Hepatocellular carcinoma (HCC) develops within a profoundly immunosuppressive tumor immune microenvironment (TIME), which limits the efficacy of immunotherapy. Polarization of tumor-associated macrophages (TAMs) toward a pro-tumorigenic M2 phenotype is a major driver of immune escape. Ferroptosis, an iron-dependent regulated cell death program, intersects with hepatic iron metabolism and immune regulation and thus offers promising points of therapeutic intervention. This review systematically elucidates the mechanistic role of TAM ferroptosis in HCC immune evasion and highlights a “bidirectional regulation” intervention strategy grounded in the Traditional Chinese medicine (TCM) principle of “fortifying healthy qi and eliminating pathogens” (Fuzheng Quxie). This strategy employs “eliminating pathogens” (Quxie) approaches to exploit the metabolic vulnerability of M2-like TAMs and precisely induce their ferroptosis. Moreover, it utilizes “fortifying healthy qi” (Fuzheng) approaches to protect M1-like TAMs and CD8⁺ T cells from oxidative damage. This parallel “induction-protection” paradigm demonstrates the unique advantages of TCM in systemically remodeling TIME through multitarget synergistic actions. Accordingly, precision regulation of TAM ferroptosis based on the Fuzheng Quxie theory represents a promising integrative Chinese-Western medicine strategy for overcoming current bottlenecks in HCC immunotherapy, although its clinical translational potential warrants further validation.

Plant-derived exosome-like nanovesicles (PELNs), characterized by a natural lipid bilayer membrane, have rapidly emerged as a prominent research frontier in medicine owing to their unique biological properties and robust therapeutic potential. This review comprehensively examines the biological profiles, mechanistic functions, and recent engineering advancements of PELNs. In terms of composition, PELNs are uniquely enriched in plant-specific glycolipids, phosphatidylserine, secondary metabolites, and highly stable 2'-O-methylated miRNAs. This distinct molecular makeup endows them with exceptional biocompatibility, negligible immunogenicity, and the capacity for cross-species molecular communication. Mechanistically, PELNs demonstrate profound anti-inflammatory efficacy by suppressing the NF-κB and NLRP3 inflammasome pathways. They also serve as potent immune modulators, driving macrophage M1/M2 polarization and regulating T cell activity. Additionally, PELNs exhibit promising antitumor capabilities, targeting malignancies via reactive oxygen species (ROS) induction, TRAIL pathway activation, and tumor microenvironment remodeling. Crucially, the plant miRNAs encapsulated within PELNs remain highly stable in the gastrointestinal tract, allowing them to selectively alter gene expression in specific gut microbiota communities. This interaction deeply influences host immunity and metabolism, highlighting the vital role in cross-species regulation. Advancements in bioengineering have further expanded the clinical utility of PELNs. Targeted delivery efficiency can be significantly amplified via surface functionalization (e.g., folate and RGD sequences) and state-of-the-art drug loading technologies such as sonication and electroporation. Consequently, engineered PELNs surpass traditional synthetic nanocarriers in penetrating natural physiological barriers, particularly for oral and transdermal drug administration. Despite these advantages, clinical translation is currently hindered by the lack of standardized isolation protocols, challenges in scalable manufacturing, and the need for robust quality control frameworks. Looking forward, the integration of multi-omics approaches and AI-driven “molecular fingerprinting”—coupled with the design of synthetic biomimetic vesicles—will be instrumental in overcoming these bottlenecks, ultimately establishing PELNs as a next-generation platform for precision medicine and targeted nanotherapeutic delivery.

Objective To investigate the associations of shear wave elastography (SWE) parameters and AST-to-platelet ratio index (APRI) with Child-Pugh grade in patients with hepatitis B cirrhosis. Methods The clinical data of 103 patients with hepatitis B cirrhosis who underwent SWE and APRI testing between July 2022 and October 2024 were retrospectively analyzed. These patients comprised the observation group. The clinical data of 99 non-cirrhotic patients were retrospectively analyzed and the patients were enrolled as control group. Liver stiffness (LS), spleen stiffness (SS), APRI and Child-Pugh score were compared in the two groups. According to Child-Pugh grading, the 103 cirrhosis patients were divided into three groups: Group A (grade A, 5-6 points, n=35), Group B (grade B, 7-9 points, n=38), and Group C (grade C, 10-15 points, n=30). SWE parameters and APRI were compared among the three groups. Pearson correlation analysis was used to examine the correlations of LS, SS, and APRI with Child-Pugh score. Results SWE parameters, APRI, and Child-Pugh scores were significantly higher in the observation group than in the control group (P<0.05). Among the three cirrhosis groups, SWE parameters and APRI were highest in Group C, followed by Group B, and lowest in Group A (P<0.05). SWE parameters and APRI were significantly positively correlated with Child-Pugh score (P<0.05). Conclusion SWE parameters and APRI are positively correlated with Child-Pugh grade and are useful for assessing the severity of liver cirrhosis.

OBJECTIVES: To investigate the inhibitory effect of Zheng GanDecoction (ZGF) on tumor progression in a rat model of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) and explore the possible mechanism. METHODS: Seventy SD rats were subjected to regular intraperitoneal injections of DEN (50 mg/kg) for 12 weeks to induce HCC tumorigenesis, with another 10 rats receiving saline injections as the normal control. After successful modeling, the rats were randomized into 5 groups (n=10) for daily treatment with distilled water ( model group), Huaier Granules (4 g/kg; positive control group), or ZGF at low, medium, and high doses (2, 4, and 8 g/kg, respectively) via gavage for 17 weeks. Body weight changes of the rats were monitored, and after completion of the treatments, the rats were euthanized for measurement of liver, spleen and thymus indices and morphological and histopathological examinations of the liver tissues using HE staining. The expressions of YAP, p-YAP, MST1, LATS1 and p-LATS1 in the liver tissues were detected using immunohistochemistry and Western blotting. RESULTS: Compared with the normal control rats, the rat models with DEN-induced HCC exhibited much poorer general condition with a significantly reduced survival rate, increased body weight and liver and spleen indices, and a lowered thymus index. ZGF treatment obviously reduced liver and spleen indices, increased the thymus index, and improved pathologies of the liver tissues of the rat models. Immunohistochemistry and Western blotting showed a dose-dependent reduction of YAP expression and an increment of p-YAP expression in ZGF-treated rats, which also exhibited significantly upregulated hepatic expressions of MST1, LATS1 and p-LATS1. CONCLUSIONS ZGF inhibits DEN-induced HCC in rats by activating the Hippo/YAP pathway via upregulating MST1 and LATS1 expression, which promotes YAP phosphorylation and degradation to suppress proliferation and induce apoptosis of the tumor cells.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Diethylnitrosamine ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Protein Serine-Threonine Kinases/metabolism* ; Carcinoma, Hepatocellular/drug therapy* ; YAP-Signaling Proteins ; Liver Neoplasms/drug therapy* ; Hippo Signaling Pathway ; Male ; Liver Neoplasms, Experimental/metabolism* ; Transcription Factors/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism*

OBJECTIVE To study the improvement effects and mechanisms of Tujia medicine musk needle therapy on cognitive dysfunction in ischemic stroke model rats. METHODS Totally 44 rats were randomly divided into sham operation group， model group， musk needle treatment group and ordinary acupuncture group， with 11 rats in each group. Except for the sham operation group， ischemic stroke model was induced by modified suture method in other groups. After modeling， musk needle treatment group and the ordinary acupuncture group were treated with Tujia musk needle （containing 3 mg of artificial musk） and traditional filiform needle respectively to intervene in the muscle layer of the contralateral scalp motor area， with an intervention duration of 3 courses. The sham operation group and model group were not given any treatment. The neurological deficits score in rats were recorded and Morris water maze behavioral tests were conducted. The morphology of neurons in the cortical area of rats was observed， and the expression of DCX/BrdU and NeuN/BrdU co-labeled cells in the ischemic subependymal area was observed. The plasma levels of hypoxia-inducible factor-1α （HIF-1α） and vascular endothelial growth factor（VEGF） in rats were tested. RESULTS Compared with sham operation group， neurological deficit score of model group was increased significantly， escape latency prolonged significantly， and the times of crossing platform significantly reduced （P＜0.05）； the neuronal structure was significantly damaged， and the number of surrounding Nissl bodies decreased； the number of DCX/BrdU and NeuN/BrdU co- labeled cells in the ischemic subependymal area were significantly increased （P＜0.05）； the levels of HIF-1α and VEGF in plasma were significantly increased （P＜0.05）. Compared with model group， neurological deficits score， escape latency， the times of crossing platform were all reversed significantly in musk needle treatment group and ordinary acupuncture group （P＜0.05）； the neuronal structure was improved， and the number of Nissl bodies increased； the number of DCX/BrdU and NeuN/BrdU co-labeled cells in the ischemic subependymal area were significantly increased （P＜0.05）； the plasma levels of HIF-1α and VEGF were significantly increased （P＜0.05）. Compared with ordinary acupuncture group， the plasma level of HIF-1α was reduced （the difference was not statistically significant）， while the level of VEGF was significantly increased （P＜0.05）. CONCLUSIONS Tujia medicine musk needle therapy can significantly improve the cognitive dysfunction in ischemic stroke model rats， and its mechanism of action may be associated with promoting migration and differentiation of neural stem cell in ischemic subependymal area， preventing the excessive release of HIF-1α and increasing the expression of VEGF.

OBJECTIVE To screen the active site of Jiegu ointment in promoting fracture healing in New Zealand rabbits. METHODS The ethanol extract of Jiegu ointment， as well as the ethyl acetate and n-butanol parts， were prepared and mixed with honey to form a plaster with appropriate viscosity. The radial fracture model of left forelimb in New Zealand rabbit was established and divided into model control group， ethanol extract group， ethyl acetate fraction group and n-butanol fraction group， with 6 rabbits in each group. Except for model control group， rabbits of all other groups were treated with corresponding polar part of Jiegu ointment for external application， for 4 weeks. The radial fracture healing of rabbits was studied by X-ray examination. Enzyme-linked immunosorbent assay was used to detect the serum levels of interleukin-6 （IL-6）， tumor necrosis factor α （TNF-α）， osteocalcin （OC）， vascular endothelial growth factor A （VEGFA）， basic fibroblast growth factor 2 （bFGF2） and alkaline phosphatase （ALP）. HE staining was adopted to observe the changes of pathological morphology of rabbit fracture site， and immunohistochemical method was used to detect the protein expression of bFGF2 in fracture site of rabbits. RESULTS The healing speed of the fracture site in the n-butanol fraction group was the fastest， followed by ethanol extract group， and the ethyl acetate fraction group was the slowest； the serum levels of TNF-α and IL-6 in n-butanol fraction group decreased the fastest， while the levels of ALP， bFGF2， OC and VEGFA increased the fastest [significant increase compared with ethanol extract group （P＜0.01）]； the chondrocytes at the fracture fraction completely disappeared， forming a large number of bone marrow cavities， and the bone trabeculae in the bone marrow cavity were officially formed. The expression level of bFGF2 was also higher than ethanol extract group. CONCLUSIONS The effect of n-butanol fraction on promoting fracture healing is more significant than ethyl acetate fraction and ethanol extract， and n-butanol fraction is the active fraction of Jiegu ointment to promote fracture healing.

The effect of Tujia medicine Berberidis Radix on endogenous metabolites in the serum and feces of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) was analyzed by metabolomics technology to explore the metabolic pathway and underlying mechanism of Berberidis Radix in the intervention of UC. The UC model was induced in mice by DSS. Body weight, disease activity index(DAI), and colon length were recorded. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in colon tissues were determined by ELISA. The levels of endogenous metabolites in the serum and feces were detected by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites. The potential metabolic pathways were analyzed by MetaboAnalyst 5.0. The results showed that Berberidis Radix could significantly improve the symptoms of UC mice and increase the level of the anti-inflammatory factor IL-10. A total of 56 and 43 differential metabolites were identified in the serum and feces, respectively, belonging to lipids, amino acids, fatty acids, etc. After the intervention by Berberidis Radix, the metabolic disorder gradually recovered. The involved metabolic pathways included biosynthesis of phenylalanine, tyrosine, and tryptophan, linoleic acid metabolism, phenylalanine metabolism, and glycerophospholipid metabolism. Berberidis Radix can alleviate the symptoms of mice with DSS-induced UC, and the mechanism may be closely related to the re-gulation of lipid metabolism, amino acid metabolism, and energy metabolism.
Mice ; Animals ; Colitis, Ulcerative/drug therapy* ; Interleukin-10 ; Metabolomics/methods* ; Chromatography, High Pressure Liquid

Chikusetsusaponin IVa (CsIVa) is a natural active monomer of triterpene saponins in the Chinese herbal medicine of Panax japonicus, which has anti-inflammatory, anti-tumor and other effects. However, its function and mechanism in triple negative breast cancer (TNBC) remain unclear. This study investigated the inhibitory effect and mechanisms of CsIVa on the proliferation of triple negative breast cancer cell line MDA-MB-231. In this study, we found that CsIVa could significantly inhibit the proliferation of MDA-MB-231 cells and eliminate its potential toxic effect on normal breast cells (MCF-10A). The transcriptome sequencing results showed that the inhibition of proliferation of MDA-MB-231 cells by CsIVa was closely related to cell cycle and the pathway regulating cell cycle. Further studies confirmed that CsIVa blocked the cell cycle in G2/M phase by down-regulating the expression of cyclin dependent kinase 1 (CDK1), cyclin B1 and up-regulating the expression of cyclin dependent kinase inhibitor 1A (p21). Moreover, CsIVa can block cell cycle through inhibiting PI3K/AKT signal pathway. In conclusion, CsIVa regulates the expression of cell cycle related proteins (p21, CDK1, cyclin B1) via inhibiting the activity of PI3K/AKT signaling pathway, blocks TNBC cell cycle, and thus exerts its anti-tumor activity.

Exosomes have the dual characteristics of promoting and inhibiting cancer and can induce the proliferation, invasion, and metastasis of hepatoma cells by altering tumor microenvironment, promoting neovascularization, and regulating epithelial-mesenchymal transition. Exosomes can regulate hepatocellular carcinoma and inhibit the growth and metastasis of hepatoma cells by regulating a variety of physiological and pathological processes, thus playing an important role in clinical diagnosis and treatment. It is pointed out that exosomes may become an effective antitumor treatment method through immune regulation and remodeling of tumor microcirculation.

Craniopharyngioma ; Humans ; Parapharyngeal Space ; Pharyngeal Neoplasms ; Pituitary Neoplasms