Intravenous administration of vesicants or irritants frequently leads to chemical phlebitis. We aimed to establish a chemical phlebitis rat model by injection vinorelbine via dorsal pedal vein and evaluate the general symptoms as well as the pathological features of lesion venous tissues. Rats in 6 groups with each 8 were injected 0.1 mL saline or vinorelbine (1-5 mg/mL) via the dorsalis pedis vein in hind paw, respectively. The edema and pain were assessed daily by swelling rates (water displacement) and weight-bearing ratio (bipedal balance test), respectively. Phlebitis severity was evaluated by phlebitis scale. Venous tissues harvested on day 7 were underwent histopathological and ultrastructural evaluation. Vinorelbine administration elicited dose-dependent inflammatory responses, with erythema, edema, pain, palpable cord formation, and purulent drainage. Edema and pain peaked on day 3, as evidenced by increased swelling rates and reduced weight-bearing ratios. Persistent symptomatology was observed in the 3-5 mg/mL groups through day 7. Histopathological analysis demonstrated venous wall thickening characterized by intimal hyperplasia and collagen deposition, along with vascular lumen stenosis accompanied by thrombosis. Furthermore, disruption of the intimal lining was observed, with shrunken endothelial cells interspersed among extracellular matrix. These pathological changes also exhibited a dose-dependent exacerbation with increasing concentrations of vinorelbine. Dorsal pedal vein injection of 0.1 mL vinorelbine (3-5 mg/mL) successfully induced chemical phlebitis in rats, mimicking human clinical presentations. Furthermore, vinorelbine-induced endothelial damage resulted in distinct venous lesions, characterized by vascular wall thickening with intimal hyperplasia, luminal stenosis and thrombus.
Introduction: Colorectal cancer has been ranked third among the most common cancers worldwide and raised to the second leading cause of cancer death with nearly one-tenth of cancer-related deaths globally, and nearly half of colorectal cancer patients present with or develop colorectal cancer liver metastasis (CRLM). Buzhong Tiaogan Formula (BTF) has been proven to treat CRLM in our team, but there are lacking of evidence on its effective in delaying colorectal liver metastasis (liver depression spleen deficiency type), so we will evaluate the efficacy and safety of BTF in preventing the occurrence of CRLM. Methods: This randomized controlled trial (RCT) will be carried out in 3 different hospitals in Shanxi Province planning to recruit 150 CRLM patients with the type of liver depression spleen deficiency. The control group will be treated by basic antitumor therapy and the treatment group will use BTF plus basic antitumor therapy. The primary outcomes will be quality of life of included patients, the time of occurrence of liver metastasis, the score of traditional Chinese medicine symptom for the type of liver depression spleen deficiency; and the secondary outcomes will include overall survival, progression-free survival, DFS, tumor microenvironment and immune state of the included patient. Safety evaluation will be recorded during the whole study. All data in this RCT will be analyzed by SPSS 23.0 software. This study has been approved by the Clinical Research Ethics Committee of Shanxi Province Hospital of Traditional Chinese medicine (2021Y-06016). Discussion: The results of this RCT will contribute to BTF for delaying colorectal liver metastasis (liver depression spleen deficient type). And the results from this RCT will be published in a relevant journal after finished. Trial registration: ChiMCTR2100005268 (September 4, 2021).
Background: Lung adenocarcinoma (LUAD) is a major lung cancer subtype influenced by environmental factors. Benzo[a]anthracene (BaA), a common Group 2B carcinogen found in pollutants, smoke, and food, shows genotoxic and oncogenic activity; however, its specific mechanisms in LUAD pathogenesis remain unclear and warrant systematic investigation. Objective: This study aims to elucidate the mechanisms of BaA-induced LUAD, identify core targets, validate their expression, immunorelevance and clinical significance, and construct a hypothesis framework for AOP in BaA-exposed LUAD. Methods: We integrated network toxicology, multi-machine learning algorithms (LASSO, SVM-RFE, and Random Forest) and multidimensional bioinformatics analysis. Potential BaA-LUAD intersection targets were collected from public databases and subjected to functional enrichment analysis. Core targets were screened and validated using GEO and TCGA-LUAD (via UALCAN) datasets for differential expression, immune infiltration and prognostic value. Molecular docking and 100 ns molecular dynamics (MD) simulations were applied to evaluate the binding stability between BaA and core targets. Results: A total of 248 intersection targets were identified, with significant enrichment in chemokine signaling, ErbB signaling, and viral protein–cytokine receptor interaction pathways. Machine learning prioritized five core targets: TNNC1, ABCC3, CRABP2, CXCL12 , and OLR1 . These genes were consistently dysregulated in LUAD samples across cohorts ( p < 0.05) and correlated distinctly with immune cell infiltration: TNNC1 was associated with anti-tumor immunity, while the others linked to immunosuppressive cells. Prognostic analysis showed trends of ABCC3/CRABP2 high-expression and TNNC1/CXCL12/OLR1 low-expression correlating with patient outcomes ( p > 0.05). Molecular docking confirmed stable binding between BaA and all core targets, with the strongest affinity for CRABP2 (–8.4 kcal/mol). MD simulations further supported complex stability. Conclusion: BaA promotes LUAD progression via multi-target regulation and tumor immune microenvironment remodeling. This study offers an integrated computational framework and an AOP-based theoretical foundation for assessing pollutant health risks and informing targeted LUAD interventions.
Objective: To evaluate the clinical efficacy and safety of Buzhong Tiaogan granule (BTG) in treatment of colorectal cancer patients with liver metastasis and provide high-level evidence for clinical practice.Methods and analysis: This is a prospective, randomized, controlled, multi-center controlled trial. A total of 210 patients diagnosed with spleen deficiency and liver depression, as well as colorectal cancer liver metastasis (CRLM) of the stasis and toxin interception type, will be enrolled in the study. The participants will be randomly allocated into two groups: a treatment group that will receive BTG plus conventional first-line anti-tumor therapy and a control group that will receive conventional first-line anti-tumor therapy alone. The primary outcomes are progression-free survival (PFS) and quality of life scores. The secondary outcomes are as follows: (a) overall survival (OS); (b) objective response rate (ORR); (c) liver-specific progression-free survival; (d) disease control rate (DCR); (e) traditional Chinese medicine (TCM) syndrome score; (f) Piper Fatigue Scale, and (g) Karnofsky Performance Status (KPS) score. Safety evaluations will be conducted throughout the study period.Discussion: The results of this trial will provide scientific and objective data necessary for the evaluation of the efficacy and safety of BTG for colorectal cancer patients with liver metastasis.Clinical trial registration: The trial was registered at ClinicalTrials.gov (ChiCTR2400084861) on May 27, 2024.