Objective This study focuses on the Jinyinhua (Lonicerae Japonicae Flos, LJF) concentration process in the production of Reduning Injection (热毒宁注射液, RI), with the objective of developing and validating a data-driven technical framework. The framework is designed to enable objective evaluation, intelligent identification, and process optimization of “golden batches”, while fundamentally elucidating the key process mechanisms and quantitative control strategies influencing their formation. Ultimately, this approach aims to enhance the efficiency and stability of the production process. Methods This study collected production process data for 170 batches of LJF concentrate, and innovatively established “comprehensive concentration efficiency ratio” (E) as an evaluation index for process performance. A latent-space guided adaptive performance thresholding (LGAPT) strategy was employed to objectively classify the production batches into golden and non-golden categories. Subsequently, a classification prediction model based on extreme gradient boosting (XGBoost) was constructed. By integrating model explanation techniques such as SHAP (Shapley additive explanations) and partial dependence plots (PDP), the key process features affecting batch quality and their optimal control ranges were systematically investigated. Finally, the model findings were statistically verified through non-parametric tests, effect size analysis, and kernel density estimation. Results The study established a threshold of E = 0.136 3 kg/(m³∙min), classifying the 170 batches into 61 golden and 109 non-golden batches. The XGBoost model demonstrated excellent performance in identifying golden batches, achieving an F1-score of 0.84 on the test set. Model interpretation identified features such as LT_std-2, LT_skew-1, and T3_abd-2 as core determinants for golden batch formation and defined their optimal ranges. The statistical validation results were highly consistent with the model interpretations, confirming the reliability of the findings. Conclusion This study established a comprehensive technical framework encompassing performance quantification, intelligent classification, and model-based optimization. By successfully identifying the key process features and their optimal control ranges, this work lays a methodological foundation for the standardization and intelligent control of traditional Chinese medicine (TCM) manufacturing, driving a paradigm shift in process optimization from an empirical-based to a data-driven approach.

Objective To prepare transdermal peptide-modified osthole liposomes (TD-Ost-Lips), and to explore the transdermal permeation performance and its therapeutic effects on atopic dermatitis (AD). Methods TD-Ost-Lips were prepared by film dispersion method. Phospholipid to osthole amount ratio, phospholipid to cholesterol amount ratio and phospholipid to DSPE-mPEG₂₀₀₀-TD amount ratio were selected as main influencing factors, overall desirability (OD) of entrapment efficiency, drug loading and particle size acted as response values, and the Box-Behnken design-response surface method (BBD-RSM) was used to optimize preparations of TD-Ost-Lips. Shape of TD-Ost-Lips was observed by transmission electron microscopy (TEM). TD-Ost-Lips gel was prepared using carbomer 940 as matrix, drug release behavior in vitro was studied by dialysis method and the mechanism of drug delivery was also studied. The rheology of TD-Ost-Lips gel was explored. The Franz diffusion cell method was used to study the transdermal permeation performance of TD-Ost-Lips gels. Atopic dermatitis (AD) model was stablished, the changes of skin lesions on the back of the mice were observed, and the inflammatory factors and pathological changes of skin lesions were detected. Results The optimal formulations of TD-Ost-Lips: phospholipid to osthole amount ratio was 8.81:1, phospholipid to cholesterol amount ratio was 6.27:1 and phospholipid to DSPE-mPEG2000-TD amount ratio was 6.27:1. The encapsulation efficiency, drug loading, particle size and ζ potential of TD-Ost-Lips were (86.77 ± 0.71)%, (6.65 ± 0.10)%, (220.25 ± 5.69) nm, and (−17.31 ± 0.85) mV, respectively. The shape of TD-Ost-Lips were vesicular. The cumulative release rate of TD-Ost-Lips gel in 24 h was 77.06%, and the drug behavior accorded with Weibull model. The rheological properties of TD-Ost-Lips gels showed solid elastic properties, and did not flow when inverted. TD-Ost-Lips gel increased the permeation rate, cumulative penetration and skin retention of osthole to 5.00, 5.04 and 2.84 times, respectively. TD-Ost-Lips gel significantly reduced the psoriasis area and severity index (PASI), effectively suppressed the elevation of inflammatory factors in skin tissue, and enhanced the treatment effect of osthole on AD. Conclusion TD-Ost-Lips gel greatly promoted the transdermal permeation of osthole, significantly enhanced its therapeutic effects on atopic dermatitis, and laid a foundation for further development and application.

Objective To elucidate the mechanism by which Danhong Injection (丹红注射液, DHI) ameliorates mitochondrial dynamics imbalance and inhibits NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis in H9c2 cells subjected to oxygen-glucose deprivation based on AMP-activated protein kinase (AMPK)/dynamin-related protein 1 (Drp1) pathway. Methods Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) was employed to identify the core active components of DHI. Molecular docking was performed using AutoDock Vina software to assess the affinity between DHI core components and target proteins, including AMPK, Drp1, optic atrophy 1 (OPA1) and cystein-asparate protease-1 (Caspase-1). An H9c2 cell oxygen-glucose deprivation model was established, control group, model group, DHI group, DHI + Compound C (AMPK inhibitor) group, AICAR (AMPK agonist) group, MCC950 (NLRP3 inhibitor) group and Mdivi-1 (Drp1 inhibitor) group were set up. The optimal intervention concentration of DHI was screened using CCK-8 assay. Mitochondrial membrane potential (MMP) was measured using JC-1 probe, and mitochondrial reactive oxygen species (mtROS) level was determined using MitoSOX^TM. Mitochondrial ultrastructure was observed via transmission electron microscopy. Immunofluorescence was used to detect the protein expressions of p-AMPK and p-Drp1. Western blotting was performed to detect the expressions of AMPK/Drp1 pathway-related proteins, mitochondrial dynamics-related proteins [mitochondrial fission 1 protein (FIS1), mitofusin 2 (MFN2) and OPA1] and pyroptosis-related proteins [NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1 and N-terminal fragment of gasdermin D (GSDMD-NT)]. ELISA was used to determine the levels of interleukin-1β (IL-1β), IL-18 and adenosine triphosphate (ATP). Results UHPLC-MS identified eight active components of DHI, including salvianolic acid, lithospermic acid B, danshensu, caffeic acid, sodium danshensu, etc. The molecular docking results showed that each target and active ingredient had strong affinity. The in vitro experimental results showed that compared with model group, mitochondrial morphology in DHI group was significantly improved, with continuous outer membrane and relatively intact cristae structure, increased quantity, and matrix density restored to near normal. MMP and ATP levels were increased (P < 0.01), mtROS release was decreased (P < 0.01), p-AMPK/AMPK value was increased (P < 0.01), p-Drp1/Drp1 value was decreased (P < 0.01), MFN2 and OPA1 protein expressions were upregulated (P < 0.01), FIS1, NLRP3, ASC, Caspase-1 and GSDMD-NT protein expressions were downregulated (P < 0.01), and IL-1β and IL-18 levels were significantly decreased (P < 0.01), consistent with the effects of AICAR, MCC950 and Mdivi-1. Compound C could partially inhibit the above-mentioned effects of DHI. Conclusion DHI activates AMPK/Drp1 pathway, inhibits mitochondrial excessive division and promotes mitochondrial fusion, reduces NLRP3 inflammasome activation and pyroptosis, thereby alleviating hypoxia/hypoglycemia induced H9c2 cell damage.

Objective To investigate the therapeutic effect of pedunculoside (PE) on dextran sulfate sodium salt (DSS)-induced ulcerative colitis (UC) and elucidate its molecular mechanism through in vitro and in vivo models. Methods DSS was used to establish a mouse UC model, combined with transcriptome analysis, the effect of PE on changes in body weight, colon length, colon tissue pathology, pro-inflammatory cytokine levels in colon tissue, and expressions of tight junction proteins (Occludin, E-cadherin, Claudin-1) were evaluated. Caco-2 monolayer cell model was established, the cell permeability was detected using fluorescein isothiocyanate-glucan (FITC-glucan) to evaluate the effect of PE on intestinal mucosal barrier function. Further validation of the regulatory effect of PE on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, inflammatory factors, and tight junction protein expression and distribution was achieved through molecular biology experiments such as Western blotting and ELISA. Results The results of in vivo experiments showed that PE could significantly reduce the disease activity index (DAI) score of mice (P < 0.001), alleviate pathological damage to colon tissue, reduce pro-inflammatory cytokine levels (P < 0.05, 0.001), and upregulate the expressions of tight junction proteins in colon tissue (P < 0.001). Transcriptome sequencing revealed that PE had a significant inhibitory effect on the overactivated PI3K/Akt signaling pathway in colon tissue of UC mice (P < 0.001). In vitro experimental results showed that PE could significantly reduce the permeability of Caco-2 monolayer cells (P < 0.001), inhibit the phosphorylation of Akt and PI3K in DSS-induced Caco-2 cell model (P < 0.01, 0.001), reduce the levels of inflammatory factors (P < 0.01, 0.001), and upregulate the expressions of Occludin, E-cadherin and Claudin-1 (P < 0.001). Conclusion PE could downregulate inflammatory response and enhance intestinal epithelial barrier function by inhibiting PI3K/Akt signaling pathway in both in vivo and in vitro models, thereby exerting a protective effect on DSS-induced UC.

Objective To investigate the effects and underlying molecular mechanisms of glycyrrhetinic acid (GLG) and glycyrrhizic acid (GLA) on alleviation of cisplatin (CP)-induced acute liver injury (ALI) based on proteomics. Methods A total of 50 SPF male Wistar rats were randomly divided into control group, model group, amifostine (200 mg/kg) group, GLG (100 mg/kg) group and GLA (200 mg/kg) group. Rats in GLG group and GLA group were given intragastric administration for eight consecutive days. Rats in amifostine group was given intraperitoneal administration from the 5th to the 8th day of the experiment, control group and model group were given intragastric administration of physiological saline. On the 5th day of the experiment, except for the control group, all other rats were induced to ALI with a single dose of cisplatin solution (8 mg/kg) via ip. Liver index, liver function and pathological changes in liver tissue were detected. Label free non-standard quantitative proteomics technology was used to analyze protein expressions in liver tissue, differentially expressed proteins were screen, and bioinformatics analysis was performed. The protein-protein interaction (PPI) integration network of drug and disease prediction intersection targets and differentially expressed proteins was constructed by integrating network pharmacology methods. The core targets were screened by cytoNCA, MCODE and cytoHubba, gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed. Key target expressions were validated using Western blotting, immunohistochemistry and other techniques. Results Compared with model group, the liver index and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of rats in GLG group and GLA group were significantly reduced (P < 0.05, 0.01, 0.001), and the pathological damage of liver tissue was significantly improved. Proteomic identification identified 23 potential key differentially expressed proteins each in cisplatin-induced ALI treated with GLG and GLA, enriched in multiple biological processes related to redox reactions, inflammation and apoptosis. PPI integrated network showed that signal transducer and activator of transcription 3 (STAT3), heme oxygenase 1 (HMOX1), protein kinase B1 (AKT1), B-cell lymphoma-2 (Bcl-2), cysteine aspartate protease-3 (Caspase-3) and tumor protein p53 (TP53) were key targets of GLG action network, HMOX1, Bcl-2, epidermal growth factor receptor (EGFR) and TP53 were key targets of GLA action network, and they can be enriched in phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, tumor necrosis factor-α (TNF-α) signaling pathway, interleukin-17 (IL-17) signaling pathway, p53 signaling pathway, etc. The validation results showed that both GLG and GLA could significantly upregulate the p-Akt/Akt value and Bcl-2, superoxide dismutase (SOD) levels in liver tissue of ALI rats (P < 0.01, 0.001), and downregulate the expressions of Akt, HMOX1, STAT3, high mobility group box 1 protein (HMGB1) and levels of TNF-α, IL-1β, malondialdehyde (MDA) in liver tissue (P < 0.05, 0.01, 0.001). Conclusion GLG and GLA could effectively alleviate cisplatin-induced ALI, and their protective effects may be closely related to regulating Akt/STAT3/HMOX1 signaling axis, thereby inhibiting liver oxidative damage, cell apoptosis and inflammatory response.

Objective To investigate the intervention effect of Jingfang Granules (荆防颗粒) on airway inflammation and airway remodeling in asthmatic mice based on lung-gut axis, and elucidate the underlying molecular mechanism. Methods BALB/c mice were randomly divided into control group, model group, Jingfang Granules low-, medium-, high-dose (1, 2, 4 g/kg) groups and dexamethasone (1 mg/kg) group. A mouse asthma model was established by ip ovalbumin/aluminum hydroxide. After drug intervention, levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) in serum and interleukin-1β (IL-1β), IL-6 in lung tissue were detected. Hematoxylin-eosin (HE), PAS and Masson staining were used to detect pathological changes in lung tissue of mice. Immunohistochemistry was used to detect mucin 5AC (MUC5AC) protein expression in lung tissue. Western blotting was used to detect the expressions of transforming growth factor-β1 (TGF-β1)/Smad2/3 pathway, NOD nuclear factor-κB (NF-κB) signaling pathway in lung tissue and intestinal barrier related proteins. 16S rRNA sequencing, untargeted metabolomics and proteomics analyses were integrated to systematically explore the potential mechanism of Jingfang Granules in asthma intervention from a multi-omics perspective. Results Compared with model group, Jingfang Granules significantly reduced the levels of TNF-α in serum and IL-1β, IL-6 in lung tissue of asthma model mice (P < 0.01), increased the level of IFN-γ in serum (P < 0.01), significantly reduced the infiltration of inflammatory cells in lung tissue, decreased the expression of MUC5AC in lung tissue, inhibited the activity of TGF-β1/Smad2/3 signaling pathway, thereby alleviating airway mucus secretion and airway remodeling. The results of multi-omics analysis further indicated that Jingfang Granules could upregulate the expressions of Occludin, Claudin1 and ZO-1, promote intestinal barrier repair, regulate gut microbiota imbalance and fecal metabolic disorders, and inhibit the abnormal activation of the NOD-NF-κB signaling pathway. Conclusion Jingfang Granules may ameliorate airway inflammation and airway remodeling in asthmatic mice by repairing intestinal barrier function, improving gut microbiota structure, correcting fecal metabolic disorders, and modulating NOD-NF-κB signaling pathway.

Objective To observe the effect of water extract of Crataegus pinnatifida leaves on vascular inflammatory injury and systemic lipid metabolism disorders in apolipoprotein E knockout (ApoE^−/−) mice induced by homocysteine (Hcy) and high fat. Methods Eight C57BL/6J mice fed a normal diet were served as the control group, 40 ApoE^−/− mice were randomly divided into high-fat group, high-fat + methionine group, simvastatin (5.7 mg/kg) group, C. pinnatifida leaves low-and high-dose (12, 24 g/kg) groups, with eight mice in each group. Except for the control group, all other mice were fed a 21% high-fat diet for 18 weeks. Starting from the 11th week, except for the control and high-fat groups, the remaining mice were received daily intragastric administration of methionine (1 g/kg) to induce hyperhomocysteinemia. Corresponding drugs were administered to each treatment group, while the control and high-fat groups received an equivalent volume of saline. Counts of white blood cells, red blood cells, hemoglobin and platelets in peripheral blood were measured. Levels of Hcy, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1β, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (SCr) and blood urea nitrogen (BUN) in serum were assessed. Oil red O staining was used to observe lipid plaques in aortic intima and lipid content in liver sections. Filipin staining was used to measure hepatic cholesterol level. Hematoxylin-eosin (HE) staining was used to examine pathological morphological changes in aortic tissue. Masson staining was used to detecte collagen fiber deposition in aorta. Immunofluorescence staining was used to evaluate the expressions of p50, p65 in aorta and sterol regulatory element binding protein 1 (SREBP1) and SREBP2 in liver. Results Compared with control group, levels of Hcy, TC, TG, LDL-C and inflammatory factors in serum of mice in high-fat group and high-fat + methionine group were significantly increased (P < 0.01), while the level of HDL-C was significantly decreased (P < 0.01). The red stained area of aorta was significantly increased (P < 0.01), the endometrium was thickened and showed obvious pathological changes, lipid accumulation was increased (P < 0.01), and expressions of p50, p65 were increased (P < 0.01). The expressions of SREBP1 and SREBP2 in liver were increased (P < 0.01), and the lipid content was increased (P < 0.01). Compared with high-fat + methionine group, levels of Hcy, TC, TG, LDL-C and inflammatory factors in serum of mice in each treatment group were significantly reduced (P < 0.01), while the level of HDL-C was significantly increased (P < 0.05, 0.01). The red stained area of aorta was significantly reduced (P < 0.01), pathological changes were alleviated, lipid accumulation was reduced (P < 0.01), and the expressions of p50, p65 were reduced (P < 0.01). The expressions of SREBP1 and SREBP2 in liver were decreased (P < 0.01), and the lipid content was decreased (P < 0.01). Conclusion The water extract of C. pinnatifida leaves could improve the atherosclerosis of blood vessels in mice, and its mechanism may be closely related to the inhibition of inflammatory damage of vascular endothelium and liver lipid synthesis.

Objective To explore the effects of verbascoside combined with electroacupuncture on neuroinflammation and brain tissue damage in ischemic stroke (IS) rats based on Ras-related C3 botulinum toxin substrate 1 (Rac1)/protein kinase B (Akt)/nuclear factor-κB (NF-κB) pathway. Methods A rat model of IS was constructed using middle cerebral artery occlusion. The successfully modeled rats were randomly divided into model group, verbascoside (10 mg/kg) group, electroacupuncture group, averbascoside + electroacupuncture group, nifedipine (10 mg/kg) group, Rac1/Akt/NF-κB pathway activator phorbol 12-myristate 13-acetate (PMA, 10 μg/kg) group and verbascoside + electroacupuncture + PMA group, with 10 rats in each group. Another 10 normal rats were selected as the control group. After 2 h of successful modeling, each treatment group began intervention and continued treatment for 14 d. The neurological deficit and cerebral infarction area of rats in each group were evaluated. The levels of interleukin-17 (IL-17), IL-1β and monocyte chemoattractant protein-1 (MCP-1) in brain tissue of rats were detected. The pathological damage and cell apoptosis in brain tissue of rats were detected. The expressions of S100β, arginase-1 (Arg-1) and Rac1/Akt/NF-κB pathway related proteins in brain tissue of rats were detected. Results Compared with control group, the neurological severity score (NSS) and cerebral infarction area ratio of rats in model group were significantly increased (P < 0.05), the levels of IL-17, IL-1β and MCP-1 in brain tissue were significantly increased (P < 0.05), the pathological damage in brain tissue was severe, the apoptosis rate was significantly increased (P < 0.05), the protein expression levels of S100β, Rac1, p-Akt/Akt, p-NF-κB p65/NF-κB p65 in brain tissue were significantly increased (P < 0.05), and the expression of Arg-1 was significantly decreased (P < 0.05). Compared with model group, the above indicators were significantly improved in verbascoside group, electroacupuncture group, nifedipine group and verbascoside + electroacupuncture group (P < 0.05), among which the verbascoside + electroacupuncture group had a significantly better improvement effect than the verbascoside group and electroacupuncture group (P < 0.05). PMA could significantly reverse the improvement effect of verbascoside combined with electroacupuncture on IS rats (P < 0.05). Conclusion The combination of acteoside and electroacupuncture may alleviate neuroinflammation and brain tissue damage in IS rats by inhibiting Rac1/Akt/NF-κB pathway.

Objective To screen characteristic genes driving gastric mucosal “inflammation-cancer transformation” based on multi-omics data and Mendelian randomization (MR) causal inference methods, and to explore potential traditional Chinese medicine (TCM) intervention strategies. Methods Transcriptomic data and large-scale genetic data were integrated. Differential analysis, MR analysis, and protein-protein interaction network construction were performed to screen characteristic genes causally associated with gastric cancer risk. Subsequently, survival analysis, immune infiltration analysis, and immune mediation mechanism analysis were conducted on the identified genes. Finally, molecular docking-based virtual screening was performed on a TCM small-molecule compound library using core characteristic genes as targets to predict potential active components. Results A total of 30 continuously up-regulated differentially expressed genes were identified during the “inflammation-cancer transformation” process. MR analysis identified five core characteristic genes (S100A8, CXCR1, S100A9, S100A12, ZBED2) showing positive causal associations with gastric cancer risk. Among them, high expression of S100A12 was significantly associated with poor prognosis in patients, positively correlated with neutrophil infiltration, and negatively correlated with B-cell and CD4⁺ T-cell infiltration. Mediation analysis revealed that S100A12 may promote carcinogenic effects by negatively regulating CD25⁺CD4⁺ T cells (primarily regulatory T cells). Phenome-wide MR analysis suggested good potential safety for targeting S100A12. Virtual screening identified several TCM small-molecule compounds with high binding affinity to the S100A12 protein (e.g., C-curarine, physalin D). Conclusion S100A12 is a key characteristic gene linking chronic inflammation to gastric cancer development, driving “inflammation-cancer transformation” by reshaping the immune microenvironment. The screening of TCM small molecules targeting this gene provides lead compound candidates for intervening in gastric precancerous lesions. The established research framework integrating multi-omics and reverse drug screening offers a new approach for the precise prevention and drug development of gastric cancer.

Objective To investigate the clinical characteristics and medication patterns of traditional Chinese medicine (TCM) in the treatment of stable chronic obstructive pulmonary disease (COPD) based on real-world data and provide a scientific basis for syndrome differentiation-based medication selection and the development of new TCM therapies. Methods Electronic medical records of 6 240 outpatients with stable COPD treated at the First Affiliated Hospital of Guangxi University of Chinese Medicine, Liuzhou Hospital of Traditional Chinese Medicine, and Wuzhou Hospital of Traditional Chinese Medicine between January 2019 and January 2025 were retrospectively collected. Disease characteristics and TCM prescription compatibility patterns were systematically analyzed using the Ancient and Modern Medical Record Cloud Platform through frequency analysis, association rule mining, and hierarchical cluster analysis. Results The predominant syndrome types in patients with stable COPD were lung-kidney deficiency syndrome and lung-spleen qi deficiency syndrome. The core symptoms were cough, sputum production, shortness of breath, and chest distension. Commonly used herbs included Gancao (Glycyrrhizae Radix et Rhizoma), Banxia (Pinelliae Rhizoma), Chenpi (Citri Reticulatae Pericarpium), Baizhu (Atractylodis Macrocephalae Rhizoma), and Huangqi (Astragali Radix). Important herb combinations included Glycyrrhizae Radix et Rhizoma-Pinelliae Rhizoma and Astragali Radix-Dangshen (Codonopsis Radix). These herbs were predominantly warm in nature and sweet, pungent, and bitter in flavor, and were mainly associated with the lung, spleen, and kidney meridians. Conclusion This study suggests that the stable stage of COPD is primarily characterized by lung-kidney deficiency syndrome and lung-spleen qi deficiency syndrome. Therapeutic strategies should focus on tonifying the lung, spleen, and kidney, warming yang, resolving phlegm, activating blood, and resolving stasis. The identified core herb combinations may provide an important reference for precise syndrome differentiation and treatment, future clinical validation, and the development of new TCM-based therapies.