Growing evidence has demonstrated exercise as an effective way to promote cardiovascular health and protect against cardiovascular diseases However,the underlying mechanisms of the beneficial effects of exercise have ...Growing evidence has demonstrated exercise as an effective way to promote cardiovascular health and protect against cardiovascular diseases However,the underlying mechanisms of the beneficial effects of exercise have yet to be elucidated.Animal exercise studies are widely used to investigate the key mechanisms of exercise-induced cardiovascular protection.However,standardized procedures and well-established evaluation indicators for animal exercise models are needed to guide researchers in carrying out effective,high-quality animal studies using exercise to prevent and treat cardiovascular diseases.In our review,we present the commonly used animal exercise models in cardiovascular research and propose a set of standard procedures for exercise training,emphasizing the appropriate measurements and analysis in these chronic exercise models.We also provide recommendations for optimal design of animal exercise studies in cardiovascular research,including the choice of exercise models,control of exercise protocols,exercise at different stages of disease,and other considerations,such as age,sex,and genetic background.We hope that this position paper will promote basic research on exercise-induced cardiovascular protection and pave the way for successful translation of exercise studies from bench to bedside in the prevention and treatment of cardiovascular diseases.展开更多
BACKGROUND: It is challenging to establish peripheral intravenous access in adult critically patients. This study aims to compare the success rate of the first attempt, procedure time, operator satisfaction with the u...BACKGROUND: It is challenging to establish peripheral intravenous access in adult critically patients. This study aims to compare the success rate of the first attempt, procedure time, operator satisfaction with the used devices, pain score, and complications between intraosseous(IO) access and central venous catheterization(CVC) in critically ill Chinese patients.METHODS: In this prospective clustered randomized controlled trial, eight hospitals were randomly divided into either the IO group or the CVC group. Patients who needed emergency vascular access were included. From April 1, 2017 to December 31, 2018, each center included 12 patients. We recorded the data mentioned above.RESULTS: A total of 96 patients were enrolled in the study. There were no statistically significant differences between the two groups regarding sex, age, body mass index, or operator satisfaction with the used devices. The success rates of the first attempt and the procedure time were statistically significant between the IO group and the CVC group(91.7% vs. 50.0%, P<0.001;52.0 seconds vs. 900.0 seconds, P<0.001). During the study, 32 patients were conscious. There was no statistically significant difference between the two groups regarding the pain score associated with insertion. There were statistically significant differences between the two groups regarding the pain score associated with IO or CVC infusion(1.5 vs. 0.0, P=0.044). Complications were not observed in the two groups.CONCLUSIONS: IO access is a safe, rapid, and effective technique for gaining vascular access in critically ill adults with inaccessible peripheral veins in the emergency departments.展开更多
Immunoglobulin light chain amyloidosis(AL)is one of the most frequent causes of cardiac amyloidosis(CA),[1]with an estimated prevalence of 8 to 12 per million.[2−4]Multiple myeloma(MM)is hematological neoplasia origin...Immunoglobulin light chain amyloidosis(AL)is one of the most frequent causes of cardiac amyloidosis(CA),[1]with an estimated prevalence of 8 to 12 per million.[2−4]Multiple myeloma(MM)is hematological neoplasia originating from plasma cells,which is the most common disease that can lead to CA.The median age of patients with MM at diagnosis is about 65 years old.In this age group,cardiovascular diseases often co-exist,increasing the risk of adverse events related to MM treatment.By convention,the prognosis of AL-CA with MM is extremely poor,with a median survival time of five months.[5]The degree of cardiac involvement has a decisive impact on the prognosis of AL-CA pati-ents.展开更多
BACKGROUND Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism.However,the causal relationship of thyroid function and cardiometabolic health remai...BACKGROUND Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism.However,the causal relationship of thyroid function and cardiometabolic health remains partly unknown.METHODS The Mendelian randomization(MR)was used to test genetic,potentially causal relationships between instrumental variables and cardiometabolic traits.Genetic variants of free thyroxine(FT4)and thyrotropin(TSH)levels within the reference range were used as instrumental variables.Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen,CARDIoGRAM and CARDIoGRAMplusC4D,CHARGE,and MEGASTROKE.This study was conducted using summary statistic data from large,previously described cohorts.Association between thyroid function and essential hypertension(EHTN),secondary hypertension(SHTN),hyperlipidemia(HPL),type 2 diabetes mellitus(T2DM),ischemic heart disease(IHD),myocardial infarction(MI),heart failure(HF),pulmonary heart disease(PHD),stroke,and non-rheumatic valve disease(NRVD)were examined.RESULTS Genetically predicted FT4 levels were associated with SHTN(odds ratio=0.48;95%CI=0.04−0.82,P=0.027),HPL(odds ratio=0.67;95%CI=0.18−0.88,P=0.023),T2DM(odds ratio=0.80;95%CI=0.42−0.86,P=0.005),IHD(odds ratio=0.85;95%CI=0.49−0.98,P=0.039),NRVD(odds ratio=0.75;95%CI=0.27−0.97,P=0.039).Additionally,genetically predicted TSH levels were associated with HF(odds ratio=0.82;95%CI=0.68−0.99,P=0.042),PHD(odds ratio=0.75;95%CI=0.32−0.82,P=0.006),stroke(odds ratio=0.95;95%CI=0.81−0.97,P=0.007).However,genetically predicted thyroid function traits were not associated with EHTN and MI.CONCLUSIONS Our study suggests FT4 and TSH are associated with cardiometabolic diseases,underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.展开更多
OBJECTIVE To formulate a nomogram to predict the risk of one-year mortality after percutaneous coronary intervention(PCI)based on a large-scale real-world Asian cohort.METHODS This study cohort included consecutive pa...OBJECTIVE To formulate a nomogram to predict the risk of one-year mortality after percutaneous coronary intervention(PCI)based on a large-scale real-world Asian cohort.METHODS This study cohort included consecutive patients undergoing PCI in the National Center for Cardiovascular Diseases of China.The endpoint was all-cause mortality.Least absolute shrinkage and selection operator Cox regression and backward stepwise regression were used to select potential risk factors.A nomogram based on the predictors was accordingly constructed to predict one-year mortality.The performance of the nomogram was evaluated.Patients were stratified into low-,intermediate-and high-risk groups according to the tertile points in the nomogram and compared by the Kaplan-Meier analysis.RESULTS A total of 9603 individuals were included in this study and randomly divided into the derivation cohort(60%)and the validation cohort(40%).Six variables were selected to formulate the nomogram,including age,renal insufficiency,cardiac dysfunction,previous cerebrovascular disease,previous PCI,and TIMI 0–1 before PCI.The area under the curve of this nomogram regarding one-year mortality risks were 0.792 and 0.754 in the derivation cohort and validation cohort,respectively.Kaplan-Meier curve successfully stratified the patients according to three risk groups.This nomogram calibrated well and exhibited satisfactory clinical utility in the decision curve analysis.CONCLUSIONS This study developed and validated a simple-to-use nomogram predicting one-year mortality risk in Asian patients undergoing PCI and could help clinicians make risk-dependent decisions.展开更多
The core treatment of rapid arrhythmiainduced heart failure(HF)is to control the ventricular rate to an optimized lower level,which is usually achieved with various anti-arrhythmic drugs.However,arrhythmias may not re...The core treatment of rapid arrhythmiainduced heart failure(HF)is to control the ventricular rate to an optimized lower level,which is usually achieved with various anti-arrhythmic drugs.However,arrhythmias may not respond well to pharmaceutical treatment for various reasons.Iatrogenic atrioventricular(AV)node ablation needs to be performed under these extreme conditions to lower the patient’s heart rate.展开更多
BACKGROUND:The predictive scoring systems for early stent thrombosis(EST)remains blank in China.The study aims to evaluate the risk factors and conduct a prediction model of EST in the Chinese population.METHODS:EST w...BACKGROUND:The predictive scoring systems for early stent thrombosis(EST)remains blank in China.The study aims to evaluate the risk factors and conduct a prediction model of EST in the Chinese population.METHODS:EST was defined as thrombosis that occurs within the first 30 days after primary percutaneous coronary intervention(PCI).Patients from ten Chinese hospitals diagnosed as stent thrombosis(ST)from January 2010 to December 2016 were retrospectively included as the study group.A control group(1 case:2 controls)was created by including patients without ST,major adverse cardiovascular events,or cerebrovascular events during follow-up.The present study evaluated 426 patients with single-vessel lesions and ultimately included 40 patients with EST and 80 control patients,who were included to identify factors that predicted EST and to develop a prediction scoring system.The other 171 patients without integrated 1:2 pair were used for external validation.RESULTS:EST was independently associated with a low hemoglobin concentration(adjusted odds ratio[OR]0.946,95%confi dence interval[95%CI]0.901-0.993,P=0.026),a high pre-PCI Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery(SYNTAX)score(OR 1.166,95%CI 1.049-1.297,P=0.004),and a DAPT(DAPT)duration of<30 days(OR 28.033,95%CI 5.302-272.834,P<0.001).The simple EST prediction score provided an area under the curve(AUC)of 0.854(95%CI 0.777-0.932,P<0.001)with 70.0%sensitivity and 90.0%specifi city,and 0.742(95%CI 0.649-0.835,P<0.001)with 54.5%sensitivity and 81.0%specifi city for external validation dataset.CONCLUSIONS:EST may be independently associated with DAPT discontinuation within 30 days,a low hemoglobin concentration,and a high SYNTAX score.The scoring system also has a good ability to predict the risk of EST and may be useful in the clinical setting.展开更多
Aortic aneurysm is a chronic aortic disease affected by many factors.Although it is generally asymptomatic,it poses a significant threat to human life due to a high risk of rupture.Because of its strong concealment,it...Aortic aneurysm is a chronic aortic disease affected by many factors.Although it is generally asymptomatic,it poses a significant threat to human life due to a high risk of rupture.Because of its strong concealment,it is difficult to diagnose the disease in the early stage.At present,there are no effective drugs for the treatment of aneurysms.Surgical intervention and endovascular treatment are the only therapies.Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm,the specific mechanisms remain unclear.Researchers are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and treatment.To better understand aortic aneurysm,this review elaborates on the discovery history of aortic aneurysm,main classification and clinical manifestations,related molecular mechanisms,clinical cohort studies and animal models,with the ultimate goal of providing insights into the treatment of this devastating disease.The underlying problem with aneurysm disease is weakening of the aortic wall,leading to progressive dilation.If not treated in time,the aortic aneurysm eventually ruptures.An aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic wall.The disease is usually asymptomatic but leads to high mortality due to the risk of artery rupture.展开更多
Background Coronary artery calcification(CAC)is common in end-stage renal disease(ESRD)patients,and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients.Cartilage oligomeric matrix protein(...Background Coronary artery calcification(CAC)is common in end-stage renal disease(ESRD)patients,and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients.Cartilage oligomeric matrix protein(COMP),as a component of the vascular matrix,has been found to be an inhibitor of arterial calcification in basic studies.However,there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis(MHD)patients.The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients.Methods Serum COMP levels were compared between 54 MHD patients and 66 healthy people.MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events(MACEs),which were defined as a combined end point of new onset angina pectoris,nonfatal myocardial infarction,heart failure,coronary artery revascularization,hospitalization due to angina pectoris and all-cause deaths.The CAC score was calculated based on computed tomography scans.Results The serum COMP level in MHD patients was significantly higher than that in the general population[984.23(248.43-1902.61)ng/mL vs.219.01(97.26-821.92)ng/mL,P<0.01].Serum COMP levels were positively correlated with CAC(r=0.313,P=0.021)and serum parathyroid hormone in MHD patients(r=0.359,P<0.01).Linear regression suggested that after adjusting for age,fasting blood glucose(Glu)and glycosylated hemoglobin(HbAlc),CAC score was an independent predictor in the final model for COMP level(β=0.424,t=3.130,P<0.01).The receiver operating characteristic(ROC)curve showed that COMP≥994 mg/mL had 68.0%sensitivity and 72.4%specificity for the prediction of severe CAC[area under the curve(AUC):0.674,P=0.030,95%CI:0.526-0.882].After a median follow-up of 16 months(8-24 months),there was no difference in the incidence rate of MACEs between the upper,middle and lower serum COMP groups.Conclusions Our study found that MHD patients have higher levels of circulating COMP than controls.The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients.However,there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.展开更多
Purpose:Given the information overload of scientific literature,there is an increasing need for computable biomedical knowledge buried in free text.This study aimed to develop a novel approach to extracting and measur...Purpose:Given the information overload of scientific literature,there is an increasing need for computable biomedical knowledge buried in free text.This study aimed to develop a novel approach to extracting and measuring uncertain biomedical knowledge from scientific statements.Design/methodology/approach:Taking cardiovascular research publications in China as a sample,we extracted subject-predicate-object triples(SPO triples)as knowledge units and unknown/hedging/conflicting uncertainties as the knowledge context.We introduced information entropy(IE)as potential metric to quantify the uncertainty of epistemic status of scientific knowledge represented at subject-object pairs(SO pairs)levels.Findings:The results indicated an extraordinary growth of cardiovascular publications in China while only a modest growth of the novel SPO triples.After evaluating the uncertainty of biomedical knowledge with IE,we identified the Top 10 SO pairs with highest IE,which implied the epistemic status pluralism.Visual presentation of the SO pairs overlaid with uncertainty provided a comprehensive overview of clusters of biomedical knowledge and contending topics in cardiovascular research.Research limitations:The current methods didn’t distinguish the specificity and probabilities of uncertainty cue words.The number of sentences surrounding a given triple may also influence the value of IE.Practical implications:Our approach identified major uncertain knowledge areas such as diagnostic biomarkers,genetic polymorphism and co-existing risk factors related to cardiovascular diseases in China.These areas are suggested to be prioritized;new hypotheses need to be verified,while disputes,conflicts,and contradictions need to be settled.Originality/value:We provided a novel approach by combining natural language processing and computational linguistics with informetric methods to extract and measure uncertain knowledge from scientific statements.展开更多
Background:Exercise training protects against heart failure.However,the mechanism underlying the protective effect of exercise training on angiotensinⅡ(AngⅡ)-induced cardiac fibrosis remains unclear.Methods:An exerc...Background:Exercise training protects against heart failure.However,the mechanism underlying the protective effect of exercise training on angiotensinⅡ(AngⅡ)-induced cardiac fibrosis remains unclear.Methods:An exercise model involving C57BL/6N mice and 6 weeks of treadmill training was used.AngⅡ(1.44 mg/kg/day)was administered to induce cardiac fibrosis.RNA sequencing and bioinformatic analysis were used to identify the key factors mediating the effects of exercise training on cardiac fibrosis.Primary adult mouse cardiac fibroblasts(CFs)were used in vitro.Adeno-associated virus serotype 9 was used to overexpress POU domain,class 2,transcription factor 1(POU2F1)in vivo.Results:Exercise training attenuated AngⅡ-induced cardiac fibrosis and reversed 39 gene expression changes.The transcription factor regulating the largest number of these genes was POU2F1.Compared to controls,POU2F1 was shown to be signififcantly upregulated by AngⅡ,which is itself reduced by exercise training.In vivo,POU2F1 overexpression nullified the benefits of exercise training on cardiac fibrosis.In CFs,POU2F1 promoted cardiac fibrosis.CCAAT enhancer-binding proteinβ(C/EBPβ)was predicted to be the transcription factor of POU2F1and verified using a dual-luciferase reporter assay.In vivo,exercise training activated AMP-activated protein kinase(AMPK)and alleviated the increase in C/EBPβinduced by AngⅡ.In CFs,AMPK agonist inhibited the increase in C/EBPβand POU2F1 induced by Ang II,whereas AMPK inhibitor reversed this effect.Conclusion:Exercise training attenuates AngⅡ-induced cardiac fibrosis by reducing POU2F1.Exercise training inhibits POU2F1 by activating AMPK,which is followed by the downregulation of C/EBPβ,the transcription factor of POU2F1.展开更多
The concentration of biomarkers in sweat can be used to evaluate human health,making efficient sweat sensing a focus of research.While flow channel design is often used to detect sweat velocity,it is rarely incorporat...The concentration of biomarkers in sweat can be used to evaluate human health,making efficient sweat sensing a focus of research.While flow channel design is often used to detect sweat velocity,it is rarely incorporated into the sensing of biomarkers,limiting the richness of sensing results.In this study,we report a time sequential sensing scheme for uric acid in sweat through a sequential design of Tesla valve channels.Graphene electrodes for detecting uric acid and directional Tesla valve flow channels were fabricated using laser engraving technology to realize time sequential sensing.The performance of the channels was verified through simulation.The time sequential detection of uric acid concentration in sweat can help researchers improve the establishment of human health management systems through flexible wearable devices.展开更多
Dear Editor,In development,after cells make a commitment to their fates,they undergo a continuous and adaptive maturation process to eventually reach their terminal states.Cell maturity often decays during aging and p...Dear Editor,In development,after cells make a commitment to their fates,they undergo a continuous and adaptive maturation process to eventually reach their terminal states.Cell maturity often decays during aging and pathogenesis.The immature phenotypes of stem cell-differentiated cells deposit a major bottleneck in regenerative medicine.展开更多
Background:Angiopoietin-2(Ang-2)is a type of endothelial growth factor involved in angiogenesis and vascular remodeling.Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease(CAD).T...Background:Angiopoietin-2(Ang-2)is a type of endothelial growth factor involved in angiogenesis and vascular remodeling.Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease(CAD).This study aimed to evaluate the association between serum Ang-2 levels and coronary microvascular dysfunction in patients without obstructive CAD.Methods:A total of 125 patients with angina in the absence of obstructive CAD were included in this cross-sectional study.Coronary flow reserve(CFR)was measured in the distal left anterior descending coronary artery by trans-thoracic Doppler echocardiography.The patients were divided into the following two sub-groups according to CFR:the impaired CFR group with CFR values<2.5 and the preserved CFR group with CFR values≥2.5.Serum Ang-2 levels were determined using enzyme-linked immunosorbent assay.Independent predictors for impaired CFR were identified by binary logistic regression analysis.The receiveroperating characteristic curve was determined to evaluate the ability of serum Ang-2 in predicting impaired CFR.Results:We found that age,percentage of female sex,N-terminal pro-B-type natriuretic peptide levels,Ang-2 levels(763.3±264.9 vs.579.7±169.3 pg/mL,P<0.001),and the left atrial volume index were significantly higher in patients with impaired CFR than in patients with preserved CFR.Serum Ang-2 levels were negatively correlated with CFR(r=0.386,P<0.001).Binary logistic regression analysis showed that Ang-2(odds ratio:1.004,95%confidence interval[CI]:1.001–1.006,P=0.003)and age(odds ratio:1.088,95%CI:1.023–1.156,P=0.007)were independently associated with impaired CFR.Furthermore,Ang-2 was a significant predictor of impaired CFR on the receiver-operating characteristic curve(P<0.001).The area under the curve was 0.712(95%CI:0.612–0.813).Conclusions:High serum Ang-2 levels are independently associated with impaired CFR in patients with angina in the absence of obstructive CAD.展开更多
Population aging has emerged as one of the most pressing global demographic issues.Rapid population aging is being caused by a sharp drop in fertility rates over time,as well as a significant increase in life expectan...Population aging has emerged as one of the most pressing global demographic issues.Rapid population aging is being caused by a sharp drop in fertility rates over time,as well as a significant increase in life expectancy in the past decades.The World Health Organization(WHO)estimates that the proportion of those aged 60 years and older in the world’s population will almost double from approximately 12%in 2015 to 22%in 2050,with an absolute increase of 900 million to a total of 2 billion older adults(1).At the same time,the burden of global disease has changed greatly and the main diseases affecting human health have switched from acute and chronic infectious diseases to chronic non-communicable diseases(NCDs)(2).Such changing demographics and disease spectrum will profoundly affect all aspects of human society.展开更多
Summary What is already known about this topic?Rehabilitation is an essential part of achieving health for all,whereas the estimates of rehabilitation needs,especially for elderly individuals in China,are not clear.Wh...Summary What is already known about this topic?Rehabilitation is an essential part of achieving health for all,whereas the estimates of rehabilitation needs,especially for elderly individuals in China,are not clear.What is added by this report?Compared with 1990,the prevalence and years of life lived with disability for health conditions in need of rehabilitation in China increased by 71.3%and 77.0%in 2019,respectively,at a rate much higher than the global average.What are the implications for public health practices?This study mainly presents scientific data and a systematic analysis of the current state and challenges of rehabilitation needs for elderly individuals(aged 60 and above)in China based on the World Health Organization Rehabilitation Need Estimator.展开更多
In an era of rapid advancements in artificial intelligence(AI),the potential role of large language models(LLMs)in the medical field is receiving increasing attention.The progression of this technology not only highli...In an era of rapid advancements in artificial intelligence(AI),the potential role of large language models(LLMs)in the medical field is receiving increasing attention.The progression of this technology not only highlights upcoming revolutionary changes in medical services but also offers unprecedented opportunities for the health care sector.1 LLMs’formidable capability to process natural language opens vast prospects for application in the medical field,including in the contexts of emergency triage,geriatric care,and digital medical workflows.展开更多
Heart failure(HF) is a major clinical concern owing to its high prevalence and high mortality.Metabolomics,an effective approach to predict diagnostic biomarkers and to explore the altered metabolic pathways in pathog...Heart failure(HF) is a major clinical concern owing to its high prevalence and high mortality.Metabolomics,an effective approach to predict diagnostic biomarkers and to explore the altered metabolic pathways in pathogenesis,has been extensively applied in evaluating the course of diseases.In this study,we used this approach to analyse the abundance of metabolites,with liquid chromatograph-mass spectrometer,in plasma samples from rats with transverse aortic constriction(TAC) and patients at different stages of HF.We compared the metabolic parameters within and between TAC rats and patients.An apparent metabolic shift was observed in rats,from compensated hypertrophy stage to decompensated hypertrophy stage,and in patients with HF,from stage A to stage B and subsequently stage C.Diagnostic biomarkers were predicted by comparing the variable importance in the projection scores and fold change analysis within and between rats and patients.Enrichment pathway analysis and network analysis provided an overview of the largely disturbed metabolic pathways,and those interfered at different stages and across species were confirmed.The significantly changed metabolites and pathways revealed the underlying mechanisms of HF pathogenesis,hinted at novel potential biomarkers,and provided potential therapeutic intervention targets for HF.展开更多
Macrophage migration inhibitory factor(MIF) is an inflammatory cytokine. It is elevated early in the blood of acute myocardial infarction patients. However, it is unclear whether and how MIF is released. This study in...Macrophage migration inhibitory factor(MIF) is an inflammatory cytokine. It is elevated early in the blood of acute myocardial infarction patients. However, it is unclear whether and how MIF is released. This study investigated the cellular source and mechanism of MIF release from hearts. An ischemia-mimic treatment induced the secretion of MIF from neonatal rat cardiomyocytes but not from fibroblasts. The treatment did not cause significant leakage of lactate dehydrogenase, suggesting that ischemia induced the MIF secretion without causing severe cell damage. Plasma samples from patients with acute chest pain at the emergency department were collected for the detection of MIF. MIF levels in patients with acute coronary syndrome(ACS)increased early, when cardiac injury markers were not yet elevated, suggesting that ischemia can induce MIF secretion before the occurrence of severe myocardial damage. Serum-starvation caused MIF secretion from rat cardiomyocytes and Langendorffperfused rat hearts. The secretion was suppressed by the inhibition of autophagy by inhibitors or by silencing of Atg5. In conclusion, serum-starvation induces the secretion of MIF from cardiomyocytes via autophagy dependent pathway. Clarifying the mechanism of MIF secretion will be helpful for its application in the early diagnosis and treatment of ACS.展开更多
Chloroquine(CQ)phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019(COVID-19).To develop a physiologically-based pharmacokinetic(PBPK)model for predicting tissue distrib...Chloroquine(CQ)phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019(COVID-19).To develop a physiologically-based pharmacokinetic(PBPK)model for predicting tissue distribution of CQ and apply it to optimize dosage regimens,a PBPK model,with parameterization of drug distribution extrapolated from animal data,was developed to predict human tissue distribution of CQ.The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism.Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships.The model was also validated by clinical data from Chinese patients with COVID-19.The novel PBPK model allows indepth description of the pharmacokinetics of CQ in several key organs(lung,heart,liver,and kidney),and was applied to design dosing strategies in patients with acute COVID-19(Day 1:750 mg BID,Days 2-5:500 mg BID,CQ phosphate),patients with moderate COVID-19(Day 1:750 mg and 500 mg,Days 2-3:500 mg BID,Days 4-5:250 mg BID,CQ phosphate),and other vulnerable populations(e.g.,renal and hepatic impairment and elderly patients,Days 1-5:250 mg BID,CQ phosphate).A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.展开更多
基金This work was supported by grants from the National Key Research and Development Project(2020YFA0803800 to YB)National Natural Science Foundation of China(82020108002 and 81911540486 to JX,81772444 to LW,81772466 to RD)+2 种基金Innovation Program of Shanghai Municipal Education Commission(2017-01-07-00-09-E00042 to JX)Science and Technology Commission of Shanghai Municipality(18410722200 and 17010500100 to JX)“Dawn”Program of the Shanghai Education Commission(19SG34 to JX)。
文摘Growing evidence has demonstrated exercise as an effective way to promote cardiovascular health and protect against cardiovascular diseases However,the underlying mechanisms of the beneficial effects of exercise have yet to be elucidated.Animal exercise studies are widely used to investigate the key mechanisms of exercise-induced cardiovascular protection.However,standardized procedures and well-established evaluation indicators for animal exercise models are needed to guide researchers in carrying out effective,high-quality animal studies using exercise to prevent and treat cardiovascular diseases.In our review,we present the commonly used animal exercise models in cardiovascular research and propose a set of standard procedures for exercise training,emphasizing the appropriate measurements and analysis in these chronic exercise models.We also provide recommendations for optimal design of animal exercise studies in cardiovascular research,including the choice of exercise models,control of exercise protocols,exercise at different stages of disease,and other considerations,such as age,sex,and genetic background.We hope that this position paper will promote basic research on exercise-induced cardiovascular protection and pave the way for successful translation of exercise studies from bench to bedside in the prevention and treatment of cardiovascular diseases.
基金supported by the Capital Clinical Characteristic Applied Research Project(z151100004015118)the Fostering and Exploring Project of Key Clinical Projects in the Peking University Third Hospital(BYSY2014006)the Health Science Promotion Project of Beijing(TG-2017-83)。
文摘BACKGROUND: It is challenging to establish peripheral intravenous access in adult critically patients. This study aims to compare the success rate of the first attempt, procedure time, operator satisfaction with the used devices, pain score, and complications between intraosseous(IO) access and central venous catheterization(CVC) in critically ill Chinese patients.METHODS: In this prospective clustered randomized controlled trial, eight hospitals were randomly divided into either the IO group or the CVC group. Patients who needed emergency vascular access were included. From April 1, 2017 to December 31, 2018, each center included 12 patients. We recorded the data mentioned above.RESULTS: A total of 96 patients were enrolled in the study. There were no statistically significant differences between the two groups regarding sex, age, body mass index, or operator satisfaction with the used devices. The success rates of the first attempt and the procedure time were statistically significant between the IO group and the CVC group(91.7% vs. 50.0%, P<0.001;52.0 seconds vs. 900.0 seconds, P<0.001). During the study, 32 patients were conscious. There was no statistically significant difference between the two groups regarding the pain score associated with insertion. There were statistically significant differences between the two groups regarding the pain score associated with IO or CVC infusion(1.5 vs. 0.0, P=0.044). Complications were not observed in the two groups.CONCLUSIONS: IO access is a safe, rapid, and effective technique for gaining vascular access in critically ill adults with inaccessible peripheral veins in the emergency departments.
基金This work was supported by grants from the National Natural Science Foundation of China(grant No.81972149,81871850)Beijing Natural Science Foundation(grant No.7212125).
文摘Immunoglobulin light chain amyloidosis(AL)is one of the most frequent causes of cardiac amyloidosis(CA),[1]with an estimated prevalence of 8 to 12 per million.[2−4]Multiple myeloma(MM)is hematological neoplasia originating from plasma cells,which is the most common disease that can lead to CA.The median age of patients with MM at diagnosis is about 65 years old.In this age group,cardiovascular diseases often co-exist,increasing the risk of adverse events related to MM treatment.By convention,the prognosis of AL-CA with MM is extremely poor,with a median survival time of five months.[5]The degree of cardiac involvement has a decisive impact on the prognosis of AL-CA pati-ents.
文摘BACKGROUND Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism.However,the causal relationship of thyroid function and cardiometabolic health remains partly unknown.METHODS The Mendelian randomization(MR)was used to test genetic,potentially causal relationships between instrumental variables and cardiometabolic traits.Genetic variants of free thyroxine(FT4)and thyrotropin(TSH)levels within the reference range were used as instrumental variables.Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen,CARDIoGRAM and CARDIoGRAMplusC4D,CHARGE,and MEGASTROKE.This study was conducted using summary statistic data from large,previously described cohorts.Association between thyroid function and essential hypertension(EHTN),secondary hypertension(SHTN),hyperlipidemia(HPL),type 2 diabetes mellitus(T2DM),ischemic heart disease(IHD),myocardial infarction(MI),heart failure(HF),pulmonary heart disease(PHD),stroke,and non-rheumatic valve disease(NRVD)were examined.RESULTS Genetically predicted FT4 levels were associated with SHTN(odds ratio=0.48;95%CI=0.04−0.82,P=0.027),HPL(odds ratio=0.67;95%CI=0.18−0.88,P=0.023),T2DM(odds ratio=0.80;95%CI=0.42−0.86,P=0.005),IHD(odds ratio=0.85;95%CI=0.49−0.98,P=0.039),NRVD(odds ratio=0.75;95%CI=0.27−0.97,P=0.039).Additionally,genetically predicted TSH levels were associated with HF(odds ratio=0.82;95%CI=0.68−0.99,P=0.042),PHD(odds ratio=0.75;95%CI=0.32−0.82,P=0.006),stroke(odds ratio=0.95;95%CI=0.81−0.97,P=0.007).However,genetically predicted thyroid function traits were not associated with EHTN and MI.CONCLUSIONS Our study suggests FT4 and TSH are associated with cardiometabolic diseases,underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.
基金supported by the National Key R&D Program of China(2020YFC2004705)the National Natural Science Foundation of China(No.81825003&No.91957123&No.82270376)the Beijing Nova Program from Beijing Municipal Science&Technology Commission(Z201100006820002)。
文摘OBJECTIVE To formulate a nomogram to predict the risk of one-year mortality after percutaneous coronary intervention(PCI)based on a large-scale real-world Asian cohort.METHODS This study cohort included consecutive patients undergoing PCI in the National Center for Cardiovascular Diseases of China.The endpoint was all-cause mortality.Least absolute shrinkage and selection operator Cox regression and backward stepwise regression were used to select potential risk factors.A nomogram based on the predictors was accordingly constructed to predict one-year mortality.The performance of the nomogram was evaluated.Patients were stratified into low-,intermediate-and high-risk groups according to the tertile points in the nomogram and compared by the Kaplan-Meier analysis.RESULTS A total of 9603 individuals were included in this study and randomly divided into the derivation cohort(60%)and the validation cohort(40%).Six variables were selected to formulate the nomogram,including age,renal insufficiency,cardiac dysfunction,previous cerebrovascular disease,previous PCI,and TIMI 0–1 before PCI.The area under the curve of this nomogram regarding one-year mortality risks were 0.792 and 0.754 in the derivation cohort and validation cohort,respectively.Kaplan-Meier curve successfully stratified the patients according to three risk groups.This nomogram calibrated well and exhibited satisfactory clinical utility in the decision curve analysis.CONCLUSIONS This study developed and validated a simple-to-use nomogram predicting one-year mortality risk in Asian patients undergoing PCI and could help clinicians make risk-dependent decisions.
基金This study was supported by the National Natural Science Foundation of China(No.31700674).
文摘The core treatment of rapid arrhythmiainduced heart failure(HF)is to control the ventricular rate to an optimized lower level,which is usually achieved with various anti-arrhythmic drugs.However,arrhythmias may not respond well to pharmaceutical treatment for various reasons.Iatrogenic atrioventricular(AV)node ablation needs to be performed under these extreme conditions to lower the patient’s heart rate.
基金from National Key R&D Program of China(2016YFC1301300,2016YFC1301302)。
文摘BACKGROUND:The predictive scoring systems for early stent thrombosis(EST)remains blank in China.The study aims to evaluate the risk factors and conduct a prediction model of EST in the Chinese population.METHODS:EST was defined as thrombosis that occurs within the first 30 days after primary percutaneous coronary intervention(PCI).Patients from ten Chinese hospitals diagnosed as stent thrombosis(ST)from January 2010 to December 2016 were retrospectively included as the study group.A control group(1 case:2 controls)was created by including patients without ST,major adverse cardiovascular events,or cerebrovascular events during follow-up.The present study evaluated 426 patients with single-vessel lesions and ultimately included 40 patients with EST and 80 control patients,who were included to identify factors that predicted EST and to develop a prediction scoring system.The other 171 patients without integrated 1:2 pair were used for external validation.RESULTS:EST was independently associated with a low hemoglobin concentration(adjusted odds ratio[OR]0.946,95%confi dence interval[95%CI]0.901-0.993,P=0.026),a high pre-PCI Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery(SYNTAX)score(OR 1.166,95%CI 1.049-1.297,P=0.004),and a DAPT(DAPT)duration of<30 days(OR 28.033,95%CI 5.302-272.834,P<0.001).The simple EST prediction score provided an area under the curve(AUC)of 0.854(95%CI 0.777-0.932,P<0.001)with 70.0%sensitivity and 90.0%specifi city,and 0.742(95%CI 0.649-0.835,P<0.001)with 54.5%sensitivity and 81.0%specifi city for external validation dataset.CONCLUSIONS:EST may be independently associated with DAPT discontinuation within 30 days,a low hemoglobin concentration,and a high SYNTAX score.The scoring system also has a good ability to predict the risk of EST and may be useful in the clinical setting.
基金This work was supported by the National Natural Science Foundation of China(81970425)by the National High Technology Research and Development Program of China(2020YFA0803700),and by Hangzhou Qianjiang Distinguished Expert Project(Prof.Lemin Zheng).
文摘Aortic aneurysm is a chronic aortic disease affected by many factors.Although it is generally asymptomatic,it poses a significant threat to human life due to a high risk of rupture.Because of its strong concealment,it is difficult to diagnose the disease in the early stage.At present,there are no effective drugs for the treatment of aneurysms.Surgical intervention and endovascular treatment are the only therapies.Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm,the specific mechanisms remain unclear.Researchers are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and treatment.To better understand aortic aneurysm,this review elaborates on the discovery history of aortic aneurysm,main classification and clinical manifestations,related molecular mechanisms,clinical cohort studies and animal models,with the ultimate goal of providing insights into the treatment of this devastating disease.The underlying problem with aneurysm disease is weakening of the aortic wall,leading to progressive dilation.If not treated in time,the aortic aneurysm eventually ruptures.An aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic wall.The disease is usually asymptomatic but leads to high mortality due to the risk of artery rupture.
基金supported by the National Natural Science Foundation of China(81400262)the Backbone Fund of Peking University Third Hospital(Y72497-04)
文摘Background Coronary artery calcification(CAC)is common in end-stage renal disease(ESRD)patients,and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients.Cartilage oligomeric matrix protein(COMP),as a component of the vascular matrix,has been found to be an inhibitor of arterial calcification in basic studies.However,there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis(MHD)patients.The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients.Methods Serum COMP levels were compared between 54 MHD patients and 66 healthy people.MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events(MACEs),which were defined as a combined end point of new onset angina pectoris,nonfatal myocardial infarction,heart failure,coronary artery revascularization,hospitalization due to angina pectoris and all-cause deaths.The CAC score was calculated based on computed tomography scans.Results The serum COMP level in MHD patients was significantly higher than that in the general population[984.23(248.43-1902.61)ng/mL vs.219.01(97.26-821.92)ng/mL,P<0.01].Serum COMP levels were positively correlated with CAC(r=0.313,P=0.021)and serum parathyroid hormone in MHD patients(r=0.359,P<0.01).Linear regression suggested that after adjusting for age,fasting blood glucose(Glu)and glycosylated hemoglobin(HbAlc),CAC score was an independent predictor in the final model for COMP level(β=0.424,t=3.130,P<0.01).The receiver operating characteristic(ROC)curve showed that COMP≥994 mg/mL had 68.0%sensitivity and 72.4%specificity for the prediction of severe CAC[area under the curve(AUC):0.674,P=0.030,95%CI:0.526-0.882].After a median follow-up of 16 months(8-24 months),there was no difference in the incidence rate of MACEs between the upper,middle and lower serum COMP groups.Conclusions Our study found that MHD patients have higher levels of circulating COMP than controls.The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients.However,there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.
基金funded by the National Natural Science Foundation of China(nos.71603280,72074006,and 82070235)the Beijing Municipal Natural Science Foundation(7191013)+1 种基金Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases,Chinese Academy of Medical Sciences(2021RU003)Peking University Health Science Center and the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(2017QNRC001).
文摘Purpose:Given the information overload of scientific literature,there is an increasing need for computable biomedical knowledge buried in free text.This study aimed to develop a novel approach to extracting and measuring uncertain biomedical knowledge from scientific statements.Design/methodology/approach:Taking cardiovascular research publications in China as a sample,we extracted subject-predicate-object triples(SPO triples)as knowledge units and unknown/hedging/conflicting uncertainties as the knowledge context.We introduced information entropy(IE)as potential metric to quantify the uncertainty of epistemic status of scientific knowledge represented at subject-object pairs(SO pairs)levels.Findings:The results indicated an extraordinary growth of cardiovascular publications in China while only a modest growth of the novel SPO triples.After evaluating the uncertainty of biomedical knowledge with IE,we identified the Top 10 SO pairs with highest IE,which implied the epistemic status pluralism.Visual presentation of the SO pairs overlaid with uncertainty provided a comprehensive overview of clusters of biomedical knowledge and contending topics in cardiovascular research.Research limitations:The current methods didn’t distinguish the specificity and probabilities of uncertainty cue words.The number of sentences surrounding a given triple may also influence the value of IE.Practical implications:Our approach identified major uncertain knowledge areas such as diagnostic biomarkers,genetic polymorphism and co-existing risk factors related to cardiovascular diseases in China.These areas are suggested to be prioritized;new hypotheses need to be verified,while disputes,conflicts,and contradictions need to be settled.Originality/value:We provided a novel approach by combining natural language processing and computational linguistics with informetric methods to extract and measure uncertain knowledge from scientific statements.
基金supported by the National Natural Science Foundation of China(82030072 to HX,81871850 to HY,81972149 to WG,and 81830009 to YZ)Beijing Natural Science Foundation(No.7212125 to HY)+2 种基金National Key R&D Program of China(Grant No.2020YFA0803800 to HY)the Key Clinical Projects of Peking University Third Hospital(BYSYZD2019022 to HX)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(No.2021-I2M-5-003 to HX and YZ)。
文摘Background:Exercise training protects against heart failure.However,the mechanism underlying the protective effect of exercise training on angiotensinⅡ(AngⅡ)-induced cardiac fibrosis remains unclear.Methods:An exercise model involving C57BL/6N mice and 6 weeks of treadmill training was used.AngⅡ(1.44 mg/kg/day)was administered to induce cardiac fibrosis.RNA sequencing and bioinformatic analysis were used to identify the key factors mediating the effects of exercise training on cardiac fibrosis.Primary adult mouse cardiac fibroblasts(CFs)were used in vitro.Adeno-associated virus serotype 9 was used to overexpress POU domain,class 2,transcription factor 1(POU2F1)in vivo.Results:Exercise training attenuated AngⅡ-induced cardiac fibrosis and reversed 39 gene expression changes.The transcription factor regulating the largest number of these genes was POU2F1.Compared to controls,POU2F1 was shown to be signififcantly upregulated by AngⅡ,which is itself reduced by exercise training.In vivo,POU2F1 overexpression nullified the benefits of exercise training on cardiac fibrosis.In CFs,POU2F1 promoted cardiac fibrosis.CCAAT enhancer-binding proteinβ(C/EBPβ)was predicted to be the transcription factor of POU2F1and verified using a dual-luciferase reporter assay.In vivo,exercise training activated AMP-activated protein kinase(AMPK)and alleviated the increase in C/EBPβinduced by AngⅡ.In CFs,AMPK agonist inhibited the increase in C/EBPβand POU2F1 induced by Ang II,whereas AMPK inhibitor reversed this effect.Conclusion:Exercise training attenuates AngⅡ-induced cardiac fibrosis by reducing POU2F1.Exercise training inhibits POU2F1 by activating AMPK,which is followed by the downregulation of C/EBPβ,the transcription factor of POU2F1.
基金supported by the National Key R&D Program of China(No.2018YFA0108100)the National Natural Science Foundation of China(No.62104009)Experiments on human sweat were conducted in accordance with the approved protocol from the institutional review board at Peking University Third Hospital,Beijing,China(No.M2021610).
文摘The concentration of biomarkers in sweat can be used to evaluate human health,making efficient sweat sensing a focus of research.While flow channel design is often used to detect sweat velocity,it is rarely incorporated into the sensing of biomarkers,limiting the richness of sensing results.In this study,we report a time sequential sensing scheme for uric acid in sweat through a sequential design of Tesla valve channels.Graphene electrodes for detecting uric acid and directional Tesla valve flow channels were fabricated using laser engraving technology to realize time sequential sensing.The performance of the channels was verified through simulation.The time sequential detection of uric acid concentration in sweat can help researchers improve the establishment of human health management systems through flexible wearable devices.
基金supported by the National Key Research and Development Program of China (2022YFA1104800)the National Natural Science Foundation of China (82222006,32100660,82170367)+5 种基金Beijing Nova Program (Z211100002121003,20220484205)Beijing Natural Science Foundation (7232094)supported by National Institute of Health (R01HL146634 and UM1HL098166)supported by the Natural Science Foundation of China (82070235 and 92168113)the CAMS Innovation Fund for Medical Sciences (2021-I2M-5003)Haihe Laboratory of Cell Ecosystem Innovation Fund (HH22KYZX0047)。
文摘Dear Editor,In development,after cells make a commitment to their fates,they undergo a continuous and adaptive maturation process to eventually reach their terminal states.Cell maturity often decays during aging and pathogenesis.The immature phenotypes of stem cell-differentiated cells deposit a major bottleneck in regenerative medicine.
基金This work was supported by grants from the National Natural Sciences Foundation of China(No.81400177)Natural Science Foundation of Beijing Municipality(No.7154249).
文摘Background:Angiopoietin-2(Ang-2)is a type of endothelial growth factor involved in angiogenesis and vascular remodeling.Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease(CAD).This study aimed to evaluate the association between serum Ang-2 levels and coronary microvascular dysfunction in patients without obstructive CAD.Methods:A total of 125 patients with angina in the absence of obstructive CAD were included in this cross-sectional study.Coronary flow reserve(CFR)was measured in the distal left anterior descending coronary artery by trans-thoracic Doppler echocardiography.The patients were divided into the following two sub-groups according to CFR:the impaired CFR group with CFR values<2.5 and the preserved CFR group with CFR values≥2.5.Serum Ang-2 levels were determined using enzyme-linked immunosorbent assay.Independent predictors for impaired CFR were identified by binary logistic regression analysis.The receiveroperating characteristic curve was determined to evaluate the ability of serum Ang-2 in predicting impaired CFR.Results:We found that age,percentage of female sex,N-terminal pro-B-type natriuretic peptide levels,Ang-2 levels(763.3±264.9 vs.579.7±169.3 pg/mL,P<0.001),and the left atrial volume index were significantly higher in patients with impaired CFR than in patients with preserved CFR.Serum Ang-2 levels were negatively correlated with CFR(r=0.386,P<0.001).Binary logistic regression analysis showed that Ang-2(odds ratio:1.004,95%confidence interval[CI]:1.001–1.006,P=0.003)and age(odds ratio:1.088,95%CI:1.023–1.156,P=0.007)were independently associated with impaired CFR.Furthermore,Ang-2 was a significant predictor of impaired CFR on the receiver-operating characteristic curve(P<0.001).The area under the curve was 0.712(95%CI:0.612–0.813).Conclusions:High serum Ang-2 levels are independently associated with impaired CFR in patients with angina in the absence of obstructive CAD.
文摘Population aging has emerged as one of the most pressing global demographic issues.Rapid population aging is being caused by a sharp drop in fertility rates over time,as well as a significant increase in life expectancy in the past decades.The World Health Organization(WHO)estimates that the proportion of those aged 60 years and older in the world’s population will almost double from approximately 12%in 2015 to 22%in 2050,with an absolute increase of 900 million to a total of 2 billion older adults(1).At the same time,the burden of global disease has changed greatly and the main diseases affecting human health have switched from acute and chronic infectious diseases to chronic non-communicable diseases(NCDs)(2).Such changing demographics and disease spectrum will profoundly affect all aspects of human society.
基金Supported by Chinese Academy of Engineering(No.2021-XY-15)National Natural Science Fundation of China(No.L2124021)+1 种基金CAMS Innovation Fund for Medical Sciences(No.2021-I2M-5-003)Haihe Laboratory of Cell Ecosystem Innovation Fund(No.HH22KYZX0047).
文摘Summary What is already known about this topic?Rehabilitation is an essential part of achieving health for all,whereas the estimates of rehabilitation needs,especially for elderly individuals in China,are not clear.What is added by this report?Compared with 1990,the prevalence and years of life lived with disability for health conditions in need of rehabilitation in China increased by 71.3%and 77.0%in 2019,respectively,at a rate much higher than the global average.What are the implications for public health practices?This study mainly presents scientific data and a systematic analysis of the current state and challenges of rehabilitation needs for elderly individuals(aged 60 and above)in China based on the World Health Organization Rehabilitation Need Estimator.
文摘In an era of rapid advancements in artificial intelligence(AI),the potential role of large language models(LLMs)in the medical field is receiving increasing attention.The progression of this technology not only highlights upcoming revolutionary changes in medical services but also offers unprecedented opportunities for the health care sector.1 LLMs’formidable capability to process natural language opens vast prospects for application in the medical field,including in the contexts of emergency triage,geriatric care,and digital medical workflows.
基金supported by the National Natural Science Foundation of China (81625001, 81700010)National Key Research & Development Program of China (2018YFC1312700, 2018YFC1312701)
文摘Heart failure(HF) is a major clinical concern owing to its high prevalence and high mortality.Metabolomics,an effective approach to predict diagnostic biomarkers and to explore the altered metabolic pathways in pathogenesis,has been extensively applied in evaluating the course of diseases.In this study,we used this approach to analyse the abundance of metabolites,with liquid chromatograph-mass spectrometer,in plasma samples from rats with transverse aortic constriction(TAC) and patients at different stages of HF.We compared the metabolic parameters within and between TAC rats and patients.An apparent metabolic shift was observed in rats,from compensated hypertrophy stage to decompensated hypertrophy stage,and in patients with HF,from stage A to stage B and subsequently stage C.Diagnostic biomarkers were predicted by comparing the variable importance in the projection scores and fold change analysis within and between rats and patients.Enrichment pathway analysis and network analysis provided an overview of the largely disturbed metabolic pathways,and those interfered at different stages and across species were confirmed.The significantly changed metabolites and pathways revealed the underlying mechanisms of HF pathogenesis,hinted at novel potential biomarkers,and provided potential therapeutic intervention targets for HF.
基金supported by the Beijing Municipal Natural Science Foundation (7144254)the National Nature Science Foundation of China (81530009, 81670205)+1 种基金the Open Foundation from Beijing Key Laboratory of Hypertension Research (2017GXY-KFKT-05)the Fund for Fostering Young Scholars of Peking University Health Science Center (BMU2017PY016)
文摘Macrophage migration inhibitory factor(MIF) is an inflammatory cytokine. It is elevated early in the blood of acute myocardial infarction patients. However, it is unclear whether and how MIF is released. This study investigated the cellular source and mechanism of MIF release from hearts. An ischemia-mimic treatment induced the secretion of MIF from neonatal rat cardiomyocytes but not from fibroblasts. The treatment did not cause significant leakage of lactate dehydrogenase, suggesting that ischemia induced the MIF secretion without causing severe cell damage. Plasma samples from patients with acute chest pain at the emergency department were collected for the detection of MIF. MIF levels in patients with acute coronary syndrome(ACS)increased early, when cardiac injury markers were not yet elevated, suggesting that ischemia can induce MIF secretion before the occurrence of severe myocardial damage. Serum-starvation caused MIF secretion from rat cardiomyocytes and Langendorffperfused rat hearts. The secretion was suppressed by the inhibition of autophagy by inhibitors or by silencing of Atg5. In conclusion, serum-starvation induces the secretion of MIF from cardiomyocytes via autophagy dependent pathway. Clarifying the mechanism of MIF secretion will be helpful for its application in the early diagnosis and treatment of ACS.
基金supported by the“13th Five-Year”National Science and Technology Major Project(grant Nos.2017ZX09101001-002-001 and 2017ZX09304012,China)Bill&Melinda Gates Foundation(OPP1204780,USA)
文摘Chloroquine(CQ)phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019(COVID-19).To develop a physiologically-based pharmacokinetic(PBPK)model for predicting tissue distribution of CQ and apply it to optimize dosage regimens,a PBPK model,with parameterization of drug distribution extrapolated from animal data,was developed to predict human tissue distribution of CQ.The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism.Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships.The model was also validated by clinical data from Chinese patients with COVID-19.The novel PBPK model allows indepth description of the pharmacokinetics of CQ in several key organs(lung,heart,liver,and kidney),and was applied to design dosing strategies in patients with acute COVID-19(Day 1:750 mg BID,Days 2-5:500 mg BID,CQ phosphate),patients with moderate COVID-19(Day 1:750 mg and 500 mg,Days 2-3:500 mg BID,Days 4-5:250 mg BID,CQ phosphate),and other vulnerable populations(e.g.,renal and hepatic impairment and elderly patients,Days 1-5:250 mg BID,CQ phosphate).A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.
