Efficacy and safety of low-dose esketamine for painless gastrointestinal endoscopy in adults: a systematic evaluation and meta-analysis.

Object: The benefits of low-dose esketamine for painless gastrointestinal endoscopy remain unclear. As such, the present study aimed to investigate the efficacy and safety of low-dose esketamine for this procedure. Methods: Seven common databases were searched for clinical studies investigating low-dose esketamine for painless gastrointestinal endoscopy. Subsequently, a meta-analysis was performed to synthesize and analyze the data extracted from studies fulfilling the inclusion criteria. Results: Meta-analysis revealed that, compared with propofol, low-dose esketamine in combination with propofol significantly reduced recovery time by 0.56 min (mean difference [MD] -0.56%, 95% confidence interval (CI) -1.08 to -0.05, p = 0.03), induction time by 9.84 s (MD -9.84, 95% CI -12.93 to -6.75, p < 0.00001), propofol dosage by 51.05 mg (MD -51.05, 95% CI -81.53 to -20.57, p = 0.01), and increased mean arterial pressure by 6.23 mmHg (MD 6.23, 95% CI 1.37 to 11.08, p = 0.01). Meanwhile, low-dose esketamine reduced injection pain by 63% (relative risk [RR] 0.37, 95% CI 0.28 to 0.49, p < 0.00001), involuntary movements by 40% (RR 0.60, 95% Cl 0.42 to 0.85, p < 0.005), choking by 42% (RR 0.58, 95% Cl 0.38 to 0.88, p = 0.01), bradycardia by 68% (RR 0.32, 95% Cl 0.18 to 0.58, p = 0.0002), hypotension by 71% (RR 0.29, 95% Cl 0.21 to 0.40, p < 0.00001), respiratory depression by 63% (RR 0.37, 95% 0.26 to 0.51, p < 0.00001), additional cases of propofol by 53% (RR 0.47, 95% Cl 0.29 to 0.77, p = 0.002), and increased hypertension by 1000% (RR 11.00, 95% Cl 1.45 to 83.28, p = 0.02). There were no significant differences in mean heart rate, mean oximetry saturation, delirium, dizziness, vomiting, tachycardia, and hypoxemia. Subgroup analyses revealed that, compared with other dose groups, 0.25 mg/kg esketamine afforded additional benefits in recovery and induction time, mean arterial pressure, involuntary movements, hypoxemia, and respiratory depression. Conclusion: Low-dose esketamine was found to be safe and effective for providing anesthesia during gastrointestinal endoscopy, with 0.25 mg/kg identified as the optimal dose within the dosage ranges examined. However, caution should be exercised when administering this drug to patients with inadequate preoperative blood pressure control.

Exosomes Derived from Astragaloside IV-pretreated Endothelial Progenitor Cells (AS-IV-Exos) Alleviated Endothelial Oxidative Stress and Dysfunction Via the miR-210/ Nox2/ROS Pathway.

BACKGROUND: Chronic hyperglycemia in diabetes induces oxidative stress, leading to damage to the vascular system. In this study, we aimed to evaluate the effects and mechanisms of AS-IV-Exos in alleviating endothelial oxidative stress and dysfunction caused by high glucose (HG). METHODS: Histopathological changes were observed using HE staining, and CD31 expression was assessed through immunohistochemistry (IHC). Cell proliferation was evaluated through CCK8 and EDU assays. The levels of ROS, SOD, and GSH-Px in the skin tissues of each group were measured using ELISA. Cell adhesion, migration, and tube formation abilities were assessed using adhesion, Transwell, and tube formation experiments. ROS levels in HUVEC cells were measured using flow cytometry. The levels of miR-210 and Nox2 were determined through quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of Nox2, SOD, GSH-Px, CD63, and CD81 was confirmed using WB. RESULTS: The level of miR-210 was reduced in diabetes-induced skin damage, while the levels of Nox2 and ROS increased. Treatment with AS-IV increased the level of miR-210 in EPC-Exos. Compared to Exos, AS-IV-Exos significantly reduced the proliferation rate, adhesion number, migration speed, and tube-forming ability of HGdamaged HUVEC cells. AS-IV-Exos also significantly decreased the levels of SOD and GSH-Px in HG-treated HUVEC cells and reduced the levels of Nox2 and GSH-Px. However, ROS levels and Nox2 could reverse this effect. CONCLUSION: AS-IV-Exos effectively alleviated endothelial oxidative stress and dysfunction induced by HG through the miR-210/Nox2/ROS pathway.

Astragaloside IV (ASIV) Mediates Endothelial Progenitor Cell (EPC) Exosomal LINC01963 to Inhibit Pyroptosis and Oxidative Stress in High Glucose-impaired Endothelial Cells.

BACKGROUND: Hyperglycemia is widespread in the world's population, increasing the risk of many diseases. This study aimed to explore the regulatory effect and mechanism of astragaloside IV (ASIV)-mediated endothelial progenitor cells (EPCs) exosomal LINC01963 in endothelial cells (HUVECs) impaired by high glucose. METHODS: Morphologies of exosomes were observed by light microscope and electron microscope. Immunofluorescence was used to identify EPCs and detect the expressions of caspase-1. LINC01963 was detected by quantitative reverse transcription PCR. NLRP3, ASC, and caspase-3 were detected by Western Blot. Nanoparticle tracking analysis was carried out to analyze the exosome diameter. High-throughput sequencing was applied to screen target lncRNAs. The proliferation of endothelial cells was measured by cell counting kit-8 assay. The apoptosis level of HUVECs was detected by flow cytometry and TdT-mediated dUTP Nick-End labeling. The levels of IL- 1ß, IL-18, ROS, SOD, MDA, and LDH were measured by enzyme-linked immunosorbent assay. RESULTS: ASIV could promote the secretion of the EPC exosome. LINC01963 was obtained by high-throughput sequencing. It was observed that high glucose could inhibit the proliferation, reduce the level of SOD, the expression of NLRP3, ASC, and caspase- 1, increase the levels of IL-1ß, IL-18, ROS, MDA, and LDH, and promote apoptosis of HUVECs. Whereas LINC01963 could inhibit the apoptosis of HUVECs, the increase the expression of NLRP3, ASC, and caspase-1, and decrease the levels of IL-1ß, IL-18, ROS, MDA, and LDH. CONCLUSION: EPCs exosomal LINC01963 play an inhibitory role in high glucoseinduced pyroptosis and oxidative stress of HUVECs. This study provides new ideas and directions for treating hyperglycemia and researching exosomal lncRNAs.

Endothelial Progenitor-Cell-Derived Exosomes Induced by Astragaloside IV Accelerate Type I Diabetic-wound Healing via the PI3K/AKT/mTOR Pathway in Rats.

OBJECTIVE: We explore the effects of endothelial progenitor cell (EPC)-derived exosomes (EPCexos) and of astragaloside IV (ASIV)-stimulated EPCexos (ASIV-EPCexos) on type I diabetic-wound healing, and determine the basic molecular mechanisms of action. METHODS: EPCs were exposed to different concentrations of ASIV to generate ASIV-EPCexos. A chronic-wound healing model involving streptozotocin-stimulated diabetic rats was established. These rats were treated with EPCexos, ASIV-EPCexos, rapamycin, and wortmannin. Wound healing was evaluated by direct photographic observation, hematoxylin and eosin staining, and Masson's trichrome staining. RESULTS: ASIV treatment increased the abilities of EPCs (e.g., proliferation), as well as exosome secretion. EPCexo showed a "cup holder" like structure. Treatment with ASIV-EPCexos increased the wound-healing rate, collagen-deposition area, bromodeoxyuridine uptake, VEGF expression, and the number of CD31- and αSMA- positive cells, whereas decreased epidermal thickness and CD45 expression. The expression of the PI3K/AKT/mTOR pathway increased, whereas the expression of inflammatory factor decreased. However, rapamycin and wortmannin reversed these changes. CONCLUSIONS: ASIV-EPCexos may accelerate type I diabetic-wound healing via the PI3K/AKT/mTOR pathway. This study may lay the foundation for new clinical treatment options for patients with type I diabetic wounds.

Is IgA nephropathy induced by abnormalities of CD4+CD25+Treg cells in the tonsils?

IgA nephropathy (IgAN) is characterized by the accumulation of IgA deposits, predominantly in the glomerular mesangium, and represents the most common form of glomerulonephritis. Much evidence showed that tonsils were closely related to IgAN. Urinary findings were deteriorated after tonsil stimulation in patients with IgAN. Tonsillectomy can improve the urinary findings, keep stable renal function, improve mesangial proliferation, decrease IgA deposits and have a favorable effect on long-term renal survival in some IgAN patients. Recent studies indicate that CD4(+)CD25(+) regulatory T cells (Treg) are of critical importance to the maintenance of tolerance by inhibiting the activation and proliferation of autoreactive T cells. Depletion of the minor CD4(+)CD25(+)Treg cells results in the development of organ-specific autoimmunity. Autoimmune diseases can be prevented by reconstitution of the animals with CD4(+)CD25(+)Treg cells. CD4(+)CD25(+)Treg cells are regulators in almost all of the animal models of human organ-specific diseases, transplant rejection and allergic diseases. Some patients with recurrent chronic tonsillitis have not suffered from renal disease, implying that it is possible to find a balance between immunity and tolerance. Some patients, however, suffered from IgAN along with recurrent chronic tonsillitis. It could be hypothesized that a numerical and/or functional deficit of CD4(+)CD25(+)Treg cells in the tonsils of IgAN patients might trigger the development of the diseases. If the hypothesis is correct, altering CD4(+)CD25(+)Treg cell numbers and/or enhancing CD4(+)CD25(+)Treg responses might be useful in the prevention and treatment of IgAN.