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
Objective： The high expression of cell division cycle 42 protein （CDC42） may be involved in the occurrence and progression of several tumors. However, the expression and function of CDC42 in cervical squamous cell ...Objective： The high expression of cell division cycle 42 protein （CDC42） may be involved in the occurrence and progression of several tumors. However, the expression and function of CDC42 in cervical squamous cell carcinoma remains unclear. This study aimed to investigate the expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics. Methods： The expression of CDC42 in 162 cervical squamous cell carcinoma tissue samples and 33 normal cervical tissue samples was investigated by immunohistochemistry. The CDC42 mRNA expression was detected by reverse transcription-polymerase chain reaction （RT-PCR）. Results： The cervical squamous cell carcinoma group showed a significantly higher CDC42 positive rate, compared to the normal cervical tissues （P〈0.05）. Fttrthermore, the tissues of stage Ⅱ-Ⅳ carcinoma patients showed higher CDC42 expression levels compared to stage I patients （P=0.05）. In addition, the expression of CDC42 was not correlated to age of patients, differentiation degree of cancer cells, or lymph node metastasis （P〉0.05）. Furthermore, compare with normal cervical tissues, the CDC42 mRNA expression in cervical cancer had no significant difference. Conclusions： CDC42 was up-regulated at protein level, but not mRNA level, in cervical squamous cell carcinoma. The high expression of CDC42 was correlated to the clinical stage of the patients, indicating that CDC42 might contribute to the progression of cervical squamous cell carcinoma.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
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
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: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
In recent years,the use of coronary functional evaluation derived by fractional flow reserve(FFR)to guide percutaneous coronary intervention(PCI)treatment has been recommended by several mainstream guidelines.Typicall...In recent years,the use of coronary functional evaluation derived by fractional flow reserve(FFR)to guide percutaneous coronary intervention(PCI)treatment has been recommended by several mainstream guidelines.Typically,FFR>0.80 in coronary artery indicates the lesions do not affect the coronary blood flow.展开更多
OBJECTIVES To analyze the differential expression of lipid spectrum between ST-segment elevated myocardial infarction(STEMI)and patients with emergency chest pain and excluded coronary artery disease(CAD),and establis...OBJECTIVES To analyze the differential expression of lipid spectrum between ST-segment elevated myocardial infarction(STEMI)and patients with emergency chest pain and excluded coronary artery disease(CAD),and establish the predictive model which could predict STEMI in the early stage.METHODS We conducted a single-center,nested case-control study using the emergency chest pain cohort of Peking Univer-sity Third Hospital.Untargeted lipidomics were conducted while LASSO regression as well as XGBoost combined with greedy algorithm were used to select lipid molecules.RESULTS Fifty-two STEMI patients along with 52 controls were enrolled.A total of 1925 lipid molecules were detected.There were 93 lipid molecules in the positive ion mode which were differentially expressed between the STEMI and the control group,while in the negative ion mode,there were 73 differentially expressed lipid molecules.In the positive ion mode,the differentially expressed lipid subclasses were mainly diacylglycerol(DG),lysophophatidylcholine(LPC),acylcarnitine(CAR),lysophospha-tidyl ethanolamine(LPE),and phosphatidylcholine(PC),while in the negative ion mode,significantly expressed lipid subclasses were mainly free fatty acid(FA),LPE,PC,phosphatidylethanolamine(PE),and phosphatidylinositol(PI).LASSO regression se-lected 22 lipids while XGBoost combined with greedy algorithm selected 10 lipids.PC(15:0/18:2),PI(19:4),and LPI(20:3)were the overlapping lipid molecules selected by the two feature screening methods.Logistic model established using the three lipids had excellent performance in discrimination and calibration both in the derivation set(AUC:0.972)and an internal validation set(AUC:0.967).In 19 STEMI patients with normal cardiac troponin,18 patients were correctly diagnosed using lipid model.CONCLUSIONS The differentially expressed lipids were mainly DG,CAR,LPC,LPE,PC,PI,PE,and FA.Using lipid molecules selected by XGBoost combined with greedy algorithm and LASSO regression to establish model could accurately predict STEMI even in the more earlier stage.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: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 coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has been significantly alleviated.However,long-term health effects and prevention strategy remain un...The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has been significantly alleviated.However,long-term health effects and prevention strategy remain unresolved.Thus,it is essential to explore the pathophysiological mechanisms and intervention for SARS-CoV-2 infection.Emerging research indicates a link between COVID-19 and bile acids,traditionally known for facilitating dietary fat absorption.The bile acid ursodeoxycholic acid potentially protects against SARS-CoV-2 infection by inhibiting the farnesoid X receptor,a bile acid nuclear receptor.The activation of G-protein-coupled bile acid receptor,another membrane receptor for bile acids,has also been found to regulate the expression of angiotensin-converting enzyme 2,the receptor through which the virus enters human cells.Here,we review the latest basic and clinical evidence linking bile acids to SARS-CoV-2,and reveal their complicated pathophysiological mechanisms.展开更多
Background Recently,studies have disclosed soluble CD40 ligand （sCD40L） during atherosclerosis development and plaque destabilization.The objective of the present study was to test the hypothesis that sCD40L levels ...Background Recently,studies have disclosed soluble CD40 ligand （sCD40L） during atherosclerosis development and plaque destabilization.The objective of the present study was to test the hypothesis that sCD40L levels are higher in acute coronary syndrome （ACS） patients with a greater extent of angiographic coronary involvement.Methods This cross-sectional study examined ACS patients who underwent coronary angiography by measuring their sCD40L levels.In order to estimate the serum levels of sCD40L,10 ml of peripheral venous blood was drawn within 24 hours of admission.sCD40L levels were measured using an enzyme-linked immunosorbent assay （ELISA,RapidBio,West Hills,CA,USA）.Demographic data,presence of concomitant diseases,ACS characteristics,and angiographic findings were evaluated.A review of medical records and patient interviews were conducted to assess coronary risk factors.And the severity of coronary artery disease was evaluated using the Gensini score index.Results Two hundred and eighty-nine patients were included in the study,of whom 186 were male,with an average age of 64.1±10.0 years.Median sCD40L levels were 1.7 ng/ml （0.3-7.3 ng/ml） and Gensini scores were 50 （0-228）.After adjusting for demographic variables and cardiovascular risk factors,the Gensini score was associated with the natural logarithm of the sCD40L level （Coefficient b=0.002,95％ CI 0.000-0.003,P=0.029）.Conclusion sCD40L levels were independently associated with angiographic severity of coronary artery disease in patients with ACS.展开更多
Background Baseline white blood cell （WBC） count was correlated with ischemic events occurrence in patients with ST-elevated myocardial infarction （STEMI）. However, circulating WBC count is altered after percutane...Background Baseline white blood cell （WBC） count was correlated with ischemic events occurrence in patients with ST-elevated myocardial infarction （STEMI）. However, circulating WBC count is altered after percutaneous coronary intervention （PCI）. The aim of this study was to assess the relationship between postprocedural WBC count and clinical outcomes in STEMI patients who underwent PCI. Methods A total of 242 consecutive acute STEMI patients who underwent successful primary PCI were enrolled and followed up for two years. WBC counts were measured within 12 hours after PCI. ST-segment resolution （ST-R） and myocardial blush grades （MBG） were evaluated immediately after PCI. Left ventricular ejection fraction （LVEF） was obtained at baseline and 12-18 months after PCI. Results Postprocedural WBC count was an independent inverse predictor of ST-R （OR 0.80, P 〈0.0001） and MBG 3 （OR 0.82, P 〈0.0001）. It was negatively correlated with LVEF （baseline r=0.22, P=0.001; 12-18 months r=0.29, P 〈0.0001）. The best cutoff value of WBC for predicting death was determined to be 13.0×10^9/L. The patients with a postprocedural WBC count above 13.0×10^9/L showed a significantly lower cumulative survival rate （30 days, 82.4% vs. 99.0%, P 〈0.0001 and 2 years 75.0% vs. 96.4%, P 〈0.0001）. Multivariate Cox regression analysis showed that a postprocedural WBC count was a strong independent predictor of 30-day mortality （HR 8.48, P=0.019） and 2-year mortality （HR 4.93, P=0.009）. Conclusions Increased postprocedural WBC count is correlated with myocardial malperfusion and left ventricular dysfunction, and is an independent predictor of poor clinical outcomes in STEMI patients who underwent PCI.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supported by the National Natural Science Foundation of China(No.11072006,No.10772007 and No.81070078)National Basic Research Program of China(973 Program,2013CB933702)
文摘Objective： The high expression of cell division cycle 42 protein （CDC42） may be involved in the occurrence and progression of several tumors. However, the expression and function of CDC42 in cervical squamous cell carcinoma remains unclear. This study aimed to investigate the expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics. Methods： The expression of CDC42 in 162 cervical squamous cell carcinoma tissue samples and 33 normal cervical tissue samples was investigated by immunohistochemistry. The CDC42 mRNA expression was detected by reverse transcription-polymerase chain reaction （RT-PCR）. Results： The cervical squamous cell carcinoma group showed a significantly higher CDC42 positive rate, compared to the normal cervical tissues （P〈0.05）. Fttrthermore, the tissues of stage Ⅱ-Ⅳ carcinoma patients showed higher CDC42 expression levels compared to stage I patients （P=0.05）. In addition, the expression of CDC42 was not correlated to age of patients, differentiation degree of cancer cells, or lymph node metastasis （P〉0.05）. Furthermore, compare with normal cervical tissues, the CDC42 mRNA expression in cervical cancer had no significant difference. Conclusions： CDC42 was up-regulated at protein level, but not mRNA level, in cervical squamous cell carcinoma. The high expression of CDC42 was correlated to the clinical stage of the patients, indicating that CDC42 might contribute to the progression of cervical squamous cell carcinoma.
基金Acknowledgements This work was supported by the National Natural Sciences Foundation of China （81400177, CHEN SM） and Beijing Natural Science Foundation （7154249, CHEN SM）. The authors have no financial disclosures.
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grants from the National Nat-ural Science Foundation of China，the PhD Programs Foundation of Ministry of Education of China (20120001120131). The authors of this article do not have potential conflicts of interest
文摘In recent years,the use of coronary functional evaluation derived by fractional flow reserve(FFR)to guide percutaneous coronary intervention(PCI)treatment has been recommended by several mainstream guidelines.Typically,FFR>0.80 in coronary artery indicates the lesions do not affect the coronary blood flow.
基金This work was supported by the National Key Research and Development Program of China(2017 YFC0908701)National Natural Science Foundation of China(81972149,81871850)Beijing Natural Science Foundation(grant No.7212125).
文摘OBJECTIVES To analyze the differential expression of lipid spectrum between ST-segment elevated myocardial infarction(STEMI)and patients with emergency chest pain and excluded coronary artery disease(CAD),and establish the predictive model which could predict STEMI in the early stage.METHODS We conducted a single-center,nested case-control study using the emergency chest pain cohort of Peking Univer-sity Third Hospital.Untargeted lipidomics were conducted while LASSO regression as well as XGBoost combined with greedy algorithm were used to select lipid molecules.RESULTS Fifty-two STEMI patients along with 52 controls were enrolled.A total of 1925 lipid molecules were detected.There were 93 lipid molecules in the positive ion mode which were differentially expressed between the STEMI and the control group,while in the negative ion mode,there were 73 differentially expressed lipid molecules.In the positive ion mode,the differentially expressed lipid subclasses were mainly diacylglycerol(DG),lysophophatidylcholine(LPC),acylcarnitine(CAR),lysophospha-tidyl ethanolamine(LPE),and phosphatidylcholine(PC),while in the negative ion mode,significantly expressed lipid subclasses were mainly free fatty acid(FA),LPE,PC,phosphatidylethanolamine(PE),and phosphatidylinositol(PI).LASSO regression se-lected 22 lipids while XGBoost combined with greedy algorithm selected 10 lipids.PC(15:0/18:2),PI(19:4),and LPI(20:3)were the overlapping lipid molecules selected by the two feature screening methods.Logistic model established using the three lipids had excellent performance in discrimination and calibration both in the derivation set(AUC:0.972)and an internal validation set(AUC:0.967).In 19 STEMI patients with normal cardiac troponin,18 patients were correctly diagnosed using lipid model.CONCLUSIONS The differentially expressed lipids were mainly DG,CAR,LPC,LPE,PC,PI,PE,and FA.Using lipid molecules selected by XGBoost combined with greedy algorithm and LASSO regression to establish model could accurately predict STEMI even in the more earlier stage.
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(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This study was supported by National Natural Science Foundation of China(NSFC Grant Nos.U21A20336,81820108031,and 91939301)National Key Research and Development Program of China(Grant No.2022YFC3602400)+1 种基金Beijing Municipal Natural Science Foundation(Grant No.7222218,China)Medical research management/basic and clinical research unit of metabolic cardiovascular diseases,Chinese Academy of Medical Sciences(Grant No.2021RU003,China).
文摘The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has been significantly alleviated.However,long-term health effects and prevention strategy remain unresolved.Thus,it is essential to explore the pathophysiological mechanisms and intervention for SARS-CoV-2 infection.Emerging research indicates a link between COVID-19 and bile acids,traditionally known for facilitating dietary fat absorption.The bile acid ursodeoxycholic acid potentially protects against SARS-CoV-2 infection by inhibiting the farnesoid X receptor,a bile acid nuclear receptor.The activation of G-protein-coupled bile acid receptor,another membrane receptor for bile acids,has also been found to regulate the expression of angiotensin-converting enzyme 2,the receptor through which the virus enters human cells.Here,we review the latest basic and clinical evidence linking bile acids to SARS-CoV-2,and reveal their complicated pathophysiological mechanisms.
文摘Background Recently,studies have disclosed soluble CD40 ligand （sCD40L） during atherosclerosis development and plaque destabilization.The objective of the present study was to test the hypothesis that sCD40L levels are higher in acute coronary syndrome （ACS） patients with a greater extent of angiographic coronary involvement.Methods This cross-sectional study examined ACS patients who underwent coronary angiography by measuring their sCD40L levels.In order to estimate the serum levels of sCD40L,10 ml of peripheral venous blood was drawn within 24 hours of admission.sCD40L levels were measured using an enzyme-linked immunosorbent assay （ELISA,RapidBio,West Hills,CA,USA）.Demographic data,presence of concomitant diseases,ACS characteristics,and angiographic findings were evaluated.A review of medical records and patient interviews were conducted to assess coronary risk factors.And the severity of coronary artery disease was evaluated using the Gensini score index.Results Two hundred and eighty-nine patients were included in the study,of whom 186 were male,with an average age of 64.1±10.0 years.Median sCD40L levels were 1.7 ng/ml （0.3-7.3 ng/ml） and Gensini scores were 50 （0-228）.After adjusting for demographic variables and cardiovascular risk factors,the Gensini score was associated with the natural logarithm of the sCD40L level （Coefficient b=0.002,95％ CI 0.000-0.003,P=0.029）.Conclusion sCD40L levels were independently associated with angiographic severity of coronary artery disease in patients with ACS.
文摘Background Baseline white blood cell （WBC） count was correlated with ischemic events occurrence in patients with ST-elevated myocardial infarction （STEMI）. However, circulating WBC count is altered after percutaneous coronary intervention （PCI）. The aim of this study was to assess the relationship between postprocedural WBC count and clinical outcomes in STEMI patients who underwent PCI. Methods A total of 242 consecutive acute STEMI patients who underwent successful primary PCI were enrolled and followed up for two years. WBC counts were measured within 12 hours after PCI. ST-segment resolution （ST-R） and myocardial blush grades （MBG） were evaluated immediately after PCI. Left ventricular ejection fraction （LVEF） was obtained at baseline and 12-18 months after PCI. Results Postprocedural WBC count was an independent inverse predictor of ST-R （OR 0.80, P 〈0.0001） and MBG 3 （OR 0.82, P 〈0.0001）. It was negatively correlated with LVEF （baseline r=0.22, P=0.001; 12-18 months r=0.29, P 〈0.0001）. The best cutoff value of WBC for predicting death was determined to be 13.0×10^9/L. The patients with a postprocedural WBC count above 13.0×10^9/L showed a significantly lower cumulative survival rate （30 days, 82.4% vs. 99.0%, P 〈0.0001 and 2 years 75.0% vs. 96.4%, P 〈0.0001）. Multivariate Cox regression analysis showed that a postprocedural WBC count was a strong independent predictor of 30-day mortality （HR 8.48, P=0.019） and 2-year mortality （HR 4.93, P=0.009）. Conclusions Increased postprocedural WBC count is correlated with myocardial malperfusion and left ventricular dysfunction, and is an independent predictor of poor clinical outcomes in STEMI patients who underwent PCI.
