Tregs subsets in peripheral blood were measured by flow cytometry.Plasma cytokine level was determined by ELISA.The m RNA expression of Foxp3 and Helios in purified CD4+ T cells was detected by RT-PCR.Proportion of CD4+Foxp3+Helios+ Tregs was decreased significantly in patients with hypertension(62.52%±1.18% vs.71.89%±1.03%,P〈0.01),and it was correlated with plasma level of IL-10 positively(r=0.505,P〈0.05) and plasma level of IFN-gamma negatively(r=–0.551,P〈0.05).The m RNA expression of Foxp3(7.23±1.00 vs.10.58±0.54,P〈0.05) and Helios(8.47±0.95 vs.15.52±2.0,P〈0.05) was decreased in CD4+ T cells from patients with hypertension.Helios+ Tregs were decreased in patients with hypertension and may play a protective role in hypertension progression.展开更多
Background:The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer.The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world settin...Background:The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer.The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting.Methods:The HELIOS registry is a prospective,multicenter,cohort study conducted at 38 centers across China between November 2018 and December 2019.A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria.The primary endpoint was target lesion failure(TLF),defined as a composite of cardiac death,non-fatal target vessel myocardial infarction(MI),and clinically indicated target lesion revascularization(TLR)at 1-year follow-up.Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves.Results:A total of 2998(98.0%)patients completed the 1-year follow-up.The 1-year incidence of TLF was 3.10%(94/2998,95%closed interval:2.54-3.78%).The rates of cardiac death,non-fatal target vessel MI and clinically indicated TLR were 2.33%(70/2998),0.20%(6/2998),and 0.70%(21/2998),respectively.The rate of stent thrombosis was 0.33%(10/2998).Age≥60 years,diabetes mellitus,family history of coronary artery disease,acute myocardial infarction at admission,and device success were independent predictors of TLF at 1 year.Conclusion:The 1-year incidence rates of TLF and stent thrombosis were 3.10%and 0.33%,respectively,in patients treated with HELIOS stents.Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent.Clinical trial registration:ClinicalTrials.gov,NCT03916432.展开更多
At present the study of the interplanetary shock wave concentrates mostly within 1 AU region from the sun, and for large heliocentrical distances (>2—3 AU)the study of shock wave propagation still remains in the e...At present the study of the interplanetary shock wave concentrates mostly within 1 AU region from the sun, and for large heliocentrical distances (>2—3 AU)the study of shock wave propagation still remains in the experimental stage. According to large amounts of space observations, the interplanetary space can be divided into three re-展开更多
Background:Malignant pleural effusion(MPE)is a complicated condition of patients with advanced tumors.Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand...Background:Malignant pleural effusion(MPE)is a complicated condition of patients with advanced tumors.Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression.Methods:The possible involvement of microRNAs(miRNAs)in malignant pleural fluid was investigated using small RNA sequencing.Regulatory T cell(Treg)markers(CD4,CD25,forkhead box P3),and Helios(also known as IKAROS Family Zinc Finger 2[IKZF2])were detected using flow cytometry.The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction.The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays.The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system.Correlation assays between miR-4772-3p and functional molecules of Tregs were performed.Results:Compared with non-malignant controls,patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells.The verified downregulation of miR-4772-3p was inversely related to the Helios*Tregs frequency and Helios expression in the MPE.Overexpression of miR-4772-3p could inhib让Helios expression in in vitro experiments.However,ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression.Additionally,miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA.Conclusion:Downregulation of miR-4772-3p,by targeting Helios,contributes to enhanced Tregs activities in the MPE microenvironment.展开更多
基金supported by the National Natural Science Foundation of China(No.81370324)
文摘Regulatory T cells(Tregs) play a pivotal role in the pathological development of hypertension.Helios,a transcription factor from the Ikaros family,was recently reported to be a bona fide marker for natural Tregs or activated Tregs with suppression function,however,little has been known about its role in hypertension.This study was aimed to find whether Helios+ Tregs really play a vital role in hypertension.A total of 60 hypertension patients,and 46 normotension subjects were enrolled in this study.Frequencies of different Tregs subsets in peripheral blood were measured by flow cytometry.Plasma cytokine level was determined by ELISA.The m RNA expression of Foxp3 and Helios in purified CD4+ T cells was detected by RT-PCR.Proportion of CD4+Foxp3+Helios+ Tregs was decreased significantly in patients with hypertension(62.52%±1.18% vs.71.89%±1.03%,P〈0.01),and it was correlated with plasma level of IL-10 positively(r=0.505,P〈0.05) and plasma level of IFN-gamma negatively(r=–0.551,P〈0.05).The m RNA expression of Foxp3(7.23±1.00 vs.10.58±0.54,P〈0.05) and Helios(8.47±0.95 vs.15.52±2.0,P〈0.05) was decreased in CD4+ T cells from patients with hypertension.Helios+ Tregs were decreased in patients with hypertension and may play a protective role in hypertension progression.
文摘Background:The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer.The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting.Methods:The HELIOS registry is a prospective,multicenter,cohort study conducted at 38 centers across China between November 2018 and December 2019.A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria.The primary endpoint was target lesion failure(TLF),defined as a composite of cardiac death,non-fatal target vessel myocardial infarction(MI),and clinically indicated target lesion revascularization(TLR)at 1-year follow-up.Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves.Results:A total of 2998(98.0%)patients completed the 1-year follow-up.The 1-year incidence of TLF was 3.10%(94/2998,95%closed interval:2.54-3.78%).The rates of cardiac death,non-fatal target vessel MI and clinically indicated TLR were 2.33%(70/2998),0.20%(6/2998),and 0.70%(21/2998),respectively.The rate of stent thrombosis was 0.33%(10/2998).Age≥60 years,diabetes mellitus,family history of coronary artery disease,acute myocardial infarction at admission,and device success were independent predictors of TLF at 1 year.Conclusion:The 1-year incidence rates of TLF and stent thrombosis were 3.10%and 0.33%,respectively,in patients treated with HELIOS stents.Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent.Clinical trial registration:ClinicalTrials.gov,NCT03916432.
文摘At present the study of the interplanetary shock wave concentrates mostly within 1 AU region from the sun, and for large heliocentrical distances (>2—3 AU)the study of shock wave propagation still remains in the experimental stage. According to large amounts of space observations, the interplanetary space can be divided into three re-
基金grants from the Precision Medicine Research of the National Key Research and Development Plan of China(No.2016YFC0905800)National Natural Science Foundation of China(Nos.81970031,81700028)+4 种基金National Science Foundation of Jiangsu Province(Nos.BK20171501,BK20171080,BK20181497)Jiangsu Province's Young Medical Talent Program,China(No.QNRC2016600)Jiangsu Provincial Health and Family Planning Commission Foundation(No.Q2017001)Taizhou Municipal Science and Technology Bureau(No.TS201726)Jiangsu Provincial Medical Youth Talent(No.QNRC2016508).
文摘Background:Malignant pleural effusion(MPE)is a complicated condition of patients with advanced tumors.Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression.Methods:The possible involvement of microRNAs(miRNAs)in malignant pleural fluid was investigated using small RNA sequencing.Regulatory T cell(Treg)markers(CD4,CD25,forkhead box P3),and Helios(also known as IKAROS Family Zinc Finger 2[IKZF2])were detected using flow cytometry.The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction.The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays.The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system.Correlation assays between miR-4772-3p and functional molecules of Tregs were performed.Results:Compared with non-malignant controls,patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells.The verified downregulation of miR-4772-3p was inversely related to the Helios*Tregs frequency and Helios expression in the MPE.Overexpression of miR-4772-3p could inhib让Helios expression in in vitro experiments.However,ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression.Additionally,miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA.Conclusion:Downregulation of miR-4772-3p,by targeting Helios,contributes to enhanced Tregs activities in the MPE microenvironment.