Background. Kanglaite injection (KLTi) has shown good clinical efficacy in the treatment of pancreatic ductal adenocarcinoma (PDAC). While previous studies have demonstrated the antitumor effects of the oil compounds in KLTi, it is unclear whether the unsaponifiable matter (USM) also has antitumor effects. This study used network pharmacology, molecular docking, and database verification methods to investigate the molecular biological mechanisms of USM. Methods. Compounds of USM were obtained from GC-MS, and targets from DrugBank. Next, the GEO database was searched for differentially expressed genes in cancerous tissues and healthy tissues of PDAC to identify targets. Subsequently, the protein-protein interaction of USM and PDAC targets was constructed by BisoGenet to extract candidate genes. The candidate genes were enriched using GO and KEGG by Metascape, and the gene-pathway network was constructed to screen the key genes. Molecular docking and molecular dynamic simulations of core compound targets were finally performed and to explore the diagnostic, survival, and prognosis value of targets. Results. A total of 10 active compounds and 36 drug targets were screened for USM, 919 genes associated with PDAC, and 139 USM candidate genes against PDAC were excavated. The enrichment predicted USM by acting on RELA, NFKB1, IKBKG, JUN, MAPK1, TP53, and AKT1. Molecular docking and dynamic simulations confirmed the screened core targets had good affinity and stability with the corresponding compounds. In diagnostic ROC validation, the above targets have certain accuracy for diagnosing PDAC, and the combined diagnosis is more advantageous. As the most diagnostic value of RELA, it is equally significant in predicting disease-specific survival and progression-free interval. Conclusions. USM in KLTi plays an anti-PDAC role by intervening in the cell cycle, inducing apoptosis, and downregulating the NF-κB, MAPK, and PI3K-Akt pathways. It might participate in the pancreatic cancer pathway, and core target groups have diagnostic, survival, and prognosis value biomarker significance.

Introduction. Brain metastases (BMs) are common in non-small-cell lung cancer (NSCLC), which leads to a poor prognosis. As the two most effective strategies available, the use of combination of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and radiotherapy (RT) is still controversial. This protocol proposes a methodology for carrying out a systematic review and meta-analysis that is aimed at (1) focusing on the efficacy and safety role of EGFR-TKIs combined with RT for BMs from NSCLC and (2) displaying the difference in efficacy of EGFR-TKIs owing to the sites and number of BMs, different types of RT, EGFR mutation status, and the subtypes of EGFR mutations by subgroup analysis. Methods and Analysis. Electronic databases including PubMed, Embase, CENTRAL, Web of Science, CBM, CNKI, Wanfang database, and VIP database will be searched from their inception until May 2022. Only randomized controlled trials evaluating the clinical efficacy and safety of EGFR-TKIs combined with RT on BMs of NSCLC will be included. Two reviewers will select the articles, assess the risk of bias, and extract data independently and in duplicate. The RoB 2 tool will be used to assess the quality of included studies. The meta-analysis of data synthesis will be performed with Stata 16. Publication bias will be assessed with the funnel plot method and the Egger test. Quality of the evidence will be evaluated by the GRADE system. Discussion. The approval of an ethical committee is not required. All the included trials will comply with the current ethical standards and the Declaration of Helsinki. Given the ongoing controversies regarding the optimal sequencing of the available and expanding treatment options for EGFR-TKIs in NSCLC with BMs, a synthesis of available, high-quality clinical research evidence is essential to advance our understanding in the treatment of this complex and common disease. This systematic review will evaluate available evidence, will try to provide optimized advice in the applications of EGFR-TKIs, and will be published in a high-quality journal. This study is registered with PROSPERO registration number CRD42021291509.