Background: Liuwei Dihuang Pill is widely used to treat tinnitus in China. However, the underlying mechanism of Liuwei Dihuang Pill in treating tinnitus still remains unclear.Objective: To explore the potential pharmacological mechanism of Liuwei Dihuang Pill in the treatment of tinnitus based on network pharmacology and molecular docking. Methods:The active components of the Liuwei Dihuang Pill were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database. Cytoscape software was used to draw the active componenttarget network diagram of Liuwei Dihuang Pill, and obtain the core components. Then the corresponding targets were also obtained from the TCMSP database. Targets related to tinnitus were obtained from the GeneCards, DisGeNET, TTD and DrugBank databases. The String database was used to construct protein-protein interaction (PPI) network of common targets of drugs and diseases, then the core targets were screened out. The Annotation, Visualization and Integrated Discovery (DAVID) database was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis of common targets. Finally, the molecular docking between the core component and the core target was carried out by AutoDock.Results: The core components of Liuwei Dihuang Pill in the treatment of tinnitus including quercetin, stigmasterol, kaempferol, β-sitosterol, tetrahydroalstonine, which may act on core targets such as STAT3, transcription factor AP-1 (JUN), tumor necrosis factor (TNF), interleukin-6 and MAPK3. HIF-1 signaling pathway, Influenza A, P53 signaling pathway, and Toll-like receptor signaling pathway play a role in anti-inflammatory, improving microcirculation in the blood-labyrinth barrier, increasing cochlear blood flow, and preventing hair cell damage. The molecular docking results showed that the affinity between core components and core targets was good. Conclusion:The potential mechanism of Liuwei Dihuang Pill in the treatment of tinnitus was preliminarily discussed in this study, which may provide a theoretical basis and evidence for further experimental research.Abbreviations: AKT1 = serine/threonine kinase 1, BP = biological processes, CC = closeness centrality, DAVID = the Annotation, Visualization and Integrated Discovery, DL = drug-likeness, GO = gene ontology, HIF = hypoxia-inducible factor, JUN = transcription factor AP-1, KEGG = Kyoto encyclopedia of genes and genomes, MAPK = mitogen-activated protein kinase, OB = oral bioavailability, PPI = protein-protein interaction, STAT = signal transducer and activator of transcription, TCM = traditional Chinese medicines, TCMSP = traditional Chinese medicine systems pharmacology database and analysis platform, Th = helper T cell, TNF = tumor necrosis factor, TP53 = tumor protein P53.

Objectives: HNSCC is the world's sixth most prevalent cancer. CELSR3 is engaged in immune system regulation and has activation and inhibition potential. However, it is unknown whether CELSR3 impacts the prognosis of HNSCC. The purpose of this study was to look at the diagnostic value of the CELSR3 gene in HNSCC and its effect on tumor immune invasion, which is important for enhancing HNSCC treatment. Materials and Methods: Several bioinformatics tools were employed to investigate CELSR3's putative oncogenic pathway in HNSCC, and datasets from the TCGA, TIMER, GEPIA, and LinkedOmics were extracted and evaluated. CELSR3 has been linked to tumor immune cell infiltration, immunological checkpoints, and immune-related genes. CELSR3's putative roles were investigated using GO, KEGG, and pathway enrichment analysis. The expression level of CELSR3 in HNSCC tissues and cells was detected by RT-qPCR. The effects of CELSR3 on proliferation of HNSCC cells were detected by CCK-8 assay. Results: CELSR3 was shown to be expressed differently in different types of cancer and normal tissues. CELSR3 gene expression was linked to pN-stage, pM-stage, and age. Patients with high CELSR3 expression also have a well prognosis. CELSR3 expression was found to be an independent predictive factor for HNSCC in both univariate and multivariate Cox regression analyses. We discovered the functional network of CELSR3 in HNSCC using GO and KEGG analysis. CELSR3 expression levels were found to be favorably associated with immune cell infiltration levels. Furthermore, CELSR3 expression levels were significantly correlated with the expression levels of many immune molecules, such as MHC genes, immune activation genes, chemokine receptors, and chemokines. CELSR3 is highly expressed in HNSCC tissues and cells. CELSR3 overexpression significantly inhibited the proliferation of HNSCC cells. CELSR3 expression may affect the immune microenvironment and, as a result, the prognosis of HNSCC. Conclusion: CELSR3 expression is elevated in HNSCC tumor tissues, and high CELSR3 expression is associated with well prognosis, which inhibited the proliferation of NHSCC cells. CELSR3 has the potential to influence tumor formation by controlling tumor-infiltrating cells in the TME. As a result, CELSR3 may have diagnostic significance in HNSCC.