Association of sleep duration and sleep quality with gestational diabetes mellitus in pregnant women after treatment with assisted reproductive technology: A birth cohort study.

Maternal sleep is closely related to subsequent gestational diabetes mellitus (GDM) in natural pregnancies. However, whether this connection exists in pregnant women conceiving with the help of assisted reproductive technology (ART) has not been confirmed. Hence, in this study, we evaluated whether early pregnancy sleep duration or sleep quality is associated with gestational diabetes mellitus in ART-pregnant women, as well as the influence of maternal age on this association. This prospective birth cohort study included 856 pregnant women who successfully conceived with the help of ART treatment. The sleep parameters of ART-pregnant women were assessed using the Pittsburgh Sleep Quality Index (PSQI) in early pregnancy. We explored the association between sleep and the risk of gestational diabetes mellitus using an unconditional binary logistic regression model. Different models were constructed to examine the robustness of the estimation by incorporating different confounding factors. Multivariable logistic regression revealed that sleep duration of more than 10 h among ART-pregnant women was significantly associated with the risk of GDM, and the association between sleep duration and gestational diabetes mellitus varied by maternal age. We found an increased risk of subsequent gestational diabetes mellitus with increasing sleep duration only in pregnant women aged <35 years. Additionally, no statistically significant association between sleep quality and gestational diabetes mellitus was found in this study. In conclusion, excessive sleep duration (≥10 h) is associated with a high risk of gestational diabetes mellitus in pregnant women who conceived with the help of assisted reproductive technology, and maternal age may modify this effect.

Epigenetic modifications in the accumulation and function of myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSCs) are key players under various pathologic conditions, such as cancer. Epigenetic modifications such as DNA methylation, RNA-mediated processes, and histone modification can alter gene transcription, and thus regulating pathological process. Studies have shown that epigenetic modification contributes to the accumulation and function of MDSCs. This review summarizes the crosstalk between the epigenetic alterations and MDSCs functions, and briefly introduces how the accumulation and function of MDSCs caused by epigenetic modification impact on the disease development, which represents as a promising therapeutic strategy for the related disorders.

Maternal pre-pregnancy body mass index, gestational weight gain trajectory, and risk of adverse perinatal outcomes.

OBJECTIVE: To evaluate the relationships of pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) trajectory with adverse perinatal outcomes (APOs). METHODS: A retrospective cohort study was conducted in China, and 12 855 women who had a singleton birth were included. The WHO classification categorized pre-pregnancy BMI, and five GWG trajectories were identified using the latent class growth model. RESULTS: The adjusted odds ratios for the risks of cesarean delivery, preterm birth, and large-for-gestational-age (LGA) infant were significantly higher in women with whoe were overweight or obese pre-pregnancy, but were lower in underweight (except preterm birth) than in normal weight women. Five GWG trajectories were identified: (1) retaining GWG (6.6 kg), (2) moderately slow GWG (10.5 kg), (3) moderate GWG (13.7 kg), (4) moderately fast GWG (16.3 kg), and (5) rapid GWG (19.8 kg). Compared with women in trajectory 3, the risks of cesarean delivery and LGA increase by about 35%-96% for the women in trajectory 4 or 5, whereas the women in trajectory 1 or 2 are inclined to have a higher risk of small for gestational age, but lower risk of LGA. Association of GWG trajectory with APOs varies across pre-pregnancy BMI subgroups. CONCLUSION: This study highlights the influence of inappropriate pre-pregnancy maternal weight and GWG trajectories on the risk of APOs.

Impaired Autophagy Induced by oxLDL/ß2GPI/anti-ß2GPI Complex through PI3K/AKT/mTOR and eNOS Signaling Pathways Contributes to Endothelial Cell Dysfunction.

Endothelial cell dysfunction plays a fundamental role in the pathogenesis of atherosclerosis (AS), and endothelial autophagy has protective effects on the development of AS. Our previous study had shown that oxidized low-density lipoprotein/ß2-glycoprotein I/anti-ß2-glycoprotein I antibody (oxLDL/ß2GPI/anti-ß2GPI) complex could promote the expressions of inflammatory cytokines and enhance the adhesion of leukocytes to endothelial cells. In the present study, we aimed to assess the effects of oxLDL/ß2GPI/anti-ß2GPI complex on endothelial autophagy and explore the associated potential mechanisms. Human umbilical vein endothelial cells (HUVECs) and mouse brain endothelial cell line (bEnd.3) were used as models of the vascular endothelial cells. Autophagy was evaluated by examining the expressions of autophagic proteins using western blotting analysis, autophagosome accumulation using transmission electron microscopy, and RFP-GFP-LC3 adenoviral transfection and autophagic flux using lysosome inhibitor chloroquine. The expressions of phospho-PI3K, phospho-AKT, phospho-mTOR, and phospho-eNOS were determined by western blotting analysis. 3-Methyladenine (3-MA) and rapamycin were used to determine the role of autophagy in oxLDL/ß2GPI/anti-ß2GPI complex-induced endothelial cell dysfunction. We showed that oxLDL/ß2GPI/anti-ß2GPI complex suppressed the autophagy, evidenced by an increase in p62 protein, a decrease in LC3-II and Beclin1, and a reduction of autophagosome generation in endothelial cells. Moreover, inhibition of autophagy was associated with PI3K/AKT/mTOR and eNOS signaling pathways. Rapamycin attenuated oxLDL/ß2GPI/anti-ß2GPI complex-induced endothelial inflammation, oxidative stress, and apoptosis, whereas 3-MA alone induced the endothelial injury. Our results suggested that oxLDL/ß2GPI/anti-ß2GPI complex inhibited endothelial autophagy via PI3K/AKT/mTOR and eNOS signaling pathways and further contributed to endothelial cell dysfunction. Collectively, our findings provided a novel mechanism for vascular endothelial injury in AS patients with an antiphospholipid syndrome (APS) background.

Contributions of Costimulatory Molecule CD137 in Endothelial Cells.

CD137 (4-1BB, tumor necrosis factor receptor superfamily 9) is a surface glycoprotein of the tumor necrosis factor receptor family that can be induced on a variety of immunocytes and nonimmune cells, including endothelial cells and smooth muscle cells. The importance of CD137 in immune response has been well recognized; however, the precise biological effects and underlying mechanisms of CD137 in endothelial cells are unclear. A single layer of cells called the endothelium constitutes the innermost layer of blood vessels including larger arteries, veins, the capillaries, and the lymphatic vessels. It not only acts as an important functional interface, but also participates in local inflammatory response. This review covers recent findings to illuminate the role of CD137 in endothelial cells in different pathophysiologic settings.

T helper 17 cell responses induce cardiac hypertrophy and remodeling in essential hypertension.

INTRODUCTION: An increasing body of evidence has shown that type 17 helper T (TH17) cell responses play an important role in the progression of cardiac remodeling stimulated by long­term pressure overload. OBJECTIVES: We aimed to investigate the relationship between TH17 responses and cardiac remodeling, and the prognostic value of TH17 responses in hypertensive patients. PATIENTS AND METHODS: A total of 187 adults with hypertension and 70 healthy controls were enrolled in the present study. TH17 cell frequencies, matrix metallopeptidase 9, procollagen type I, and procollagen type III were studied at baseline. All adults underwent routine echocardiography to assess left ventricular diastolic function (LVDF) at baseline and after 24 months of follow­up. RESULTS: The percentage of TH17 cells was increased in hypertensive patients, particularly in adults with left ventricular hypertrophy (LVH). Receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) of TH17 cells for predicting of LVH was 0.943 (95% CI, 0.914-0.971; P <0.001) and the cutoff value was 2.3%. On logistic regression analysis, the percentage of TH17 cells was an independent predictor of LVH (odds ratio, 1.47; 95% CI, 2.23-2.28; P = 0.005). The percentage of TH17 cells significantly correlated with the levels of fibrotic parameters. According to the cutoff value of TH17 cells, patients with a lower level of TH17 cell differentiation had a better prognosis. CONCLUSIONS: The differentiation of TH17 cells reflected the cardiac hypertrophy and remodeling response to hypertension­induced pressure overload, and it might be a potential inflammatory marker to predict the prognosis of hypertensive patients.

Use of Inflammatory Biomarkers and Real-Time Cardiac Catheterisation to Evaluate the Left Ventricular Diastolic Function in Patients With Diastolic Heart Failure.

BACKGROUND: Interleukin (IL)-17 and its related cytokines have been shown to be involved in myocardial fibrosis and irreversible ventricular remodelling, which have predictive values in the development of left ventricular diastolic dysfunction (LVDD). This study aimed to assess the correlation between IL-17 and LVDD, and investigate the prognostic value of IL-17 among patients with normal left ventricular ejection fraction (LVEF). METHODS: A total of 120 patients with normal LVEF underwent left ventricular (LV) catheterisation for LV end-diastolic pressure (LVEDP) measurement and routine echocardiography. The follow-up period was 30 (18, 35) months. RESULTS: The levels of IL-17 and IL-6 from the systemic blood were significantly increased in non-heart failure (HF) patients with LVDD (p<0.001). Receiver operating characteristic (ROC) revealed that the combination of IL-17 and IL-6 showed the highest diagnostic accuracy in predicting LVDD (AUC, 0.890; 95% CI, 0.835-0.945; p<0.001), and the cut-off value was 41.5 pg/mL. On logistic regression analysis, the increment of the combination of IL-17 and IL-6 was an independent predictor for the prognosis of LVDD (odds ratio, 1.25; 95% CI, 1.01-1.12; p<0.05). According to the cut-off value of the combination of IL-17 and IL-6, the patients with lower levels of IL-17 and IL-6 (<41.5 pg/mL group) had a better prognosis. The increased levels of IL17 and IL-6 were significantly correlated with the levels of fibrotic parameters. CONCLUSIONS: Assessment of LVDD by measuring the combination of IL-17 and IL-6 might provide valuable prognostic significance for non-HF patients with LVDD.

OxLDL/ß2GPI/anti­ß2GPI Ab complex induces inflammatory activation via the TLR4/NF­κB pathway in HUVECs.

Patients with antiphospholipid syndrome have been identified to have higher incidence rates of atherosclerosis (AS) due to the elevated levels of anti­ß2­glycoprotein I (ß2GPI) antibody (Ab). Our previous studies revealed that the anti­ß2GPI Ab formed a stable oxidized low­density lipoprotein (oxLDL)/ß2GPI/anti­ß2GPI Ab complex, which accelerated AS development by promoting the accumulation of lipids in macrophages and vascular smooth muscle cell. However, the effects of the complex on endothelial cells, which drive the initiation and development of AS, remain unknown. Thus, the present study aimed to determine the proinflammatory roles of the oxLDL/ß2GPI/anti­ß2GPI Ab complex in human umbilical vein endothelial cells (HUVECs) in an attempt to determine the underlying mechanism. Reverse transcription­quantitative PCR, enzymy­linked immunosorbent assay, western blotting and immunofluorescence staining were performed to detect the expressions of inflammation related factors and adhesion molecules. Monocyte­binding assay was used to investigate the effects of oxLDL/ß2GPI/anti­ß2GPI Ab complex on monocyte adhesion to endothelial cells. The results demonstrated that the oxLDL/ß2GPI/anti­ß2GPI Ab complex upregulated the expression of Toll­like receptor (TLR)4 and the levels of NF­κB phosphorylation in HUVECs, and subsequently enhanced the expression levels of inflammatory cytokines, including TNF­α, IL­1ß and IL­6, as well as those of adhesion molecules, such as intercellular adhesion molecule 1 and vascular adhesion molecule 1. In addition, the complex facilitated the recruitment of monocytes by promoting the secretion of monocyte chemotactic protein 1 in HUVECs. Notably, the described effects of the oxLDL/ß2GPI/anti­ß2GPI Ab complex in HUVECs were abolished by either TLR4 or NF­κB blockade. In conclusion, these findings suggested that the oxLDL/ß2GPI/anti­ß2GPI Ab complex may induce a hyper­inflammatory state in endothelial cells by promoting the secretion of proinflammatory cytokines and monocyte recruitment, which was discovered to be largely dependent on the TLR4/NK­κB signaling pathway.

Echocardiographic evaluation of left ventricular end diastolic pressure in patients with diastolic heart failure: A comparative study with real-time catheterization.

To evaluate the left ventricular end diastolic pressure (LVEDP) in patients with diastolic heart failure by echocardiography and explore the clinical value of echocardiography.From July 2017 to January 2018, 120 patients were prospectively selected from the affiliated hospital of Jiangsu university diagnosed as diastolic heart failure (York Heart Association class ≥II, LVEF ≥50%). The patients were divided into group with LVEDP ≤15 mm hg (1 mm hg = 0.133 kpa) (43 cases) and the group with LVEDP >15 mm hg (77 cases) according to the real-time measurement of LVEDP. Receiver operator characteristic curves of each parameter of echocardiography in diagnosis of LVEDP were compared between the 2 groups.Common ultrasonic parameters such as left ventricular inflow tract blood flow propagation velocity, mitral valve diastole e peak velocity/mitral valve diastole a peak velocity, e peak deceleration time, a peak duration, and early diastole interventricular septum bicuspid annulus velocity e' (e'sep) were used to evaluate LVEDP elevation with low accuracy (AUC is only between 0.5 and 0.7). Other ultrasonic parameters such as left atrial volume index (LAVI), tricuspid regurgitation maximum flow rate (TRmax), early diastole left ventricular sidewall bicuspid annulus velocity e' (e'lat), average e', E/e'sep, E/e'lat, average E/e' were used to evaluate LVEDP elevation with a certain improvement in accuracy (AUC between 0.7 and 0.9). Propagation velocity, mitral valve diastole e peak velocity/mitral valve diastole a peak velocity, e peak deceleration time, a peak duration, e'sep, average e', E/e'sep have very low correlation with LVEDP (r = -0.283 to 0.281); LAVI, TRmax, e'lat, E/e'lat, average E/e' and LVEDP are not highly correlated (r = 0.330-0.478). Through real-time left ventricular manometry, multiple regression analysis showed that TRmax, average e', e'lat, LAVI were independently correlated with the actual measured LVEDP.Echocardiography can recognize the increase of LVEDP in patients with heart failure preserved by LVEF, and estimate the value of LVEDP roughly, which can reflect LVEDP to a certain extent, with high feasibility and accuracy.

Serial assessment of focal myocardial function after percutaneous coronary intervention for ST-elevation myocardial infarction: Value of layer-specific speckle tracking echocardiography.

BACKGROUND: Ischemia-reperfusion injury (IRI) frequently follows successful PCI for STEMI and is recognized by multiple modalities. Multilayer speckle tracking echocardiography (STE) has the potential of detecting myocardial dysfunction in different myocardial layers. Our objective was to describe the changes in layer-specific myocardial function over the 24 hours after successful PCI for ST-elevation myocardial infarction (STEMI). METHODS: Patients (n = 120) with STEMI and no prior myocardial infarction underwent echocardiography prior to PCI, immediately after and at 3- and 24-hours post-PCI. Worsening focal dysfunction (WFD) was defined as an immediate reduction, compared to the pre-PCI value, in the amplitude of endo-myocardial longitudinal strain (endo-MLS) within the infarction territory. RESULTS: Patients with WFD (52%) had further reductions in endo-MLS, mid-MLS, and epi-MLS in the infarction region immediately post-PCI; at 3 hours strain began to improve and continued to improve at 24 hours. Reductions of endo-MLS strain were more evident than those of global, mid-MLS, and epi-MLS. This same pattern was seen in each of the ischemic territories of the anterior descending, circumflex, and right coronary arteries. Immediate improvement in endo-MLS following PCI was seen in 48% of patients. The time from symptom onset to balloon time was markedly longer in those with WFD (P < .0001). CONCLUSIONS: Multilayer SPE is a sensitive method that identifies serial alterations in focal myocardial function following successful PCI for STEMI. Layer-specific reductions in endo-MLS appeared more evident than decreases in global LV strain. Prolonged total ischemic time prior to PCI was directly related to the incidence of WFD.

Echocardiographic assessment of simultaneously measured left ventricular filling pressures in patients with normal left ventricular ejection fraction.

BACKGROUND: Assessment of left ventricular (LV) diastolic function is part of routine echocardiographic examinations. Accuracy of the 2016 ASE/EACVI algorithm to detect LV diastolic dysfunction in patients with a normal LV ejection fraction (LVEF) has been examined but simultaneous measurements of LV pressures and echocardiographic parameters of diastolic function are sparse. METHODS: The accuracy of multiple echo parameters of diastolic dynamics and the 2016 guidelines were assessed by simultaneous transthoracic echocardiography and LV pressure recordings in 120 patients (derivation cohort) and 60 patients (validation cohort) with suspected coronary artery disease and normal LVEF. Receiver-operating characteristic (ROC) curves defined optimal cut points for each echocardiographic parameter. A new algorithm was proposed to estimate LV diastolic pressures using 5 parameters based on ROC data: tricuspid regurgitation velocity >280cm/s, average e' <9 cm/s, average E/e' ratio >13, velocity of pulmonary vein A-wave reversal >32 cm/s, and left atrial volume index >32 mL/m2 . Performances of the 2016 guidelines and a proposed algorithm were examined for detecting a LV pre-A >12 and LV end-diastolic pressure (LVEDP) >15 mm Hg. RESULTS: In the derivation cohort, the 2016 algorithm identified an elevated LVEDP >15 mm Hg with an accuracy of 74.2% (63.8-82.9); the modified algorithm improved accuracy to 86.0% (77.6-92.1), P < .05. In the validation cohort, the proposed algorithm improved sensitivities with accuracies remaining like the 2016 algorithm. CONCLUSIONS: LV diastolic pressures in patients with normal LVEF were reliably assessed by the 2016 guidelines. The proposed algorithm improved sensitivities and may improve the accuracies for detecting abnormal LV filling pressures.

CD137 Signaling Promotes Endothelial Apoptosis by Inhibiting Nrf2 Pathway, and Upregulating NF-κB Pathway.

BACKGROUND: Endothelial dysfunction and apoptosis resulting from oxidative stress can lead to the development of atherosclerosis. Our group has previously showed that CD137 signaling contributes to the progression of atherosclerosis and the vulnerability of plaques. The aim of this study is to investigate the effects of CD137 signaling in atherosclerosis on endothelial cells (ECs) apoptosis and to explore the underlying mechanisms. METHODS: Serum samples were collected from 11 patients with acute myocardial infarction and 4 controls. Peritoneal injection of agonist-CD137 recombinant protein in ApoE-/- mice was used to determine whether CD137 signaling can promote apoptosis in vivo, and human umbilical vein endothelial cells treated with agonist-CD137 recombinant protein, M5580 (a Nrf2 pathway agonist) and CAPE (a NF-κB pathway inhibitor) were used to explore the effect of Nrf2 and NF-κB pathway in CD137 signaling-induced ECs apoptosis in vitro. RESULTS: ELISA showed that Bcl-2 in the serum of AMI patients was lower than that of the control group, while TNF-α and sCD137 were higher than that of the control group. Confocal microscopy and Western blot analysis showed that the nuclear translocation of Nrf2 in the agonist-CD137 group was significantly inhibited, and the expression of its downstream antioxidant enzymes was also decreased when compared with control. Immunofluorescence and Western blot results showed that the nuclear translocation of NF-κB in the agonist-CD137 group was enhanced, and ELISA results showed that the secretion of proinflammatory cytokines in the agonist-CD137 group was increased. Immunofluorescence results revealed that ROS production in the agonist-CD137 group was higher than that in control, M5580 (a Nrf2 pathway agonist) and CAPE (a NF-κB pathway inhibitor) groups. In vitro studies using HUVECs and in vivo studies using high-fat-fed ApoE-/- mice showed that the number of apoptotic endothelial cells was the highest in the agonist-CD137 group. By contrast, both M5580 and CAPE treatments were able to reduce CD137 induced ECs apoptosis. CONCLUSIONS: Our results showed that CD137 signaling promotes ECs apoptosis through prooxidative and proinflammatory mechanisms, mediated by Nrf2 and NF-κB pathways, respectively.

CD137 signaling induces macrophage M2 polarization in atherosclerosis through STAT6/PPARδ pathway.

CD137 signaling plays an important role in the formation and development of atherosclerotic plaques. The purpose of the present study was to investigate the effects of CD137 signaling on macrophage polarization during atherosclerosis and to explore the underlying mechanisms. The effect of CD137 signaling on macrophage phenotype in atherosclerotic plaques was determined by intraperitoneal injection of agonist-CD137 recombinant protein in apolipoprotein E-deficient (ApoE-/-) mice, an established in vivo model of atherosclerosis. Murine peritoneal macrophages and RAW 264.7 cells were treated with AS1517499 and siPPARδ (peroxisome proliferator-activated receptor δ) to study the role of STAT6 (signal transducers and activators of transcription 6)/PPARδ signaling in CD137-induced M2 macrophage polarization in vitro. Results from both in vivo and in vitro experiments showed that CD137 signaling can transform macrophages into the M2 phenotype during the process of atherosclerotic plaque formation and regulate the angiogenic features of M2 macrophages. Furthermore, activation of the CD137 signaling pathway induces phosphorylation of STAT6 and enhances the expression of PPARδ. We further found that macrophage M2 polarization is reduced when the STAT6/PPARδ pathway is inhibited. Together, these data show a role for the STAT6/PPARδ signaling pathway in the CD137 signaling-induced M2 macrophage polarization pathway.

Exosome derived from CD137-modified endothelial cells regulates the Th17 responses in atherosclerosis.

The role of exosomes derived from endothelial cells (ECs) in the progression of atherosclerosis (AS) and inflammation remains largely unexplored. We aimed to investigate whether exosome derived from CD137-modified ECs (CD137-Exo) played a major role in AS and to elucidate the potential mechanism underlying the inflammatory effect. Exosomes derived from mouse brain microvascular ECs treated with agonist anti-CD137 antibody were used to explore the effect of CD137 signalling in AS and inflammation in vitro and vivo. CD137-Exo efficiently induced the progression of AS in ApoE-/- mice. CD137-Exo increased the proportion of Th17 cells both in vitro and vivo. The IL-6 contained in CD137-Exo which is regulated by Akt and NF-КB pathway was verified to activate Th17 cell differentiation. IL-17 increased apoptosis, inhibited cell viability and improved lactate dehydrogenase (LDH) release in ECs subjected to inflammation induced by lipopolysaccharide (LPS). The expression of soluble intercellular adhesion molecule1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1) and E-selectin in the supernatants of ECs after IL-17 treatment was dramatically increased. CD137-Exo promoted the progression of AS and Th17 cell differentiation via NF-КB pathway mediated IL-6 expression. This finding provided a potential method to prevent local and peripheral inflammation in AS.

What factors predict drivers' self-reported lane change violation behavior at urban intersections? A study in China.

Lane change violations are a major cause of traffic conflicts and accidents at urban intersections and one of many road-safety issues in China. This study aims to explore the socio-psychological factors underlying drivers' motivation for lane change violation behavior at urban intersections and examines how these factors predict this violation behavior. A self-reported questionnaire is designed by applying the construct of the theory of planned behavior (TPB) to collect data. Five hundred-six valid responses are received from the questionnaire survey conducted on the Internet in China. The data are then analyzed using structural equation modeling (SEM). The results of the analysis show that behavioral intention is the strongest predictor of self-reported lane change violation behavior at urban intersections. Perceived behavioral control has both direct and indirect effects on self-reported lane change violation behavior. Furthermore, attitude, subjective norms and perceived behavioral control are found to have significant correlations with drivers' intention of lane change violations at urban intersections. The results of this study could provide a reference for designing more effective interventions to modify drivers' lane change violation behavior at urban intersections.

Quantitative evaluation of myocardial layer-specific strain using two-dimensional speckle tracking echocardiography among young adults with essential hypertension in China.

The myocardial wall of the left ventricle is a complex, multilayered structure, which is altered in young adults with hypertension. The aim of this study was to define the characteristics of longitudinal and circumferential strain in young adults with hypertension.Two-dimensional speckle tracking echocardiography was used to analyze longitudinal and circumferential strain parameters in 67 young adults with hypertension, 70 older young adults with essential hypertension and 62 healthy adults.The global longitudinal strain (GLS) and global circumferential strain (GCS) was the highest at endocardium, and lowest at epicardium. A layer-specific analysis of myocardial deformation in all adults revealed that all of the peak systolic longitudinal strain (LS) and the peak systolic circumferential strain (CS) in the endocardium, mid-myocardium and epicardium were gradually increased from the base to the apex. The peak systolic LS showed significant differences at basal, mid-ventricular, and apical level among normal adults, young NLVH (nonleft ventricular hypertrophy), and young LVH (left ventricular hypertrophy). In all the adults with hypertension, young adults were associated with higher peak systolic longitudinal strain values compared with older adults, but the small differences of LS may be meaningless in clinical settings. Between the young LVH and older LVH, the peak systolic CS showed significant differences except data of epicardium at basal and mid-ventricular level.This study provides reference values for layer-specific strain in young adults with hypertension. This detailed strain analysis provides layer-oriented information to reveal the different characteristics of circumferential and longitudinal strain in young adults with hypertension. This systolic dysfunction could be detected conveniently and accurately by 2DSTE.

Ghrelin attenuates vascular calcification in diabetic patients with amputation.

Vascular calcification is established to be a critical factor in diabetes mellitus, which causes cardiovascular and amputation complication of diabetic patients. OPG/RANKL/RANK axis serves as a regulatory role in vascular calcification. Ghrelin, an endogenous ligand of growth hormone secretagogue receptor (GHSR), has been reported to exhibit potent cardiovascular protective effects. However, the role of ghrelin in the regulation of diabetic vascular calcification is still elusive. Here, we reported the role of ghrelin and its relationship with OPG/RANKL/RANK system in patients with diabetic foot amputation. In vivo and in vitro investigations were performed. Sixty type 2 diabetic patients with foot amputation were enrolled in vivo investigation, and they were divided into three groups through Doppler ultrasound: mild stenosis group (n=20), moderate stenosis group (n=20), and severe stenosis/occlusion group (n=20). Morphological analysis results showed diffused calcium depositions in the anterior tibial artery of diabetic amputees. Compared with the mild and moderate stenosis group, the severe stenosis/occlusion group had more spotty calcium depositions in atherosclerotic plaques. Western blot analysis indicated the expressions of osteoprotegerin (OPG) and ghrelin were downregulated, while the expression of receptor activator of nuclear factor kappa B ligand (RANKL) was upregulated with the vascular stenosis aggravation. Pearson correlation analysis revealed a negative correlation between calcium content and ghrelin levels (r=-0.58, P<0.001), as well as the ghrelin levels and sRANKL levels (r=-0.57, P<0.001). Meanwhile, OPG levels were positively correlated with ghrelin levels (r=0.63, P<0.001). From in vitro investigation, we found that the high-glucose (HG), high-lipid (HL), and ß-glycerophosphate (ß-GP) considerably increased the total calcium content, ALP activity, and expression of osteogenic markers in vascular smooth muscle cells (VSMCs). Ghrelin blunted calcification in a dose-dependent manner. In addition, ghrelin upregulated OPG expression and downregulated RANKL expression in VSMC calcification when anti-OPG antibody and RANKL were performed. Collectively, we therefore conclude serum ghrelin level may be a predictor of diabetic vascular calcification. The possible mechanism may be related with OPG/RANKL signal.