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Background: The benefit-risk profile of direct oral anticoagulants (DOAC) therapy in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) has not been well established yet. This study aimed to evaluate the efficacy and safety of DOAC compared with vitamin K antagonists (VKA) in patients with HCM and AF. Methods: PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov were searched to identify studies comparing DOAC with VKA in patients with HCM and AF. The primary endpoint was thromboembolic events. The relative risks and standard errors were pooled by random-effect models using the generic inverse variance method. Results: Seven observational studies involving 9395 patients were included in this meta-analysis. Compared to the VKA group, the DOAC group displayed a similar risk of thromboembolic events [RR (95%CI): 0.93 (0.73–1.20), p = 0.59] and ischemic stroke [RR (95%CI): 0.65 (0.33–1.28), p = 0.22]. The incidence of major bleeding was comparable between the two groups [RR (95%CI): 0.75 (0.49–1.15), p = 0.19]. Meanwhile, DOAC therapy was superior to VKA therapy in reducing the incidences of all-cause death [RR (95%CI): 0.44 (0.35–0.55), p < 0.001], cardiovascular death [RR (95%CI): 0.41 (0.22–0.75), p = 0.004], and intracranial hemorrhage [RR (95%CI): 0.42 (0.24–0.74), p = 0.003]. Conclusion: In patients with HCM and AF, DOAC therapy was similar to VKA therapy in reducing the risk of thromboembolic events, without increasing bleeding risk. In addition, the DOAC group displayed significant advantages in reducing mortality and intracranial hemorrhage compared with the VKA group. Further randomized controlled trials are needed to provide more evidence for DOAC therapy in this population. [ABSTRACT FROM AUTHOR]

Background: Ganoderma (Lingzhi in Chinese) has shown good clinical outcomes in the treatment of insomnia, restlessness, and palpitation. However, the mechanism by which Ganoderma ameliorates insomnia is unclear. We explored the mechanism of the anti-insomnia effect of Ganoderma using systems pharmacology from the perspective of central-peripheral multi-level interaction network analysis. Methods: The active components and central active components of Ganoderma were obtained from the TCMIP and TCMSP databases, then screened to determine their pharmacokinetic properties. The potential target genes of these components were identified using the Swiss Target Prediction and TCMSP databases. The results were matched with the insomnia target genes obtained from the GeneCards, OMIM, DisGeNET, and TCMIP databases. Overlapping targets were subjected to multi-level interaction network analysis and enrichment analysis using the STRING, Metascape, and BioGPS databases. The networks analysed were protein-protein interaction (PPI), drug-component-target gene, component-target gene-organ, and target gene-extended disease; we also performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: In total, 34 sedative-hypnotic components (including 5 central active components) were identified, corresponding to 51 target genes. Multi-level interaction network analysis and enrichment analysis demonstrated that Ganoderma exerted an anti-insomnia effect via multiple central-peripheral mechanisms simultaneously, mainly by regulating cell apoptosis/survival and cytokine expression through core target genes such as TNF, CASP3, JUN, and HSP90αA1; it also affected immune regulation and apoptosis. Therefore, Ganoderma has potential as an adjuvant therapy for insomnia-related complications. Conclusion: Ganoderma exerts an anti-insomnia effect via complex central-peripheral multi-level interaction networks. [ABSTRACT FROM AUTHOR]