目的探讨酸性环境对高磷诱导的大鼠血管平滑肌细胞(VSMCs)钙化的影响及其机制。方法体外分离培养大鼠VSMCs,采用免疫细胞化学法鉴定。将VSMCs按随机数字表法分为正常对照组、高磷+p H 7.4组、高磷+p H 7.1组。刺激4 d后,采用逆转录聚合...目的探讨酸性环境对高磷诱导的大鼠血管平滑肌细胞(VSMCs)钙化的影响及其机制。方法体外分离培养大鼠VSMCs,采用免疫细胞化学法鉴定。将VSMCs按随机数字表法分为正常对照组、高磷+p H 7.4组、高磷+p H 7.1组。刺激4 d后,采用逆转录聚合酶链反应和Western blot检测活化T细胞核因子c1(NFATc1)、Runt相关转录因子2(Runx2)基因和蛋白的表达。刺激14 d后,对各组细胞进行钙化染色、钙含量和碱性磷酸酶(ALP)活性测定。结果与正常对照组比较,高磷+p H 7.4组的钙含量、ALP活性、Runx2和NFATc1表达升高(P<0.05);与高磷+p H 7.4组比较,高磷+p H 7.1组的钙含量、ALP活性、Runx2和NFATc1表达降低(P<0.05)。相关性分析发现,NFATc1蛋白表达水平与ALP活性、Runx2蛋白表达水平呈正相关(P<0.05)。结论酸性环境可以抑制高磷诱导的大鼠VSMCs钙化,其机制可能是通过降低NFATc1表达,抑制VSMCs表型转化来实现的。展开更多
Background The determinants of pulmonary hypertension(PH)due to heart failure with preserved ejection fraction(HFpEF)have been poorly investigated in patients with cardiovascular diseases(CVD).Methods From July 12017 ...Background The determinants of pulmonary hypertension(PH)due to heart failure with preserved ejection fraction(HFpEF)have been poorly investigated in patients with cardiovascular diseases(CVD).Methods From July 12017 to March 312019,a total of 149 consecutive HFp EF patients hospitalized with CVD were enrolled in this prospective cross-sectional study.A systolic pulmonary artery pressure(PASP)>35 mm Hg estimated by echocardiography was defined as PH-HFp EF.Logistic regression was performed to establish predictors of PH in HFpEF patients.Results Overall,the mean age of participants was 72±11 years,and 74(49.7%)patients were females.A total of 59(39.6%)patients were diagnosed with PH-HFpEF by echocardiography.The left atrial diameter(LAD)was related to the ratio of the transmitral flow velocities/mitral annulus tissue velocities in early diastole(E/E’)and the left ventricular diameter in systole(LVDs).N-Terminal pro B-type natriuretic peptide(NT-proBNP)was not found to be associated with LAD and impaired diastolic or systolic function of the left ventricle.Multivariable logistic regression showed that atrial fibrillation(AF)increased the risk of PH-HFpEF incidence 3.46-fold with a 95%confidence interval(CI)of 1.44–8.32,P=0.005.Meanwhile,LAD≥45 mm resulted in a 3.43-fold increased risk,95%CI:1.51–7.75,P=0.003.However,the significance levels of NT-proBNP,age and LVEF were underpowered in the regression model.Two variables,AF and LAD≥45 mm,predicted the PH-HFpEF incidence(C-statistic=0.773,95%CI:0.695–0.852,P<0.001).Conclusions Two parameters associated with electrical and anatomical remodelling of the left atrium were related to the incidence of PH in HFpEF patients with CVD.展开更多
Background Endogenous aldehyde damages DNA and potentiates an ageing phenotype. The aldehyde dehydrogenase 2(ALDH2) rs671 polymorphism has a prevalence of 30%–50% in Asian populations. In this study, we aimed to anal...Background Endogenous aldehyde damages DNA and potentiates an ageing phenotype. The aldehyde dehydrogenase 2(ALDH2) rs671 polymorphism has a prevalence of 30%–50% in Asian populations. In this study, we aimed to analyze risk factors contributing to the development of heart failure with preserved ejection fraction(HFpEF) along with the genetic exposure in Chinese patients hospitalized with cardiovascular diseases(CVD). Methods From July 2017 to October 2018, a total of 770 consecutive Chinese patients with normal left ventricular ejection fractions(LVEF) and established CVD(hypertension, coronary heart diseases, or diabetes) were enrolled in this prospective cross-sectional study. HFpEF was defined by the presence of at least one of symptom(dyspnoea and fatigue) or sign(rales and ankle swelling) related to heart failure;N-terminal pro-B-Type natriuretic peptide(NT pro-BNP ≥ 280 pg/mL);LVEF ≥ 50%;and at least one criterion related to elevated ventricular filling pressure or diastolic dysfunction(left atrial diameter > 40 mm, E/E’ ≥ 13, E’/A’ < 1 or concurrent atrial fibrillation). Logistic regression was performed to yield adjusted odds ratios(ORs) for HFp EF incidence associated with traditional and/or genetic exposures. Results Finally, among 770 patients with CVD, 92(11.9%) patients were classified into the HFpEF group according to the diagnostic criteria. The mean age of the participants was 67 ± 12 years, and 278(36.1%) patients were females. A total of 303(39.4%) patients were ALDH2*2 variant carriers. In the univariate analysis, eight exposures were found to be associated with HFpEF: atrial fibrillation, ALDH2*2 variants, hypertension, age, anaemia, smoking, alcohol consumption and sex. Multivariable logistic regression showed that 4 ‘A’ variables(atrial fibrillation, ALDH2*2 variants, age and anaemia) were significantly associated with an increased risk of HFpEF. Atrial fibrillation was associated with a 3.8-fold increased HFpEF risk(95% CI: 2.21–6.61, P < 0.001), and the other three exposures associated with increased HFpEF risk were the ALDH2*2 variant(OR = 2.41, 95% CI: 1.49–3.87, P < 0.001), age(OR = 2.14, 95% CI: 1.27–3.60, P = 0.004), and anaemia(OR = 1.79, 95% CI: 1.05–3.03, P = 0.032). These four variables predicted HFpEF incidence in Chinese CVD patients(C-statistic = 0.745, 95% CI: 0.691–0.800, P < 0.001). Conclusions 4 A traits(atrial fibrillation, ALDH2*2 variants, age and anaemia) were associated with an increased risk of HFpEF in Chinese CVD patients. Our results provide potential clues to the aetiology, pathophysiology and therapeutic targets of HFpEF.展开更多
Background: Accurately, characterizing plaques is critical for selecting the optimal intervention strategy for the left main coronary artery (LMCA) bifurcation. Coronary angiography cannot precisely assess the loca...Background: Accurately, characterizing plaques is critical for selecting the optimal intervention strategy for the left main coronary artery (LMCA) bifurcation. Coronary angiography cannot precisely assess the location or nature of plaques in bifurcation lesions. Few intravascular ultrasound (IVUS) classification scheme has been reported for angiographic imaging of true bifurcation lesions of the unprotected LMCA thus far. In addition, the plaque composition at the bifurcation has not been elucidated. This study aimed to detect plaque composition at LMCA bifurcation lesions by IVUS. Methods: Fifty-eight patients were recruited. The location, concentricity or eccentricity, site of maximum thickness, and composition of plaques of the distal LMCA, ostial left anterior descending (LAD) coronary artery and, left circumflex (LCX) coronary artery were assessed using IVUS and described using illustrative diagrams. Results: True bifurcation lesions of the unprotected LMCA were classified into four types: Type A, with continuous involvement from the distal LMCA to the ostial LAD and the ostial LCX with eccentric plaques; Type B, with concentric plaques at the distal LMCA, eccentric plaques at the ostial LAD, and no plaques at the LCX; Type C, with continuous involvement from the distal LMCA to the ostial LCX, with eccentric plaques, and to the ostial LAD, with eccentric plaques; and Type D, with continuous involvement from the distal LMCA to the ostial LAD, with eccentric plaques, and to the ostial LCX, with concentric plaques. The carina was involved in only 3.5% of the plaques. A total of 51.7% of the plaques at the ostium of the LAD were soft, while 44.8% and 44.6% were fibrous in the distal LMCA and in the ostial LCX, respectively. Conclusions: We classified LMCA true bifurcation lesions into four types. The carina was always free from disease. Plaques at the ostial LAD tended to be soft, whereas those at the ostial LCX and the distal LMCA tended to be fibrous.展开更多
To the Editor:Esophageal cancer is the sixth most common cancer globally according to the World Health Organization.[1] Due to rapid clinical progression and extremely poor prognosis,the 5-year survival rate of esopha...To the Editor:Esophageal cancer is the sixth most common cancer globally according to the World Health Organization.[1] Due to rapid clinical progression and extremely poor prognosis,the 5-year survival rate of esophageal squamous cell carcinomas(ESCC)remains less than 20%;[2]therefore,further developments in this field are needed.Human papillomavirus(HPV)is a small circular non-enveloped double-stranded DNA virus that primarily infects mucosa and cutaneous keratinocytes[3] and its infection rates in ESCC range from 11.7% to 38.9% worldwide.[4] P16 which is encoded by the CDKN2A gene and known as cyclin-dependent kinase inhibitor 2A,is a widely used immunohistochemical marker in squamous cell carcinomas and associated with high-risk HPV.[5]展开更多
To the Editor:Autophagy is reported to play a critical role in low shear stress (LSS)-induced endothelial cell injury and the formation of atherosclerotic plaques.[1] However,the corresponding mechanisms remain unc...To the Editor:Autophagy is reported to play a critical role in low shear stress (LSS)-induced endothelial cell injury and the formation of atherosclerotic plaques.[1] However,the corresponding mechanisms remain unclear.[2-8] This study was to investigate the changes and mechanism of LSS-induced autophagy in human umbilical vein endothelial cells (HUVECs).HUVECs were treated with LSS of 5 dyn/cm2 for 0,5,15,30,and 60 min in a parallel plate flow chamber system.Light chain (LC) Ⅱ,LC3 Ⅰ,and p62,p38 mitogen-activated protein kinase (MAPK) and their protein of phosphorylation of p38 (p-p38) were detected with Western blot analysis.The protein levels of p-p53 (ser15) and their distribution were detected by immunofluorescence (IF).展开更多
In this article, we study the masses and pole residues of the pseudoscalar-diquark-pseudoscalar-antidiquark type and vector-diquark-vector-antidiquark type scalar hidden-charm cucd (cucs) tetraquark states with QCD ...In this article, we study the masses and pole residues of the pseudoscalar-diquark-pseudoscalar-antidiquark type and vector-diquark-vector-antidiquark type scalar hidden-charm cucd (cucs) tetraquark states with QCD sum rules by taking into account the contributions of the vacuum condensates up to dimension-lO in the operator product expansion. The predicted masses can be confronted with the experimental data in the future. Possible decays of those tetraquark states are also discussed.展开更多
文摘目的探讨酸性环境对高磷诱导的大鼠血管平滑肌细胞(VSMCs)钙化的影响及其机制。方法体外分离培养大鼠VSMCs,采用免疫细胞化学法鉴定。将VSMCs按随机数字表法分为正常对照组、高磷+p H 7.4组、高磷+p H 7.1组。刺激4 d后,采用逆转录聚合酶链反应和Western blot检测活化T细胞核因子c1(NFATc1)、Runt相关转录因子2(Runx2)基因和蛋白的表达。刺激14 d后,对各组细胞进行钙化染色、钙含量和碱性磷酸酶(ALP)活性测定。结果与正常对照组比较,高磷+p H 7.4组的钙含量、ALP活性、Runx2和NFATc1表达升高(P<0.05);与高磷+p H 7.4组比较,高磷+p H 7.1组的钙含量、ALP活性、Runx2和NFATc1表达降低(P<0.05)。相关性分析发现,NFATc1蛋白表达水平与ALP活性、Runx2蛋白表达水平呈正相关(P<0.05)。结论酸性环境可以抑制高磷诱导的大鼠VSMCs钙化,其机制可能是通过降低NFATc1表达,抑制VSMCs表型转化来实现的。
基金funded by the National Natural Science Foundation of China (Grant No. 81700398No. 81970309 and No. 81770441)+1 种基金the Natural Science Foundation of Guangdong Province No. 2016A030 313430Nanjing Municipal Healthcare Grant YKK16127。
文摘Background The determinants of pulmonary hypertension(PH)due to heart failure with preserved ejection fraction(HFpEF)have been poorly investigated in patients with cardiovascular diseases(CVD).Methods From July 12017 to March 312019,a total of 149 consecutive HFp EF patients hospitalized with CVD were enrolled in this prospective cross-sectional study.A systolic pulmonary artery pressure(PASP)>35 mm Hg estimated by echocardiography was defined as PH-HFp EF.Logistic regression was performed to establish predictors of PH in HFpEF patients.Results Overall,the mean age of participants was 72±11 years,and 74(49.7%)patients were females.A total of 59(39.6%)patients were diagnosed with PH-HFpEF by echocardiography.The left atrial diameter(LAD)was related to the ratio of the transmitral flow velocities/mitral annulus tissue velocities in early diastole(E/E’)and the left ventricular diameter in systole(LVDs).N-Terminal pro B-type natriuretic peptide(NT-proBNP)was not found to be associated with LAD and impaired diastolic or systolic function of the left ventricle.Multivariable logistic regression showed that atrial fibrillation(AF)increased the risk of PH-HFpEF incidence 3.46-fold with a 95%confidence interval(CI)of 1.44–8.32,P=0.005.Meanwhile,LAD≥45 mm resulted in a 3.43-fold increased risk,95%CI:1.51–7.75,P=0.003.However,the significance levels of NT-proBNP,age and LVEF were underpowered in the regression model.Two variables,AF and LAD≥45 mm,predicted the PH-HFpEF incidence(C-statistic=0.773,95%CI:0.695–0.852,P<0.001).Conclusions Two parameters associated with electrical and anatomical remodelling of the left atrium were related to the incidence of PH in HFpEF patients with CVD.
基金supported by the he National Natural Science Foundation of China (No. 81770441, No. 81700398, No. 81970309)Nanjing Municipal Healthcare Grant YKK16127
文摘Background Endogenous aldehyde damages DNA and potentiates an ageing phenotype. The aldehyde dehydrogenase 2(ALDH2) rs671 polymorphism has a prevalence of 30%–50% in Asian populations. In this study, we aimed to analyze risk factors contributing to the development of heart failure with preserved ejection fraction(HFpEF) along with the genetic exposure in Chinese patients hospitalized with cardiovascular diseases(CVD). Methods From July 2017 to October 2018, a total of 770 consecutive Chinese patients with normal left ventricular ejection fractions(LVEF) and established CVD(hypertension, coronary heart diseases, or diabetes) were enrolled in this prospective cross-sectional study. HFpEF was defined by the presence of at least one of symptom(dyspnoea and fatigue) or sign(rales and ankle swelling) related to heart failure;N-terminal pro-B-Type natriuretic peptide(NT pro-BNP ≥ 280 pg/mL);LVEF ≥ 50%;and at least one criterion related to elevated ventricular filling pressure or diastolic dysfunction(left atrial diameter > 40 mm, E/E’ ≥ 13, E’/A’ < 1 or concurrent atrial fibrillation). Logistic regression was performed to yield adjusted odds ratios(ORs) for HFp EF incidence associated with traditional and/or genetic exposures. Results Finally, among 770 patients with CVD, 92(11.9%) patients were classified into the HFpEF group according to the diagnostic criteria. The mean age of the participants was 67 ± 12 years, and 278(36.1%) patients were females. A total of 303(39.4%) patients were ALDH2*2 variant carriers. In the univariate analysis, eight exposures were found to be associated with HFpEF: atrial fibrillation, ALDH2*2 variants, hypertension, age, anaemia, smoking, alcohol consumption and sex. Multivariable logistic regression showed that 4 ‘A’ variables(atrial fibrillation, ALDH2*2 variants, age and anaemia) were significantly associated with an increased risk of HFpEF. Atrial fibrillation was associated with a 3.8-fold increased HFpEF risk(95% CI: 2.21–6.61, P < 0.001), and the other three exposures associated with increased HFpEF risk were the ALDH2*2 variant(OR = 2.41, 95% CI: 1.49–3.87, P < 0.001), age(OR = 2.14, 95% CI: 1.27–3.60, P = 0.004), and anaemia(OR = 1.79, 95% CI: 1.05–3.03, P = 0.032). These four variables predicted HFpEF incidence in Chinese CVD patients(C-statistic = 0.745, 95% CI: 0.691–0.800, P < 0.001). Conclusions 4 A traits(atrial fibrillation, ALDH2*2 variants, age and anaemia) were associated with an increased risk of HFpEF in Chinese CVD patients. Our results provide potential clues to the aetiology, pathophysiology and therapeutic targets of HFpEF.
文摘Background: Accurately, characterizing plaques is critical for selecting the optimal intervention strategy for the left main coronary artery (LMCA) bifurcation. Coronary angiography cannot precisely assess the location or nature of plaques in bifurcation lesions. Few intravascular ultrasound (IVUS) classification scheme has been reported for angiographic imaging of true bifurcation lesions of the unprotected LMCA thus far. In addition, the plaque composition at the bifurcation has not been elucidated. This study aimed to detect plaque composition at LMCA bifurcation lesions by IVUS. Methods: Fifty-eight patients were recruited. The location, concentricity or eccentricity, site of maximum thickness, and composition of plaques of the distal LMCA, ostial left anterior descending (LAD) coronary artery and, left circumflex (LCX) coronary artery were assessed using IVUS and described using illustrative diagrams. Results: True bifurcation lesions of the unprotected LMCA were classified into four types: Type A, with continuous involvement from the distal LMCA to the ostial LAD and the ostial LCX with eccentric plaques; Type B, with concentric plaques at the distal LMCA, eccentric plaques at the ostial LAD, and no plaques at the LCX; Type C, with continuous involvement from the distal LMCA to the ostial LCX, with eccentric plaques, and to the ostial LAD, with eccentric plaques; and Type D, with continuous involvement from the distal LMCA to the ostial LAD, with eccentric plaques, and to the ostial LCX, with concentric plaques. The carina was involved in only 3.5% of the plaques. A total of 51.7% of the plaques at the ostium of the LAD were soft, while 44.8% and 44.6% were fibrous in the distal LMCA and in the ostial LCX, respectively. Conclusions: We classified LMCA true bifurcation lesions into four types. The carina was always free from disease. Plaques at the ostial LAD tended to be soft, whereas those at the ostial LCX and the distal LMCA tended to be fibrous.
基金This work was supported by grants from the Henan Medical Science and Technology Project(general)(No.201401017)the National Natural Science Foundation of China(No.81602637).
文摘To the Editor:Esophageal cancer is the sixth most common cancer globally according to the World Health Organization.[1] Due to rapid clinical progression and extremely poor prognosis,the 5-year survival rate of esophageal squamous cell carcinomas(ESCC)remains less than 20%;[2]therefore,further developments in this field are needed.Human papillomavirus(HPV)is a small circular non-enveloped double-stranded DNA virus that primarily infects mucosa and cutaneous keratinocytes[3] and its infection rates in ESCC range from 11.7% to 38.9% worldwide.[4] P16 which is encoded by the CDKN2A gene and known as cyclin-dependent kinase inhibitor 2A,is a widely used immunohistochemical marker in squamous cell carcinomas and associated with high-risk HPV.[5]
基金This study was supported by grants from the Natural Science Foundation of Guangdong Province (No. 2016A030313430), the Scientific and Technological Program of Guangzhou City (No. 201510010024), and the Natural Science Foundation of Guangdong Province (No. 2014A030310049).
文摘To the Editor:Autophagy is reported to play a critical role in low shear stress (LSS)-induced endothelial cell injury and the formation of atherosclerotic plaques.[1] However,the corresponding mechanisms remain unclear.[2-8] This study was to investigate the changes and mechanism of LSS-induced autophagy in human umbilical vein endothelial cells (HUVECs).HUVECs were treated with LSS of 5 dyn/cm2 for 0,5,15,30,and 60 min in a parallel plate flow chamber system.Light chain (LC) Ⅱ,LC3 Ⅰ,and p62,p38 mitogen-activated protein kinase (MAPK) and their protein of phosphorylation of p38 (p-p38) were detected with Western blot analysis.The protein levels of p-p53 (ser15) and their distribution were detected by immunofluorescence (IF).
基金Supported by the National Natural Science Foundation of China under Grant No.11375063the Fundamental Research Funds for the Central Universities under Grant Nos.2016MS155 and 2016MS133
文摘In this article, we study the masses and pole residues of the pseudoscalar-diquark-pseudoscalar-antidiquark type and vector-diquark-vector-antidiquark type scalar hidden-charm cucd (cucs) tetraquark states with QCD sum rules by taking into account the contributions of the vacuum condensates up to dimension-lO in the operator product expansion. The predicted masses can be confronted with the experimental data in the future. Possible decays of those tetraquark states are also discussed.