Objective To investigate whether admission time was associated with the delay of reperfusion therapy and in-hospital death in patients with ST-elevation myocardial infarction （STEMI）. Methods All patients with STEMI...Objective To investigate whether admission time was associated with the delay of reperfusion therapy and in-hospital death in patients with ST-elevation myocardial infarction （STEMI）. Methods All patients with STEMI who were admitted to the emergency depart- ment and underwent primary percutaneous coronary intervention at Peking University People＇s Hospital between April 2012 and March 2015 were included. We examined differences in clinical characteristics, total ischemic time, and in-hospital death between patients admitted during off-hours and those admitted during regular hours. Multivariate logistic regression was used to estimate the relationship between off-hours admission and clinical outcome. Results The sample comprised 184 and 105 patients with STEMI admitted to hospital during off-hours and regular hours, respectively. Total ischemic and onset-to-door times were significantly shorter in patients admitted during off-hours than among those admitted during regular hours （all P 〈 0.05）. Door-to-balloon （DTB） time, the rate of DTB time 〈 90 min, and in-hospital death were comparable between groups. Multivariate logistic regression showed that age and creatinine level, but not off-hours admission, were associated independently with increased in-hospital death. Conclusions Off-hours admission did not result in delayed reperfusion therapy or increased in-hospital mortality in patients with STEMI. Further efforts should focus on identifying pivotal factors associated with the pre-hospital and in-hospital delay of reperfusion therapy, and implementing quality improvement initiatives for reperfusion programs.展开更多
Background Percutaneous left atrial appendage occlusion(LAAO)requires puncture of the interatrial septum.The immediate hemodynamic effects of iatrogenic atrial septal defects(iASD)after LAAO have not been examined so ...Background Percutaneous left atrial appendage occlusion(LAAO)requires puncture of the interatrial septum.The immediate hemodynamic effects of iatrogenic atrial septal defects(iASD)after LAAO have not been examined so far.We aimed at evaluat-ing these effects through invasive measurements of pressure and oxygen saturation.Moreover,we assessed the incidence of per-sistent iASD at three months.METHODS Forty-eight patients scheduled for percutaneous LAAO were prospectively included in the study.Pressure and oxygen saturation were measured(1)in the right atrium(RA)before transseptal puncture,(2)in the left atrium(LA)through the transseptal sheath after transseptal puncture,(3)in the LA after removal of introducer sheath,and(4)in the RA after removal of introducer sheath.Transesophageal echocardiography was performed at three months to detect iASD.RESULTS Pressure in the RA increased significantly after removing the introducer sheath(P=0.034),whereas no difference was found in oxygen saturation in the RA(P=0.623).Pressure measurement in the LA showed no significant difference after re-moving the introducer sheath(P=0.718).Oxygen saturation in the LA also showed no significant difference(P=0.129).Follow-up transesophageal echocardiogram at 3 months revealed a persistent iASD in 4 patients(8.5%).CONCLUSIONS Our study suggests that iASD after percutaneous LAAO does not result in significant shunts directly after the procedure,although a significant increase of mean right atrial pressure can be observed.Persistent iASDs after percutaneous LAAO seem to be relatively rare at three months.展开更多
Non-human primates play a key role in the preclinical validation of pluripotent stem cell-based cell replacement therapies.Pluripotent stem cells used as advanced therapy medical products boost the possibility to rege...Non-human primates play a key role in the preclinical validation of pluripotent stem cell-based cell replacement therapies.Pluripotent stem cells used as advanced therapy medical products boost the possibility to regenerate tissues and organs affected by degenerative diseases.Therefore,the methods to derive human induced pluripotent stem cell and embryonic stem cell lines following clinical standards have quickly developed in the last 15 years.For the preclinical validation of cell replacement therapies in non-human primates,it is necessary to generate non-human primate pluripotent stem cell with a homologous quality to their human counterparts.However,pluripotent stem cell technologies have developed at a slower pace in non-human primates in comparison with human cell systems.In recent years,however,relevant progress has also been made with non-human primate pluripotent stem cells.This review provides a systematic overview of the progress and remaining challenges for the generation of non-human primate induced pluripotent stem cells/embryonic stem cells for the preclinical testing and validation of cell replacement therapies.We focus on the critical domains of(1)reprogramming and embryonic stem cell line derivation,(2)cell line maintenance and characterization and,(3)application of non-human primate pluripotent stem cells in the context of selected preclinical studies to treat cardiovascular and neurodegenerative disorders performed in non-human primates.展开更多
Large animal models of cardiac ischemia-reperfusion are critical for evaluation of the efficacy of cardioprotective interventions prior to clinical translation.Nonetheless,current cardioprotective strategies/intervent...Large animal models of cardiac ischemia-reperfusion are critical for evaluation of the efficacy of cardioprotective interventions prior to clinical translation.Nonetheless,current cardioprotective strategies/interventions formulated in preclinical cardiovascular research are often limited to small animal models,which are not transferable or reproducible in large animal models due to different factors such as:(i)complex and varied features of human ischemic cardiac disease(ICD),which are challenging to mimic in animal models,(ii)significant differences in surgical techniques applied,and(iii)differences in cardiovascular anatomy and physiology between small versus large animals.This article highlights the advantages and disadvantages of different large animal models of preclinical cardiac ischemic reperfusion injury(IRI),as well as the different methods used to induce and assess IRI,and the obstacles faced in using large animals for translational research in the settings of cardiac IR.展开更多
BACKGROUND As a result of improved and novel treatment strategies,the spectrum of patients with cardiovascular disease is consistently changing.Overall,those patients are typically older and characterized by increased...BACKGROUND As a result of improved and novel treatment strategies,the spectrum of patients with cardiovascular disease is consistently changing.Overall,those patients are typically older and characterized by increased burden with comorbidities.Limited data on the prognostic impact of age in cardiogenic shock(CS)is available.Therefore,this study investigates the prognostic impact of age in patients with CS.METHODS From 2019 to 2021,consecutive patients with CS of any cause were included.The prognostic value of age(i.e.,60-80 years and>80 years)was investigated for 30-day all-cause mortality.Spearman’s correlations,Kaplan-Meier analyses,as well as multivariable Cox proportional regression analyses were performed for statistics.Subsequent risk assessment was performed based on the presence or absence of CS related to acute myocardial infarction(AMI).RESULTS 223 CS patients were included with a median age of 77 years(interquartile range:69-82 years).No significant difference in 30-day all-cause mortality was observed for both age-groups(54.6%vs.63.4%,log-rank P=0.169;HR=1.273,95%CI:0.886-1.831,P=0.192).In contrast,when analyzing subgroups stratified by CS-etiology,AMI-related CS patients of the group>80 years showed an increased risk of 30-day all-cause mortality(78.1%vs.60.0%,log-rank P=0.032;HR=1.635,95%CI:1.000-2.673,P=0.050),which was still evident after multivariable adjustment(HR=2.072,95%CI:1.174-3.656,P=0.012).CONCLUSIONS Age was not associated with 30-day all-cause mortality in patients with CS of mixed etiology.However,increasing age was shown to be a significant predictor of increased mortality-risk in the subgroup of patients presenting with AMI-CS.展开更多
micro RNAs(mi RNAs) are powerful regulators of posttranscriptional gene expression and play an important role in pathophysiological processes. Circulating mi RNAs can be quantified in body liquids and are promising bi...micro RNAs(mi RNAs) are powerful regulators of posttranscriptional gene expression and play an important role in pathophysiological processes. Circulating mi RNAs can be quantified in body liquids and are promising biomarkers in numerous diseases. In cardiovascular disease mi RNAs have been proven to be reliable diagnostic biomarkers for different disease entities. In cardiac fibrosis(CF) and heart failure(HF) dysregulated circulating mi RNAs have been identified,indicating their promising applicability as diagnostic biomarkers. Some mi RNAs were successfully tested in risk stratification of HF implementing their potential use as prognostic biomarkers. In this respect mi RNAs might soon be implemented in diagnostic clinical routine. In the young field of mi RNA based research advances have been made in identifying mi RNAs as potential targets for the treatment of experimental CF and HF. Promising study results suggest their potential future application as therapeutic agents in treatment of cardiovascular disease. This article summarizes the current state of the various aspects of mi RNA research in the field of CF and HF with reduced ejection fraction as well as preserved ejection fraction. The review provides an overview of the application of circulating mi RNAs as biomarkers in CF and HF and current approaches to therapeutically utilize mi RNAs in this field of cardiovascular disease.展开更多
Almost every experimental treatment strategy using non-autologous cell, tissue or organ transplantation is tested in small and large animal models before clinical translation. Because these strategies require immunosu...Almost every experimental treatment strategy using non-autologous cell, tissue or organ transplantation is tested in small and large animal models before clinical translation. Because these strategies require immunosuppression in most cases, immunosuppressive protocols are a key element in transplantation experiments. However, standard immunosuppressive protocols are often applied without detailed knowledge regarding their efficacy within the particular experimental setting and in the chosen model species. Optimization of such protocols is pertinent to the translation of experimental results to human patients and thus warrants further investigation. This review summarizes current knowledge regarding immunosuppressive drug classes as well as their dosages and application regimens with consideration of species-specific drug metabolization and side effects. It also summarizes contemporary knowledge of novel immunomodulatory strategies, such as the use of mesenchymal stem cells or antibodies. Thus, this review is intended to serve as a state-of-the-art compendium for researchers to refine applied experimental immunosuppression and immunomodulation strategies to enhance the predictive value of preclinical transplantation studies.展开更多
Objective To investigate the contributing factors and in-hospital prognosis of patients with or without recurrent acute myocardial infarction （AMI）. Methods A total of 1686 consecutive AMI patients admitted to Pekin...Objective To investigate the contributing factors and in-hospital prognosis of patients with or without recurrent acute myocardial infarction （AMI）. Methods A total of 1686 consecutive AMI patients admitted to Peking University People＇s Hospital from January 2010 to December 2015 were recruited. Their clinical characteristics were retrospectively compared between patients with or without a recurrent AMI. Then multivariable logistic regression was used to estimate the predictors of recurrent myocardial infarction. Results Recurrent AMI patients were older （69.3 ± 11.5 vs. 64.7 ± 12.8 years, P 〈 0.001） and had a higher prevalence of diabetes mellitus （DM） （52.2% vs. 35.0%, P 〈 0.001） compared with incident AMI patients, they also had worse heart function at admission, more severe coronary disease and lower reperfusion therapy. Age （OR = 1.03, 95% CI： 1.02-1.05; P 〈 0.001）, DM （OR = 1.86, 95% CI： 1.37-2.52; P 〈 0.001） and reperfusion therapy （OR = 0.74; 95% CI： 0.52-0.89; P 〈 0.001） were independent risk factors for recurrent AMI Recurrent AMI patients had a higher in-hospital death rate （12.1% vs. 7.8%, P = 0.039） than incident AMI patients. Conclusions Recurrent AMI patients presented with more severe coronary artery conditions. Age, DM and reperfusion therapy were independent risk factors for recurrent AMI, and recurrent AM1 was related with a high risk of in-hospital death.展开更多
1 Introduction Effective and timely reperfusion of infarcted coronary artery is crucial to the treatment of patients with ST-segment elevation myocardial infarction(STEMI).[1,2]Current guidelines highly recommend that...1 Introduction Effective and timely reperfusion of infarcted coronary artery is crucial to the treatment of patients with ST-segment elevation myocardial infarction(STEMI).[1,2]Current guidelines highly recommend that the door-to-balloon(D2B)time,as a quality metric of primary percutaneous coronary intervention(PCI)in patients with STEMI,should be≤90 min and preferably less than 60 min.[3,4]However,significant variations from guidelines exist in the real world practices at hospitals.展开更多
Objective To study prognostic characteristics of cardiac troponin I （cTnI） elevation in acute ischemic stroke. Methods We retrospectively studied patients （n = 248） with acute ischemic stroke, acute ST-segment ele...Objective To study prognostic characteristics of cardiac troponin I （cTnI） elevation in acute ischemic stroke. Methods We retrospectively studied patients （n = 248） with acute ischemic stroke, acute ST-segment elevation myocardial infarction, and acute non-ST-elevation myocardial infarction who were treated between January 2013 and October 2015. Baseline demographic data and changes in cTnI levels among these three groups were compared. Patients with acute ischemic stroke were assigned to either the cTnI elevation group （cTnI 〉 0.034 ng/mL） or the no cTnI elevation group （cTnI ≤ 0.034 ng/mL）. Logistic regression analysis was used to identify risk factors associated with elevated serum cTnI in patients with acute ischemic stroke. Moreover, the duration of hospital stay and incidence of major cardiovascular outcomes were compared in patients with acute ischemic stroke, with or without elevated cTnI. Results In this study population of patients with acute ischemic stroke （n = 178）, acute ST-segment elevation myocardial infarction （n = 35）, and acute non-ST-elevation myocardial infarction （n = 35）, patients with acute ischemic stroke with elevated cTnI comprised 18.54% of subjects. Patients with elevated cTnI were older and more likely to have a history of hypertension. In addition, these patients had higher levels of inflammatory markers, reduced renal functions, increased D-dimer levels, higher NIH stroke scores, and lower left ventricular ejection fractions. Logistic regression analysis showed that both percentage of neutrophil and NIH stroke scores were elevated; estimated glomerular filtration rate and left ventricular ejection fraction were decreased in patients with acute ischemic stroke who had elevated cTnI, and they had more frequent major cardiovascular events during hospital stay. Conclusion Elevated cTnI detected in patients with acute ischemic stroke, indicated a greater likelihood of poor short-term prognosis during hospital stay.展开更多
Cardiogenic shock(CS)following acute myocardial infarction(AMI)is a major challenge in cardiovascular care.Mortality remains high with 40%-50%after thirty days.Randomised controlled trials(RCTs)play a key role to gene...Cardiogenic shock(CS)following acute myocardial infarction(AMI)is a major challenge in cardiovascular care.Mortality remains high with 40%-50%after thirty days.Randomised controlled trials(RCTs)play a key role to generate evidence on optimal care in this field.However,the number of completed or ongoing RCTs is still relatively low compared to the gaps in evidence.Challenges in the conduct of these trials are in particular the selection of patients and ethical issues in the informed consent process.When determining eligibility criteria,special attention should be paid to the severity of CS,to the inclusion of patients with cardiac arrest and to potential age limits.Median age of AMI-CS patients is increasing.Age limits are therefore controversial as it is important to include elderly patients in RCTs in order to make the results generalisable and to address the special needs of this group.As patients with AMI-CS are in most cases unable to provide informed consent themselves,a step-wise approach with acute consent by a legal representative or independent physicians and later informed consent by the patient if possible might be established depending on regularities of the respective ethical review board and country legislation.Multicenter studies should be sought to generate adequate power.展开更多
Background Recurrence of takotsubo cardiomyopathy （TTC） is a well-known complication. However, current literature lists only a few isolated cases. We aimed to determine the incidence and clinical significance of rec...Background Recurrence of takotsubo cardiomyopathy （TTC） is a well-known complication. However, current literature lists only a few isolated cases. We aimed to determine the incidence and clinical significance of recurrent TTC. Methods ＆ Results Our institutional database constituted a collective of 114 patients diagnosed with TTC since 2003. Close follow-up of these patients revealed a recurrence of TTC in seven of these （6.1%）. The time interval between the index event and its recurrence varied between six months and six years. Arterial hypertension was more revealed in the recurrence group of TTC compared to non-recurrence group, （P = 0.02）. Chronic obstructive pulmo- nary disease and/or asthma was more diagnosed in the recurrence group, （P = 0.04）. Clinical events like fight ventficular involvement, TTC related complications such as life-threatening arrhythmias, pulmonary congestion and in hospital death were observed more frequently in the recurrent episode. Over a mean follow-up of one year the mortality rate was similar in both groups. Conclusions Recurrence of TTC within six years after index event is not an uncommon phenomenon. In the event of right ventricular involvement in the relapse phase, it might be associated with a higher complication rate. TTC recurrence should be the first differential diagnosis in patients with a past history of TTC.展开更多
AIM To investigate matrix metalloproteinase-11(MMP-11) expression in adipose tissue dysfunction, using in vitro and in vivo models of insulin resistance.METHODS Culture of mouse 3T3-L1 preadipocytes were induced to di...AIM To investigate matrix metalloproteinase-11(MMP-11) expression in adipose tissue dysfunction, using in vitro and in vivo models of insulin resistance.METHODS Culture of mouse 3T3-L1 preadipocytes were induced to differentiation into mature 3T3-L1 adipocytes. Cellular insulin resistance was induced by treating differentiated cultured adipocytes with hypoxia and/or tumor necrosis factor(TNF)-α, and transcriptional changes were analyzed in each condition thereafter. For the in vivo studies, MMP-11 expression levels were measured in white adipose tissue(WAT) from C57BL/6J mice that underwent low fat diet or high-fat feeding in order to induce obesity and obesity-related insulin resistance. Statistical analysis was carried out with GraphP ad Prism Software.RESULTS MMP-11 m RNA expression levels were significantly higher in insulin resistant 3T3-L1 adipocytes compared to control cells(1.46±0.49vs0.83±0.21, respectively;P<0.00036). The increase in MMP-11 expression was observed even in the presence of TNF-α alone(3.79±1.11vs1±0.17, P<0.01) or hypoxia alone(1.79±0.7vs0.88±0.1, P<0.00023). The results obtained in in vitro experiments were confirmed in the in vivo model of insulin resistance. In particular, MMP-11 m RNA was upregulated in WAT from obese mice compared to lean mice(5.5±2.8vs1.1±0.7, respectively; P<3.72E-08). The increase in MMP-11 levels in obese mice was accompanied by the increase in typical markers of fibrosis, such as collagen type Ⅵ alpha 3(Col6_α3), and fibroblast-specific protein 1.CONCLUSION Our results indicate that dysregulation of MMP-11 expression is an early process in the adipose tissue dysfunction, which leads to obesity and obesity-related insulin resistance.展开更多
Background: Up to 60% of patients with ulcerative colitis are seen with nutrient deficiency;however, no specific diet is recommended. The aim of this study was to obtain knowledge on whether restriction or addition of...Background: Up to 60% of patients with ulcerative colitis are seen with nutrient deficiency;however, no specific diet is recommended. The aim of this study was to obtain knowledge on whether restriction or addition of specific food items might contribute to malnutrition in these patients. Methods: A qualitative semi-structured interview study of outpatient clinic patients with ulcerative colitis aimed to investigate preferences for or avoidance of specific food items related to abdominal symptoms. Results: The study included 25 patients (12 M, 13 F), average age 46.7 years (SD 15.6). Duration of disease ranged from 1 to 35 years. Restriction of food items was mainly due to discomfort associated with bowel symptoms, e.g. diarrhoea caused by sugar, dairies, alcohol, spices, red meat, and bread. Restrictions were based mainly on personal experience rather than professional guidance or knowledge search. Addition of specific food items most often included vitamin supplements. Only 20% took supplementary calcium, although many restricted the consumption of dairies from their diet. Conclusion: Many patients with ulcerative colitis restrict consumption of dairy products from their diet. This may lead to calcium deficiency. No other dietary restrictions, which might explain specific nutrient deficiencies, were identified.展开更多
Coronary angiography is considered to be the gold standard in the morphological evaluation of coronary artery stenosis. The morphological assessment of the severity of a coronary lesion is very subjective. Thus, the i...Coronary angiography is considered to be the gold standard in the morphological evaluation of coronary artery stenosis. The morphological assessment of the severity of a coronary lesion is very subjective. Thus, the invasive fractional flow reserve(FFR) measurement represents the current standard for estimation of the hemodynamic significance of coronary artery stenosis. The FFR-guided revascularization strategy was initially classified as a Class-IA-recommendation in the 2014 European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines on myocardial revascularization. Both the Deferral vs Performance of Percutaneous Coronary Intervention of Functionally Non-Significant Coronary Stenosis and Flow Reserve vs Angiography for Multivessel Evaluation studies showed no treatment advantage for hemodynamically insignificant stenoses. With the help of FFR(and targeted interventions), clinical results could be improved; however, the use in clinical practice is still limited due to the need of adenosine administration and a significant prolongation of the length of the procedure. Instantaneous wave-free ratio(iFR~) is a new innovative approach for the determination of the hemodynamic significance of coronary stenosis, which can be obtained at rest without the use of vasodilators. Regarding the periprocedural complications as well as prognosis, iFR~ showed non-inferiority to FFR in the SWEDEHEART and DEFINE-FLAIR trials. Furthermore, iFR~, enhanced by iFR~-pullback, provides the possibility to display the iFR~-change over the course of the vessel to create a hemodynamic map.展开更多
A 67-year-old woman with a history of diabetes mellitus and smoking was admitted to our hospital with chest pain for one month. Her resting electrocardiogram and serial troponin I measurements were normal. As the coro...A 67-year-old woman with a history of diabetes mellitus and smoking was admitted to our hospital with chest pain for one month. Her resting electrocardiogram and serial troponin I measurements were normal. As the coronary artery angiography performed in another hospital showed severe lesions in the left anterior descending artery, we planned to perform the intervention on the left anterior descending artery by stent. Before the procedure, clopidogrel （300 mg loading dose） was initiated.展开更多
文摘Objective To investigate whether admission time was associated with the delay of reperfusion therapy and in-hospital death in patients with ST-elevation myocardial infarction （STEMI）. Methods All patients with STEMI who were admitted to the emergency depart- ment and underwent primary percutaneous coronary intervention at Peking University People＇s Hospital between April 2012 and March 2015 were included. We examined differences in clinical characteristics, total ischemic time, and in-hospital death between patients admitted during off-hours and those admitted during regular hours. Multivariate logistic regression was used to estimate the relationship between off-hours admission and clinical outcome. Results The sample comprised 184 and 105 patients with STEMI admitted to hospital during off-hours and regular hours, respectively. Total ischemic and onset-to-door times were significantly shorter in patients admitted during off-hours than among those admitted during regular hours （all P 〈 0.05）. Door-to-balloon （DTB） time, the rate of DTB time 〈 90 min, and in-hospital death were comparable between groups. Multivariate logistic regression showed that age and creatinine level, but not off-hours admission, were associated independently with increased in-hospital death. Conclusions Off-hours admission did not result in delayed reperfusion therapy or increased in-hospital mortality in patients with STEMI. Further efforts should focus on identifying pivotal factors associated with the pre-hospital and in-hospital delay of reperfusion therapy, and implementing quality improvement initiatives for reperfusion programs.
文摘Background Percutaneous left atrial appendage occlusion(LAAO)requires puncture of the interatrial septum.The immediate hemodynamic effects of iatrogenic atrial septal defects(iASD)after LAAO have not been examined so far.We aimed at evaluat-ing these effects through invasive measurements of pressure and oxygen saturation.Moreover,we assessed the incidence of per-sistent iASD at three months.METHODS Forty-eight patients scheduled for percutaneous LAAO were prospectively included in the study.Pressure and oxygen saturation were measured(1)in the right atrium(RA)before transseptal puncture,(2)in the left atrium(LA)through the transseptal sheath after transseptal puncture,(3)in the LA after removal of introducer sheath,and(4)in the RA after removal of introducer sheath.Transesophageal echocardiography was performed at three months to detect iASD.RESULTS Pressure in the RA increased significantly after removing the introducer sheath(P=0.034),whereas no difference was found in oxygen saturation in the RA(P=0.623).Pressure measurement in the LA showed no significant difference after re-moving the introducer sheath(P=0.718).Oxygen saturation in the LA also showed no significant difference(P=0.129).Follow-up transesophageal echocardiogram at 3 months revealed a persistent iASD in 4 patients(8.5%).CONCLUSIONS Our study suggests that iASD after percutaneous LAAO does not result in significant shunts directly after the procedure,although a significant increase of mean right atrial pressure can be observed.Persistent iASDs after percutaneous LAAO seem to be relatively rare at three months.
基金supported by the German Centre for Cardiovascular Research(DZHK)the German Primate Center-Leibniz Institute for Primate Research,which is financed by the Bundesrepublik Deutschland and the Bundesländer(Federal states)(Grant number 81Z0300201 to RB).
文摘Non-human primates play a key role in the preclinical validation of pluripotent stem cell-based cell replacement therapies.Pluripotent stem cells used as advanced therapy medical products boost the possibility to regenerate tissues and organs affected by degenerative diseases.Therefore,the methods to derive human induced pluripotent stem cell and embryonic stem cell lines following clinical standards have quickly developed in the last 15 years.For the preclinical validation of cell replacement therapies in non-human primates,it is necessary to generate non-human primate pluripotent stem cell with a homologous quality to their human counterparts.However,pluripotent stem cell technologies have developed at a slower pace in non-human primates in comparison with human cell systems.In recent years,however,relevant progress has also been made with non-human primate pluripotent stem cells.This review provides a systematic overview of the progress and remaining challenges for the generation of non-human primate induced pluripotent stem cells/embryonic stem cells for the preclinical testing and validation of cell replacement therapies.We focus on the critical domains of(1)reprogramming and embryonic stem cell line derivation,(2)cell line maintenance and characterization and,(3)application of non-human primate pluripotent stem cells in the context of selected preclinical studies to treat cardiovascular and neurodegenerative disorders performed in non-human primates.
基金supported by the Early Career Scheme(ECS)2022/23(CUHK 24110822)from the Research Grants Council of Hong Kongthe Direct Grant for Research 2020/21(2020.035)+3 种基金Project Impact Enhancement Fund(PIEF)(PIEF/Ph2/COVID/08)Improvement on Competitiveness in Hiring New Faculties Funding Scheme from CUHK as well as the Centre for Cardiovascular Genomics and Medicine(CCGM)of the Lui Che Woo Institute of Innovative Medicine CUHK(to S.B.O.)a CUHK Department of Medicine&Therapeutics(MEDT)-funded PhD studenta CUHK Vice-Chancellor’s PhD Scholarship holder。
文摘Large animal models of cardiac ischemia-reperfusion are critical for evaluation of the efficacy of cardioprotective interventions prior to clinical translation.Nonetheless,current cardioprotective strategies/interventions formulated in preclinical cardiovascular research are often limited to small animal models,which are not transferable or reproducible in large animal models due to different factors such as:(i)complex and varied features of human ischemic cardiac disease(ICD),which are challenging to mimic in animal models,(ii)significant differences in surgical techniques applied,and(iii)differences in cardiovascular anatomy and physiology between small versus large animals.This article highlights the advantages and disadvantages of different large animal models of preclinical cardiac ischemic reperfusion injury(IRI),as well as the different methods used to induce and assess IRI,and the obstacles faced in using large animals for translational research in the settings of cardiac IR.
文摘BACKGROUND As a result of improved and novel treatment strategies,the spectrum of patients with cardiovascular disease is consistently changing.Overall,those patients are typically older and characterized by increased burden with comorbidities.Limited data on the prognostic impact of age in cardiogenic shock(CS)is available.Therefore,this study investigates the prognostic impact of age in patients with CS.METHODS From 2019 to 2021,consecutive patients with CS of any cause were included.The prognostic value of age(i.e.,60-80 years and>80 years)was investigated for 30-day all-cause mortality.Spearman’s correlations,Kaplan-Meier analyses,as well as multivariable Cox proportional regression analyses were performed for statistics.Subsequent risk assessment was performed based on the presence or absence of CS related to acute myocardial infarction(AMI).RESULTS 223 CS patients were included with a median age of 77 years(interquartile range:69-82 years).No significant difference in 30-day all-cause mortality was observed for both age-groups(54.6%vs.63.4%,log-rank P=0.169;HR=1.273,95%CI:0.886-1.831,P=0.192).In contrast,when analyzing subgroups stratified by CS-etiology,AMI-related CS patients of the group>80 years showed an increased risk of 30-day all-cause mortality(78.1%vs.60.0%,log-rank P=0.032;HR=1.635,95%CI:1.000-2.673,P=0.050),which was still evident after multivariable adjustment(HR=2.072,95%CI:1.174-3.656,P=0.012).CONCLUSIONS Age was not associated with 30-day all-cause mortality in patients with CS of mixed etiology.However,increasing age was shown to be a significant predictor of increased mortality-risk in the subgroup of patients presenting with AMI-CS.
基金Supported by The European Union,Biomar Ca RE,No.HEALTH-2011-278913
文摘micro RNAs(mi RNAs) are powerful regulators of posttranscriptional gene expression and play an important role in pathophysiological processes. Circulating mi RNAs can be quantified in body liquids and are promising biomarkers in numerous diseases. In cardiovascular disease mi RNAs have been proven to be reliable diagnostic biomarkers for different disease entities. In cardiac fibrosis(CF) and heart failure(HF) dysregulated circulating mi RNAs have been identified,indicating their promising applicability as diagnostic biomarkers. Some mi RNAs were successfully tested in risk stratification of HF implementing their potential use as prognostic biomarkers. In this respect mi RNAs might soon be implemented in diagnostic clinical routine. In the young field of mi RNA based research advances have been made in identifying mi RNAs as potential targets for the treatment of experimental CF and HF. Promising study results suggest their potential future application as therapeutic agents in treatment of cardiovascular disease. This article summarizes the current state of the various aspects of mi RNA research in the field of CF and HF with reduced ejection fraction as well as preserved ejection fraction. The review provides an overview of the application of circulating mi RNAs as biomarkers in CF and HF and current approaches to therapeutically utilize mi RNAs in this field of cardiovascular disease.
文摘Almost every experimental treatment strategy using non-autologous cell, tissue or organ transplantation is tested in small and large animal models before clinical translation. Because these strategies require immunosuppression in most cases, immunosuppressive protocols are a key element in transplantation experiments. However, standard immunosuppressive protocols are often applied without detailed knowledge regarding their efficacy within the particular experimental setting and in the chosen model species. Optimization of such protocols is pertinent to the translation of experimental results to human patients and thus warrants further investigation. This review summarizes current knowledge regarding immunosuppressive drug classes as well as their dosages and application regimens with consideration of species-specific drug metabolization and side effects. It also summarizes contemporary knowledge of novel immunomodulatory strategies, such as the use of mesenchymal stem cells or antibodies. Thus, this review is intended to serve as a state-of-the-art compendium for researchers to refine applied experimental immunosuppression and immunomodulation strategies to enhance the predictive value of preclinical transplantation studies.
文摘Objective To investigate the contributing factors and in-hospital prognosis of patients with or without recurrent acute myocardial infarction （AMI）. Methods A total of 1686 consecutive AMI patients admitted to Peking University People＇s Hospital from January 2010 to December 2015 were recruited. Their clinical characteristics were retrospectively compared between patients with or without a recurrent AMI. Then multivariable logistic regression was used to estimate the predictors of recurrent myocardial infarction. Results Recurrent AMI patients were older （69.3 ± 11.5 vs. 64.7 ± 12.8 years, P 〈 0.001） and had a higher prevalence of diabetes mellitus （DM） （52.2% vs. 35.0%, P 〈 0.001） compared with incident AMI patients, they also had worse heart function at admission, more severe coronary disease and lower reperfusion therapy. Age （OR = 1.03, 95% CI： 1.02-1.05; P 〈 0.001）, DM （OR = 1.86, 95% CI： 1.37-2.52; P 〈 0.001） and reperfusion therapy （OR = 0.74; 95% CI： 0.52-0.89; P 〈 0.001） were independent risk factors for recurrent AMI Recurrent AMI patients had a higher in-hospital death rate （12.1% vs. 7.8%, P = 0.039） than incident AMI patients. Conclusions Recurrent AMI patients presented with more severe coronary artery conditions. Age, DM and reperfusion therapy were independent risk factors for recurrent AMI, and recurrent AM1 was related with a high risk of in-hospital death.
基金the National Natural Science Foundation of China(No.81770356&No.81470473)the Capital Health Research and Development of Special(No.2016-2-4083).
文摘1 Introduction Effective and timely reperfusion of infarcted coronary artery is crucial to the treatment of patients with ST-segment elevation myocardial infarction(STEMI).[1,2]Current guidelines highly recommend that the door-to-balloon(D2B)time,as a quality metric of primary percutaneous coronary intervention(PCI)in patients with STEMI,should be≤90 min and preferably less than 60 min.[3,4]However,significant variations from guidelines exist in the real world practices at hospitals.
文摘Objective To study prognostic characteristics of cardiac troponin I （cTnI） elevation in acute ischemic stroke. Methods We retrospectively studied patients （n = 248） with acute ischemic stroke, acute ST-segment elevation myocardial infarction, and acute non-ST-elevation myocardial infarction who were treated between January 2013 and October 2015. Baseline demographic data and changes in cTnI levels among these three groups were compared. Patients with acute ischemic stroke were assigned to either the cTnI elevation group （cTnI 〉 0.034 ng/mL） or the no cTnI elevation group （cTnI ≤ 0.034 ng/mL）. Logistic regression analysis was used to identify risk factors associated with elevated serum cTnI in patients with acute ischemic stroke. Moreover, the duration of hospital stay and incidence of major cardiovascular outcomes were compared in patients with acute ischemic stroke, with or without elevated cTnI. Results In this study population of patients with acute ischemic stroke （n = 178）, acute ST-segment elevation myocardial infarction （n = 35）, and acute non-ST-elevation myocardial infarction （n = 35）, patients with acute ischemic stroke with elevated cTnI comprised 18.54% of subjects. Patients with elevated cTnI were older and more likely to have a history of hypertension. In addition, these patients had higher levels of inflammatory markers, reduced renal functions, increased D-dimer levels, higher NIH stroke scores, and lower left ventricular ejection fractions. Logistic regression analysis showed that both percentage of neutrophil and NIH stroke scores were elevated; estimated glomerular filtration rate and left ventricular ejection fraction were decreased in patients with acute ischemic stroke who had elevated cTnI, and they had more frequent major cardiovascular events during hospital stay. Conclusion Elevated cTnI detected in patients with acute ischemic stroke, indicated a greater likelihood of poor short-term prognosis during hospital stay.
文摘Cardiogenic shock(CS)following acute myocardial infarction(AMI)is a major challenge in cardiovascular care.Mortality remains high with 40%-50%after thirty days.Randomised controlled trials(RCTs)play a key role to generate evidence on optimal care in this field.However,the number of completed or ongoing RCTs is still relatively low compared to the gaps in evidence.Challenges in the conduct of these trials are in particular the selection of patients and ethical issues in the informed consent process.When determining eligibility criteria,special attention should be paid to the severity of CS,to the inclusion of patients with cardiac arrest and to potential age limits.Median age of AMI-CS patients is increasing.Age limits are therefore controversial as it is important to include elderly patients in RCTs in order to make the results generalisable and to address the special needs of this group.As patients with AMI-CS are in most cases unable to provide informed consent themselves,a step-wise approach with acute consent by a legal representative or independent physicians and later informed consent by the patient if possible might be established depending on regularities of the respective ethical review board and country legislation.Multicenter studies should be sought to generate adequate power.
文摘Background Recurrence of takotsubo cardiomyopathy （TTC） is a well-known complication. However, current literature lists only a few isolated cases. We aimed to determine the incidence and clinical significance of recurrent TTC. Methods ＆ Results Our institutional database constituted a collective of 114 patients diagnosed with TTC since 2003. Close follow-up of these patients revealed a recurrence of TTC in seven of these （6.1%）. The time interval between the index event and its recurrence varied between six months and six years. Arterial hypertension was more revealed in the recurrence group of TTC compared to non-recurrence group, （P = 0.02）. Chronic obstructive pulmo- nary disease and/or asthma was more diagnosed in the recurrence group, （P = 0.04）. Clinical events like fight ventficular involvement, TTC related complications such as life-threatening arrhythmias, pulmonary congestion and in hospital death were observed more frequently in the recurrent episode. Over a mean follow-up of one year the mortality rate was similar in both groups. Conclusions Recurrence of TTC within six years after index event is not an uncommon phenomenon. In the event of right ventricular involvement in the relapse phase, it might be associated with a higher complication rate. TTC recurrence should be the first differential diagnosis in patients with a past history of TTC.
文摘AIM To investigate matrix metalloproteinase-11(MMP-11) expression in adipose tissue dysfunction, using in vitro and in vivo models of insulin resistance.METHODS Culture of mouse 3T3-L1 preadipocytes were induced to differentiation into mature 3T3-L1 adipocytes. Cellular insulin resistance was induced by treating differentiated cultured adipocytes with hypoxia and/or tumor necrosis factor(TNF)-α, and transcriptional changes were analyzed in each condition thereafter. For the in vivo studies, MMP-11 expression levels were measured in white adipose tissue(WAT) from C57BL/6J mice that underwent low fat diet or high-fat feeding in order to induce obesity and obesity-related insulin resistance. Statistical analysis was carried out with GraphP ad Prism Software.RESULTS MMP-11 m RNA expression levels were significantly higher in insulin resistant 3T3-L1 adipocytes compared to control cells(1.46±0.49vs0.83±0.21, respectively;P<0.00036). The increase in MMP-11 expression was observed even in the presence of TNF-α alone(3.79±1.11vs1±0.17, P<0.01) or hypoxia alone(1.79±0.7vs0.88±0.1, P<0.00023). The results obtained in in vitro experiments were confirmed in the in vivo model of insulin resistance. In particular, MMP-11 m RNA was upregulated in WAT from obese mice compared to lean mice(5.5±2.8vs1.1±0.7, respectively; P<3.72E-08). The increase in MMP-11 levels in obese mice was accompanied by the increase in typical markers of fibrosis, such as collagen type Ⅵ alpha 3(Col6_α3), and fibroblast-specific protein 1.CONCLUSION Our results indicate that dysregulation of MMP-11 expression is an early process in the adipose tissue dysfunction, which leads to obesity and obesity-related insulin resistance.
文摘Background: Up to 60% of patients with ulcerative colitis are seen with nutrient deficiency;however, no specific diet is recommended. The aim of this study was to obtain knowledge on whether restriction or addition of specific food items might contribute to malnutrition in these patients. Methods: A qualitative semi-structured interview study of outpatient clinic patients with ulcerative colitis aimed to investigate preferences for or avoidance of specific food items related to abdominal symptoms. Results: The study included 25 patients (12 M, 13 F), average age 46.7 years (SD 15.6). Duration of disease ranged from 1 to 35 years. Restriction of food items was mainly due to discomfort associated with bowel symptoms, e.g. diarrhoea caused by sugar, dairies, alcohol, spices, red meat, and bread. Restrictions were based mainly on personal experience rather than professional guidance or knowledge search. Addition of specific food items most often included vitamin supplements. Only 20% took supplementary calcium, although many restricted the consumption of dairies from their diet. Conclusion: Many patients with ulcerative colitis restrict consumption of dairy products from their diet. This may lead to calcium deficiency. No other dietary restrictions, which might explain specific nutrient deficiencies, were identified.
文摘Coronary angiography is considered to be the gold standard in the morphological evaluation of coronary artery stenosis. The morphological assessment of the severity of a coronary lesion is very subjective. Thus, the invasive fractional flow reserve(FFR) measurement represents the current standard for estimation of the hemodynamic significance of coronary artery stenosis. The FFR-guided revascularization strategy was initially classified as a Class-IA-recommendation in the 2014 European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines on myocardial revascularization. Both the Deferral vs Performance of Percutaneous Coronary Intervention of Functionally Non-Significant Coronary Stenosis and Flow Reserve vs Angiography for Multivessel Evaluation studies showed no treatment advantage for hemodynamically insignificant stenoses. With the help of FFR(and targeted interventions), clinical results could be improved; however, the use in clinical practice is still limited due to the need of adenosine administration and a significant prolongation of the length of the procedure. Instantaneous wave-free ratio(iFR~) is a new innovative approach for the determination of the hemodynamic significance of coronary stenosis, which can be obtained at rest without the use of vasodilators. Regarding the periprocedural complications as well as prognosis, iFR~ showed non-inferiority to FFR in the SWEDEHEART and DEFINE-FLAIR trials. Furthermore, iFR~, enhanced by iFR~-pullback, provides the possibility to display the iFR~-change over the course of the vessel to create a hemodynamic map.
文摘A 67-year-old woman with a history of diabetes mellitus and smoking was admitted to our hospital with chest pain for one month. Her resting electrocardiogram and serial troponin I measurements were normal. As the coronary artery angiography performed in another hospital showed severe lesions in the left anterior descending artery, we planned to perform the intervention on the left anterior descending artery by stent. Before the procedure, clopidogrel （300 mg loading dose） was initiated.
