In summary, dysfunction of the vascular H2S synthase/H2S pathway was found in l-NAME-induced hypertensive rats. Exogenous H2S effectively prevented the development of hypertension induced by l-NAME. These findings suggest that the H2S synthase/H2S pathway participates in hypertension.

A physiological membrane-receptor agonist typically stimulates oscillations, of varying frequencies, in cytosolic Ca2+ concentration ([Ca2+]i). Whether and how [Ca2+]i oscillation frequency regulates agonist-stimulated downstream events, such as gene expression, in non-excitable cells remain unknown. By precisely manipulating [Ca2+]i oscillation frequency in histamine-stimulated vascular endothelial cells (ECs), we demonstrate that the gene expression of vascular cell adhesion molecule 1 (VCAM1) critically depends on [Ca2+]i oscillation frequency in the presence, as well as the absence, of histamine stimulation. However, histamine stimulation enhanced the efficiency of [Ca2+]i-oscillation-frequency-regulated VCAM1 gene expression, versus [Ca2+]i oscillations alone in the absence of histamine stimulation. Furthermore, a [Ca2+]i oscillation frequency previously observed to be the mean frequency in histamine-stimulated ECs was found to optimize VCAM1 mRNA expression. All the above effects were abolished or attenuated by blocking histamine-stimulated generation of intracellular reactive oxygen species (ROS), another intracellular signaling pathway, and were restored by supplementary application of a low level of H2O2. Endogenous NF-κB activity is similarly regulated by [Ca2+]i oscillation frequency, as well as its co-operation with ROS during histamine stimulation. This study shows that [Ca2+]i oscillation frequency cooperates with ROS to efficiently regulate agonist-stimulated gene expression, and provides a novel and general strategy for studying [Ca2+]i signal kinetics in agonist-stimulated downstream events.

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Background:The purpose of this study was to evaluate the effectiveness between percutaneous and open pedicle screw fixation for treating thoracolumbar fractures with spinal injuries.Methods:A total of 105 patients with thoracolumbar fractures and spinal injuries were divided into a percutaneous pedicle screw fixation (PPSF) group with 56 patients, who underwent percutaneous pedicle screw fixation, and an open pedicle screw fixation (OPSF) group with 49 patients, who underwent open pedicle screw fixation in accordance with the treatment project. Relative operation indexes, radiologic, and effectiveness parameters were assessed and compared between the 2 groups.Results:Demographic and clinical features including age, body mass index, gender, fracture level, fracture classification, and Frankel grade in both groups were not significantly different (all P >.05). The PPSF group exhibits significantly lower operation time, intraoperative blood loss, postoperative drainage volume, and hospital stay on average compared with the OPSF group (all P < .05). Besides, the average postoperative radiologic parameters, including Cobb angle (CA), vertebral wedge angle (VWA), vertebral front height percentage (VFHP), and sagittal index (SI), in both the groups were not significantly different (all P > .05). Nevertheless, both visual analogue scale (VAS) and Oswestry disability index (ODI) after surgery decreased more substantially in the PPSF group than in the OPSF group (all P < .05) while no significant difference in VAS scores or ODI during the last follow-up period was demonstrated in both the groups (both P > .05). Frankel classifications were stimulated in both the groups during the last follow-up period.Conclusion:PPSF has a smaller incision, less intraoperative blood loss, shorter recovery time, higher safety measures on average compared with OPSF with respect to managing thoracolumbar fractures with spinal injuries.

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Psychiatric disorders such as anxiety and depression precipitated by substance use occurred during both use and withdrawal. Exosomes play significant roles in biological functions and regulate numerous physiological and pathological processes in various diseases, in particular substance use disorders (SUDs) and other psychiatric disorders. To better understand the role of exosomal miRNAs in the pathology of symptoms of anxiety and depression in patients with SUDs, we first isolated circulating exosomes from heroin-dependent patients (HDPs) and methamphetamine-dependent patients (MDPs) and identified exosomal miRNAs that were differentially expressed between patients and healthy controls (HCs). Furthermore, the correlations between exosomal DE-miRNAs and symptoms of anxiety and depression which were measured using Hamilton-Anxiety (HAM-A)/Hamilton-Depression (HAM-D) Rating Scales in the participants. Notably, the expression level of exosomal hsa-miR-16-5p, hsa-miR-129-5p, hsa-miR-363-3p, and hsa-miR-92a-3p showed significantly negative correlations with HAM-A scores in both HDPs and MDPs. But all of the 4 DE-miRNAs lost significant correlations with HAM-D scores in HDPs. Functional annotation analyses showed that the target genes of the DE-miRNAs were mainly enriched for “synapse”, “cell adhesion”, “focal adhesion” and “MHC class II protein complex”. Our study suggests that a set of circulating exosomal miRNAs were associated with anxiety and depression in SUD patients and may have clinical utility as diagnostic and prognostic biomarkers.