Pulmonary fibrosis (PF) is a chronic progressive end-stage lung disease. However, the mechanisms underlying the progression of this disease remain elusive. Presently, clinically employed drugs are scarce for the treatment of PF. Hence, there is an urgent need for developing novel drugs to address such diseases. Our study found for the first time that a natural source of Prismatomeris connata Y. Z. Ruan (Huang Gen, HG) ethyl acetate extract (HG-2) had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic (TGF-β1/Smad) pathway. Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation, cellular response to reactive oxygen species, and extracellular matrix (ECM) disassembly. Moreover, mass spectrometry imaging (MSI) was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2, which was related to arginine biosynthesis and alanine, asparate and glutamate metabolism, the downregulation of arachidonic acid metabolism, and the upregulation of glycerophospholipid metabolism. In conclusion, we elaborated on the relationship between metabolite distribution and the progression of PF, constructed the regulatory metabolic network of HG-2, and discovered the multi-target therapeutic effect of HG-2, which might be conducive to the development of new drugs for PF.

Background/Objectives: The external oblique intercostal (EOI) plane block shows promise for postoperative analgesia after open liver surgery. Pharmacokinetic profiles of ropivacaine after EOI plane block remain unclear. Meanwhile the pharmacokinetic data informs safety assessment, guides post-block monitoring duration, and predicts blockade duration. This study aimed to characterize ropivacaine pharmacokinetics and propose a safe dosing regimen. Methods: In this prospective study, patients undergoing open liver surgery received a unilateral single-shot ultrasound-guided EOI plane block with 30 mL of 0.375% ropivacaine. Plasma ropivacaine concentrations were measured to define pharmacokinetics, identify influencing factors, and develop physiology-based pharmacokinetic (PBPK) models for dose optimization. Results: Twenty-eight patients (Child-Pugh A, ≤3 liver segments resected) were included. Peak plasma ropivacaine concentration occurred at 10 min and remained below the toxic threshold in all patients. No adverse events were observed. Demographic and surgical factors did not significantly affect pharmacokinetics. The PBPK model-predicted safe doses of ropivacaine were comparable across age groups and relatively high. Conclusions: A single-shot EOI plane block with ropivacaine is safe for patients undergoing open liver surgery (Child-Pugh A) with limited resection (≤3 segments). This study provides critical pharmacokinetic data and validated PBPK model, guiding safe dosing to reduce toxicity risks.