Increased numbers of circulating ECs are associated with systemic GVHD

Introduction: Circulating endothelial cells (ECs) are known to reflect endothelial injury, and endothelial injury is associated with graft‐versus‐host disease (GVHD). We hypothesised that circulating ECs might be associated with systemic acute graft‐versus‐host disease (aGVHD). Methods: BALB/c (H‐2k^d) mice were treated with total body irradiation and then infused with C57B/6‐derived T‐cell‐depleted bone marrow (TCD‐BM) cells or TCD‐BM cells and splenocytes. Cyclosporine was used to prevent aGVHD. Circulating ECs and allogeneic lymphocytes were analysed by flow cytometry at multiple time points. The morphology and ultrastructure of the endothelium were examined by light microscopy or transmission electron microscopy. Results: The results indicated that the number of circulating ECs peaked at day 5 after lethal irradiation in all mice; allogenic transplanted mice (TCD‐BM cells and splenocytes) developed typical aGVHD beginning at day 7, exhibiting both histological and clinical symptoms of disease. Circulating ECs peaked a second time at day 9 with aGVHD progression. However, following the administration of CSA, an absence of or a reduction in the amount of subsequent endothelial injury was observed. Conclusion: Circulating ECs might be associated with systemic aGVHD.     

冠心病患者动脉弹性与血管舒张功能受损的关系

目的探讨冠心病患者动脉弹性和内皮与非内皮依赖性血管舒张功能的关系。方法采用高分辨率血管超声法检测30例冠心病患者(冠心病组)与健康体检非冠心病者30例(对照组)肱动脉血流介导的内皮依赖性血管舒张功能及硝酸甘油介导的非内皮依赖性血管舒张功能;动脉弹性功能检测仪测定受试者的大动脉弹性指数(C1)和小动脉弹性指数(C2)。结果冠心病组与对照组的C1差异无显著性意义,但冠心病组的C2明显低于对照组,冠心病组内皮依赖性血管舒张功能与非内皮依赖性血管舒张功能均明显低于对照组;冠心病组C2不仅与内皮依赖性血管舒张功能呈正相关,且同非内皮依赖性血管舒张功能呈正相关。结论冠心病组C2降低,C2降低不仅同血管内皮功能的受损相关,而且也受非内皮因素的影响,提示C2反映总体血管舒张功能受损的程度。     

Endothelial dysfunction, ambulatory pulse pressure and albuminuria are associated in Type 2 diabetic subjects.

AIM: Elevated pulse pressure (PP) is associated with microvascular complications in Type 2 diabetic patients. In non-diabetic subjects, elevated PP has been associated with endothelial dysfunction. The relation between endothelial dysfunction and PP in diabetic subjects has not previously been examined. We examined the relation between PP, markers of endothelial activation and albuminuria in Type 2 diabetic patients. METHODS: In 46 Type 2 diabetic patients and 19 non-diabetic subjects, we performed 24-h ambulatory blood pressure (AMBP) monitoring. Urinary albumin excretion rate was measured as three urinary albumin/creatinine ratios. Von Willebrand factor (vWF), fibrinogen, E-selectin and soluble intercellular adhesion molecule 1 (ICAM-1) were measured in plasma. RESULTS: Thirty-four patients had normoalbuminuria (group N) and 12 had micro- or macroalbuminuria (group A). PP levels increased in a stepwise manner from the control group (group C) to group N and group A; night PP 43 +/- 5, 48 +/- 10 and 59 +/- 12 mmHg (groups C, N and A, respectively, P < 0.001). Likewise, plasma levels of vWF, fibrinogen, E-selectin and ICAM-1 increased from group C to group A; e.g. ICAM-1 [median (interquartile range)] 191 (160-217), 213 (189-262) and 316 (260-417) ng/ml, groups C, N and A, respectively, P < 0.001). In diabetic patients, night PP and plasma levels of E-selectin and ICAM-1 correlated (r = 0.38, P < 0.01 and r = 0.37, P = 0.01, night PP with E-selectin and ICAM-1, respectively). CONCLUSION: Increased PP is associated with endothelial activation and albuminuria in Type 2 diabetic patients. Thus, endothelial dysfunction may represent a pathophysiological link between an elevated PP and microvascular complications in these subjects. Prospective studies are needed to further elucidate these associations.     

老年高血压患者血压昼夜节律变化与心率变异及颈动脉弹性功能的相关性

目的探讨老年高血压患者血压昼夜节律变化与心率变异、颈动脉弹性功能的相关性。方法我科2005～2006年老年高血压患者56例，用动态血压观察血压昼夜节律，根据夜间血压下降率[夜间平均收缩压（nMSP）与白天平均收缩压（dMSP）比值]分组，nMSP／dMSP≥100％为反杓型组，nMSP／dMSP≤90％为杓型组，90％〈nMSP／dMSP〈100％为非杓型组。用动态心电图测定时域值和频域值，用彩色多普勒超声检测患者颈动脉血流受阻情况。结果心率变异频域指标低频和高频比率（LF／HF）随着nMSP／dMSP升高而下降，3组之间有显著性差异（P〈0．05）。颈部动脉阻力指数（RI）随nMSP／dMSP比值升高有增加趋势，其中右侧颈总动脉RI在杓型组与反杓型组以及杓型组与非杓型组有显著性差异（P〈0．05），左侧椎动脉RI在杓型组与反杓型组以及非杓型组与反杓型组有显著性差异（P〈0．05），右侧椎动脉RI在杓型组与反杓型组有显著性差异（P〈0．05）。结论老年高血压患者血压昼夜节律同自主神经功能及颈动脉弹性功能有相关性。     

High blood pressure, hypertension, and high pulse pressure are associated with poorer cognitive function in persons aged 60 and older: the Third National Health and Nutrition Examination Survey

OBJECTIVES: To test the hypothesis that hypertension, high blood pressure, and high pulse pressure (PP) are independently associated with lower cognitive function. DESIGN: Cross‐sectional study of persons examined in 1988 to 1994. SETTING: U.S. noninstitutionalized population. PARTICIPANTS: Six thousand one hundred sixty‐three men and women aged 60 and older who participated in the Third National Health and Nutrition Examination Survey (NHANES III). MEASUREMENTS: Measurements included blood pressure, short‐portable Mini‐Mental State Examination (sp‐MMSE), self‐reported history of hypertension, diagnosis, and treatment. RESULTS: In the initial bivariate analysis within age groups of 60 to 64, 65 to 69, and 70 to 74, optimal blood pressure (<120/80 mmHg) was associated with best cognitive performance; the severe hypertension group had the poorest performance in all age groups except the very old (≥80), where the pattern was reversed, showing poorest performance in the optimal blood pressure group and best in the group with moderate hypertension. This pattern changed slightly in multiple regression analyses modeling sp‐MMSE as the outcome variable. Higher stage of hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and higher PP were associated with worse cognitive performance than normal blood pressure at ages 70 to 79 and 80 and older. No significant negative association was seen in subjects aged 60 to 69. Subjects with treated but uncontrolled hypertension had significantly lower sp‐MMSE scores than those without hypertension or with controlled hypertension after controlling for age, sex, ethnicity, income, and PP. CONCLUSION: At age 70 and older, high blood pressure, hypertension, and uncontrolled blood pressure are associated with poorer cognitive function than normal blood pressure. Optimal control of blood pressure may be useful in preserving neurocognitive loss as the population ages.     

Increased CD4(+) CD69(+) CD25(-) T cells in patients with hepatocellular carcinoma are associated with tumor progression

Background and Aim: A new subset of Treg cells, CD4⁺CD69⁺CD25^‐ T cells, has been identified in mice. Herein, we aimed to identify this subset of T cells and to evaluate its function in patients with hepatocellular carcinoma (HCC). Methods: We detected CD4⁺CD69⁺CD25^‐ T cells and its expression of CCR6 and transforming growth factor‐β1 (TGF‐β1) in peripheral blood of 91 HCC patients, 38 chronic hepatitis patients and 34 healthy donors by flow cytometry. CD4⁺CD69⁺CD25^‐ T cells in HCC tissues were also analyzed. Results: CD4⁺CD69⁺CD25^‐ T cells were significantly increased in peripheral blood of HCC patients compared with healthy persons and chronic hepatitis patients (8.74% ± 0.42% vs 4.55% ± 0.33% and 5.15% ± 0.36%, P < 0.0001). The percentage of peripheral CD4⁺CD69⁺CD25^‐ T cells was significantly higher in HCC patients with Tumor Node Metastasis (TNM) stage III plus IV (P < 0.05). Patients with large tumor size and tumor vascular invasion were inclined to obtain high percentage of CD4⁺CD69⁺CD25^‐ T cells (P < 0.05). The frequency of membrane‐bound TGF‐β1 positive cells in CD4⁺CD69⁺CD25^‐ T cells from HCC patients was higher than that from the other two groups (P < 0.0001). A considerable proportion of CD4⁺CD69⁺CD25^‐ T cells were present in HCC tissues, which has significant correlation with tumor size and TNM stage. Few CD4⁺CD69⁺CD25^‐ T cells express CCR6 both in peripheral blood and tumor tissues from HCC patients. Conclusions: Increased CD4⁺CD69⁺CD25^‐ T cells in HCC patients are significantly correlated with tumor size, vascular invasion and TNM stage. Thus, increased CD4⁺CD69⁺CD25^‐ T cells exert a critical role in HCC progression and might be a clinically aggressive phenotype of HCC.     

Increased regulatory T cells and impaired functions of circulating CD8 T lymphocytes is associated with viral persistence in Hepatitis B virus‐positive newborns

Hepatitis B Virus (HBV) infection in infancy or early childhood leads to high rate of persistent infection (25–90%). The immunological basis of high rate of viral persistence in vertically acquired HBV infections is not completely understood. CD8 T cells play a pivotal role in clearing the Hepatitis B virus infection in adults. Herein, we sought to delineate the role of T cells in viral persistence in HBsAg+ve newborns . At birth peripheral and cord blood of HBsAg+ve (N = 12), HBsAg‐ve (N = 10) and healthy newborns (HC: N = 15) were evaluated for T‐cell frequency and functionality by flow cytometry. No significant differences were observed in the frequency of CD8 and CD4 T cells in all the three groups. However, significantly higher frequency of FoxP3 expressing regulatory T cells were observed in HBsAg+ve (63.79%) compared with HBsAg‐ve (28.12%) and HC (11.06%) (P < 0.05). Moreover, HBsAg+ve newborns showed functional defect in CD8 T cells by decreased IFN‐γ production and lower CD107A expression (cytotoxic capacity) compared with HBsAg‐ve and HC, which positively correlated with decreased TCRζ‐chain expression CD8 T cells (r² > 0.93, P < 0.05). Despite equal frequency of CD8 T cells in all the three groups, CD8 T cells in HBsAg+ve newborns are dysfunctional. An expansion of regulatory T cells and impaired TCR signalling may represent the immune tolerant state of the adaptive immune system in response to chronic HBV infection.     

Serum levels of advanced glycation end products (AGEs) are inversely associated with the number and migratory activity of circulating endothelial progenitor cells in apparently healthy subjects

Objectives: Endothelial progenitor cells (EPCs) have been shown to participate in the process of vascular repair, thus playing a protective role against cardiovascular disease (CVD). It is known that atherosclerotic risk factors could affect EPC number and function. Advanced glycation end products (AGEs) contribute to the pathogenesis of atherosclerosis as well. However, as far as we know, there is no report to show the relationship between serum AGE levels and circulating EPCs in humans. Therefore, in this study, we investigated whether serum level of AGEs was associated with EPC number and functions in apparently healthy subjects, independent of traditional cardiovascular risk factors. Research Design and Methods: Apparently healthy volunteers (34.6 ± 6.9 years old, 40 males and 8 females) who were not on any medications underwent a complete history and physical examination, determination of blood chemistries, including AGEs, and number, differentiation and migratory activity of circulating EPCs. Results: Serum AGEs levels were 9.20 ± 1.85 U/mL. Multiple stepwise regression analysis revealed that serum levels of AGEs and smoking were independently correlated with reduced number of EPCs. Further, female, AGEs, and reduced HDL‐cholesterol levels were independently associated with impaired migratory activity of circulating EPCs. Conclusions: This study demonstrated for the first time that the serum level of AGEs was one of the independent correlates of decreased cell number and impaired migratory activity of circulating EPCs in apparently healthy subjects. Our present observations suggest that even in young healthy subjects, serum level of AGEs may be a biomarker that could predict the progression of atherosclerosis and future cardiovascular events.     

Potassium excretion and blood pressure are associated with heart rate variability in healthy black adults: The African-PREDICT study

Background and aimsHeart rate variability (HRV) is a main determinant of autonomic function and related to the development of hypertension and cardiovascular (CV) disease. Hypertension develops in black populations at an earlier age, which could be due to differences in the autonomic nervous system activity and sodium/potassium handling in black and white populations. We investigated whether HRV is associated with 24 h urinary sodium and potassium excretion and blood pressure (BP) in a young bi-ethnic cohort.Methods and resultsWe examined 423 black and 483 white healthy adults (aged 24.5 ± 3.1 years) for 24 h HRV, including standard deviation of normal RR intervals (SDNN) reflecting autonomic variations over time, and root mean square of successive differences (RMSSD) reflecting parasympathetic activity. We measured 24 h urinary sodium and potassium concentration and BP. The black group had lower SDNN and potassium excretion as well as higher RMSSD, sodium and Na/k ratio compared to the white group (all p < 0.05). Only in black individuals, urinary potassium excretion was independently and negatively associated with SDNN (β[95% CI];-0.26[-0.50;-0.02]ms) and RMSSD (?0.14[-0.27;-0.01]ms, p < 0.05). One unit increase in sodium/potassium (Na/K) ratio was associated with higher SDNN (β[95% CI]; 3.04[0.89; 5.19]ms) and RMSSD (1.60[0.41; 2.78]ms) in the black cohort only (both p < 0.001). In both groups elevated 24 h diastolic BP was associated with lower RMSSD (p < 0.05).ConclusionLower potassium excretion and higher Na/K ratio related independently to higher HRV in young and healthy black adults. A better ethnic-specific understanding of sodium and potassium handling is required as part of preventive cardiology, especially in black individuals.Clinical trial registrationClinicalTrials.gov Identifier: NCT03292094; URL: https://clinicaltrials.gov/ct2/show/NCT03292094.