Therapeutic association and mechanistic exploration of modified Sijunzi Decoction in radiation-induced sinusitis: an integrated retrospective analysis and network pharmacology study.

Purpose: Nasopharyngeal carcinoma (NPC) is highly sensitive to radiotherapy, which, however, may trigger complications such as radiation-induced sinusitis (RIS) to impair patients' quality of life. Modified Sijunzi decoction (SJZD), a traditional Chinese medicine (TCM) formulation, has been revealed to exert therapeutic potential in RIS prevention and management. However, at this stage, we know little about its specific composition and molecular mechanism, which was a focus of our current study.

Methods: This cross-sectional study was conducted on 86 NPC patients treated at our institution between August 2019 and August 2022. This study further assessed the association between TCM use and RIS incidence by using univariate analysis and multivariate logistic regression. Association rule mining and cluster analysis were employed to identify modified SJZD as the core prescription. Network pharmacology analysis was further applied to elucidate its mechanism of action.

Results: Univariate analysis demonstrated that TCM exposure was associated with reduced RIS prevalence (55.81%) (P = 0.002), and binary logistic regression analysis confirmed TCM use as an independent protective factor against RIS development (P = 0.001, OR = 0.156, 95% CI: 0.050-0.487). Furthermore, cluster analysis and association rule mining indicated that modified SJZD emerged as the core therapeutic prescription. Network pharmacology analysis identified 67 potential molecular targets of modified SJZD in RIS treatment. In addition, KEGG pathway enrichment revealed that modified SJZD exerted its therapeutic effects through multi-target mechanisms, particularly involving pathways in cancer, microRNAs in cancer, the JAK-STAT signaling pathway, and the NF-κB signaling pathway.

Conclusion: There is a potential inverse association between TCM use and RIS incidence. Modified SJZD is identified as the core therapeutic formula, which appears to exert its protective effects through multiple bioactive components, diverse molecular targets, and multiple pathways.