The accurate assessment of cardiac motion is crucial for diagnosing and monitoring cardiovascular diseases.In this context,digital volume correlation(DVC)has emerged as a promising technique for tracking cardiac motio...The accurate assessment of cardiac motion is crucial for diagnosing and monitoring cardiovascular diseases.In this context,digital volume correlation(DVC)has emerged as a promising technique for tracking cardiac motion from cardiac computed tomography angiographic(CTA)images.This paper presents a comprehensive performance evaluation of the DVC method,specifically focusing on tracking the motion of the left atrium using cardiac CTA data.The study employed a comparative experimental approach while simultaneously optimizing the existing DVC algorithm.Multiple sets of controlled experiments were designed to conduct quantitative analyses on the parameters“radius”and“step”.The results revealed that the optimized DVC algorithm enhanced tracking accuracy within a reasonable computational time.These findings contributed to the understanding of the efficacy and limitations of the DVC algorithm in analyzing heart deformation.展开更多
Image-based computational models have been used for vulnerable plaque progression and rupture predictions,and good results have been reported.However,mechanisms and predictions for plaque erosion are underinvestigated...Image-based computational models have been used for vulnerable plaque progression and rupture predictions,and good results have been reported.However,mechanisms and predictions for plaque erosion are underinvestigated.Patient-specific fluid-structure interaction(FSI)models based on optical coherence tomography(OCT)follow-up data from patients with plaque erosion and who received conservative antithrombotic treatment(using medication,no stenting)to identify risk factors that could be used to predict the treatment outcome.OCT and angiography datawere obtained from10 patientswho received conservative antithrombotic treatment.Five participants had worse outcomes(WOG,stenosis severity≥70%at one-year follow-up),while the other five had better outcomes(BOG,stenosis severity<70%at one-year follow-up).Patient-specific 3D FSI models were constructed to obtain morphological and biomechanical risk factor values(a total of nine risk factors)for comparison and prediction.A logistic regressionmodel was used to identify optimal predictors with the best treatment outcome prediction accuracies.Our results indicated that the combination of wall shear stress(WSS),lipid percent,and thrombus burden was the best group predictor according to the mean area under the curve(AUC)of 0.96(90%confidence interval=(0.85,1.00)).WSS was the best single predictor withmean AUC=0.70(90%confidence interval=(0.20,1.00)).Thrombus burden was the only risk factor showing statistically significant group difference,suggesting its crucial role in the outcomes of conservative anti-thrombotic therapy.This pilot study indicated that integratingmorphological and biomechanical risk factors could improve treatment outcome prediction accuracy in patients with plaque erosion compared to predictions using single predictors.Large-scale patient studies are needed to further validate our findings.展开更多
Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the myocardium.While elevated testosterone levels have been implicated in the pathologi...Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the myocardium.While elevated testosterone levels have been implicated in the pathological process of ARVC,its exact contribution to cardiac fibrosis in ARVC remains unclear.In this study,we analyzed the potential contribution of gender-based differences on the distribution of the low-voltage area in an ARVC cohort undergoing an electrophysiological study,which was indicated by feature selection.Additionally,we established engineered cardiac spheroid models in vitro using patient-specific induced pluripotent stem cell(iPSC)-derived cardiomyocytes(iPSC-CMs)and iPSC-derived cardiac fibroblasts(icFBs).We elucidated the pathogenicity of abnormal splicing in the plakophilin-2(PKP2)gene caused by an intronic mutation.Additionally,pathogenic validation of the desmoglein-2(DSG2)point mutation further confirms the reliability of the models.Moreover,testosterone exacerbated the DNA damage in the mutated cardiomyocytes and further activated myofibroblasts in a chain reaction.In conclusion,we designed and constructed an in vitro three-dimensionally-engineered cardiac spheroid model of ARVC based on clinical findings and provided direct evidence of the fibrotic role of testosterone in ARVC.展开更多
The electrical storm (ES) is defined as a state of electrical instability with three or more sustained ventricular arrhythmias (VAs) occurring within twenty-four hours, which needs intravenous antiarrhythmic medic...The electrical storm (ES) is defined as a state of electrical instability with three or more sustained ventricular arrhythmias (VAs) occurring within twenty-four hours, which needs intravenous antiarrhythmic medications and frequent defibrillation. Recently, radiofrequency catheter ablation evolved as a sole therapy to terminate ES in patients with ICD, and the survival has been reported to be improved with successful ablation during follow-up. In this review, we briefly summarize substrate mapping and substrate ablation strategy in patients with ES, and discuss the reason of recurrence after ablation.展开更多
Recent studies have shown that premature ventricular contractions (PVCs) could enlarge the heart, but its risk factors are incompletely understood as a single 24-hour recording cannot reflect the true PVC burden due...Recent studies have shown that premature ventricular contractions (PVCs) could enlarge the heart, but its risk factors are incompletely understood as a single 24-hour recording cannot reflect the true PVC burden due to day-to-day variability. Our purpose was to investigate the effect of burden and origin sites on left ventricular (LV) function in patients with PVCs by 7-day Holter electrocardiography (ECG). From May 2012 to August 2013, 112 consecutive patients with PVCs were recruited from the authors' affiliated hospital. All patients received 2-dimensional transthoracic echocardiography, 12-lead routing ECG and 7-days Holter ECG. Serum N-terminal pro- brain natriuretic peptide (NT-proBNP) levels were measured. A total of 102 participants with PVCs were included in the final analysis. Origin of PVCs from the tricuspid annulus had the highest burden and NT-proBNP level. LV papillary muscle had a higher LV ejection fraction (EF) level and a lower LV end-systolic dimension (ESD) than other PVC foci (P〈0.05). The high burden group had a higher LV end-diastolic dimension (EDD) and LVESD but lower LVEF than the other two groups (P〈0.05). Female, older age, physical work, and history of PVCs had a significantly positive correlation with symptoms. Male, older age, physical work, and high burden were positive predictors of enlarged LVEDD, LVESD and higher serum NT-proBNP level, but lower LVEF. Seven-day dynamic ECG Holter monitor showed the true PVC burden on patients with PVCs. PVCs with a lower burden or origin from the LV papillary muscle and the fascicle were relatively benign, while PVCs with a higher burden or origin from the tricuspid annulus may lead to cardiac dysfunction.展开更多
Arrhythmias are very common in the healthy populations as well as patients with cardiovascular diseases.Among them,atrial fibrillation(AF)and malignant ventricular arrhythmias are usually associated with some clinical...Arrhythmias are very common in the healthy populations as well as patients with cardiovascular diseases.Among them,atrial fibrillation(AF)and malignant ventricular arrhythmias are usually associated with some clinical events.Early diagnosis of arrhythmias,particularly AF and ventricular arrhythmias,is very important for the treatment and prognosis of patients.Holter is a gold standard commonly recommended for noninvasive detection of paroxysmal arrhythmia.However,it has some shortcomings such as fixed detection timings,delayed report and inability of remote real-time detection.To deal with such problems,we designed and applied a new wearable 72-hour triple-lead H3-electrocardiogram(ECG)device with a remote cloud-based ECG platform and an expertsupporting system.In this study,31 patients were recruited and 24-hour synchronous ECG data by H3-ECG and Holter were recorded.In the H3-ECG group,ECG signals were transmitted using remote real-time modes,and confirmed reports were made by doctors in the remote expert-supporting system,while the traditional modes and detection systems were used in the Holter group.The results showed no significant differences between the two groups in 24-hour total heart rate(HR),averaged HR,maximum HR,minimum HR,premature atrial complexes(PACs)and premature ventricular complexes(PVCs)(P>0.05).The sensitivity and specificity of capture and remote automatic cardiac events detection of PACs,PVCs,and AF by H3-ECG were 93%and 99%,98%and 99%,94%and 98%,respectively.Therefore,the long-term limb triple-lead H3-ECG device can be utilized for domiciliary ECG self-monitoring and remote management of patients with common arrhythmia under medical supervision.展开更多
Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic bac...Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic background,the application of patient-specific induced pluripotent stem cell-derived cardiomyocytes(iPSC-CMs)may help to reveal cell phenotype characteristics underlying different genetic variations.Here,to verify and compare the pathogenicity of mutations(SCN5A c.4213G>A and SCN1B c.590C>T)identified from two BrS patients,we generated two novel BrS iPS cell lines that carried missense mutations in SCN5A or SCN1B,compared their structures and electrophysiology,and evaluated the safety of quinidine in patient-specific iPSC-derived CMs.Compared to the control group,BrS-CMs showed a significant reduction in sodium current,prolonged action potential duration,and varying degrees of decreased Vmax,but no structural difference.After applying different concentrations of quinidine,drug-induced cardiotoxicity was not observed within 3-fold unbound effective therapeutic plasma concentration(ETPC).The data presented proved that iPSC-CMs with variants in SCN5A c.4213G>A or SCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events.展开更多
We sought to investigate variation of atrial electromechanical interval after catheter ablation procedure in patients with persistent atrial fibrillation using pulse Doppler(PW) and pulse tissue Doppler imaging(PW-...We sought to investigate variation of atrial electromechanical interval after catheter ablation procedure in patients with persistent atrial fibrillation using pulse Doppler(PW) and pulse tissue Doppler imaging(PW-TDI).A total of 25 consecutive in-patients with persistent atrial fibrillation,who restored sinus rhythm after ablation procedure,were recruited in our cardiac center.Echocardiography was performed on each patient at 2 hours,1 day,5 days,1 month and 3 months after the ablation therapy,and atrial electromechanical delay was measured simultaneously by PW and PW-TDI.There was no significant difference between PW and TDI in measuring atrial electromechanical delay.However,at postoperative 2 hours,peak A detection rates were mathematically but nonsignificantly greater by PWTDI than by PW.Second,there was a significant decreasing trend in atrial electromechanical interval from postoperative 2 hours to 3 months,but only postoperative 2-hour atrial electromechanical interval was significantly greater than atrial electromechanical interval at other time.Lastly,patients without postoperative 2-hour atrial electromechanical interval had a significantly longer duration of atrial fibrillation as compared to those with postoperative 2-hour atrial electromechanical interval,by the PW or by PW-TDI,respectively.In patients with persistent atrial fibrillation,atrial electromechanical interval may decrease significantly within the first 24 hours after ablation but remain consistent later,and was significantly related to patients' duration of atrial fibrillation.Atrial electromechanical interval,as a potential predicted factor,is recommended to be measured by either PW or TDI after24 hours,when patients had recovered sinus rhythm by radiofrequency ablation.展开更多
The superior vena cava(SVC)is the main component of non-pulmonary vein(PV)ectopy in patients with atrial fibrillation(AF).Researchers have found that epicardial adipose tissue(EAT)volume is related to the AF substrate...The superior vena cava(SVC)is the main component of non-pulmonary vein(PV)ectopy in patients with atrial fibrillation(AF).Researchers have found that epicardial adipose tissue(EAT)volume is related to the AF substrate,which can be defined by the low voltage area(LVA).This study aimed to investigate the relationship between SVC-EAT and SVC-AF.Twenty-six patients with SVC-AF triggers were identified as the SVC-AF group.Other three groups were defined and included as the LVA-AF group(LVA>5%),non-LVA-AF group(LVA<5%),and physical examination(PE)group.EAT around left atrium(LA-EAT)and SVC-EAT volumes were obtained using a cardiac risk assessment module.According to the SVC/LA-EAT ratio,there are significant differences between the SVC-AF group and the three control groups(the SVC-AF group 0.092±0.041 vs.the LVA-AF group 0.054±0.026,the non-LVA-AF group 0.052±0.022,and the PE group 0.052±0.019,all P<0.001).Receiver operating characteristic curve analysis suggests the optimal cut-off point of SVC/LA-EAT ratio is 6.8%for detecting SVC-AF patients,with 81.1%sensitivity,73.1%specificity,and an area under the curve of 0.83(95%confidence interval,0.75-0.91).Those with SVC-AF have a higher SVC/LA-EAT ratio and empirical SVC isolation could be considered if the SVC/LA-EAT ratio was over 6.8%.展开更多
Proteins and peptides have become a significant therapeutic modality for various diseases because of their high potency and specificity.However,the inherent properties of these drugs,such as large molecular weight,poo...Proteins and peptides have become a significant therapeutic modality for various diseases because of their high potency and specificity.However,the inherent properties of these drugs,such as large molecular weight,poor stability,and conformational flexibility,make them difficult to be formulated and delivered.Injection is the primary route for clinical administration of protein and peptide drugs,which usually leads to poor patient’s compliance.As a portable,minimally invasive device,microneedles(MNs)can overcome the skin barrier and generate reversible microchannels for effective macromolecule permeation.In this review,we highlighted the recent advances in MNs-mediated transdermal delivery of protein and peptide drugs.Emphasis was given to the latest development in representative MNs design and fabrication.We also summarize the current application status of MNs-mediated transdermal protein and peptide delivery,especially in the field of infectious disease,diabetes,cancer,and other disease therapy.Finally,the current status of clinical translation and a perspective on future development are also provided.展开更多
Nanomedicine with high specificity has been a promising tool for cancer diagnosis and therapy.However,the successful application of nanoparticle-based superficial cancer therapy is severely hindered by restricted deep...Nanomedicine with high specificity has been a promising tool for cancer diagnosis and therapy.However,the successful application of nanoparticle-based superficial cancer therapy is severely hindered by restricted deep tumor tissue accumulation and penetration.Herein,a self-assembly nanomicelle dissolving microneedle(DMN)patch according to the“nano in micro”strategy was conducted to co-deliver a first-line chemotherapeutic agent paclitaxel(PTX),and a photosensitizer IR780(PTX/IR780-NMs@DMNs)for chemo-photothermal synergetic melanoma therapy.Upon direct insertion into the tumor site,DMNs created a regular and multipoint three-dimensional drug depot to maximize the tumor accumulation.Accompanied by the DMN dissolution,the composition of the needle matrixes self-assembled into nanomicelles,which could efficiently penetrate deep tumor tissue.Upon laser irradiation,the nanomicelles could not only ablate tumor cells directly by photothermal conversion but also trigger PTX release to induce tumor cell apoptosis.In vivo results showed that compared with intravenous injection,IR780 delivered by PTX/IR780-NMs@DMNs was almost completely accumulated at the tumor site.The antitumor results revealed that the PTX/IR780-NMs@DMNs could effectively eliminate tumors with an 88%curable rate without any damage to normal tissues.This work provides a versatile and generalizable framework for designing self-assembly DMN-mediated combination therapy to fight against superficial cancer.展开更多
To the Editor:Dilated cardiomyopathy(DCM)is a type of primary myocardial disease with unknown etiology.[1]It is a disorder of the heart muscle mainly characterized by left ventricular dilation and systolic dysfunction...To the Editor:Dilated cardiomyopathy(DCM)is a type of primary myocardial disease with unknown etiology.[1]It is a disorder of the heart muscle mainly characterized by left ventricular dilation and systolic dysfunction,resulting from the response of the myocardium to genetic and environmental insults.The clinical manifestations arc progressive heart failure,arrhythmia,thromboembolism,and even sudden death.展开更多
基金supported by the Australian Research Council(ARC)(Grant No.DP200103492)the National Natural Science Foundation of China(Grant Nos.12172089,12372307,and 61821002)+2 种基金Medical Research Future Fund(Grant Nos.2016165 and 2023977)the CBT Early Career Researcher Grant funded and the Roland Bishop Biomedical Engineering Research Award by Queensland University of Technologythe Springboard Funding and the Global Collaboration Funding by London South Bank University.Computational resources and services used in this work were provided by the High-Performance Computing and Research Support Group,Queensland University of Technology,Brisbane,Australia.
文摘The accurate assessment of cardiac motion is crucial for diagnosing and monitoring cardiovascular diseases.In this context,digital volume correlation(DVC)has emerged as a promising technique for tracking cardiac motion from cardiac computed tomography angiographic(CTA)images.This paper presents a comprehensive performance evaluation of the DVC method,specifically focusing on tracking the motion of the left atrium using cardiac CTA data.The study employed a comparative experimental approach while simultaneously optimizing the existing DVC algorithm.Multiple sets of controlled experiments were designed to conduct quantitative analyses on the parameters“radius”and“step”.The results revealed that the optimized DVC algorithm enhanced tracking accuracy within a reasonable computational time.These findings contributed to the understanding of the efficacy and limitations of the DVC algorithm in analyzing heart deformation.
基金supported in part by National Sciences Foundation of China grants 11972117a Jiangsu Province Science and Technology Agency under grant number BE2016785+4 种基金support from Natural Science Foundation of China(81827806 and 62135002)support from Natural Science Foundation of China(81722025)Key R&D Project of Heilongjiang Province grant 2022ZX06C07support from the Natural Science Foundation of Shandong Province under grant number ZR2024QA110Shandong Province Medical Health Science and Technology Project(Nos.202425020256,and 202403010254).
文摘Image-based computational models have been used for vulnerable plaque progression and rupture predictions,and good results have been reported.However,mechanisms and predictions for plaque erosion are underinvestigated.Patient-specific fluid-structure interaction(FSI)models based on optical coherence tomography(OCT)follow-up data from patients with plaque erosion and who received conservative antithrombotic treatment(using medication,no stenting)to identify risk factors that could be used to predict the treatment outcome.OCT and angiography datawere obtained from10 patientswho received conservative antithrombotic treatment.Five participants had worse outcomes(WOG,stenosis severity≥70%at one-year follow-up),while the other five had better outcomes(BOG,stenosis severity<70%at one-year follow-up).Patient-specific 3D FSI models were constructed to obtain morphological and biomechanical risk factor values(a total of nine risk factors)for comparison and prediction.A logistic regressionmodel was used to identify optimal predictors with the best treatment outcome prediction accuracies.Our results indicated that the combination of wall shear stress(WSS),lipid percent,and thrombus burden was the best group predictor according to the mean area under the curve(AUC)of 0.96(90%confidence interval=(0.85,1.00)).WSS was the best single predictor withmean AUC=0.70(90%confidence interval=(0.20,1.00)).Thrombus burden was the only risk factor showing statistically significant group difference,suggesting its crucial role in the outcomes of conservative anti-thrombotic therapy.This pilot study indicated that integratingmorphological and biomechanical risk factors could improve treatment outcome prediction accuracy in patients with plaque erosion compared to predictions using single predictors.Large-scale patient studies are needed to further validate our findings.
基金supported by the National Natural Science Foundation of China(Nos.82370322 to CC,82200352 to FZ,82300352 to YZ,22275034 to HX,and 82070343 to MLC)the Natural Science Foundation of Jiangsu Province of China(Nos.BK20220710 to FZ and BK20230733 to YZ)Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.JX13414086 to HYC).
文摘Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the myocardium.While elevated testosterone levels have been implicated in the pathological process of ARVC,its exact contribution to cardiac fibrosis in ARVC remains unclear.In this study,we analyzed the potential contribution of gender-based differences on the distribution of the low-voltage area in an ARVC cohort undergoing an electrophysiological study,which was indicated by feature selection.Additionally,we established engineered cardiac spheroid models in vitro using patient-specific induced pluripotent stem cell(iPSC)-derived cardiomyocytes(iPSC-CMs)and iPSC-derived cardiac fibroblasts(icFBs).We elucidated the pathogenicity of abnormal splicing in the plakophilin-2(PKP2)gene caused by an intronic mutation.Additionally,pathogenic validation of the desmoglein-2(DSG2)point mutation further confirms the reliability of the models.Moreover,testosterone exacerbated the DNA damage in the mutated cardiomyocytes and further activated myofibroblasts in a chain reaction.In conclusion,we designed and constructed an in vitro three-dimensionally-engineered cardiac spheroid model of ARVC based on clinical findings and provided direct evidence of the fibrotic role of testosterone in ARVC.
基金This work was financially supported by the Natural Science Foundation of China(21925110,21890751,91745113)the National Program for Support of Top-Notch Young Professionals+9 种基金USTC Research Funds of the Double First-Class Initiative(YD2060002004)the Key R&D Program of Shandong Province(2021CXGC010302)the Major Program of Development Foundation of Hefei Center for Physical Science and Technology(2016FXZY001)the Users with Excellence Project of Hefei Science Center CAS(2021HSCUE004)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB36000000)the Anhui Provincial Natural Science Foundation(1808085MB26)The authors also appreciate the support from the beamline 1W1B of Beijing Synchrotron Radiation Facility(BSRF,Beijing,China)the beam-lines BL11U,BL10B,and BL12B-a of National Synchrotron Radiation Laboratory(NSRL,Hefei,China)the fellowship of China National Postdoctoral Program for Innovative Talents(BX2021280)the fellowship of China Postdoctoral Science Foundation(2022M710141).
文摘The electrical storm (ES) is defined as a state of electrical instability with three or more sustained ventricular arrhythmias (VAs) occurring within twenty-four hours, which needs intravenous antiarrhythmic medications and frequent defibrillation. Recently, radiofrequency catheter ablation evolved as a sole therapy to terminate ES in patients with ICD, and the survival has been reported to be improved with successful ablation during follow-up. In this review, we briefly summarize substrate mapping and substrate ablation strategy in patients with ES, and discuss the reason of recurrence after ablation.
基金supported by the innovation project in Jiangsu province,Chinathe Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU(IRT-004)
文摘Recent studies have shown that premature ventricular contractions (PVCs) could enlarge the heart, but its risk factors are incompletely understood as a single 24-hour recording cannot reflect the true PVC burden due to day-to-day variability. Our purpose was to investigate the effect of burden and origin sites on left ventricular (LV) function in patients with PVCs by 7-day Holter electrocardiography (ECG). From May 2012 to August 2013, 112 consecutive patients with PVCs were recruited from the authors' affiliated hospital. All patients received 2-dimensional transthoracic echocardiography, 12-lead routing ECG and 7-days Holter ECG. Serum N-terminal pro- brain natriuretic peptide (NT-proBNP) levels were measured. A total of 102 participants with PVCs were included in the final analysis. Origin of PVCs from the tricuspid annulus had the highest burden and NT-proBNP level. LV papillary muscle had a higher LV ejection fraction (EF) level and a lower LV end-systolic dimension (ESD) than other PVC foci (P〈0.05). The high burden group had a higher LV end-diastolic dimension (EDD) and LVESD but lower LVEF than the other two groups (P〈0.05). Female, older age, physical work, and history of PVCs had a significantly positive correlation with symptoms. Male, older age, physical work, and high burden were positive predictors of enlarged LVEDD, LVESD and higher serum NT-proBNP level, but lower LVEF. Seven-day dynamic ECG Holter monitor showed the true PVC burden on patients with PVCs. PVCs with a lower burden or origin from the LV papillary muscle and the fascicle were relatively benign, while PVCs with a higher burden or origin from the tricuspid annulus may lead to cardiac dysfunction.
基金This research was funded by the Key Research and Development Plan of Jiangsu Province under grant BE2017735.Q.S.conceived the study and wrote the manuscript.Q.S.,C.C.,H.G.X.W.collected,analyzed,and interpreted the data.H.G.and X.W.contributed substantially to the development of ECG signal conversion Matlab software and remote automatic detection algorithm.J.L.,M.C.and C.L.revised the manuscript,evaluated and supervised the study.
文摘Arrhythmias are very common in the healthy populations as well as patients with cardiovascular diseases.Among them,atrial fibrillation(AF)and malignant ventricular arrhythmias are usually associated with some clinical events.Early diagnosis of arrhythmias,particularly AF and ventricular arrhythmias,is very important for the treatment and prognosis of patients.Holter is a gold standard commonly recommended for noninvasive detection of paroxysmal arrhythmia.However,it has some shortcomings such as fixed detection timings,delayed report and inability of remote real-time detection.To deal with such problems,we designed and applied a new wearable 72-hour triple-lead H3-electrocardiogram(ECG)device with a remote cloud-based ECG platform and an expertsupporting system.In this study,31 patients were recruited and 24-hour synchronous ECG data by H3-ECG and Holter were recorded.In the H3-ECG group,ECG signals were transmitted using remote real-time modes,and confirmed reports were made by doctors in the remote expert-supporting system,while the traditional modes and detection systems were used in the Holter group.The results showed no significant differences between the two groups in 24-hour total heart rate(HR),averaged HR,maximum HR,minimum HR,premature atrial complexes(PACs)and premature ventricular complexes(PVCs)(P>0.05).The sensitivity and specificity of capture and remote automatic cardiac events detection of PACs,PVCs,and AF by H3-ECG were 93%and 99%,98%and 99%,94%and 98%,respectively.Therefore,the long-term limb triple-lead H3-ECG device can be utilized for domiciliary ECG self-monitoring and remote management of patients with common arrhythmia under medical supervision.
基金supported by the Natural Science Foundation of Jiangsu Province of China(Grant No.BK20160134 to LW and BK20191071 to CC)National Natural and Science Foundation of China(Grant No.81900295 to CC)Special Foundation for Clinical Science and Technology of Jiangsu Province(Grant No.BE2017754 to HWC).
文摘Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic background,the application of patient-specific induced pluripotent stem cell-derived cardiomyocytes(iPSC-CMs)may help to reveal cell phenotype characteristics underlying different genetic variations.Here,to verify and compare the pathogenicity of mutations(SCN5A c.4213G>A and SCN1B c.590C>T)identified from two BrS patients,we generated two novel BrS iPS cell lines that carried missense mutations in SCN5A or SCN1B,compared their structures and electrophysiology,and evaluated the safety of quinidine in patient-specific iPSC-derived CMs.Compared to the control group,BrS-CMs showed a significant reduction in sodium current,prolonged action potential duration,and varying degrees of decreased Vmax,but no structural difference.After applying different concentrations of quinidine,drug-induced cardiotoxicity was not observed within 3-fold unbound effective therapeutic plasma concentration(ETPC).The data presented proved that iPSC-CMs with variants in SCN5A c.4213G>A or SCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events.
文摘We sought to investigate variation of atrial electromechanical interval after catheter ablation procedure in patients with persistent atrial fibrillation using pulse Doppler(PW) and pulse tissue Doppler imaging(PW-TDI).A total of 25 consecutive in-patients with persistent atrial fibrillation,who restored sinus rhythm after ablation procedure,were recruited in our cardiac center.Echocardiography was performed on each patient at 2 hours,1 day,5 days,1 month and 3 months after the ablation therapy,and atrial electromechanical delay was measured simultaneously by PW and PW-TDI.There was no significant difference between PW and TDI in measuring atrial electromechanical delay.However,at postoperative 2 hours,peak A detection rates were mathematically but nonsignificantly greater by PWTDI than by PW.Second,there was a significant decreasing trend in atrial electromechanical interval from postoperative 2 hours to 3 months,but only postoperative 2-hour atrial electromechanical interval was significantly greater than atrial electromechanical interval at other time.Lastly,patients without postoperative 2-hour atrial electromechanical interval had a significantly longer duration of atrial fibrillation as compared to those with postoperative 2-hour atrial electromechanical interval,by the PW or by PW-TDI,respectively.In patients with persistent atrial fibrillation,atrial electromechanical interval may decrease significantly within the first 24 hours after ablation but remain consistent later,and was significantly related to patients' duration of atrial fibrillation.Atrial electromechanical interval,as a potential predicted factor,is recommended to be measured by either PW or TDI after24 hours,when patients had recovered sinus rhythm by radiofrequency ablation.
文摘The superior vena cava(SVC)is the main component of non-pulmonary vein(PV)ectopy in patients with atrial fibrillation(AF).Researchers have found that epicardial adipose tissue(EAT)volume is related to the AF substrate,which can be defined by the low voltage area(LVA).This study aimed to investigate the relationship between SVC-EAT and SVC-AF.Twenty-six patients with SVC-AF triggers were identified as the SVC-AF group.Other three groups were defined and included as the LVA-AF group(LVA>5%),non-LVA-AF group(LVA<5%),and physical examination(PE)group.EAT around left atrium(LA-EAT)and SVC-EAT volumes were obtained using a cardiac risk assessment module.According to the SVC/LA-EAT ratio,there are significant differences between the SVC-AF group and the three control groups(the SVC-AF group 0.092±0.041 vs.the LVA-AF group 0.054±0.026,the non-LVA-AF group 0.052±0.022,and the PE group 0.052±0.019,all P<0.001).Receiver operating characteristic curve analysis suggests the optimal cut-off point of SVC/LA-EAT ratio is 6.8%for detecting SVC-AF patients,with 81.1%sensitivity,73.1%specificity,and an area under the curve of 0.83(95%confidence interval,0.75-0.91).Those with SVC-AF have a higher SVC/LA-EAT ratio and empirical SVC isolation could be considered if the SVC/LA-EAT ratio was over 6.8%.
基金funded by the National Natural Science Foundation(Project No.81803466,China)Guangdong Macao joint innovation funding project(Project No.2020A050515009,China)+1 种基金the Research and Development Plan for Key Areas in Guangdong Province(Project No.2019B020204002,China)the Foundation of Traditional Chinese Medicine Bureau of Guangdong Province(Project No.20191057,China)
文摘Proteins and peptides have become a significant therapeutic modality for various diseases because of their high potency and specificity.However,the inherent properties of these drugs,such as large molecular weight,poor stability,and conformational flexibility,make them difficult to be formulated and delivered.Injection is the primary route for clinical administration of protein and peptide drugs,which usually leads to poor patient’s compliance.As a portable,minimally invasive device,microneedles(MNs)can overcome the skin barrier and generate reversible microchannels for effective macromolecule permeation.In this review,we highlighted the recent advances in MNs-mediated transdermal delivery of protein and peptide drugs.Emphasis was given to the latest development in representative MNs design and fabrication.We also summarize the current application status of MNs-mediated transdermal protein and peptide delivery,especially in the field of infectious disease,diabetes,cancer,and other disease therapy.Finally,the current status of clinical translation and a perspective on future development are also provided.
基金the National Natural Science Foundation of China(No.81803466)the Key Areas Research and Development Program of Guangdong Province(No.2019B020204002)the Natural Science Foundation of Guangdong Province(No.2021A1515012525).
文摘Nanomedicine with high specificity has been a promising tool for cancer diagnosis and therapy.However,the successful application of nanoparticle-based superficial cancer therapy is severely hindered by restricted deep tumor tissue accumulation and penetration.Herein,a self-assembly nanomicelle dissolving microneedle(DMN)patch according to the“nano in micro”strategy was conducted to co-deliver a first-line chemotherapeutic agent paclitaxel(PTX),and a photosensitizer IR780(PTX/IR780-NMs@DMNs)for chemo-photothermal synergetic melanoma therapy.Upon direct insertion into the tumor site,DMNs created a regular and multipoint three-dimensional drug depot to maximize the tumor accumulation.Accompanied by the DMN dissolution,the composition of the needle matrixes self-assembled into nanomicelles,which could efficiently penetrate deep tumor tissue.Upon laser irradiation,the nanomicelles could not only ablate tumor cells directly by photothermal conversion but also trigger PTX release to induce tumor cell apoptosis.In vivo results showed that compared with intravenous injection,IR780 delivered by PTX/IR780-NMs@DMNs was almost completely accumulated at the tumor site.The antitumor results revealed that the PTX/IR780-NMs@DMNs could effectively eliminate tumors with an 88%curable rate without any damage to normal tissues.This work provides a versatile and generalizable framework for designing self-assembly DMN-mediated combination therapy to fight against superficial cancer.
基金333 project of Jiangsu Province(Grant/Award Number:BRA2017544)Project of Qinghai Science and Technology Department(Grant/Award Number:2018-SF-114)+1 种基金Zhongnanshan Medical Foundation of Guangdong Province(No.ZNSA-2020017)Guiding project of Qinghai Health Commission(Grant/Award Number:2019-wjzdx-35)。
文摘To the Editor:Dilated cardiomyopathy(DCM)is a type of primary myocardial disease with unknown etiology.[1]It is a disorder of the heart muscle mainly characterized by left ventricular dilation and systolic dysfunction,resulting from the response of the myocardium to genetic and environmental insults.The clinical manifestations arc progressive heart failure,arrhythmia,thromboembolism,and even sudden death.