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Integrate transcriptional data of SCZ and SD from the GEO database, screen disease\u2010shared differential genes. Construct PPI network, identify core targets by topological analysis. Use machine learning algorithms to select cross\u2010disease hub genes. Analyze immune cell infiltration and gene\u2010immune interaction. Conduct molecular docking. Build an SCZ\u2010SD comorbidity mouse model and assess behavioral improvements. Verify key pathway regulatory effects by Western blot and qRT\u2010PCR. Cross\u2010disease analysis identified 25 shared core targets. The constructed \u201ccompound\u2010target\u201d network revealed quercetin, \u03b2\u2010sitosterol, and ADRB2 as key nodes. The PPI network identified HSPB1, THBS1, and other targets enriched in antigen presentation and PI3K\u2010Akt pathways. Machine learning algorithms highlighted HSPB1, ADRB2, and GZMM as core genes. In SCZ, resting CD4+ memory T cells were positively correlated with HSPB1, while abnormal dendritic cells and low ADRB2 expression were associated with SD. Molecular docking confirmed strong binding between baicalin, \u03b2\u2010sitosterol, and the targets. Animal experiments showed that HGTS improved neurological symptoms and sleep structure while regulating the expression of HSPB1, ADRB2, and BDNF. This study reveals shared core targets HSPB1, ADRB2, and GZMM between SCZ and SD. The compound HGTS, through the synergistic action of multiple components such as quercetin and \u03b2\u2010sitosterol, improves neurological symptoms and sleep rhythm.<\/jats:p>","DOI":"10.1096\/fj.202501425r","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T05:28:52Z","timestamp":1750224532000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hugan Tiaoshen Formula Improves the Comorbid Mechanism of Schizophrenia and Sleep Disorder via Multitarget Interaction Network"],"prefix":"10.1096","volume":"39","author":[{"given":"Zixuan","family":"Huang","sequence":"first","affiliation":[{"name":"Affiliated Mental Health Center of Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Wuxi Mental Health Center, Wannan Medical College Graduate Training Unit  Wuxi 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