Effect of low-dose terazosin on arterial stiffness improvement: A pilot study.

Arterial stiffness, a prominent hallmark of ageing arteries, is a predictor of all-cause mortality. Strategies for promoting healthy vascular ageing are encouraged. Here we conducted a pilot study to evaluate the potential effects of low-dose Terazosin on arterial stiffness. We enrolled patients aged over 40 with elevated arterial stiffness, defined as a brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s, who were administered Terazosin (0.5 and 1.0 mg/day) from December 2020 to June 2023. Treatment responses were assessed every 3 months. Linear regression analysis was used to characterise the improvement. We matched cases who took Terazosin for 1 year with Terazosin-free controls using propensity score matching (PSM). Our findings demonstrate that Terazosin administration significantly affected arterial stiffness. (1) Arterial stiffness significantly improved (at least a 5% reduction in baPWV) in 50.0% of patients at 3 months, 48.6% at 6 months, 59.3% at 9 months, and 54.4% at 12 months, respectively. (2) Those with higher baseline baPWV and hypertension exhibited a significantly reduced risk of non-response. (3) Terazosin was associated with a reduction of baPWV at 1-year follow-up (linear regression: ß = -165.16, p < 0.001). This pilot study offers valuable insights into the potential significance of Terazosin in improving arterial stiffness and paves the way for future randomised clinical trials in combating vascular ageing.

The Efficacy of Active Fistulation in Duckett Procedure for Proximal Hypospadias in Children.

PURPOSE: To explore the efficacy of active fistulation in the treatment of proximal hypospadias in children by comparing one-stage and two-stage Duckett  procedure. MATERIALS AND METHODS:  A total of sixty-seven children who were diagnosed with proximal hypospadias and underwent Duckett operation at our hospital between January 2013 and January 2021 were selected for this study. These subjects were divided into two groups: the research group (n=36), using two-stage Duckett procedure with active fistulation, and the control group (n=31), using one-stage Duckett procedure. The incidence of postoperative complications and the score of pediatric penile perception Scale were compared between the two groups. RESULTS:  The research group exhibits significantly lower incidence rate of urethral fistula (8.3% Vs 16.1%) and urethral stricture (5.6% Vs 12.9%) in comparison to the control group (P<0.01). Furthermore, the analysis of Pediatric Penile Perception Scale scores indicates that the research group achieves significantly higher scores in terms of urethral shape, penile skin shape, and overall appearance than the control group (P<0.05).  Conclusion: In the treatment of proximal hypospadias in children, The active fistulation within the two-stage Duckett procedure significantly reduces the rate of stage 1 postoperative complications and improves parental satisfaction. The active fistulation may offer a more promising option for the treatment of proximal hypospadias in children.

DHCR24 Insufficiency Promotes Vascular Endothelial Cell Senescence and Endothelial Dysfunction via Inhibition of Caveolin-1/ERK Signaling.

Endothelial cells (ECs) senescence is critical for vascular dysfunction, which leads to age-related disease. DHCR24, a 3ß-hydroxysterol δ 24 reductase with multiple functions other than enzymatic activity, has been involved in age-related disease. However, little is known about the relationship between DHCR24 and vascular ECs senescence. We revealed that DHCR24 expression is chronologically decreased in senescent human umbilical vein endothelial cells (HUVECs) and the aortas of aged mice. ECs senescence in endothelium-specific DHCR24 knockout mice was characterized by increased P16 and senescence-associated secretory phenotype, decreased SIRT1 and cell proliferation, impaired endothelium-dependent relaxation, and elevated blood pressure. In vitro, DHCR24 knockdown in young HUVECs resulted in a similar senescence phenotype. DHCR24 deficiency impaired endothelial migration and tube formation and reduced nitric oxide (NO) levels. DHCR24 suppression also inhibited the caveolin-1/ERK signaling, probably responsible for increased reactive oxygen species production and decreased eNOS/NO. Conversely, DHCR24 overexpression enhanced this signaling pathway, blunted the senescence phenotype, and improved cellular function in senescent cells, effectively blocked by the ERK inhibitor U0126. Moreover, desmosterol accumulation induced by DHCR24 deficiency promoted HUVECs senescence and inhibited caveolin-1/ERK signaling. Our findings demonstrate that DHCR24 is essential in ECs senescence.

Fibulin 1, targeted by microRNA-24-3p, promotes cell proliferation and migration in vascular smooth muscle cells, contributing to the development of atherosclerosis in APOE-/- mice.

Extracellular matrix (ECM) and vascular smooth muscle cells (VSMCs) are the main components of atherosclerosis (AS) plaque. VSMCs participate in plaque formation through phenotypic transformation. The complex interplay between ECM and VSMCs plays vital roles in the progression of AS throughout the disease. An in-depth investigation into the functions of ECM-related molecules in VSMC development might contribute to deciphering the complexity of AS pathogenesis. In this study, the roles and molecular mechanisms of the ECM-related molecule Fibulin-1 (FBLN1) in the development of AS and VSMCs were explored using RNA sequencing, bioinformatics analysis, and cell experiments. Furthermore, the expression of FBLN1, as determined by western blot analysis, immunohistochemistry, and real-time quantitative PCR, was significantly increased in AS vascular samples compared to normal vascular samples. Silencing the FBLN1 through AAV viral injection in mice revealed an improvement in AS. Functional analyses revealed that FBLN1 promoted VSMC proliferation, migration, and wound healing. Combined with RNA sequencing and TargetScan7.2 prediction data, 22 microRNAs (miRNAs) were found to have the potential for direct interaction with the FBLN1 3'UTR in VSMCs. Among these 22 miRNAs, it was demonstrated that microRNA-24-3p (miR-24-3p) could negatively regulate FBLN1 expression by directly binding to the FBLN1 3'UTR. Moreover, miR-24-3p inhibited cell proliferation, migration, and wound healing, and suppressed the expression of Ki67, matrix metalloproteinase-2 and -9 (MMP2/9) by targeting FBLN1 in VSMCs. Meanwhile, inhibition of FBLN1 expression could restrain VSMC phenotypic transformation. In conclusion, miR-24-3p inhibited VSMC proliferation and migration by targeting FBLN1. Additionally, multiple miRNAs with the potential to interact with the FBLN1 3'UTR were identified. These findings might deepen our understanding of ECM gene regulatory networks and the complex etiology of AS.

Impact of Physiological Characteristics on Chylomicron Pathway-Mediated Absorption of Nanocrystals in the Pediatric Population.

Nanocrystals exhibit significant advantages in improving the oral bioavailability of poorly soluble drugs. However, the complicated absorption properties of nanocrystals and the differences in physiological characteristics between children and adults limit pediatric applications of nanocrystals. To elucidate the absorption differences and the underlying mechanisms between children and adults, the pharmacokinetics and tissue distribution of aprepitant crystals with different particle sizes (NC200, NC500, and MC2.5) in rats and mice at different ages were studied, and their absorption mechanisms were investigated in Caco-2 cells, mice, and rats. It was found that childhood animals demonstrated higher bioavailability compared with adolescent and adult animals, which was related to higher bile salt concentration and accelerated drug dissolution in the intestine of childhood animals. The majority of nanocrystals were dissolved and formed micelles under the influence of bile salts. Compared with intact nanocrystals, the bile salt micelle-associated aprepitant was absorbed through the chylomicron pathway, wherein Apo B assisted in the reassembling of the aprepitant micelles after endocytosis. Higher bile salt concentration and Apo B expression in the intestines of childhood animals are both responsible for the higher chylomicron transport pathways. Elucidation of the chylomicron pathway in the varied absorption of nanocrystals among children, adolescents, and adults provides strong theoretical guidance for promoting the rational and safe use of nanocrystals in pediatric populations.

Effect of high intensity interval training on cardiorespiratory fitness in sedentary female college students / 中国学校卫生

Objective@#The aim of this study was to observe the changes in cardiorespiratory fitness after high intensity interval training(HIIT), and to provide a reference basis for scientific and reasonable sports plans.@*Methods@#A total of 26 female college students with sedentary lifestyle were randomly allocated into MCT group (n=13) and HIIT group(n=13). All the participants undertook a graded exercise test to obtain VO 2max. The MCT group was trained with 60% VO 2max intensity for 30 min, while HIIT group received exercises with 90% VO 2max intensity every 3 min, intermittent 2 min, for 6 sessions three times a week for 8 weeks. Before and after 8 weeks of training, the subjects were tested for body shape, cardiorespiratory function and aerobic exercise capacity.@*Results@#BMI[(22.34±2.73)(21.56±2.39)kg/m2], percentage of body fat [(31.43±5.65)%, (28.85±5.52)%] of HIIT group and BMI [(22.98±3.23)(22.35±3.09)kg/m2], percentage of body fat [(33.15±4.48)%, (31.48±4.73)%] of MCT group showed significant changes before and after training(P<0.01). For cardiorespiratory function, there was a significant change in VC [(3.30±0.60)(3.61±0.54)L], vital capacity index(56.22±10.73, 63.51±10.53), and MVV [(81.44±20.45, 91.17±15.64)L/min] in HIIT group. There was also a significant change in VC [(3.08±0.41)(3.19±0.36)L] and vital capacity index (52.74±8.66, 55.62±7.88) in MCT group, and there was a significant difference between the two groups(P<0.01). In terms of aerobic exercise capacity, maximal oxygen uptake in HIIT group [(2 204.15±232.39)(2 539.23±339.39)mL/min] and MCT group [(2 136.15±240.76)(2 462.00±318.29)mL/min] increased significantly after training(P<0.01).@*Conclusion@#Both HIIT and MCT can significantly improve lung function and aerobic performance of sedentary female college students, but HIIT is found more effective than MCT training.