Mounting evidence indicates that amyloid β protein（Aβ） exerts neurotoxicity by disrupting the blood-brain barrier（BBB） in Alzheimer＇s disease. Hyperoside has neuroprotective effects both in vitro and in vivo ag...Mounting evidence indicates that amyloid β protein（Aβ） exerts neurotoxicity by disrupting the blood-brain barrier（BBB） in Alzheimer＇s disease. Hyperoside has neuroprotective effects both in vitro and in vivo against Aβ. Our previous study found that hyperoside suppressed Aβ1-42-induced leakage of the BBB, however, the mechanism remains unclear. In this study, bEnd.3 cells were pretreated with 50, 200, or 500 μM hyperoside for 2 hours, and then exposed to Aβ1-42 for 24 hours. Cell viability was determined using 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide assay. Flow cytometry and terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay were used to analyze cell apoptosis. Western blot assay was carried out to analyze expression levels of Bax, Bcl-2, cytochrome c, caspase-3, caspse-8, caspase-9, caspase-12, occludin, claudin-5, zonula occludens-1, matrix metalloproteinase-2（MMP-2）, and MMP-9. Exposure to Aβ1-42 alone remarkably induced bEnd.3 cell apoptosis; increased ratios of cleaved caspase-9/caspase-9, Bax/Bcl-2, cleav ed caspase-8/caspase-8, and cleaved caspase-12/caspase-12; increased expression of cytochrome c and activity of caspase-3; diminished levels of zonula occludens-1, claudin-5, and occludin; and increased levels of MMP-2 and MMP-9. However, hyperoside pretreatment reversed these changes in a dose-dependent manner. Our findings confirm that hyperoside alleviates fibrillar Aβ1-42-induced BBB disruption, thus offering a feasible therapeutic application in Alzheimer＇s disease.展开更多
目的通过比较聚乙二醇洛塞那肽与利拉鲁肽治疗肥胖2型糖尿病的疗效,为临床治疗该类疾病选择更高效的用药方案。方法选取东南大学医学院附属南京同仁医院2022年1月至2023年10月予以相应治疗的肥胖2型糖尿病患者共136例作为此次试验对象,...目的通过比较聚乙二醇洛塞那肽与利拉鲁肽治疗肥胖2型糖尿病的疗效,为临床治疗该类疾病选择更高效的用药方案。方法选取东南大学医学院附属南京同仁医院2022年1月至2023年10月予以相应治疗的肥胖2型糖尿病患者共136例作为此次试验对象,按照随机数字表法分成68例A组(聚乙二醇洛塞那肽治疗)与68例B组(利拉鲁肽治疗)。比较治疗前后两组肥胖相关指标、治疗前后两组血脂相关指标、治疗前后两组血糖指标以及治疗后不良反应发生率。结果治疗后两组体质量、腰臀比、体质量指数(BMI)和腰围均下降,B组体质量和BMI[分别为(80.31±7.62)kg和(24.13±1.82)kg·m^(-2)]低于A组体质量[分别为(83.65±7.93)kg和BMI(25.34±1.84)kg·m^(-2)](体质量:t=2.504,P=0.014;BMI:t=3.855,P<0.05);治疗后两组甘油三酯(TG)、血清总胆固醇(TC)和低密度脂蛋白(LDL)均下降,高密度脂蛋白胆固醇(HDL-C)上升(均P<0.05);治疗后两组餐后2 h血糖(2 h FBG)、空腹血糖(FBG)、糖化血红蛋白(HbAlc)、胰岛素抵抗指数(HOMA-IR)水平均下降,空腹血糖胰岛素(FINS)、β细胞功能指数(HOMA-β)水平均上升,A组2 h FBG、FBG[分别为(7.86±1.12)mmol·L^(-1)、(6.18±0.71)mmol·L^(-1)]低于B组[分别为2 h FBG(8.72±1.34)mmol·L^(-1)和FBG(7.02±0.62)mmol·L^(-1)](2 h FBG:t=4.061,P<0.05;FBG:t=7.349,P<0.05),A组HOMA-β[(74.62±3.78)%]高于B组[(62.79±3.56)%](t=18.937,P<0.05);两组不良反应发生率比较差异无统计学意义(20.59%vs 25.00%,χ^(2)=0.376,P=0.540)。结论对于肥胖2型糖尿病患者,聚乙二醇洛塞那肽与利拉鲁肽均能有效减轻体质量、调节血脂、降低血糖水平以及增强胰岛β细胞的功能,且安全性相似。然而,在降低体质量方面,利拉鲁肽的效果更为显著,而聚乙二醇洛塞那肽在改善胰岛β细胞功能和降低血糖方面则表现更为出色。展开更多
Objective To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs,as monotherapy or dual combination ther...Objective To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs,as monotherapy or dual combination therapy,to improve daytime and nighttime BP control. Methods We enrolled 1920 Chinese community-dwelling outpatients aged ≥ 60 years and compared ambulatory BP values and ambulatory BP control (24-hour BP < 130/80 mmHg;daytime mean BP < 135/85 mmHg;and nighttime mean BP < 120/70 mmHg),as well as nighttime BP dip patterns for monotherapy and dual combination therapy groups. Results Patients’ mean age was 71 years,and 59.5% of patients were women. Calcium channel blockers (CCBs) constituted the most common (60.3% of patients) monotherapy,and renin–angiotensin system (RAS) blockers combined with CCBs was the most common (56.5% of patients) dual combination therapy. Monotherapy with beta-blockers (BB) provided the best daytime BP control. The probabilities of having a nighttime dip pattern and nighttime BP control were higher in patients receiving diuretics compared with CCBs (OR = 0.52,P = 0.05 and OR = 0.41,P = 0.007,respectively). Patients receiving RAS/diuretic combination therapy had a higher probability of having controlled nighttime BP compared with those receiving RAS/CCB (OR = 0.45,P = 0.004). Compared with RAS/diuretic therapy,BB/CCB therapy had a higher probability of achieving daytime BP control (OR = 1.27,P = 0.45). Conclusions Antihypertensive monotherapy and dual combination drug therapy provided different ambulatory BP control and nighttime BP dip patterns. BB-based regimens provided lower daytime BP,whereas diuretic-based therapies provided lower nighttime BP,compared with other antihypertensive regimens.展开更多
Background: Depression and ischemic heart disease (IHD) are associated with persistent stress and autonomic nervous system (ANS) dysfunction. The former can be measured by pressure pain sensitivity (PPS) of the sternu...Background: Depression and ischemic heart disease (IHD) are associated with persistent stress and autonomic nervous system (ANS) dysfunction. The former can be measured by pressure pain sensitivity (PPS) of the sternum, and the latter by the PPS and systolic blood pressure (SBP) response to a tilt table test (TTT). Beta-blocker treatment reduces the efferent beta-adrenergic ANS function, and thus, the physiological stress response. Objective: To test the effect of beta-blockers on changes in depression score in patients with IHD, as well as the influence on persistent stress and ANS dysfunction. Methods: Three months of non-pharmacological intervention aiming at reducing PPS and depression score in patients with stable IHD. Beta-blocker users (N = 102) were compared with non-users (N = 75), with respect to signs of depression measured by the Major Depressive Inventory questionnaire (MDI), resting PPS, and PPS and SBP response to TTT. Results: MDI score decreased 30% in non-users (p = 0.005) compared to 4% (p > 0.1) among users (between-group p = 0.003;effect size = 0.4). Resting PPS decreased in both the groups. Among most vulnerable patients with MDI ≥ 15, reductions in MDI score and resting PPS score correlated in non-users, only (r = 0.69, p = 0.007). Reduction in resting PPS correlated with an increase in PPS and SBP response to TTT. Conclusions: Stress intervention in patients with IHD was anti-depressive in non-users, only. Similarly, the association between the reduction in depression, reduction in persistent stress, and restoration of ANS dysfunction was only seen in non-users, suggesting a central role of beta-adrenergic receptors in the association between these factors.展开更多
目的 探究甘精胰岛素联合利拉鲁肽对2型糖尿病患者胰岛β细胞功能及脂代谢的影响。方法 选取2021年6月—2022年12月于北京市西城区展览路医院就医的80例2型糖尿病患者为研究对象,根据随机数表法分为对照组和观察组,各40例。对照组采用...目的 探究甘精胰岛素联合利拉鲁肽对2型糖尿病患者胰岛β细胞功能及脂代谢的影响。方法 选取2021年6月—2022年12月于北京市西城区展览路医院就医的80例2型糖尿病患者为研究对象,根据随机数表法分为对照组和观察组,各40例。对照组采用甘精胰岛素进行治疗,观察组则采用甘精胰岛素联合利拉鲁肽进行治疗。比较两组治疗前后的血糖检测指标、胰岛功能指标[胰岛素抵抗指数(homeostatic model assessment of insulin resistance index,HOMA-IR)及胰岛β细胞功能指数(homeostatic model assessment of β-cell function,HOMA-β)]及脂代谢相关指标。结果 治疗前,两组的血糖检测指标、胰岛β细胞功能指标及脂代谢相关指标比较,差异无统计学意义(P>0.05)。治疗3个月后,观察组的血糖检测指标、HOMA-IR、瘦素及血脂指标显著低于对照组,血清脂联素及HOMA-β显著高于对照组,且两组的检测结果显著优于治疗前,差异有统计学意义(P<0.05)。结论 甘精胰岛素联合利拉鲁肽对2型糖尿病患者中的应用效果较好,且可显著改善胰岛β细胞功能及脂代谢状态,因此在2型糖尿病患者中的应用价值较高。展开更多
基金financially supported by the National Natural Science Foundation of China,No.81573771the Natural Science Foundation of Jiangsu Province of China,No.BK20151599
文摘Mounting evidence indicates that amyloid β protein（Aβ） exerts neurotoxicity by disrupting the blood-brain barrier（BBB） in Alzheimer＇s disease. Hyperoside has neuroprotective effects both in vitro and in vivo against Aβ. Our previous study found that hyperoside suppressed Aβ1-42-induced leakage of the BBB, however, the mechanism remains unclear. In this study, bEnd.3 cells were pretreated with 50, 200, or 500 μM hyperoside for 2 hours, and then exposed to Aβ1-42 for 24 hours. Cell viability was determined using 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide assay. Flow cytometry and terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay were used to analyze cell apoptosis. Western blot assay was carried out to analyze expression levels of Bax, Bcl-2, cytochrome c, caspase-3, caspse-8, caspase-9, caspase-12, occludin, claudin-5, zonula occludens-1, matrix metalloproteinase-2（MMP-2）, and MMP-9. Exposure to Aβ1-42 alone remarkably induced bEnd.3 cell apoptosis; increased ratios of cleaved caspase-9/caspase-9, Bax/Bcl-2, cleav ed caspase-8/caspase-8, and cleaved caspase-12/caspase-12; increased expression of cytochrome c and activity of caspase-3; diminished levels of zonula occludens-1, claudin-5, and occludin; and increased levels of MMP-2 and MMP-9. However, hyperoside pretreatment reversed these changes in a dose-dependent manner. Our findings confirm that hyperoside alleviates fibrillar Aβ1-42-induced BBB disruption, thus offering a feasible therapeutic application in Alzheimer＇s disease.
文摘目的通过比较聚乙二醇洛塞那肽与利拉鲁肽治疗肥胖2型糖尿病的疗效,为临床治疗该类疾病选择更高效的用药方案。方法选取东南大学医学院附属南京同仁医院2022年1月至2023年10月予以相应治疗的肥胖2型糖尿病患者共136例作为此次试验对象,按照随机数字表法分成68例A组(聚乙二醇洛塞那肽治疗)与68例B组(利拉鲁肽治疗)。比较治疗前后两组肥胖相关指标、治疗前后两组血脂相关指标、治疗前后两组血糖指标以及治疗后不良反应发生率。结果治疗后两组体质量、腰臀比、体质量指数(BMI)和腰围均下降,B组体质量和BMI[分别为(80.31±7.62)kg和(24.13±1.82)kg·m^(-2)]低于A组体质量[分别为(83.65±7.93)kg和BMI(25.34±1.84)kg·m^(-2)](体质量:t=2.504,P=0.014;BMI:t=3.855,P<0.05);治疗后两组甘油三酯(TG)、血清总胆固醇(TC)和低密度脂蛋白(LDL)均下降,高密度脂蛋白胆固醇(HDL-C)上升(均P<0.05);治疗后两组餐后2 h血糖(2 h FBG)、空腹血糖(FBG)、糖化血红蛋白(HbAlc)、胰岛素抵抗指数(HOMA-IR)水平均下降,空腹血糖胰岛素(FINS)、β细胞功能指数(HOMA-β)水平均上升,A组2 h FBG、FBG[分别为(7.86±1.12)mmol·L^(-1)、(6.18±0.71)mmol·L^(-1)]低于B组[分别为2 h FBG(8.72±1.34)mmol·L^(-1)和FBG(7.02±0.62)mmol·L^(-1)](2 h FBG:t=4.061,P<0.05;FBG:t=7.349,P<0.05),A组HOMA-β[(74.62±3.78)%]高于B组[(62.79±3.56)%](t=18.937,P<0.05);两组不良反应发生率比较差异无统计学意义(20.59%vs 25.00%,χ^(2)=0.376,P=0.540)。结论对于肥胖2型糖尿病患者,聚乙二醇洛塞那肽与利拉鲁肽均能有效减轻体质量、调节血脂、降低血糖水平以及增强胰岛β细胞的功能,且安全性相似。然而,在降低体质量方面,利拉鲁肽的效果更为显著,而聚乙二醇洛塞那肽在改善胰岛β细胞功能和降低血糖方面则表现更为出色。
基金supported by a grant from the Chinese Ministry of Sciences and Technology (2016YFC1300100)
文摘Objective To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs,as monotherapy or dual combination therapy,to improve daytime and nighttime BP control. Methods We enrolled 1920 Chinese community-dwelling outpatients aged ≥ 60 years and compared ambulatory BP values and ambulatory BP control (24-hour BP < 130/80 mmHg;daytime mean BP < 135/85 mmHg;and nighttime mean BP < 120/70 mmHg),as well as nighttime BP dip patterns for monotherapy and dual combination therapy groups. Results Patients’ mean age was 71 years,and 59.5% of patients were women. Calcium channel blockers (CCBs) constituted the most common (60.3% of patients) monotherapy,and renin–angiotensin system (RAS) blockers combined with CCBs was the most common (56.5% of patients) dual combination therapy. Monotherapy with beta-blockers (BB) provided the best daytime BP control. The probabilities of having a nighttime dip pattern and nighttime BP control were higher in patients receiving diuretics compared with CCBs (OR = 0.52,P = 0.05 and OR = 0.41,P = 0.007,respectively). Patients receiving RAS/diuretic combination therapy had a higher probability of having controlled nighttime BP compared with those receiving RAS/CCB (OR = 0.45,P = 0.004). Compared with RAS/diuretic therapy,BB/CCB therapy had a higher probability of achieving daytime BP control (OR = 1.27,P = 0.45). Conclusions Antihypertensive monotherapy and dual combination drug therapy provided different ambulatory BP control and nighttime BP dip patterns. BB-based regimens provided lower daytime BP,whereas diuretic-based therapies provided lower nighttime BP,compared with other antihypertensive regimens.
文摘Background: Depression and ischemic heart disease (IHD) are associated with persistent stress and autonomic nervous system (ANS) dysfunction. The former can be measured by pressure pain sensitivity (PPS) of the sternum, and the latter by the PPS and systolic blood pressure (SBP) response to a tilt table test (TTT). Beta-blocker treatment reduces the efferent beta-adrenergic ANS function, and thus, the physiological stress response. Objective: To test the effect of beta-blockers on changes in depression score in patients with IHD, as well as the influence on persistent stress and ANS dysfunction. Methods: Three months of non-pharmacological intervention aiming at reducing PPS and depression score in patients with stable IHD. Beta-blocker users (N = 102) were compared with non-users (N = 75), with respect to signs of depression measured by the Major Depressive Inventory questionnaire (MDI), resting PPS, and PPS and SBP response to TTT. Results: MDI score decreased 30% in non-users (p = 0.005) compared to 4% (p > 0.1) among users (between-group p = 0.003;effect size = 0.4). Resting PPS decreased in both the groups. Among most vulnerable patients with MDI ≥ 15, reductions in MDI score and resting PPS score correlated in non-users, only (r = 0.69, p = 0.007). Reduction in resting PPS correlated with an increase in PPS and SBP response to TTT. Conclusions: Stress intervention in patients with IHD was anti-depressive in non-users, only. Similarly, the association between the reduction in depression, reduction in persistent stress, and restoration of ANS dysfunction was only seen in non-users, suggesting a central role of beta-adrenergic receptors in the association between these factors.
文摘目的 探究甘精胰岛素联合利拉鲁肽对2型糖尿病患者胰岛β细胞功能及脂代谢的影响。方法 选取2021年6月—2022年12月于北京市西城区展览路医院就医的80例2型糖尿病患者为研究对象,根据随机数表法分为对照组和观察组,各40例。对照组采用甘精胰岛素进行治疗,观察组则采用甘精胰岛素联合利拉鲁肽进行治疗。比较两组治疗前后的血糖检测指标、胰岛功能指标[胰岛素抵抗指数(homeostatic model assessment of insulin resistance index,HOMA-IR)及胰岛β细胞功能指数(homeostatic model assessment of β-cell function,HOMA-β)]及脂代谢相关指标。结果 治疗前,两组的血糖检测指标、胰岛β细胞功能指标及脂代谢相关指标比较,差异无统计学意义(P>0.05)。治疗3个月后,观察组的血糖检测指标、HOMA-IR、瘦素及血脂指标显著低于对照组,血清脂联素及HOMA-β显著高于对照组,且两组的检测结果显著优于治疗前,差异有统计学意义(P<0.05)。结论 甘精胰岛素联合利拉鲁肽对2型糖尿病患者中的应用效果较好,且可显著改善胰岛β细胞功能及脂代谢状态,因此在2型糖尿病患者中的应用价值较高。
