Cinobufotalin injection is a water-soluble preparation extracted from the skin secretion of Bufo bufo gargarizans Cantor or B. melanotictus Schneider, which has been widely used as an adjuvant treatment in lung cancer patients. This study aimed to evaluate the clinical efficacy and safety of cinobufotalin (PubChem CID: 259776) injection as an adjunctive treatment for lung cancer. We designed a meta-analysis that performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We aim to include randomized controlled trials by systematically searching the PubMed, EMBASE, CNKI, Wanfang database, VIP, CBM, the Cochrane Central Register of Controlled Trials, and Chinese Clinical Trial Registry from inception to Mar 1, 2020, comparing the difference between the use of cinobufotalin injection as an adjunctive treatment and a control group without cinobufotalin injection. The objective response rate (ORR) and quality of life (QOL) will be defined as the primary outcomes, and the disease control rate (DCR) and adverse events will be defined as the secondary outcomes. We included 21 articles with 1735 cases of lung cancer patients. Comparison results show that combining with cinobufotalin injection can improve ORR (OR = 1.77, 95% CI [1.43, 2.21], < 0.001), with low heterogeneity ( = 0.94, I² = 0%); DCR (OR = 2.20, 95% CI [1.70, 2.85], < 0.001), with low heterogeneity ( = 0.60, I² = 0%); KPS score (OR = 3.10, 95% CI [2.23, 4.32], < 0.001), with low heterogeneity ( = 0.85, I² = 0%); and the effect of pain relief (OR = 2.68, 95% CI [1.30, 5.55], = 0.008), with low heterogeneity ( = 0.72, I² = 0%). Low-to-moderate evidence shows that cinobufotalin injection combined with chemotherapy can significantly increase ORR, DCR, QOL, and the effect of pain relief. Meanwhile, cinobufotalin injection did not bring additional adverse events such as hematological toxicity, gastrointestinal toxicity, cardiotoxicity, hepatotoxicity, and nephrotoxicity; however, multicenter, large-sample, high-quality clinical research results are still needed to reveal the therapeutic effect of cinobufotalin injection in small-cell lung cancer (PROSPERO registration number: CRD42020170052).

Background: Colorectal cancer (CRC) ranks as the third most common cancer worldwide. Tertiary lymphoid structures (TLSs), organized immune cell aggregates in non-lymphoid tissues, are linked to chronic inflammation and tumorigenesis. However, the precise relationship between TLSs and CRC prognosis remains unclear. This study aimed to develop a TLS-associated genetic signature to predict CRC prognosis and support clinical applications. Methods: Utilizing the TCGA database, we analyzed TLS-related gene expression in CRC versus normal tissues. Prognostic models were constructed using Cox and Kaplan-Meier analyses. CRC samples were stratified into high and low TLS groups via ssGSEA, with validation in the GSE75500 dataset. We identified clinical characteristics associated with TLS scores, created prognostic nomograms, analyzed the top 50 differential genes, assessed tumor mutations, estimated immune infiltration using CIBERSORT, and examined correlations between TLS scores and immune checkpoints. Results: A 13-gene TLS-associated prognostic model for CRC was developed, emphasizing immune response genes. Survival analysis indicated significantly better outcomes for the TLS-high group. Cox regression identified stage IV and M1 as independent factors influencing TLS scores. Nomogram analysis demonstrated that combining TLS scores with clinical features enhances prognostic accuracy. TLS scores were closely associated with immune checkpoint genes, suggesting potential immunotherapy benefits for TLS-high patients. Conclusions: This study developed and validated a TLS-based prognostic model for CRC, exploring relevant immune cells. The model holds promise for predicting clinical prognosis and treatment responsiveness in CRC patients.

Background. Lung metastasis of malignant tumor signifies worse prognosis and immensely deteriorates patients’ life quality. Spatholobi Caulis (SC) has been reported to reduce lung metastasis, but the mechanism remains elusive. Methods. The active components and corresponding targets of SC were obtained from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) database and the SwissTargetPrediction database. The disease targets were acquired from DisGeNET and GeneCards databases. Venn map was composed to figure out intersection targets by using R. The PPI network was constructed through STRING and Cytoscape, and MCODE plug-in was used to sift hub targets. Gene Ontology (GO)-Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out by utilizing clusterProfiler package (R3.6.1) with adjusted value <0.05. Network of SC-active components-intersection targets-KEGG pathway was accomplished with Cytoscape. Molecular docking between hub targets and active components was performed, analyzed, and visualized by AutoDockTools, AutoDock Vina, PLIP Web tool, and PYMOL. Results. 24 active components and 123 corresponding targets were screened, and the number of disease targets and intersection targets was 1074 and 47, respectively. RELA, JUN, MAPK1, MAPK14, STAT3, IL-4, ESR1, and TP53 were the 8 hub targets. GO analysis and KEGG analysis elucidated that SC could ameliorate lung metastasis mainly by intervening oxidative stress, AGE-RAGE signaling pathway, and microRNAs in cancer. All 8 hub targets were proven to combine successfully with active components of SC. Conclusion. Inflammation is the core factor that integrates all these targets, biological process, and signaling pathways, which indicates that SC prevents or reduces lung metastasis mainly by dispelling inflammation.

Background LTB4 receptor 1 (LTB4R), as the high affinity leukotriene B4 receptor, is rapidly revealing its function in malignancies. However, it is still uncertain. Methods We investigated the expression pattern and prognostic significance of LTB4R in pan-cancer across different databases, including ONCOMINE, PrognoScan, GEPIA, and Kaplan-Meier Plotter, in this study. Meanwhile, we explored the significance of LTB4R in tumor metastasis by HCMDB. Then functional enrichment analysis of related genes was performed using GeneMANIA and DAVID. Lastly, utilizing the TIMER datasets, we looked into the links between LTB4R expression and immune infiltration in malignancies. Results In general, tumor tissue displayed higher levels of LTB4R expression than normal tissue. Although LTB4R had a negative influence on pan-cancer, a high expression level of LTB4R was protective of LIHC (liver hepatocellular carcinoma) patients' survival. There was no significant difference in the distribution of LTB4R between non-metastatic and metastatic tumors. Based on Gene Set Enrichment Analysis, LTB4R was implicated in pathways involved in inflammation, immunity, metabolism, and cancer diseases. The correlation between immune cells and LTB4R was found to be distinct across cancer types. Furthermore, markers of infiltrating immune cells, such as Treg, T cell exhaustion and T helper cells, exhibited different LTB4R-related immune infiltration patterns. Conclusion The LTB4R is associated with immune infiltrates and can be used as a prognostic biomarker in pan-cancer.

Background: Siwu Decoction (SWD) is a well-known classical TCM formula that has been shown to be effective as a basis for preventing and reducing liver metastases (LM). However, the active ingredients and potential molecular mechanisms remain unclear. Objective: This study aimed to systematically analyze the active ingredients and potential molecular mechanisms of SWD on LM and validate mechanisms involved. Materials and methods: The active ingredients in SWD were extracted by UHPLC-MS/MS in a latest study. Protox II was retrieved to obtain toxicological parameters to detect safety. Swiss Target Prediction database was exploited to harvest SWD targets. Five databases, Gene Cards, DisGeNET, Drugbank, OMIM, and TTD, were employed to filter pathogenic targets of LM. STRING database was utilized to construct the protein–protein interaction network for therapeutic targets, followed by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. GEPIA database and the Human Protein Atlas were taken to observe the expression of core genes and proteins. ImmuCellAI algorithm was applied to analyze the immune microenvironment and survival relevant to core genes. Molecular docking was performed to verify the affinity of SWD effective ingredients to core targets. In vivo experiments were carried out to validate the anti-LM efficacy of SWD and verify the pivotal mechanisms of action. Results: Eighteen main bioactive phytochemicals identified were all non-hepatotoxic. PPI network acquired 118 therapeutic targets, of which VEGFA, CASP3, STAT3, etc. were identified as core targets. KEGG analysis revealed that HIF-1 pathway and others were critical. After tandem targets and pathways, HIF-1/VEGF was regarded as the greatest potential pathway. VEGFA and HIF-1 were expressed differently in various stages of cancer and normal tissues. There was a negative regulation of immunoreactive cells by VEGFA, which was influential for prognosis. Molecular docking confirmed the tight binding to VEGFA. This study revealed the exact effect of SWD against LM, and identified significant inhibition the expression of HIF-1α, VEGF, and CD31 in the liver microenvironment. Conclusion: This study clarified the active ingredients of SWD, the therapeutic targets of LM and potential molecular mechanisms. SWD may protect against LM through suppressing HIF-1/VEGF pathway.