Background Uncertainty remains regarding the association between body mass index(BMI)and the risk of bleeding in patients with non-valvular atrial fibrillation(NVAF).We aimed to investigate the association between BMI...Background Uncertainty remains regarding the association between body mass index(BMI)and the risk of bleeding in patients with non-valvular atrial fibrillation(NVAF).We aimed to investigate the association between BMI and the risk of bleeding in elderly NVAF patients taking dabigatran.Methods A total of 509 elderly NVAF patients,who were being treated at twelve centers in China from February 2015 to December 2017 and taking dabigatran,were analyzed.The exposure and outcome variables were BMI at baseline and bleeding events within the subsequent six months,respectively.Cox proportional hazards regression analysis was used to evaluate the association between BMI and the risk of bleeding.Moreover,the Cox proportional hazards regression with cubic spline functions and smooth curve fitting was conducted.Results During the six-month follow-up,50 participants experienced bleeding.Every 1 kg/m^2 increase in BMI was associated with a 12%increased risk of bleeding(P=0.021).Compared to those with BMI values in Tertile 1(<22.5 kg/m^2),the adjusted hazard ratio(HR)of bleeding for participants in Tertile 2(22.5–25.3 kg/m^2)and Tertile 3(>25.3 kg/m^2)were 2.71(95%CI:1.02–7.17)and 3.5(95%CI:1.21–8.70),respectively.The Ptrend-value was significant in all models.The adjusted smooth curve showed a linear association between BMI and bleeding.None of the stratified variables showed significant effect modification on the association between BMI and bleeding(Pinteraction>0.05).Conclusions BMI was significantly and positively associated with the risk of bleeding in elderly NVAF patients treated with dabigatran.展开更多
BACKGROUND The cardiovascular hazards of total homocysteine(tHcy)are long known.In addition,despite the acknow-ledgment on the importance of low ankle-brachial index(ABI)(<0.9),borderline ABI(0.91-0.99)was once com...BACKGROUND The cardiovascular hazards of total homocysteine(tHcy)are long known.In addition,despite the acknow-ledgment on the importance of low ankle-brachial index(ABI)(<0.9),borderline ABI(0.91-0.99)was once commonly overlooked.This study aims to explore the independent and joint effect of tHcy level and borderline ABI on all-cause death in hypertensive population.METHODS This study included 10,538 participants from China H-type Hypertension Registry Study.ABI was described into two groups:normal ABI(1.00-1.40)and borderline ABI.tHcy level was also divided into two groups:<15.02 and≥15.02μmo/L.Four groups were analyzed,using COX proportional hazard regression model,separately and pairwise to observe the independ-ent and joint effect on all-cause death.RESULTS A total of 126(1.2%)deaths were observed in the 1.7 years follow-up time.Borderline ABI has a higher predicted risk of death than normal ABI(HR=1.87,95%CI:1.17-3.00)after adjusting for potential covariates.Compare with tHcy level<15.02μmo/L(low tHcy),those with tHcy≥15.02μmo/L(high tHcy)had higher risk to event outcome(HR=1.99,95%CI:1.30-3.05).According to the cumulative hazard curve,group with borderline ABI and high tHcy level has significantly higher altitude and larger increasing rate over follow-up period compare to other groups.Among those with borderline ABI,participants with high tHcy had higher death risk than those with low tHcy,nevertheless,no significant different between borderline and normal ABI among those with low tHcy levels.CONCLUSIONS Borderline ABI and tHcy level both have independent predictive value on all-cause death.The combined group of borderline ABI and high tHcy has highest risk factor of outcomes,which suggested the mutual additive value of border-line ABI and tHcy.More attention should be given to the importance of borderline ABI in hypertensive population,especially with elevated tHcy level.展开更多
Objective:To explore the association between the Lung Immune Prognostic Index(LIPI)and 1-year all-cause mortality in patients with idiopathic inflammatory myopathy related interstitial lung disease(IIM-ILD).Methods:Pa...Objective:To explore the association between the Lung Immune Prognostic Index(LIPI)and 1-year all-cause mortality in patients with idiopathic inflammatory myopathy related interstitial lung disease(IIM-ILD).Methods:Patients who were diagnosed with IIM-ILD at West China Hospital,Sichuan University from January 2008 to December 2021 were retrospectively included and categorized into three groups based on LIPI.Univariable and multivariable Cox proportional hazards models were conducted to explore potential association between the LIPI and patients'mortality.Results:A total of 1116 patients were screened,and 830 were included in this study.The multivariable Cox analysis showed that,compared with patients with poor LIPI,the hazard ratio(HR)for all-cause 1-year mortality was 0.22(95%CI 0.05-0.93,P=0.04)for patients in the good LIPI group(LDH<250 IU/L and dNLR<3).After excluding patients lost to follow-up within one year,a similar result was found for LIPI(HR 0.20,95%CI 0.05-0.86;P=0.03).Conclusions:Good LIPI was independently associated with decreased risk of all-cause 1-year mortality in patients with IIM-ILD.This easy-to-obtain index might be served as a potential marker for assessing the prognosis of IIM-ILD.展开更多
Background: The association between peripheral leukocyte count and bleeding events in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran remains unclear. This study aimed to explore the associatio...Background: The association between peripheral leukocyte count and bleeding events in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran remains unclear. This study aimed to explore the association between leukocyte count and bleeding events after excluding other confounders in NVAF patients taking dabigatran. Methods: A total of 851 NVAF patients treated with dabigatran (110 mg bid) were recruited from 12 centers in China from February 2015 to December 2017. Follow-up was completed by May 2018. The exposure and outcome variables were leukocyte count measured at baseline and the number of bleeding events within the subsequent 6 months. Multivariate Cox proportional hazards models were constructed to analyze independent associations, and a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (penalized spline method) was used to address nonlinearity between leukocyte count and bleeding. The inflection point was calculated using a recursive algorithm, and then a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed. Results: During 6-month follow-up, 87 participants occurred bleeding events. For every 1×10^9/L increase in leukocyte count, the risk of bleeding increased by 11%(hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 0.99–1.25). The smooth curve showed nonlinear relationship between leukocyte count and bleeding events. The inflection point of the leukocyte count was 6.75×10^9/L. For leukocyte counts < 6.75×10^9/L, the HR (95% CI) was 0.88 (0.69–1.13), and for leukocyte counts ≥ 6.75×10^9/L, the HR (95% CI) was 1.28 (1.09–1.51). Conclusion: This study found a J-shaped association between baseline leukocyte count and risk of bleeding in NVAF patients treated with dabigatran.展开更多
Esophageal cancer-related gene-4(Ecrg4)is cloned from the normal epithelium of the esophagus.It is constitutively expressed in quiescent epithelial cells and downregulated during tumorigenesis,and Ecrg4 expression lev...Esophageal cancer-related gene-4(Ecrg4)is cloned from the normal epithelium of the esophagus.It is constitutively expressed in quiescent epithelial cells and downregulated during tumorigenesis,and Ecrg4 expression levels are inversely correlated with the malignant phenotype of tumor cells,validating that Ecrg4 is a real tumor suppressor gene.Unlike other tumor suppressor genes that usually encode membrane or intracellular proteins,Ecrg4 encodes a 148-amino acid pre-pro-peptide that is tethered on the cell surface in epithelial cells,specialized epithelial cells,and human leukocytes,where it can be processed tissue dependently into several small peptides upon cell activation.Ecrg4 is expressed in a wide variety of other cells/tissues,including cardiomyocytes and conduction system of the heart,,the glomus cells of the carotid body,adrenal glands,choroid plexus,and leukocytes among others,where it exerts distinct functions,such as promoting/suppressing inflammation,inducing neuron senescence,stimulating the hypothalamus--pituitary--adrenal axis,maintaining the stemness of stem cells,participating in the rhythm and rate control of the heart,and possibly gauging the responsiveness of the cardiovascular system(CVS)to hypoxia,in addition to tumor suppression.Here,we briefly review the latest discoveries on Ecrg4 and its underlying molecular mechanisms as a tumor suppressor and focus on the emerging roles of Ecrg4 in the CVS.展开更多
Dear Editor,Small conductance Ca2+-activated potassium (SK) channels are widely expressed in various tissues and play a unique role in regulating cell function by integrating cytosolic Ca2+ levels and membrane potenti...Dear Editor,Small conductance Ca2+-activated potassium (SK) channels are widely expressed in various tissues and play a unique role in regulating cell function by integrating cytosolic Ca2+ levels and membrane potential (Adelman et al., 2012). Xu et al. first identified SK channels in the heart and found that SK channels, particularly the SK2 channel, are preferentially expressed in human and mouse atrial myocytes but not in ventricular myocytes (Xu et al., 2003). This suggests that the展开更多
Backgrounds:Physical activity(PA)and sedentary behavior(SB)have been associated with mortality,while the joint association with mortality is rarely reported among Chinese population.We aimed to examine the independent...Backgrounds:Physical activity(PA)and sedentary behavior(SB)have been associated with mortality,while the joint association with mortality is rarely reported among Chinese population.We aimed to examine the independent and joint association of PA and SB with all-cause mortality in southern China.Methods:A cohort of 12,608 China Hypertension Survey participants aged≥35 years were enrolled in 2013 to 2014,with a follow-up period of 5.4 years.Baseline self-reported PA and SB were collected via the questionnaire.Kaplan–Meier curves(log-rank test)and Cox proportional hazards regression were performed to evaluate the associations of PA and SB on all-cause mortality.Results:A total of 11,744 eligible participants were included in the analysis.Over an average of 5.4 years of follow-up,796 deaths occurred.The risk of all-cause mortality was lower among participants with high PA than those with low to moderate level(5.2%vs.8.9%;hazards ratio[HR]:0.75,95%confidence interval[CI]:0.61–0.87).Participants with SB≥6 h had a higher risk of all-cause mortality than those with SB<6 h(7.8%vs.6.0%;HR:1.37,95%CI:1.17–1.61).Participants with prolonged SB(≥6 h)and inadequate PA(low to moderate)had a higher risk of all-cause mortality compared to those with SB<6 h and high PA(11.2%vs.4.9%;HR:1.67,95%CI:1.35–2.06).Even in the participants with high PA,prolonged SB(≥6 h)was still associated with the higher risk of all-cause mortality compared with SB<6 h(7.0%vs.4.9%;HR:1.33,95%CI:1.12–1.56).Conclusions:Among Chinese population,PA and SB have a joint association with the risk of all-cause mortality.Participants with inadequate PA and prolonged SB had the highest risk of all-cause mortality compared with others.展开更多
Large conductance calcium-activated potassium(BKCa)channels are broadly expressed in vascular smooth muscle cells(VSMCs)and play a crucial role in the regulation of vascular tone[1].Activation of BKCachannel by elevat...Large conductance calcium-activated potassium(BKCa)channels are broadly expressed in vascular smooth muscle cells(VSMCs)and play a crucial role in the regulation of vascular tone[1].Activation of BKCachannel by elevation of the[Ca^(2+)]idue to membrane depolarization increases the K^+ conductance of the membrane,and drives the VSMC membrane potential to hyperpolarization,which展开更多
基金supported by the Major New Drug Creation Program from National Science and Technology Major Project of China(2014ZX09303305).
文摘Background Uncertainty remains regarding the association between body mass index(BMI)and the risk of bleeding in patients with non-valvular atrial fibrillation(NVAF).We aimed to investigate the association between BMI and the risk of bleeding in elderly NVAF patients taking dabigatran.Methods A total of 509 elderly NVAF patients,who were being treated at twelve centers in China from February 2015 to December 2017 and taking dabigatran,were analyzed.The exposure and outcome variables were BMI at baseline and bleeding events within the subsequent six months,respectively.Cox proportional hazards regression analysis was used to evaluate the association between BMI and the risk of bleeding.Moreover,the Cox proportional hazards regression with cubic spline functions and smooth curve fitting was conducted.Results During the six-month follow-up,50 participants experienced bleeding.Every 1 kg/m^2 increase in BMI was associated with a 12%increased risk of bleeding(P=0.021).Compared to those with BMI values in Tertile 1(<22.5 kg/m^2),the adjusted hazard ratio(HR)of bleeding for participants in Tertile 2(22.5–25.3 kg/m^2)and Tertile 3(>25.3 kg/m^2)were 2.71(95%CI:1.02–7.17)and 3.5(95%CI:1.21–8.70),respectively.The Ptrend-value was significant in all models.The adjusted smooth curve showed a linear association between BMI and bleeding.None of the stratified variables showed significant effect modification on the association between BMI and bleeding(Pinteraction>0.05).Conclusions BMI was significantly and positively associated with the risk of bleeding in elderly NVAF patients treated with dabigatran.
基金funded by the Key R&D ProjectsJiangxi [20203BBGL73173]+4 种基金the National Natural Science Foundation of China [81960074]Project of Jiangxi Provincial Health Commission [202130440]5511 Science and Technology Innovation Talent Project of Jiangxi Province (CN)[20165BCD41005]Jiangxi Provincial Natural Science Foundation[20212ACB206019]the Second Affiliated Hospital of Nanchang University[2016YNQN12034, 2019YNLZ12010, IIT-I-2021-002, 2021YNFY2024]
文摘BACKGROUND The cardiovascular hazards of total homocysteine(tHcy)are long known.In addition,despite the acknow-ledgment on the importance of low ankle-brachial index(ABI)(<0.9),borderline ABI(0.91-0.99)was once commonly overlooked.This study aims to explore the independent and joint effect of tHcy level and borderline ABI on all-cause death in hypertensive population.METHODS This study included 10,538 participants from China H-type Hypertension Registry Study.ABI was described into two groups:normal ABI(1.00-1.40)and borderline ABI.tHcy level was also divided into two groups:<15.02 and≥15.02μmo/L.Four groups were analyzed,using COX proportional hazard regression model,separately and pairwise to observe the independ-ent and joint effect on all-cause death.RESULTS A total of 126(1.2%)deaths were observed in the 1.7 years follow-up time.Borderline ABI has a higher predicted risk of death than normal ABI(HR=1.87,95%CI:1.17-3.00)after adjusting for potential covariates.Compare with tHcy level<15.02μmo/L(low tHcy),those with tHcy≥15.02μmo/L(high tHcy)had higher risk to event outcome(HR=1.99,95%CI:1.30-3.05).According to the cumulative hazard curve,group with borderline ABI and high tHcy level has significantly higher altitude and larger increasing rate over follow-up period compare to other groups.Among those with borderline ABI,participants with high tHcy had higher death risk than those with low tHcy,nevertheless,no significant different between borderline and normal ABI among those with low tHcy levels.CONCLUSIONS Borderline ABI and tHcy level both have independent predictive value on all-cause death.The combined group of borderline ABI and high tHcy has highest risk factor of outcomes,which suggested the mutual additive value of border-line ABI and tHcy.More attention should be given to the importance of borderline ABI in hypertensive population,especially with elevated tHcy level.
基金supported by grants from the National High Technology Research and Development Program of China(Grant No.2022YFC3601500)Sichuan Science and Technology Program(Grant No.2020YFQ0011).
文摘Objective:To explore the association between the Lung Immune Prognostic Index(LIPI)and 1-year all-cause mortality in patients with idiopathic inflammatory myopathy related interstitial lung disease(IIM-ILD).Methods:Patients who were diagnosed with IIM-ILD at West China Hospital,Sichuan University from January 2008 to December 2021 were retrospectively included and categorized into three groups based on LIPI.Univariable and multivariable Cox proportional hazards models were conducted to explore potential association between the LIPI and patients'mortality.Results:A total of 1116 patients were screened,and 830 were included in this study.The multivariable Cox analysis showed that,compared with patients with poor LIPI,the hazard ratio(HR)for all-cause 1-year mortality was 0.22(95%CI 0.05-0.93,P=0.04)for patients in the good LIPI group(LDH<250 IU/L and dNLR<3).After excluding patients lost to follow-up within one year,a similar result was found for LIPI(HR 0.20,95%CI 0.05-0.86;P=0.03).Conclusions:Good LIPI was independently associated with decreased risk of all-cause 1-year mortality in patients with IIM-ILD.This easy-to-obtain index might be served as a potential marker for assessing the prognosis of IIM-ILD.
文摘Background: The association between peripheral leukocyte count and bleeding events in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran remains unclear. This study aimed to explore the association between leukocyte count and bleeding events after excluding other confounders in NVAF patients taking dabigatran. Methods: A total of 851 NVAF patients treated with dabigatran (110 mg bid) were recruited from 12 centers in China from February 2015 to December 2017. Follow-up was completed by May 2018. The exposure and outcome variables were leukocyte count measured at baseline and the number of bleeding events within the subsequent 6 months. Multivariate Cox proportional hazards models were constructed to analyze independent associations, and a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (penalized spline method) was used to address nonlinearity between leukocyte count and bleeding. The inflection point was calculated using a recursive algorithm, and then a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed. Results: During 6-month follow-up, 87 participants occurred bleeding events. For every 1×10^9/L increase in leukocyte count, the risk of bleeding increased by 11%(hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 0.99–1.25). The smooth curve showed nonlinear relationship between leukocyte count and bleeding events. The inflection point of the leukocyte count was 6.75×10^9/L. For leukocyte counts < 6.75×10^9/L, the HR (95% CI) was 0.88 (0.69–1.13), and for leukocyte counts ≥ 6.75×10^9/L, the HR (95% CI) was 1.28 (1.09–1.51). Conclusion: This study found a J-shaped association between baseline leukocyte count and risk of bleeding in NVAF patients treated with dabigatran.
基金This study was funded by the Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province,Southwest Medical University(No.xtcx-2016-16)the National Natural Science Foundation o f China(No.81770336)a seeding grant from Southwest Medical University.
文摘Esophageal cancer-related gene-4(Ecrg4)is cloned from the normal epithelium of the esophagus.It is constitutively expressed in quiescent epithelial cells and downregulated during tumorigenesis,and Ecrg4 expression levels are inversely correlated with the malignant phenotype of tumor cells,validating that Ecrg4 is a real tumor suppressor gene.Unlike other tumor suppressor genes that usually encode membrane or intracellular proteins,Ecrg4 encodes a 148-amino acid pre-pro-peptide that is tethered on the cell surface in epithelial cells,specialized epithelial cells,and human leukocytes,where it can be processed tissue dependently into several small peptides upon cell activation.Ecrg4 is expressed in a wide variety of other cells/tissues,including cardiomyocytes and conduction system of the heart,,the glomus cells of the carotid body,adrenal glands,choroid plexus,and leukocytes among others,where it exerts distinct functions,such as promoting/suppressing inflammation,inducing neuron senescence,stimulating the hypothalamus--pituitary--adrenal axis,maintaining the stemness of stem cells,participating in the rhythm and rate control of the heart,and possibly gauging the responsiveness of the cardiovascular system(CVS)to hypoxia,in addition to tumor suppression.Here,we briefly review the latest discoveries on Ecrg4 and its underlying molecular mechanisms as a tumor suppressor and focus on the emerging roles of Ecrg4 in the CVS.
基金supported by the National Natural Science Foundation of China (30870903 to Xiaorong Zeng, 31300948,81670130 to Xiaoqiu Tan, 81670313 to Jimin Cao)Science and Technology Support Program of Sichuan Province (2011FZ0106 to Xiaorong Zeng)
文摘Dear Editor,Small conductance Ca2+-activated potassium (SK) channels are widely expressed in various tissues and play a unique role in regulating cell function by integrating cytosolic Ca2+ levels and membrane potential (Adelman et al., 2012). Xu et al. first identified SK channels in the heart and found that SK channels, particularly the SK2 channel, are preferentially expressed in human and mouse atrial myocytes but not in ventricular myocytes (Xu et al., 2003). This suggests that the
基金the National Natural Science Foundation of China(No.81760049)the Jiangxi Science and Technology Innovation Platform Project(No.20165BCD41005)+2 种基金the National Key R&D Program of China(No.2018YFC1312902)the Science and Technology Plan of Health Commission of Jiangxi Province(No.20185215)the Key Project of Education Department of Jiangxi Province(No.GJJ170013).
文摘Backgrounds:Physical activity(PA)and sedentary behavior(SB)have been associated with mortality,while the joint association with mortality is rarely reported among Chinese population.We aimed to examine the independent and joint association of PA and SB with all-cause mortality in southern China.Methods:A cohort of 12,608 China Hypertension Survey participants aged≥35 years were enrolled in 2013 to 2014,with a follow-up period of 5.4 years.Baseline self-reported PA and SB were collected via the questionnaire.Kaplan–Meier curves(log-rank test)and Cox proportional hazards regression were performed to evaluate the associations of PA and SB on all-cause mortality.Results:A total of 11,744 eligible participants were included in the analysis.Over an average of 5.4 years of follow-up,796 deaths occurred.The risk of all-cause mortality was lower among participants with high PA than those with low to moderate level(5.2%vs.8.9%;hazards ratio[HR]:0.75,95%confidence interval[CI]:0.61–0.87).Participants with SB≥6 h had a higher risk of all-cause mortality than those with SB<6 h(7.8%vs.6.0%;HR:1.37,95%CI:1.17–1.61).Participants with prolonged SB(≥6 h)and inadequate PA(low to moderate)had a higher risk of all-cause mortality compared to those with SB<6 h and high PA(11.2%vs.4.9%;HR:1.67,95%CI:1.35–2.06).Even in the participants with high PA,prolonged SB(≥6 h)was still associated with the higher risk of all-cause mortality compared with SB<6 h(7.0%vs.4.9%;HR:1.33,95%CI:1.12–1.56).Conclusions:Among Chinese population,PA and SB have a joint association with the risk of all-cause mortality.Participants with inadequate PA and prolonged SB had the highest risk of all-cause mortality compared with others.
基金supported by the National Natural Science Foundation of China (31171088 and 31471126 to JMC., and 31300948 and 81670310 to XQT)
文摘Large conductance calcium-activated potassium(BKCa)channels are broadly expressed in vascular smooth muscle cells(VSMCs)and play a crucial role in the regulation of vascular tone[1].Activation of BKCachannel by elevation of the[Ca^(2+)]idue to membrane depolarization increases the K^+ conductance of the membrane,and drives the VSMC membrane potential to hyperpolarization,which
