The renin-angiotensin system(RAS)regulates vascular tone and plays a critical role in vascular remodeling,which is the result of a complex interplay of alterations in vascular tone and structure.Inhibition of the RAS ...The renin-angiotensin system(RAS)regulates vascular tone and plays a critical role in vascular remodeling,which is the result of a complex interplay of alterations in vascular tone and structure.Inhibition of the RAS has led to important pharmacological tools to prevent and treat vascular diseases such as hypertension,diabetic vasculopathy and atherosclerosis.Angiotensin converting enzyme 2(ACE2)was recently identified as a multifunctional monocarboxypeptidase responsible for the conversion of angiotensin(Ang)II to Ang-(1-7).The ACE2/Ang-(1-7)signaling has been shown to prevent cellular proliferation,pathological hypertrophy,oxidative stress and vascular fibrosis.Thus,the ACE2/Ang-(1-7)signaling is deemed to be beneficial to the cardiovascular system as a negative regulator of the RAS.The addition of the ACE2/Ang-(1-7)signaling to the complexities of the RAS may lead to the development of novel therapeutics for the treatment of hypertension and other vascular diseases.The present review considers recent findings regarding the ACE2/Ang-(1-7)signaling and focuses on its regulatory roles in processes related to proliferation,inflammation,vascular fibrosis and remodeling,providing proof of principle for the potential use of ACE2 as a novel therapy for vascular disorders related to vascular remodeling.展开更多
Objective: To investigate the relationship of insulin resistance and the polymorphisms of insulin receptor-related genes in essential hypertension patients of two different kinds of TCM constitution. Methods: Oral g...Objective: To investigate the relationship of insulin resistance and the polymorphisms of insulin receptor-related genes in essential hypertension patients of two different kinds of TCM constitution. Methods: Oral glucose tolerance test (OGTT) and insulin release test (InRT) were conducted in 217 essential hypertensive patients of either sluggish meticulous (SM) constitution (139 cases) or prosperous impetuous (PI) constitution (78 cases), and the polymorphism of three genes, including insulin-like growth factor-1 receptor (IGF-1R), insulin receptor substrate-1 (IRS-1) and 2 (IRS-2) genes were detected. Results: (1) OGTT, InRT and insulin resistance index (Homa-IR) were higher and insulin sensitive index (ISI) was lower in the patients of SM constitution than those in patients of PI constitution. (2) Significant difference of ISI and Homa-IR was shown in patients of both constitutions with genotype G of the 3 genes. Conclusion: Decrease of insulin sensitivity and increase of insulin resistance are more obvious in hypertensive patients with genotype G of the 3 genes of SM constitution than in those of PI constitution. Therefore, the difference in constitution might be one of the genetic characteristics for insulin resistance in hypertensive patients.展开更多
Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and homeostas...Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and homeostasis.However,fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely understood.Transcriptomic analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction(TAC)and Ang-l infusion.Further investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload.Conditional TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs-and myofibroblasts-specific Cre mice.Echocardiographic and histological analyses demonstrated that CFs-and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor,VT103,ameliorated TAC-induced cardiac remodeling.Mechanistically,RNA-seq and ChiP-seq analysis identified Wnt4 as a novel TEAD1 target.TEAD1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway,and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 overexpression.Furthermore,coimmunoprecipitation combined with mass spectrometry,chromatin immunoprecipitation,and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4,leading to the binding and activation of the Wnt4 promoter.In conclusion,TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signallingpathway.展开更多
OBJECTIVE To investigate three features of dietary cooking oil intake,namely,the consumption,cooking style,and composition of fatty acids in relation to several cardiometabolic measurements in an elderly Chinese popul...OBJECTIVE To investigate three features of dietary cooking oil intake,namely,the consumption,cooking style,and composition of fatty acids in relation to several cardiometabolic measurements in an elderly Chinese population.METHODS The elderly(≥65 years)participants for this study were recruited from two community health centers in the urban area of Shanghai.A questionnaire was administered to collect information on dietary oil consumption(low,medium and high)and cooking styles(fry or stir-fry vs.others)and the composition of fatty acids(poly-unsaturated vs.mono-unsaturated).The cardiometabolic measurements included anthropometry,blood pressure,fasting plasma glucose and serum lipids.RESULTS The 1186 study participants had a mean age of 70.9±5.4 years.The mean dietary oil consumption was 35.0 g/d,being low(<25 g/d),medium(25-49 g/d)and high(≥50 g/d)in 485,467 and 234 participants,respectively.The proportion of the fry or stir-fry cooking style and oils rich in mono-unsaturated fatty acids was 30.4%and 27.4%,respectively.Both before and after adjustment for sex,age,current smoking and alcohol intake,dietary oil consumption was significantly(P≤0.02)and positively associated with the prevalence of treated hypertension and fasting plasma glucose concentration.With similar adjustments as above and additional adjustment for dietary oil consumption,the fry or stir-fry cooking style was significantly(P≤0.048)and positively associated with body mass index,but inversely with systolic and diastolic blood pressure and serum low-density lipoprotein cholesterol,and the dietary intake of oils rich in mono-unsaturated fat acids was significantly(P≤0.02)and positively associated with diastolic blood pressure,serum triglycerides,total cholesterol and low-density lipoprotein cholesterol,and the prevalence of hypertriglyceridemia and hypercholesterolemia.CONCLUSIONS This study showed that both the consumption and composition of fatty acids of the dietary oils mattered with regard to several cardiometabolic measurements in 展开更多
The coronavirus disease 2019(COVID-19)has been declared as a pandemic by the World Health Organization.[1]Most COVID-19 patients exhibit mild to moderate symptoms,while approximately 15%progress rapidly to severe pneu...The coronavirus disease 2019(COVID-19)has been declared as a pandemic by the World Health Organization.[1]Most COVID-19 patients exhibit mild to moderate symptoms,while approximately 15%progress rapidly to severe pneumonia,and about 5%eventually develop acute respiratory distress syndrome(ARDS),[2]which requires mechanical ventilation(MV)and even extracorporeal membrane oxygenation.The mortality of COVID-19 patients who received MV was reported to be as high as 66%.[3]Therefore,the treatments aiming to improve mortality should focus on two aspects:first,prevention of the aggravation of the disease in mild and moderate COVID-19 patients;second,the rescue therapy for patients in serious conditions.We have been applying high-dose intravenous vitamin C(HDIVC)in the treatment of critical illnesses for almost 10 years in our center.Our previous in vivo research showed that HDIVC protected hemorrhagic shock-related multiple organ failure(MOF)by inhibiting inflammatory cytokines and oxidative indicators through activating Sirtuin1 pathway.展开更多
OBJECTIVE To investigate the association between current and former smoking and the risk of mortality in elderly Chinese men.METHODS Our study participants were elderly(≥60 years)men recruited in a suburban town of S...OBJECTIVE To investigate the association between current and former smoking and the risk of mortality in elderly Chinese men.METHODS Our study participants were elderly(≥60 years)men recruited in a suburban town of Shanghai.Cigarette smoking status was categorized as never smoking,remote(cessation>5 years)and recent former smoking(cessation≤5 years),and light-to-moderate(≤20 cigarettes/day)and heavy current smoking(>20 cigarettes/day).Cox proportional hazards models and restricted cubic splines were used to examine the associations of interest.RESULTS The 1568 participants had a mean age of 68.6±7.1 years.Of all participants,311 were never smokers,201 were remote former smokers,133 were recent former smokers,783 were light-to-moderate current smokers and 140 were heavy current smokers.During a median follow-up of 7.9 years,all-cause,cardiovascular and non-cardiovascular deaths occurred in 267,106 and 161 participants,respectively.Heavy current smokers had the highest risk of all-cause and non-cardiovascular mortality,with an adjusted hazard ratio(HR)of 2.30(95%CI:1.34-4.07)and 3.98(95%CI:2.03-7.83)versus never smokers,respectively.Recent former smokers also had a higher risk of all-cause(HR=1.62,95%CI:1.04-2.52)and non-cardiovascular mortality(HR=2.40,95%CI:1.32-4.37)than never smokers.Cox regression restricted cubic spline models showed the highest risk of all-cause and non-cardiovascular mortality within 5 years of smoking cessation and decline thereafter.Further subgroup analyses showed interaction between smoking status and pulse rate(≥70 beats/min vs.<70 beats/min)in relation to the risk of all-cause and non-cardiovascular mortality,with a higher risk in current versus never smokers in those participants with a pulse rate below 70 beats/min.CONCLUSIONS Cigarette smoking in elderly Chinese confers significant risks of mortality,especially when recent former smoking is considered together with current smoking.展开更多
Conventional therapies for hemophilia A(HA)are prophylactic or on-demand intravenous FⅧinfusions.However,they are expensive and inconvenient to perform.Thus,better strategies for HA treatment must be developed.In thi...Conventional therapies for hemophilia A(HA)are prophylactic or on-demand intravenous FⅧinfusions.However,they are expensive and inconvenient to perform.Thus,better strategies for HA treatment must be developed.In this study,a recombinant FⅧcDNA encoding a human/rat hybrid FⅧwith an enhanced procoagulant potential for adeno-associated virus(AAV)-delivered gene therapy was developed.Plasmids containing human FⅧheavy chain(hHC),human light chain(hLC),and rat light chain(rLC)were transfected into cells and hydrodynamically injected into HA mice.Purified AAV viruses were intravenously injected into HA mice at two doses.Results showed that the hHC+rLC protein had a higher activity than the hHC+hLC protein at comparable expression levels.The specific activity of hHC+rLC was about 4-to 8-fold higher than that of their counterparts.Hydrodynamic injection experiments obtained consistent results.Notably,the HA mice undergoing the AAV-delivered hHC+rLC treatment exhibited a visibly higher activity than those treated with hHC+hLC,and the therapeutic effects lasted for up to 40 weeks.In conclusion,the application of the hybrid FⅧ(hHC+rLC)via an AAV-delivered gene therapy substantially improved the hemorrhagic diathesis of the HA mice.These data might be of help to the development of optimized FⅧexpression cassette for HA gene therapy.展开更多
Aim:The transjugular intrahepatic portosystemic shunt(TIPS)procedure has been performed in China for 30 years,but our understanding of the status and difficulties associated with the use of TIPS for portal hypertensio...Aim:The transjugular intrahepatic portosystemic shunt(TIPS)procedure has been performed in China for 30 years,but our understanding of the status and difficulties associated with the use of TIPS for portal hypertension is incomplete.This study aims to investigate the current situation of the use of TIPS for portal hypertension,which should aid the development of TIPS in China.Methods:This study involved a questionnaire survey,initiated by the China Portal Hypertension Alliance(CHESS)to investigate the use of TIPS for portal hypertension in China.Questionnaires were released on the Internet between August 16,2022 and September 16,2022.Detailed information was collected from 545 hospitals contracted by the CHESS in China,which performed TIPS surgery in 2021.Results:The 545 hospitals covers the majority of hospitals in China that conduct TIPS intervention.In the survey,a total of 13,527 TIPS interventions were carried out with 94.1%(498/545)of them had a system of routine follow‐up after TIPS.The majority(42.6%[232/545])believed that the main indication of TIPS was the control of acute bleeding.Overall,48.1%(262/545)carried out early or pre‐emptive TIPS,53.0%(289/545)carried out TIPS for cavernous transformation of the portal vein,and 81.0%(441/545)chose routine embolization of collateral circulation during operation.Most used coils(97.0%[475/490])and biological glue(72.0%[353/490])as embolic materials,and 78.5%(428/545)routinely performed intraoperative portal pressure gradient measurements.When selecting TIPS stents,57.1%(311/545)chose viator‐specific stents,and 57.2%(312/545)chose conventional anticoagulation after TIPS.Conventional anticoagulation after TIPS is over a time interval of 3–6 months(55.4%[173/312]).The limitation of TIPS surgery is mainly its cost(72.3%[394/545])and insufficient understanding of the procedure by doctors in other related departments(77.4%[422/545]).Most of the hospital teams accept the use of domestic instruments in TIPS surgery(92.7%[505/545]).Conclusions:This survey shows t展开更多
Ambulatory blood pressure monitoring(ABPM)has become indispensable in the current management of hypertension.ABPM is particularly useful in the accurate diagnosis of hypertension.Its diagnostic thresholds had been rec...Ambulatory blood pressure monitoring(ABPM)has become indispensable in the current management of hypertension.ABPM is particularly useful in the accurate diagnosis of hypertension.Its diagnostic thresholds had been recently established based on hard clinical outcomes.Cross-classification of patients according to office and ambulatory blood pressure identifies white-coat,masked,and sustained hypertension.ABPM is also useful in cardiovascular(CV)risk assessment.It provides information on daytime and nighttime blood pressure and circadian rhythm,particularly nighttime blood pressure dipping.Nighttime blood pressure is predictive of CV risk independent of office and daytime blood pressure.Isolated nocturnal hypertension is a special form of masked hypertension,with normal daytime but elevated nocturnal blood pressure.It also helps in the evaluation of blood pressure fluctuation and variation,such as morning blood pressure surge and reading-to-reading blood pressure variability.ABPM may derive several other indexes,such as ambulatory blood pressure index and salt sensitivity index,which may be useful in CV evaluations.展开更多
Regulatory T(T_(reg))cells constitute a dynamic population that is critical in autoimmunity.T_(reg) cell therapies for autoimmune diseases are mainly focused on enhancing their suppressive activities.However,recent st...Regulatory T(T_(reg))cells constitute a dynamic population that is critical in autoimmunity.T_(reg) cell therapies for autoimmune diseases are mainly focused on enhancing their suppressive activities.However,recent studies demonstrated that certain inflammatory conditions induce T_(reg) cell instability with diminished FoxP3 expression and convert them into pathogenic effector cells.Therefore,the identification of novel targets crucial to both T_(reg) cell function and plasticity is of vital importance to the development of therapeutic approaches in autoimmunity.In this study,we found that conditional Pp6 knockout(cKO)in T_(reg) cells led to spontaneous autoinflammation,immune cell activation,and diminished levels of FoxP3 in CD4^(+)T cells in mice.Loss of Pp6 in T_(reg) cells exacerbated two classical mouse models of T_(reg)-related autoinflammation.Mechanistically,Pp6 deficiency increased CpG motif methylation of the FoxP3 locus by dephosphorylating Dnmt1 and enhancing Akt phosphorylation at Ser473/Thr308,leading to impaired FoxP3 expression in T_(reg) cells.In summary,our study proposes Pp6 as a critical positive regulator of FoxP3 that acts by decreasing DNA methylation of the FoxP3 gene enhancer and inhibiting Akt signaling,thus maintaining T_(reg) cell stability and preventing autoimmune diseases.展开更多
To test the hypothesis that transient nonischemic stimulation of hypertrophy would render the heart resistant to subsequent ischemic stress,short-term transverse aortic constriction(TAC)was performed in mice and then ...To test the hypothesis that transient nonischemic stimulation of hypertrophy would render the heart resistant to subsequent ischemic stress,short-term transverse aortic constriction(TAC)was performed in mice and then withdrawn for several days by aortic debanding,followed by subsequent myocardial exposure to ischemia/reperfusion(I/R).Following I/R injury,the myocardial infarct size and apoptosis were markedly reduced,and contractile function was significantly improved in the TAC preconditioning group compared with the control group.Mechanistically,hypertrophic preconditioning remarkably alleviated I/R-induced oxidative stress,as evidenced by the increased reduced nicotinamide adenine dinucleotide phosphate(NADPH)/nicotinamide adenine dinucleotide phosphate(NADP)ratio,increase in the reduced glutathione(GSH)/oxidized glutathione(GSSH)ratio,and reduced mitochondrial reactive oxygen species(ROS)production.Moreover,TAC preconditioning inhibited caspase-3 activation and mitigated the mitochondrial impairment by deacetylating isocitrate dehydrogenase 2(IDH2)via a sirtuin 3(SIRT3)-dependent mechanism.In addition,the expression of a genetic deacetylation mimetic IDH2 mutant(IDH2 K413R)in cardiomyocytes,which increased IDH2 enzymatic activity and decreased mitochondrial ROS production,and ameliorated I/R injury,whereas the expression of a genetic acetylation mimetic(IDH2 K413Q)in cardiomyocytes abolished these protective effects of hypertrophic preconditioning.Furthermore,both the activity and expression of the SIRT3 protein were markedly increased in preconditioned mice exposed to I/R.Treatment with an adenovirus encoding SIRT3 partially emulated the actions of hypertrophic preconditioning,whereas genetic ablation of SIRT3 in mice blocked the cardioprotective effects of hypertrophic preconditioning.The present study identifies hypertrophic preconditioning as a novel endogenous self-defensive and cardioprotective strategy for cardiac I/R injury that induces IDH2 deacetylation through a SIRT3-dependent mechanism.A therapeu展开更多
Objective:The randomized controlled trial(ClinicalTrials.gov identifier NCT02990741)will investigate whether more frequent electrocardiographic(ECG)recordings and analyses with an automated ECG system would improve de...Objective:The randomized controlled trial(ClinicalTrials.gov identifier NCT02990741)will investigate whether more frequent electrocardiographic(ECG)recordings and analyses with an automated ECG system would improve detection of atrial fibrillation compared with a single annual ECG screen in elderly Chinese in community health centers.Design:Men and women(≥65 years)will be randomized into intensive(n=3500)and usual(n=3500)screening groups,and within the intensive screening group into intensive screening(n=2625)and more intensive screening(n=875)subgroups.ECG recordings will be performed with an automated ECG analysis system(AliveCor heart monitor)at 1 year in the usual screening group,at 3,6,9,and 12 months in the intensive screening subgroup,and at 1,2,3,and 4 weeks and 3,6,9,and 12 months in the more intensive screening subgroup.The primary outcome is the detection rate of atrial fibrillation between the usual screening group and the intensive screening group.Sample size estimation was based on a projected detection rate of atrial fibrillation of 2.0% by a single ECG recording at 12 months,an improvement of 50% with more frequent ECG recordings,α=0.05,power of 80%,and a one-sided test.Conclusions:The trial will provide evidence on the clinical effectiveness of more frequent ECG recordings by a handheld automated analysis system in the detection of atrial fibrillation.展开更多
We evaluated the roles of calpain cleavage-related mutations of the integrin β3 cytoplasmic tail in integrin αIIbβ3 bidirectional signaling using a trans-dominant inhibition model. Chimeric Tac-β3 proteins (i.e.,...We evaluated the roles of calpain cleavage-related mutations of the integrin β3 cytoplasmic tail in integrin αIIbβ3 bidirectional signaling using a trans-dominant inhibition model. Chimeric Tac-β3 proteins (i.e., Tac-β3, Tac-β3△741, Tac-β3△747, Tac-β3△754, Tac-β3△759, and Tac-β3ANITY) consisting of the extracellular and transmembrane domains of human IL-2 receptor (Tac) and the human integrin β3 cytoplasmic domain were stably expressed in the 123 CHO cells harboring human glycoprotein Ib-IX and wild-type integrin uIIbβ3. The different cells were assayed for stable adhesion and spreading on immobilized fibrinogen, and for binding soluble fibrinogen representing outside-in and inside-out signaling events, respectively. The chimeric protein Tac-β3 inhibited, and Tac-β3△NITY partially attenuated stable adhesion and spreading. Tac-β3, Tac-β3△759, Tac-β3ANITY, and Tac-β3△754, but not Tac-β3△747 or Tac-β3△741, impaired the soluble fibrinogen binding. Results indicated that the bidirectional signaling was significantly inhibited by Tac-β3△ and Tac-β3ANITY, albeit to a much lesser extent. Moreover, only inside-out signaling was impaired in the 123/Tac-β3△759 and 123/Tac-β3△754 cells in contrast to an intact bidirectional signaling in the 123/Tac-β3△747 and 123/Tac-β3△741 cells. In conclusion, the calpain cleavage of integrin β3 resulted in the regulatory effects on signaling by interrupting its interaction with cytoplasmic proteins rather than altering its conformation, and may thus regulate platelet function.展开更多
OBJECTIVE:To reach consensus on the diagnostic criteria for Yin deficiency syndrome in hypertension(YDSH)patients by a modified Delphi method.METHODS:Our study was consistent with T/CACM 1032-2017.The methodology of R...OBJECTIVE:To reach consensus on the diagnostic criteria for Yin deficiency syndrome in hypertension(YDSH)patients by a modified Delphi method.METHODS:Our study was consistent with T/CACM 1032-2017.The methodology of RAND/UCLA appropriateness was used to develop consensus guidance statements.A nationwide panel of experienced clinical experts from 19 provinces was constructed.These experts were all prominent in Traditional Chinese Medicine(TCM)of cardiovascular diseases.This consensus process consisted of two rounds of questionnaires and a final round of consultation to analyze the weight score of each item.Moreover,the data extraction process is carried out independently by third-party researchers(LIANG Junya,SUN Yang,and DU Xiaona).When there is disagreement in all three rounds,the expert panel group(odd number)are invited to vote,and the one with more votes wins.In the questionnaires,participants were asked to rate the appropriateness of each syndrome item using a nine-point Likert scale.The consensus was defined as a panel median rating 1-3 or 7-9 without disagreement.And then the diagnostic criteria of YDSH were formed according to the weight score in the final round.RESULTS:Twenty-eight experts(84.8%)participated in the first round,and thirty-one(93.9%)finished the second round.After two rounds,the consensus of YDSH was reached on 11 items(25.6%),including symptoms,signs,and pulse condition.Twenty-one experts(63.6%)completed the final round in which they used a grading system for each item.Red tongue with scanty fur had the highest weighting(22.8%),followed by heat in the palms and soles(20.1%).CONCLUSIONS:The consensus-based diagnostic criteria for YDSH,formed by a modified Delphi method,can be widely incorporated in TCM.A further clinical study will be conducted to analyze the diagnosis value and cut-off score of our YDSH criteria.展开更多
INTRODUCTION Resistant hypertension has become a challenge in the treatment of hypertension.As the population continues to age and obesity,sleep apnea hypopnea syndrome,and chronic kidney disease increase in incidence...INTRODUCTION Resistant hypertension has become a challenge in the treatment of hypertension.As the population continues to age and obesity,sleep apnea hypopnea syndrome,and chronic kidney disease increase in incidence,resistant hypertension has become an increasingly common issue in clinical practice.Failure to control blood pressure can impair target organs such as the heart,brain,and kidney,facilitating the occurrence of clinical cardiovascular events.展开更多
BACKGROUND Alcohol consumption is a known modifiable risk factor for atrial fibrillation.The association,however,might differ according to gender.We investigated gender-specific associations between alcohol consumptio...BACKGROUND Alcohol consumption is a known modifiable risk factor for atrial fibrillation.The association,however,might differ according to gender.We investigated gender-specific associations between alcohol consumption and incident atrial fibrillation in an elderly Chinese population.METHODS Our study participants were elderly residents(≥65 years)recruited from five community health centers in the urban area of Shanghai(n=6,618).Alcohol intake was classified as never drinkers and current light-to-moderate(<40 g/day)and heavy drinkers(≥40 g/day).Atrial fibrillation was detected by a 30-s single-lead electrocardiography(ECG,AliveCor®Heart Monitor)and further evaluated with a regular 12-lead ECG.RESULTS During a median of 2.1 years(interquartile range:2.0−2.2)follow-up,the incidence rate of atrial fibrillation was 1.10%in all study participants.It was slightly but non-significantly higher in men(n=2849)than women(n=3769,1.30%vs.0.96%,P=0.19)and in current drinkers(n=793)than never drinkers(n=5825,1.64%vs.1.03%,P=0.12).In both unadjusted and adjusted analyses,there was interaction between sex and current alcohol intake in relation to the incidence of atrial fibrillation(P<0.0001).After adjustment for confounding factors,current drinkers had a significantly higher incidence rate of atrial fibrillation than never drinkers in women(12.96%[7/54]vs.0.78%[29/3715],adjusted odds ratio[OR]=10.25,95%confidence interval[CI]:3.54−29.67,P<0.0001),but not in men(0.81%[6/739]vs.1.47%[31/2110],OR=0.62,95%CI:0.25−1.51,P=0.29).CONCLUSIONS Our study showed a significant association between alcohol intake and the incidence of atrial fibrillation in elderly Chinese women,but not men.展开更多
Hypertension significantly increases the risk of embolic stroke and systemic embolism in patients with atrial fibrillation, while statin therapy can improve long-term outcomes in hypertensive patients at high risk. Ho...Hypertension significantly increases the risk of embolic stroke and systemic embolism in patients with atrial fibrillation, while statin therapy can improve long-term outcomes in hypertensive patients at high risk. However, it is still unclear whether patients with both hypertension and atrial fibrillation can benefit from intensive management of blood pressure and cholesterol. IMPRESSION is a 3-year prospective, randomized, open-label, blinded-endpoint investigation. A total of 1200 hypertensive patients with atrial fibrillation from about 40 clinical centers nationwide will be included upon confirming the presence of both hypertension and atrial fibrillation and will be randomly assigned to groups for intensive or standard management of blood pressure and cholesterol. Patients in all groups will have office and home blood pressure measured by the end of the first month and every 3 months thereafter. The effects of blood pressure and cholesterol management strategies in patients with hypertension and atrial fibrillation on fatal and non-fatal stroke, acute myocardial infarction, and cardiovascular death at 3 years will be assessed. The IMPRESSION study protocol has received approval from the Ethics Committee of Ruijin Hospital, Shanghai Jiaotong University School of Medicine. The procedures set out in this protocol are in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. The results will be published following the CONSORT statement in a peer-reviewed scientific journal (Trial registration number: NCT04111419).展开更多
The new Chinese hypertension guideline was eventually published.[1] It has been more than seven years since the previous Chinese hypertension guideline was published in 2011.[2] The guideline committee should also be ...The new Chinese hypertension guideline was eventually published.[1] It has been more than seven years since the previous Chinese hypertension guideline was published in 2011.[2] The guideline committee should also be congratulated that this new Chinese hypertension guideline was for the first time published in full length in the English language in this issue of the Journal of Geriatric Cardiology.[3] This is the fourth Chinese hypertension guideline,[3] after the first,second[4] and third[2] in 1999,2005 and 2011,respectively.The first Chinese hypertension guideline was printed in a booklet.The document was not so sophisticated,but nevertheless played a role in improving management of hypertension at that time in China.The treatment rate of hypertension increased substantially from 45.5% in 1991[5] to 81.8% in 2002[6] in patients who were aware of the disease (Table 1).展开更多
The “2018 Chinese Guidelines for Prevention and Treatment of Hypertension”[1](hereinafter referred to as the 2018 Guidelines) published in this issue was revised by the Guidelines Revision Committee which is initiat...The “2018 Chinese Guidelines for Prevention and Treatment of Hypertension”[1](hereinafter referred to as the 2018 Guidelines) published in this issue was revised by the Guidelines Revision Committee which is initiated and organized by the Chinese Hypertension League.Based on the “2010 Chinese Guidelines for the Management of Hypertension” and recent evidence from domestic and international research in the field of hypertension,considering national conditions and the current situation of hypertension management in China,and reference to the latest European and American hypertension guidelines,the 2018 Guidelines make comprehensive and in-depth elaborations and recommendations of the diagnosis and assessment of hypertension,strategies and goals of prevention and treatment of hypertension and pathway of intervention,etc.The 2018 Guidelines not only provide Chinese medical personnel with guidance and reference for the clinical practice and population management of hypertension,but also serve as the latest textbook on updating concepts and knowledge in the field of hypertension.展开更多
Baroreflex plays a significant role in modulating blood pressure for the human body.It is known that activation of the vagal nerve related to baroreflex can lead to reductions of blood pressure.However,how the vagal a...Baroreflex plays a significant role in modulating blood pressure for the human body.It is known that activation of the vagal nerve related to baroreflex can lead to reductions of blood pressure.However,how the vagal activities quantitatively relate with blood pressure can hardly be achieved.Here fine carbon nanotube yarn(CNTy)electrodes were adopted for recording intrafascicular vagal activities,synchronized with measurement of arterial blood pressure in a rat.Together with a novel algorithm,the results preliminarily quantified that there were six clusters of neural spikes within recorded vagal activities,and the number of individual vagal spikes correspondingly varied with blood pressure.Especially for Cluster 2,the neural activations decreased with arterial blood pressure increasing.This study can shed lights on the quantified neural mechanism underlying the control of vagal activities on blood pressure,and guide the vagal-nerve neuromodulation for treating hypertension.展开更多
基金supported by Training Program of the National Major Research Plan(91339108)General Program(81370362,81170246)of the National Natural Science Foundation of Chinathe National Basic Research Program of China(2014CB542300)
文摘The renin-angiotensin system(RAS)regulates vascular tone and plays a critical role in vascular remodeling,which is the result of a complex interplay of alterations in vascular tone and structure.Inhibition of the RAS has led to important pharmacological tools to prevent and treat vascular diseases such as hypertension,diabetic vasculopathy and atherosclerosis.Angiotensin converting enzyme 2(ACE2)was recently identified as a multifunctional monocarboxypeptidase responsible for the conversion of angiotensin(Ang)II to Ang-(1-7).The ACE2/Ang-(1-7)signaling has been shown to prevent cellular proliferation,pathological hypertrophy,oxidative stress and vascular fibrosis.Thus,the ACE2/Ang-(1-7)signaling is deemed to be beneficial to the cardiovascular system as a negative regulator of the RAS.The addition of the ACE2/Ang-(1-7)signaling to the complexities of the RAS may lead to the development of novel therapeutics for the treatment of hypertension and other vascular diseases.The present review considers recent findings regarding the ACE2/Ang-(1-7)signaling and focuses on its regulatory roles in processes related to proliferation,inflammation,vascular fibrosis and remodeling,providing proof of principle for the potential use of ACE2 as a novel therapy for vascular disorders related to vascular remodeling.
文摘Objective: To investigate the relationship of insulin resistance and the polymorphisms of insulin receptor-related genes in essential hypertension patients of two different kinds of TCM constitution. Methods: Oral glucose tolerance test (OGTT) and insulin release test (InRT) were conducted in 217 essential hypertensive patients of either sluggish meticulous (SM) constitution (139 cases) or prosperous impetuous (PI) constitution (78 cases), and the polymorphism of three genes, including insulin-like growth factor-1 receptor (IGF-1R), insulin receptor substrate-1 (IRS-1) and 2 (IRS-2) genes were detected. Results: (1) OGTT, InRT and insulin resistance index (Homa-IR) were higher and insulin sensitive index (ISI) was lower in the patients of SM constitution than those in patients of PI constitution. (2) Significant difference of ISI and Homa-IR was shown in patients of both constitutions with genotype G of the 3 genes. Conclusion: Decrease of insulin sensitivity and increase of insulin resistance are more obvious in hypertensive patients with genotype G of the 3 genes of SM constitution than in those of PI constitution. Therefore, the difference in constitution might be one of the genetic characteristics for insulin resistance in hypertensive patients.
基金supported by the China National Funds for Young Scientists(grant number 82000309 to Shuai Song,82200290 to Yongchao Zhao)the Shanghai Sailing Program(grant number 20YF1429600 to Shuai Song),Basic Science Center Project(grant number T2288101 to Junbo Ge)+2 种基金the National Natural Science Foundation(grant number 82130010 to Aijun Sun)the Shanghai Clinical Research Center for Interventional Medicine(grant number 19MC1910300 to Junbo Ge)Fuqing Scholar of Fudan University,Shanghai Medical School(grant number FQXZ202204B to Zihang Huang).
文摘Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and homeostasis.However,fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely understood.Transcriptomic analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction(TAC)and Ang-l infusion.Further investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload.Conditional TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs-and myofibroblasts-specific Cre mice.Echocardiographic and histological analyses demonstrated that CFs-and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor,VT103,ameliorated TAC-induced cardiac remodeling.Mechanistically,RNA-seq and ChiP-seq analysis identified Wnt4 as a novel TEAD1 target.TEAD1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway,and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 overexpression.Furthermore,coimmunoprecipitation combined with mass spectrometry,chromatin immunoprecipitation,and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4,leading to the binding and activation of the Wnt4 promoter.In conclusion,TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signallingpathway.
基金supported by the National Natural Science Foundation of China (No.82070432 & No.82070435 & No.82270469 & No.82370426)the Ministry of Science and Technology, Beijing, China (2018YFC1704902 & 2022YFC3601302)+3 种基金the Shanghai Commissions of Science and Technology and Health (a special grant for “leading academics”) (No.19DZ2340200)the Three-year Action Program of Shanghai Municipality for Strengthening the Construction of Public Health System Big Data and Artificial Intelligence Application, Shanghai, China (GWV10.1-XK05)research grants from A&D, Bayer, Omron, Salubris, and Shyndeclecture fees from A& D, Novartis, Omron, Servier, Salubris and Shyndec
文摘OBJECTIVE To investigate three features of dietary cooking oil intake,namely,the consumption,cooking style,and composition of fatty acids in relation to several cardiometabolic measurements in an elderly Chinese population.METHODS The elderly(≥65 years)participants for this study were recruited from two community health centers in the urban area of Shanghai.A questionnaire was administered to collect information on dietary oil consumption(low,medium and high)and cooking styles(fry or stir-fry vs.others)and the composition of fatty acids(poly-unsaturated vs.mono-unsaturated).The cardiometabolic measurements included anthropometry,blood pressure,fasting plasma glucose and serum lipids.RESULTS The 1186 study participants had a mean age of 70.9±5.4 years.The mean dietary oil consumption was 35.0 g/d,being low(<25 g/d),medium(25-49 g/d)and high(≥50 g/d)in 485,467 and 234 participants,respectively.The proportion of the fry or stir-fry cooking style and oils rich in mono-unsaturated fatty acids was 30.4%and 27.4%,respectively.Both before and after adjustment for sex,age,current smoking and alcohol intake,dietary oil consumption was significantly(P≤0.02)and positively associated with the prevalence of treated hypertension and fasting plasma glucose concentration.With similar adjustments as above and additional adjustment for dietary oil consumption,the fry or stir-fry cooking style was significantly(P≤0.048)and positively associated with body mass index,but inversely with systolic and diastolic blood pressure and serum low-density lipoprotein cholesterol,and the dietary intake of oils rich in mono-unsaturated fat acids was significantly(P≤0.02)and positively associated with diastolic blood pressure,serum triglycerides,total cholesterol and low-density lipoprotein cholesterol,and the prevalence of hypertriglyceridemia and hypercholesterolemia.CONCLUSIONS This study showed that both the consumption and composition of fatty acids of the dietary oils mattered with regard to several cardiometabolic measurements in
基金This study was supported by the grants from the second batch of the emergency key scientific and technological project of Shanghai Municipal Committee of Science and Technology(Nos.20411950300 and 20411950301)。
文摘The coronavirus disease 2019(COVID-19)has been declared as a pandemic by the World Health Organization.[1]Most COVID-19 patients exhibit mild to moderate symptoms,while approximately 15%progress rapidly to severe pneumonia,and about 5%eventually develop acute respiratory distress syndrome(ARDS),[2]which requires mechanical ventilation(MV)and even extracorporeal membrane oxygenation.The mortality of COVID-19 patients who received MV was reported to be as high as 66%.[3]Therefore,the treatments aiming to improve mortality should focus on two aspects:first,prevention of the aggravation of the disease in mild and moderate COVID-19 patients;second,the rescue therapy for patients in serious conditions.We have been applying high-dose intravenous vitamin C(HDIVC)in the treatment of critical illnesses for almost 10 years in our center.Our previous in vivo research showed that HDIVC protected hemorrhagic shock-related multiple organ failure(MOF)by inhibiting inflammatory cytokines and oxidative indicators through activating Sirtuin1 pathway.
基金supported by the National Natural Science Foundation of China(No.91639203&No.82070435)the Ministry of Science and Technology,Beijing,China(2018YFC1704902&2022YFC3601302)+2 种基金the Shanghai Commissions of Science and Technology and Health(a special grant for“leading academics”)(No.19DZ2340200)the Three-year Action Program of Shanghai Municipality for Strengthening the Construction of Public Health System Big Data and Artificial Intelligence Application,Shanghai,China(GWV-10.1-XK05)the Clinical Research Programme,Ruijin Hospital,Shanghai Jiaotong University School of Medicine,Shanghai,China(No.2018CR010).
文摘OBJECTIVE To investigate the association between current and former smoking and the risk of mortality in elderly Chinese men.METHODS Our study participants were elderly(≥60 years)men recruited in a suburban town of Shanghai.Cigarette smoking status was categorized as never smoking,remote(cessation>5 years)and recent former smoking(cessation≤5 years),and light-to-moderate(≤20 cigarettes/day)and heavy current smoking(>20 cigarettes/day).Cox proportional hazards models and restricted cubic splines were used to examine the associations of interest.RESULTS The 1568 participants had a mean age of 68.6±7.1 years.Of all participants,311 were never smokers,201 were remote former smokers,133 were recent former smokers,783 were light-to-moderate current smokers and 140 were heavy current smokers.During a median follow-up of 7.9 years,all-cause,cardiovascular and non-cardiovascular deaths occurred in 267,106 and 161 participants,respectively.Heavy current smokers had the highest risk of all-cause and non-cardiovascular mortality,with an adjusted hazard ratio(HR)of 2.30(95%CI:1.34-4.07)and 3.98(95%CI:2.03-7.83)versus never smokers,respectively.Recent former smokers also had a higher risk of all-cause(HR=1.62,95%CI:1.04-2.52)and non-cardiovascular mortality(HR=2.40,95%CI:1.32-4.37)than never smokers.Cox regression restricted cubic spline models showed the highest risk of all-cause and non-cardiovascular mortality within 5 years of smoking cessation and decline thereafter.Further subgroup analyses showed interaction between smoking status and pulse rate(≥70 beats/min vs.<70 beats/min)in relation to the risk of all-cause and non-cardiovascular mortality,with a higher risk in current versus never smokers in those participants with a pulse rate below 70 beats/min.CONCLUSIONS Cigarette smoking in elderly Chinese confers significant risks of mortality,especially when recent former smoking is considered together with current smoking.
基金supported by the National Key Basic Research Program of China(No.2013CB966800)National Natural Science Foundation of China(Nos.81970112,81670127,and 81101721)+2 种基金the Novo Nordisk Hemophilia Foundation,grants from the Shanghai Health Commission in China(No.201940342)grants from the Science and Technology Commission of Shanghai Municipality in China(Nos.16PJ1406100 and 16ZR1421000)Zhejiang Provincial Natural Science Foundation of China(No.LY17H080004).
文摘Conventional therapies for hemophilia A(HA)are prophylactic or on-demand intravenous FⅧinfusions.However,they are expensive and inconvenient to perform.Thus,better strategies for HA treatment must be developed.In this study,a recombinant FⅧcDNA encoding a human/rat hybrid FⅧwith an enhanced procoagulant potential for adeno-associated virus(AAV)-delivered gene therapy was developed.Plasmids containing human FⅧheavy chain(hHC),human light chain(hLC),and rat light chain(rLC)were transfected into cells and hydrodynamically injected into HA mice.Purified AAV viruses were intravenously injected into HA mice at two doses.Results showed that the hHC+rLC protein had a higher activity than the hHC+hLC protein at comparable expression levels.The specific activity of hHC+rLC was about 4-to 8-fold higher than that of their counterparts.Hydrodynamic injection experiments obtained consistent results.Notably,the HA mice undergoing the AAV-delivered hHC+rLC treatment exhibited a visibly higher activity than those treated with hHC+hLC,and the therapeutic effects lasted for up to 40 weeks.In conclusion,the application of the hybrid FⅧ(hHC+rLC)via an AAV-delivered gene therapy substantially improved the hemorrhagic diathesis of the HA mice.These data might be of help to the development of optimized FⅧexpression cassette for HA gene therapy.
文摘Aim:The transjugular intrahepatic portosystemic shunt(TIPS)procedure has been performed in China for 30 years,but our understanding of the status and difficulties associated with the use of TIPS for portal hypertension is incomplete.This study aims to investigate the current situation of the use of TIPS for portal hypertension,which should aid the development of TIPS in China.Methods:This study involved a questionnaire survey,initiated by the China Portal Hypertension Alliance(CHESS)to investigate the use of TIPS for portal hypertension in China.Questionnaires were released on the Internet between August 16,2022 and September 16,2022.Detailed information was collected from 545 hospitals contracted by the CHESS in China,which performed TIPS surgery in 2021.Results:The 545 hospitals covers the majority of hospitals in China that conduct TIPS intervention.In the survey,a total of 13,527 TIPS interventions were carried out with 94.1%(498/545)of them had a system of routine follow‐up after TIPS.The majority(42.6%[232/545])believed that the main indication of TIPS was the control of acute bleeding.Overall,48.1%(262/545)carried out early or pre‐emptive TIPS,53.0%(289/545)carried out TIPS for cavernous transformation of the portal vein,and 81.0%(441/545)chose routine embolization of collateral circulation during operation.Most used coils(97.0%[475/490])and biological glue(72.0%[353/490])as embolic materials,and 78.5%(428/545)routinely performed intraoperative portal pressure gradient measurements.When selecting TIPS stents,57.1%(311/545)chose viator‐specific stents,and 57.2%(312/545)chose conventional anticoagulation after TIPS.Conventional anticoagulation after TIPS is over a time interval of 3–6 months(55.4%[173/312]).The limitation of TIPS surgery is mainly its cost(72.3%[394/545])and insufficient understanding of the procedure by doctors in other related departments(77.4%[422/545]).Most of the hospital teams accept the use of domestic instruments in TIPS surgery(92.7%[505/545]).Conclusions:This survey shows t
基金The study was financially supported by grants from the National Natural Science Foundation of China(Nos.91639203,81770455,82070432,and 82070435)Ministry of Science and Technology(No.2018YFC1704902)+3 种基金Commission of Health,Beijing,China(No.2016YFC0900902)the Shanghai Commissions of Science and Technology(No.19DZ2340200 and"Sailing Program"19YF1441000)Health,Shanghai,China("Three-year Action Program of Shanghai Municipality for Strengthening the Construction of Public Health System"GWV-10.1-XK05 and a special grant for"leading academics")from the Clinical Research Program,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China(No.2018CR010)。
文摘Ambulatory blood pressure monitoring(ABPM)has become indispensable in the current management of hypertension.ABPM is particularly useful in the accurate diagnosis of hypertension.Its diagnostic thresholds had been recently established based on hard clinical outcomes.Cross-classification of patients according to office and ambulatory blood pressure identifies white-coat,masked,and sustained hypertension.ABPM is also useful in cardiovascular(CV)risk assessment.It provides information on daytime and nighttime blood pressure and circadian rhythm,particularly nighttime blood pressure dipping.Nighttime blood pressure is predictive of CV risk independent of office and daytime blood pressure.Isolated nocturnal hypertension is a special form of masked hypertension,with normal daytime but elevated nocturnal blood pressure.It also helps in the evaluation of blood pressure fluctuation and variation,such as morning blood pressure surge and reading-to-reading blood pressure variability.ABPM may derive several other indexes,such as ambulatory blood pressure index and salt sensitivity index,which may be useful in CV evaluations.
基金This work is supported by grants from the National Natural Science Foundation of China(No.82070509,81930088,81725018)Innovative Research Team of High-Level Local Universities in Shanghai,and the Natural Science Foundation of Shanghai Science and Technology Committee,China(No.20ZR1447400).
文摘Regulatory T(T_(reg))cells constitute a dynamic population that is critical in autoimmunity.T_(reg) cell therapies for autoimmune diseases are mainly focused on enhancing their suppressive activities.However,recent studies demonstrated that certain inflammatory conditions induce T_(reg) cell instability with diminished FoxP3 expression and convert them into pathogenic effector cells.Therefore,the identification of novel targets crucial to both T_(reg) cell function and plasticity is of vital importance to the development of therapeutic approaches in autoimmunity.In this study,we found that conditional Pp6 knockout(cKO)in T_(reg) cells led to spontaneous autoinflammation,immune cell activation,and diminished levels of FoxP3 in CD4^(+)T cells in mice.Loss of Pp6 in T_(reg) cells exacerbated two classical mouse models of T_(reg)-related autoinflammation.Mechanistically,Pp6 deficiency increased CpG motif methylation of the FoxP3 locus by dephosphorylating Dnmt1 and enhancing Akt phosphorylation at Ser473/Thr308,leading to impaired FoxP3 expression in T_(reg) cells.In summary,our study proposes Pp6 as a critical positive regulator of FoxP3 that acts by decreasing DNA methylation of the FoxP3 gene enhancer and inhibiting Akt signaling,thus maintaining T_(reg) cell stability and preventing autoimmune diseases.
基金supported by the National Natural Science Foundation of China(81870290,81521001,81800235,and 81800238)。
文摘To test the hypothesis that transient nonischemic stimulation of hypertrophy would render the heart resistant to subsequent ischemic stress,short-term transverse aortic constriction(TAC)was performed in mice and then withdrawn for several days by aortic debanding,followed by subsequent myocardial exposure to ischemia/reperfusion(I/R).Following I/R injury,the myocardial infarct size and apoptosis were markedly reduced,and contractile function was significantly improved in the TAC preconditioning group compared with the control group.Mechanistically,hypertrophic preconditioning remarkably alleviated I/R-induced oxidative stress,as evidenced by the increased reduced nicotinamide adenine dinucleotide phosphate(NADPH)/nicotinamide adenine dinucleotide phosphate(NADP)ratio,increase in the reduced glutathione(GSH)/oxidized glutathione(GSSH)ratio,and reduced mitochondrial reactive oxygen species(ROS)production.Moreover,TAC preconditioning inhibited caspase-3 activation and mitigated the mitochondrial impairment by deacetylating isocitrate dehydrogenase 2(IDH2)via a sirtuin 3(SIRT3)-dependent mechanism.In addition,the expression of a genetic deacetylation mimetic IDH2 mutant(IDH2 K413R)in cardiomyocytes,which increased IDH2 enzymatic activity and decreased mitochondrial ROS production,and ameliorated I/R injury,whereas the expression of a genetic acetylation mimetic(IDH2 K413Q)in cardiomyocytes abolished these protective effects of hypertrophic preconditioning.Furthermore,both the activity and expression of the SIRT3 protein were markedly increased in preconditioned mice exposed to I/R.Treatment with an adenovirus encoding SIRT3 partially emulated the actions of hypertrophic preconditioning,whereas genetic ablation of SIRT3 in mice blocked the cardioprotective effects of hypertrophic preconditioning.The present study identifies hypertrophic preconditioning as a novel endogenous self-defensive and cardioprotective strategy for cardiac I/R injury that induces IDH2 deacetylation through a SIRT3-dependent mechanism.A therapeu
文摘Objective:The randomized controlled trial(ClinicalTrials.gov identifier NCT02990741)will investigate whether more frequent electrocardiographic(ECG)recordings and analyses with an automated ECG system would improve detection of atrial fibrillation compared with a single annual ECG screen in elderly Chinese in community health centers.Design:Men and women(≥65 years)will be randomized into intensive(n=3500)and usual(n=3500)screening groups,and within the intensive screening group into intensive screening(n=2625)and more intensive screening(n=875)subgroups.ECG recordings will be performed with an automated ECG analysis system(AliveCor heart monitor)at 1 year in the usual screening group,at 3,6,9,and 12 months in the intensive screening subgroup,and at 1,2,3,and 4 weeks and 3,6,9,and 12 months in the more intensive screening subgroup.The primary outcome is the detection rate of atrial fibrillation between the usual screening group and the intensive screening group.Sample size estimation was based on a projected detection rate of atrial fibrillation of 2.0% by a single ECG recording at 12 months,an improvement of 50% with more frequent ECG recordings,α=0.05,power of 80%,and a one-sided test.Conclusions:The trial will provide evidence on the clinical effectiveness of more frequent ECG recordings by a handheld automated analysis system in the detection of atrial fibrillation.
基金We thank all the laboratory members for helpful discussion. This work was supported by grants from National Natural Science Foundation of China (No. 81270594), National Basic Research Program of China (No. 2012CB518000, No. 2013CB966800) and National Natural Science Foundation of China (No. 81070414). Jiansong Huang is a recipient of a fellowship from The China Postdoctoral Science Foundation (No. 2013M531185).
文摘We evaluated the roles of calpain cleavage-related mutations of the integrin β3 cytoplasmic tail in integrin αIIbβ3 bidirectional signaling using a trans-dominant inhibition model. Chimeric Tac-β3 proteins (i.e., Tac-β3, Tac-β3△741, Tac-β3△747, Tac-β3△754, Tac-β3△759, and Tac-β3ANITY) consisting of the extracellular and transmembrane domains of human IL-2 receptor (Tac) and the human integrin β3 cytoplasmic domain were stably expressed in the 123 CHO cells harboring human glycoprotein Ib-IX and wild-type integrin uIIbβ3. The different cells were assayed for stable adhesion and spreading on immobilized fibrinogen, and for binding soluble fibrinogen representing outside-in and inside-out signaling events, respectively. The chimeric protein Tac-β3 inhibited, and Tac-β3△NITY partially attenuated stable adhesion and spreading. Tac-β3, Tac-β3△759, Tac-β3ANITY, and Tac-β3△754, but not Tac-β3△747 or Tac-β3△741, impaired the soluble fibrinogen binding. Results indicated that the bidirectional signaling was significantly inhibited by Tac-β3△ and Tac-β3ANITY, albeit to a much lesser extent. Moreover, only inside-out signaling was impaired in the 123/Tac-β3△759 and 123/Tac-β3△754 cells in contrast to an intact bidirectional signaling in the 123/Tac-β3△747 and 123/Tac-β3△741 cells. In conclusion, the calpain cleavage of integrin β3 resulted in the regulatory effects on signaling by interrupting its interaction with cytoplasmic proteins rather than altering its conformation, and may thus regulate platelet function.
基金Supported by National Key R&D Program of China Project:Study on Syndrome Differentiation Standard of Yin deficiency Syndrome in Hypertension(No.2018YFC1704403)National Key R&D Program of China Project:Systematic Study on the Standard of Syndrome Differentiation of Yin Deficiency Syndrome(No.2018YFC1704400)。
文摘OBJECTIVE:To reach consensus on the diagnostic criteria for Yin deficiency syndrome in hypertension(YDSH)patients by a modified Delphi method.METHODS:Our study was consistent with T/CACM 1032-2017.The methodology of RAND/UCLA appropriateness was used to develop consensus guidance statements.A nationwide panel of experienced clinical experts from 19 provinces was constructed.These experts were all prominent in Traditional Chinese Medicine(TCM)of cardiovascular diseases.This consensus process consisted of two rounds of questionnaires and a final round of consultation to analyze the weight score of each item.Moreover,the data extraction process is carried out independently by third-party researchers(LIANG Junya,SUN Yang,and DU Xiaona).When there is disagreement in all three rounds,the expert panel group(odd number)are invited to vote,and the one with more votes wins.In the questionnaires,participants were asked to rate the appropriateness of each syndrome item using a nine-point Likert scale.The consensus was defined as a panel median rating 1-3 or 7-9 without disagreement.And then the diagnostic criteria of YDSH were formed according to the weight score in the final round.RESULTS:Twenty-eight experts(84.8%)participated in the first round,and thirty-one(93.9%)finished the second round.After two rounds,the consensus of YDSH was reached on 11 items(25.6%),including symptoms,signs,and pulse condition.Twenty-one experts(63.6%)completed the final round in which they used a grading system for each item.Red tongue with scanty fur had the highest weighting(22.8%),followed by heat in the palms and soles(20.1%).CONCLUSIONS:The consensus-based diagnostic criteria for YDSH,formed by a modified Delphi method,can be widely incorporated in TCM.A further clinical study will be conducted to analyze the diagnosis value and cut-off score of our YDSH criteria.
文摘INTRODUCTION Resistant hypertension has become a challenge in the treatment of hypertension.As the population continues to age and obesity,sleep apnea hypopnea syndrome,and chronic kidney disease increase in incidence,resistant hypertension has become an increasingly common issue in clinical practice.Failure to control blood pressure can impair target organs such as the heart,brain,and kidney,facilitating the occurrence of clinical cardiovascular events.
文摘BACKGROUND Alcohol consumption is a known modifiable risk factor for atrial fibrillation.The association,however,might differ according to gender.We investigated gender-specific associations between alcohol consumption and incident atrial fibrillation in an elderly Chinese population.METHODS Our study participants were elderly residents(≥65 years)recruited from five community health centers in the urban area of Shanghai(n=6,618).Alcohol intake was classified as never drinkers and current light-to-moderate(<40 g/day)and heavy drinkers(≥40 g/day).Atrial fibrillation was detected by a 30-s single-lead electrocardiography(ECG,AliveCor®Heart Monitor)and further evaluated with a regular 12-lead ECG.RESULTS During a median of 2.1 years(interquartile range:2.0−2.2)follow-up,the incidence rate of atrial fibrillation was 1.10%in all study participants.It was slightly but non-significantly higher in men(n=2849)than women(n=3769,1.30%vs.0.96%,P=0.19)and in current drinkers(n=793)than never drinkers(n=5825,1.64%vs.1.03%,P=0.12).In both unadjusted and adjusted analyses,there was interaction between sex and current alcohol intake in relation to the incidence of atrial fibrillation(P<0.0001).After adjustment for confounding factors,current drinkers had a significantly higher incidence rate of atrial fibrillation than never drinkers in women(12.96%[7/54]vs.0.78%[29/3715],adjusted odds ratio[OR]=10.25,95%confidence interval[CI]:3.54−29.67,P<0.0001),but not in men(0.81%[6/739]vs.1.47%[31/2110],OR=0.62,95%CI:0.25−1.51,P=0.29).CONCLUSIONS Our study showed a significant association between alcohol intake and the incidence of atrial fibrillation in elderly Chinese women,but not men.
基金financially supported by a grant from the Clinical Research Program,Ruijin Hospital,Shanghai Jiaotong University School of MedicineThe study investigators were also financially supported by grants from the National Natural Science Foundation of China(grants 91639203 and 82070435)+3 种基金Ministry of Science and Technology(grants 2015AA020105-06 and 2018YFC1704902)Ministry of Health(grant 2016YFC0900902)Beijing,China,from the Shanghai Commissions of Science and Technology(grant 19DZ2340200)Health(a special grant for“leading academics”),Shanghai,China.
文摘Hypertension significantly increases the risk of embolic stroke and systemic embolism in patients with atrial fibrillation, while statin therapy can improve long-term outcomes in hypertensive patients at high risk. However, it is still unclear whether patients with both hypertension and atrial fibrillation can benefit from intensive management of blood pressure and cholesterol. IMPRESSION is a 3-year prospective, randomized, open-label, blinded-endpoint investigation. A total of 1200 hypertensive patients with atrial fibrillation from about 40 clinical centers nationwide will be included upon confirming the presence of both hypertension and atrial fibrillation and will be randomly assigned to groups for intensive or standard management of blood pressure and cholesterol. Patients in all groups will have office and home blood pressure measured by the end of the first month and every 3 months thereafter. The effects of blood pressure and cholesterol management strategies in patients with hypertension and atrial fibrillation on fatal and non-fatal stroke, acute myocardial infarction, and cardiovascular death at 3 years will be assessed. The IMPRESSION study protocol has received approval from the Ethics Committee of Ruijin Hospital, Shanghai Jiaotong University School of Medicine. The procedures set out in this protocol are in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. The results will be published following the CONSORT statement in a peer-reviewed scientific journal (Trial registration number: NCT04111419).
基金financially supported by grants from the National Natural Science Foundation of China (grants 81170245 and 91639203)the State Ministry of Science and Technology (2018YFC1704902), Beijing, China+1 种基金the Shanghai Commissions of Science and Technology (15XD1503200)Health (grant 15GWZK0802 and a special grant for “leading academics”), Shanghai, China
文摘The new Chinese hypertension guideline was eventually published.[1] It has been more than seven years since the previous Chinese hypertension guideline was published in 2011.[2] The guideline committee should also be congratulated that this new Chinese hypertension guideline was for the first time published in full length in the English language in this issue of the Journal of Geriatric Cardiology.[3] This is the fourth Chinese hypertension guideline,[3] after the first,second[4] and third[2] in 1999,2005 and 2011,respectively.The first Chinese hypertension guideline was printed in a booklet.The document was not so sophisticated,but nevertheless played a role in improving management of hypertension at that time in China.The treatment rate of hypertension increased substantially from 45.5% in 1991[5] to 81.8% in 2002[6] in patients who were aware of the disease (Table 1).
文摘The “2018 Chinese Guidelines for Prevention and Treatment of Hypertension”[1](hereinafter referred to as the 2018 Guidelines) published in this issue was revised by the Guidelines Revision Committee which is initiated and organized by the Chinese Hypertension League.Based on the “2010 Chinese Guidelines for the Management of Hypertension” and recent evidence from domestic and international research in the field of hypertension,considering national conditions and the current situation of hypertension management in China,and reference to the latest European and American hypertension guidelines,the 2018 Guidelines make comprehensive and in-depth elaborations and recommendations of the diagnosis and assessment of hypertension,strategies and goals of prevention and treatment of hypertension and pathway of intervention,etc.The 2018 Guidelines not only provide Chinese medical personnel with guidance and reference for the clinical practice and population management of hypertension,but also serve as the latest textbook on updating concepts and knowledge in the field of hypertension.
基金the Innovation Studio from School of Biomedical Engineering,Shanghai Jiao Tong University,and the Medical-Engineering Cross Project of Shanghai Jiao Tong University(No.YG2017MS53)。
文摘Baroreflex plays a significant role in modulating blood pressure for the human body.It is known that activation of the vagal nerve related to baroreflex can lead to reductions of blood pressure.However,how the vagal activities quantitatively relate with blood pressure can hardly be achieved.Here fine carbon nanotube yarn(CNTy)electrodes were adopted for recording intrafascicular vagal activities,synchronized with measurement of arterial blood pressure in a rat.Together with a novel algorithm,the results preliminarily quantified that there were six clusters of neural spikes within recorded vagal activities,and the number of individual vagal spikes correspondingly varied with blood pressure.Especially for Cluster 2,the neural activations decreased with arterial blood pressure increasing.This study can shed lights on the quantified neural mechanism underlying the control of vagal activities on blood pressure,and guide the vagal-nerve neuromodulation for treating hypertension.