Background: Propofol is the most widely used intravenous anesthetic in endoscopic surgery, but is associated with several adverse reactions. Public research has shown that remimazolam, a safe general anesthetic, is increasingly being used as a substitute for propofol in clinical operations. Our meta-analysis aimed to analyze whether the adverse reaction rate of remimazolam in endoscopic surgery is acceptable and whether the surgical success rate is not lower than that of propofol. Aim: This meta-analysis examined the adverse events and efficacy of remimazolam vs. propofol during endoscopic surgery. Method: MEDLINE, Embase, ClinicalTrials.gov, and Google Scholar were comprehensively searched. Seven studies comparing remimazolam and propofol were included in our meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Cochrane manual were used to assess the quality of the results published in all included studies to ensure that our meta-analysis results are reliable and worthwhile. Results: Compared to propofol, the use of remimazolam reduced postoperative injection pain [relative risk (RR)=0.06, 95% confidence interval (CI): 0.03–0.12, P<0.00001], postoperative hypotension (RR=0.45, 95% CI: 0.28–0.73, P=0.001), and postoperative respiratory depression (RR=0.20, 95% CI: 0.08–0.47, P=0.0002); however, it also slightly reduced the success rate of the operation [risk difference (RD)=−0.02, 95% CI: −0.04 to −0.01, P=0.0007]. There were no significant differences in the occurrence of bradycardia symptoms after the operation (RD=−0.01, 95% CI: −0.03 to 0.01, P=0.35), recovery time after the operation [standardized mean difference (SMD)=0.68, 95% CI: −0.43 to 1.80, P=0.23] or discharge time (SMD=0.17, 95% CI: −0.58 to 0.23, P=0.41). We also performed a subgroup analysis of each corresponding outcome. Conclusion: Our analysis showed that remimazolam may be a safer shock option than propofol for endoscopic surgery. However, further research is required to determine their utility.

The pathogenesis of glucocorticoid (GC)-induced osteonecrosis of the femoral head (GIONFH) is still disputed, and abnormal bone metabolism caused by GCs may be an important factor. In vitro, Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) staining were used to evaluate cellular proliferation, and western blotting was used to investigate osteogenesis. In vivo, we used micro-computed tomography (micro-CT), H&E staining, Masson staining, and immunohistochemistry (IHC) analysis to evaluate the impact of exosomes. In addition, the mechanism by which exosomes regulate osteogenesis through the miR-365a-5p/Hippo signaling pathway was investigated using RNA sequencing (RNA-seq), luciferase reporter assays, fluorescence in situ hybridization (FISH), and western blotting. The results of western blotting verified that the relevant genes in osteogenesis, including BMP2, Sp7, and Runx2, were upregulated. RNA-seq and qPCR of the exosome and Dex-treated exosome groups showed that miR-365a-5p was upregulated in the exosome group. Furthermore, we verified that miR-365a-5p promoted osteogenesis by targeting SAV1. Additional in vivo experiments revealed that exosomes prevented GIONFH in a rat model, as shown by micro-CT scanning and histological and IHC analysis. We concluded that exosomal miR-365a-5p was effective in promoting osteogenesis and preventing the development of GIONFH via activation of the Hippo signaling pathway in rats.

Intervertebral disc (IVD) degeneration and its inflammatory microenvironment can result in discogenic pain, which has been shown to stem from the nucleus pulposus (NP). Increasing evidence suggests that mitochondrial related genes are strictly connected to cell functionality and, importantly, it can regulate cell immune activity in response to damaged associated signals. Therefore, identification of mitochondria related genes might offer new diagnostic markers and therapeutic targets for IVD degeneration. In this study, we identified key genes involved in NP tissue immune cell infiltration during IVD degeneration by bioinformatic analysis. The key modules were screened by weighted gene co-expression network analysis (WCGNA). Characteristic genes were identified by random forest analysis. Then gene set enrichment analysis (GSEA) was used to explore the signaling pathways associated with the signature genes. Subsequently, CIBERSORT was used to classify the infiltration of immune cells. Function of the hub gene was confirmed by PCR, Western blotting and ELISA. Finally, we identified MFN2 as a crucial molecule in the process of NP cell pyroptosis and NLRP3 inflammasome activation. We speculate that the increased MFN2 expression in NP tissue along with the infiltration of CD8⁺ T cells, NK cell and neutrophils play important roles in the pathogenesis of IVD degeneration.

Objective: Depression and osteoporosis are usually concurrent health problems. This study aimed to explore the development of osteoporosis in depressive mice model and investigate the beneficial effects of the classical herbal formula Chaihu-Shugan-San (CHSG) on the brain and bone. Methods: CHSG powder was prepared by spray-drying following extraction with water. The fingerprint of CHSG was analyzed using liquid chromatography. The depressive-like model was established by chronic unpredictable mild stress (CUMS) in female mice. The depressive behaviors and trabecular bone properties (measured by micro-CT) were detected at 2, 4, 6, and 8 weeks of CUMS. RT-PCR, immunoblotting and immunofluorescence were applied to measure expression of inflammatory cytokines and morphology of microglias in the hippocampus. Biochemical measurements and histological staining on the adrenal gland were carried out to assess the activity of hypothalamic-pituitary-adrenal (HPA) axis. Histological staining, three-point bending strength, and the expression of regulators involved in bone metabolism were determined. Results: The treatment with CHSG for 8 weeks could ameliorate depressive behaviors, and down-regulate mRNA expression and tissue content of inflammatory factors IL-1β and IL-6 in hippocampus of CUMS mice. The inhibition of CHSG on neuroinflammation might be attributed to its repression of activity in microglias and NLRP3-triggered inflammation pathway. The serum of rats dramatically alleviated LPS-induced phosphorylation of nuclear NFκB (P65) and IκBα and up-regulation of IL-1β and IL-6 proteins in microglia BV2 cells. CUMS induced over-activity of HPA axis shown by the elevation in serum level of ACTH and corticosterone and in area percentage of zona fasciculata, intriguingly, CHSG reversed those changes in HPA system, ameliorated the reduction in mechanical strength and bone mineral density, and regulated bone metabolism factors of CUMS mice. Conclusion: The chronic stress-induced depression resulted in bone disorders developing to osteoporosis. Chaihu-Shugan-San exerted beneficial effects on skeletal tissue by ameliorating neuroinflammation and HPA over-activity of mice with depression.