{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:56:39Z","timestamp":1791190599150,"version":"4.1.0"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroimmunomodulation"],"abstract":"<jats:p>Background: Neuroimmunomodulation examines nervous-immune interactions via hormonal and inflammatory pathways. This study investigated whether the anxiety-sleep disturbance symptom cluster in colorectal cancer (CRC) patients undergoing chemotherapy is associated with neuroendocrine dysregulation, cellular immune alterations, and quality of life (QoL), and tested whether cortisol and interleukin-6 (IL-6) act as biological mediators. Methods: In this prospective baseline observational study, 268 CRC patients scheduled to initiate systemic chemotherapy were assessed within 24 hours before their first chemotherapy cycle. Anxiety (HADS-A), sleep quality (PSQI), and QoL (EORTC QLQ-C30) were assessed. Serum cortisol, IL-6, and TNF-\u03b1 were quantified by ELISA. Lymphocyte subsets (CD3+, CD4+, CD8+, NK cells) and regulatory T cells (Tregs) were analyzed by flow cytometry. Patients with HADS-A \u22658 and PSQI &gt;5 formed the Symptom Cluster group (n=118), while the remaining patients constituted the Non-cluster comparator group (n=150). Mediation analysis using bootstrapping tested cortisol and IL-6 as intermediaries. Results: The Symptom Cluster group showed significantly elevated cortisol, IL-6, and TNF-\u03b1 (all P&lt;0.001), higher Treg proportion (8.4% vs. 4.6%, P&lt;0.001), and lower CD3+, CD4+, and NK cell counts (all P&lt;0.001). Global QoL was reduced (36.4 vs. 69.5, P&lt;0.001). Cross-sectional mediation models indicated that the association between symptom-cluster status and CD4+ T-cell count was statistically mediated by cortisol (indirect effect, -117.45; 95% bootstrap CI, -168.22 to -75.40), and the association with global QoL was statistically mediated by IL-6 (indirect effect, -13.85; 95% bootstrap CI, -18.50 to -9.80), accounting for 37.9% and 41.8% of the total effects, respectively. Conclusion: The anxiety-sleep disturbance symptom cluster in CRC chemotherapy patients is associated with neuroendocrine-inflammatory dysregulation, effector immune suppression, Treg expansion, and impaired QoL. Exploratory mediation findings suggest that cortisol and IL-6 may be involved in statistical indirect associations between this pre-chemotherapy anxiety\u2013sleep disturbance phenotype and immune\/QoL outcomes; longitudinal studies are needed to determine temporal and causal relationships.<\/jats:p>","DOI":"10.1159\/nim\/adxag002","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:27:05Z","timestamp":1788521225000},"source":"Crossref","is-referenced-by-count":0,"title":["Associations of a Pre-Chemotherapy Anxiety\u2013Sleep Disturbance Phenotype with Cellular Immunity and Quality of Life in Colorectal Cancer Patients: Statistical Mediation by Cortisol and IL-6"],"prefix":"10.1159","author":[{"given":"Xujin","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haina","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,9,5]]},"container-title":["Neuroimmunomodulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/nim\/adxag002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:31:10Z","timestamp":1791189070000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/nim\/adxag002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,5]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/nim\/adxag002","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.33314097","asserted-by":"subject"}]},"ISSN":["1021-7401","1423-0216"],"issn-type":[{"value":"1021-7401","type":"print"},{"value":"1423-0216","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,5]]}}}