Lipid metabolism reprogramming is a hallmark metabolic feature in the pathogenesis and progression of colorectal cancer(CRC), primarily involved in the aberrant activation of de novo lipogenesis(DNL), disruption of cholesterol homeostasis, enhancement of fatty acid oxidation(FAO), and resistance to ferroptosis. All of these pathological processes mediate malignant progression and multidrug resistance of tumors. According to TCM, the pathological foundation of CRC lies in the interlocking of "dampness, heat, stasis, and deficiency", which exhibits an intrinsic biological consistency with ectopic lipid accumulation, metabolic pathway perturbations, and the imbalance of microenvironmental homeostasis. This article systematically reviewed the molecular regulatory networks of lipid metabolism reprogramming in CRC, emphasizing the molecular mechanisms by which active components of TCM intervene in lipid metabolism homeostasis by modulating core targets such as sterol regulatory element-binding proteins(SREBPs), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), and carnitine palmitoyltransferase 1(CPT1). Pharmacological studies demonstrate that active ingredients, including berberine, tanshinone Ⅱ_A, ginsenosides, curcumin, and hesperetin, elucidate the molecular scientific connotations of therapeutic principles, such as "clearing heat, drying dampness, promoting blood circulation, removing toxic substances, strengthening body resistance to consolidate the constitution, and disinhibiting dampness to transform phlegm", by intervening in lipid synthesis, ferroptosis, energy metabolism, and inflammatory signaling pathways. Furthermore, the clinical application potential of active components of TCM in reversing chemotherapy resistance, synergizing with immunotherapy, and the chemoprevention of adenomas is systematically evaluated. By providing an in-depth analysis of the biological correlations between TCM syndrome theory and lipid metabolism regulation, this review aims to offer a pharmacological basis for the development of TCM candidates targeting metabolic remodeling and for the optimization of diagnostic and therapeutic protocols of integrated Chinese and western medicine.

Hepatocellular carcinoma, hereinafter referred to as liver cancer, is a prevalent malignant tumor of the digestive system in China, with persistently high incidence and mortality rates. Currently, clinical management of liver cancer faces significant challenges, including elevated postoperative recurrence rates and drug resistance in advanced-stage patients, underscoring an urgent demand for the development of novel preventive and therapeutic strategies and agents. TCM with its distinct advantages of multi-efficacy, multi-targeted action, and multi-mechanism effect, has long been employed in anti-hepatocellular carcinoma therapy. As the limitations of western medicine in liver cancer treatment become increasingly prominent, active components of TCM monomers and their compound formulas have garnered extensive attention. A growing body of research indicates that flavonoids from TCM possess notable anti-hepatocellular carcinoma effects. Quercetin, a natural flavonoid, is widely distributed in various TCM herbs, including Artemisiae Scopariae Herba, Ploygoni Cuspidati Rhizoma et Radlx, Moutan Cortex, Plantaginis Semen, Spreading Hedyotis Herba, Eucommiae Folium, Ginkgo Folium, and Mori Folium. Quercetin exhibits unique advantages and promising application prospects due to its diverse pharmacological activities, such as antioxidant, anti-inflammatory, immunomodulatory, hepatoprotective, and anti-tumor effects. Focusing on the key molecular networks and the tumor microenvironment involved in hepatocarcinogenesis and progression, this review comprehensively synthesized the mechanisms underlying the anti-hepatocellular carcinoma effects of quercetin, encompassing its regulation of hepatocellular carcinoma cell proliferation and apoptosis, modulation of signaling pathways, inhibition of cell migration and invasion, as well as its regulatory roles in tumor metabolism, the microenvironment, and drug resistance. Additionally, the progress in the clinical application of quercetin was systematically summarized. This review aims to provide a theoretical foundation for the utilization of quercetin in the clinical treatment of liver cancer, facilitate the optimization of its therapeutic regimens, and offer a relevant basis for future in-depth research and clinical translation.

This study investigated the effect of gypenosides(GPs) on anoikis resistance(AR) in human triple-negative breast cancer(TNBC) MDA-MB-231 cells and explored the underlying mechanism involving the transforming growth factor β1(TGF-β1)/forkhead box protein P3(Foxp3)/retinoic acid-related orphan receptor γt(RORγt) signaling axis. An anoikis model was established using poly-HEMA coated plates, and cells were divided into normal adherent, anoikis model, GPs(100 μg·mL~(-1)), TGF-β1 inhibitor(LY, 10 μmol·L~(-1)), and GPs + LY groups. Cell viability, apoptosis, invasion and migration were assessed by CCK-8 assay, flow cytometry with AnnexinV-FITC/PI staining, and Transwell assay, respectively. The mRNA and protein expression levels of TGF-β1, Foxp3, RORγt, B-cell Lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), cysteine aspartic acid specific protease-3(caspase-3), and Smad2/3 phosphorylation levels were measured by quantitative real-time PCR(qRT-PCR) and Western blot. Nuclear localization of Foxp3 and RORγt was examined by immunofluorescence staining. A breast cancer bone metastasis model was established in nude mice by tail vein injection. After intervention, the circulating tumor cells(CTCs) in peripheral blood and the formation of bone metastasis foci were evaluated. The mRNA and protein expression levels of TGF-β1, Foxp3, RORγt in bone metastasis foci of each nude mouse breast cancer bone metastasis model were detected using qRT-PCR and Western blot. In vitro experimental results showed that GPs inhibited the viability of human breast cancer MDA-MB-231 cells, promoted apoptosis, and reduced the number of invasive and migratory cells. GPs downregulated the mRNA and protein expression levels of TGF-β1, Foxp3, and Bcl-2, upregulated the expression levels of RORγt, Bax, and caspase-3, and inhibited Smad2/3 phosphorylation. Furthermore, GPs decreased Foxp3 nuclear accumulation and enhanced RORγt nuclear localization, and exhibited synergistic effects with LY. In vivo experimental results indicated that GPs reduced the number of CTCs in peripheral blood and the number of bone metastases in nude mice. The changes in key mRNA and protein expression levels of the TGF-β1/Foxp3/RORγt signaling axis in bone tissue were consistent with those observed in in vitro experiments. In summary, GPs inhibit the TGF-β1/Smad signaling axis, downregulate Foxp3 expression and its nuclear localization, thereby relieving its negative regulation on RORγt. This leads to upregulation of pro-apoptotic proteins Bax and caspase-3, downregulation of anti-apoptotic protein Bcl-2, disruption of anoikis resistance, and reduction of metastatic potential in MDA-MB-231 cells. These findings reveal that the TGF-β1/Foxp3/RORγt signaling axis is a key target of GPs against metastatic triple-negative breast cancer(TNBC), providing new experimental evidence and clinical strategies for natural product-based therapy in TNBC.

The incidence and mortality of malignant tumors remain persistently high, while current clinical chemotherapeutic agents are often limited by significant drug resistance and adverse reactions. Consequently, small-molecule compounds derived from traditional Chinese medicine(TCM) have emerged as a focus in anti-tumor research owing to their advantages of multi-targeting action and low toxicity. As the core active component of Glycyrrhiza uralensis, glycyrrhizic acid(GA) is an oleanane-type pentacyclic triterpenoid saponin, constituting 5%-11% of the total content of G. uralensis. Its anti-tumor activity has been validated across various tumor systems, with mechanisms of action encompassing key processes such as cell cycle arrest, induction of tumor cell apoptosis, inhibition of tumor angiogenesis, blockage of invasion and metastasis, regulation of the tumor immune microenvironment(TIME), and alleviation of chronic inflammation. In terms of its therapeutic value, the combination of glycyrrhizic acid with other agents, such as tanshinone Ⅱ_A(Chinese medicine) or cisplatin(conventional chemotherapy) can achieve enhanced efficacy, reduced toxicity, targeted delivery, and reversal of drug resistance. This positions GA as possessing dual values, functioning both as a therapeutic agent and as a drug delivery carrier. This review systematically summarized the anti-tumor pharmacological activities, mechanisms, combined medication potential, and safety profiles of GA. It elaborated on the network mechanism of core regulatory hubs, analyzed the limitations of current research, and proposed targeted strategies for clinical translation. This work aims to provide a reference for the transition of GA from fundamental research to clinical application, while also offering a paradigm for the development of anti-tumor small-molecule compounds from TCM.

The programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1) signaling pathway is a key mechanism underlying tumor immune escape. It suppresses anti-tumor immune responses through various mechanisms, including T-cell exhaustion, expanding regulatory T cells(Tregs), promoting M2 macrophage polarization, inhibiting natural killer(NK) cell function, and disrupting the balance of glycolysis/fatty acid oxidation metabolism. Immune checkpoint inhibitors(ICIs) targeting the PD-1/PD-L1 pathway have shown significant efficacy in the treatment of solid tumors. However, approximately 60%-70% of patients do not benefit due to drug resistance or immune-related adverse events(irAEs), and the heterogeneity of the tumor microenvironment(TME) further limits their effectiveness. Single-target blockade strategies are insufficient to comprehensively reverse immune escape, which highlights the urgent need for multidimensional interventions. Numerous studies have shown that various TCM active ingredients and compounds can regulate the PD-1/PD-L1 pathway through multiple targets to enhance immune responses. Their mechanisms involve modulating key signaling pathways, mediating epigenetic changes, reprogramming cellular metabolism, and reshaping the immunosuppressive microenvironment. Therefore, this review, focusing on the PD-1/PD-L1 pathway, systematically summarized the research progress on TCM active ingredients, compounds, and patent medicines in cancer immunotherapy. It aims to analyze their immunoregulatory networks, providing theoretical insights and translational directions for optimizing cancer immunotherapy strategies.

Bufonis Venenum, the dried secretory product from the postauricular and cutaneous glands of Bufonidae, exerts antitumor activity primarily through bufadienolides. This review systematically summarizes the molecular mechanisms of key bufadienolides, including cinobufagin, bufalin, resibufogenin, bufotalin, arenobufagin, gamabufotalin, and cinobufotalin, in the treatment of malignant tumors over the past five years. Current evidence demonstrates that these compounds exert broad-spectrum antitumor effects through multi-target and multi-pathway modulation. In inhibiting tumor cell proliferation, these compounds primarily regulate signaling pathways such as mitogen-activated protein kinase(MAPK), phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT), and signal transducer and activator of transcription 3(STAT3). In inducing cell death, they eliminate malignant cells through multiple modalities including mitochondrion-mediated apoptosis, ferroptosis, and autophagy. In suppressing invasion and metastasis, they modulate epithelial-mesenchymal transition(EMT), matrix metalloproteinase(MMP) expression, and macrophage polarization within the tumor microenvironment. Furthermore, these compounds inhibit angiogenesis, enhance chemosensitivity, activate antitumor immune responses, and regulate epigenetic modifications. Combination therapy studies reveal that bufadienolides exhibit synergistic efficacy when being combined with clinical chemotherapeutic agents, and TCM preparations containing these compounds demonstrate antitumor properties through multi-target regulation. This review elucidates the antitumor molecular mechanisms of bufadienolides, aiming to provide a theoretical basis for further mechanism investigation and clinical translation.

This study aimed to investigate the mechanism of total flavonoids from Smilacis Glabrae Rhizoma(SGF) against obesity-associated colorectal cancer(CRC) via regulation of fatty acid oxidation(FAO). In vivo, syngeneic subcutaneous and orthotopic xenograft models of CRC cells MC38 were established in obese mice induced by high fat diet(HFD), which was followed by the administration with SGF. The tumor volume and tumor weight were measured in the CRC subcutaneous model. The growth of CRC orthotopic tumors was monitored by a small animal in vivo imaging system. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in tumors and peritumoral adipose tissues. Immunohistochemistry, TdT-mediated dUTP nick end labeling(TUNEL), and oil red O staining were separately conducted to detect Ki67 expression, apoptosis, and lipid accumulation in tumors. Western blot was used to detect the phosphorylation levels of adenosine monophosphate-activated protein kinase(AMPK) and acetyl-CoA carboxylase(ACC), as well as the expression of FAO-related proteins and cell death-related proteins in tumor tissues. In vitro, MC38 cells cultured under low-glucose and high-oleic acid conditions were taken as the research object and treated with varying concentrations of SGF for 48 h. Apoptosis rates were assessed by flow cytometry, and the expression of FAO-related and cell death-related proteins was analyzed by Western blot. Further, the prolyl hydroxylase domain-containing protein 3(PHD3) expression was subjected to RNA interference(RNAi), and the viability and apoptosis of PHD3-knockdown MC38 cells following SGF treatment were assessed by MTT assay and flow cytometry, respectively. The results showed that both high and low doses of SGF significantly inhibited tumor growth in two obese mouse xenograft models. The SGF-treated groups exhibited extensive, scattered necrotic areas within the tumor tissue, with marked destruction of tissue structure. Compared with the HFD group, the SGF-treated groups showed a significant reduction in the rate of Ki67-positive cells and a significant increase in the proportion of TUNEL-staining-positive apoptotic cells. In obese mice, subcutaneous tumors showed significantly enhanced oil red O staining, with large lipid droplets visible. The SGF-treated groups markedly reduced lipid deposition. In both models, peritumoral adipocytes were significantly enlarged after SGF treatment. The tumor tissues of obese mice exhibited significantly increased expression of FAO-related proteins cluster of differentiation 36(CD36), carnitine palmitoyltransferase 1(CPT1), and acyl-CoA dehydrogenase long chain(ACADL), as well as elevated adenosine triphosphate(ATP) content. The phosphorylation levels of upstream regulatory proteins AMPK and ACC were significantly increased, while the expression of the energy switch protein PHD3 was significantly decreased. SGF significantly reduced the protein expression of CD36, CPT1, and ACADL, decreased ATP content, inhibited AMPK and ACC phosphorylation, and increased PHD3 protein levels. This was accompanied by a significant increase in the apoptotic protein cysteine-dependent aspartate-specific protease-3(caspase-3) and significant decreases in the anti-apoptotic protein B-cell lymphoma-2(Bcl-2) and the cell cycle protein cyclin D1. In MC38 cells cultured under low-glucose and high-oleic acid conditions, SGF significantly induced apoptosis and inhibited lipid uptake. FAO-related protein expression was significantly suppressed. Caspase-3 expression was significantly increased, while Bcl-2 and cyclin D1 expression was significantly decreased. PHD3 expression was significantly elevated. In MC38 cells transfected with siPHD3, the inhibitory effect of SGF on cell viability and its pro-apoptotic effect were both significantly enhanced. In summary, SGF effectively reduces lipid transfer between adipose tissue and tumors under obese conditions, regulates the AMPK/ACC signaling pathway, and targetedly inhibits tumor FAO, thereby exerting potent antitumor effects against obesity-associated CRC.

Right ventricular-pulmonary artery (RV-PA) uncoupling, expressed as the tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/PAPs) ratio, is a negative prognostic indicator in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). This study aims to investigate the association between the echocardiographically measured TAPSE/PAPs ratio and invasively determined pulmonary hypertension (PH) subtypes in this population, with the goal of identifying patients at higher risk.

This study is a retrospective analysis of 667 patients who underwent TAVR for native severe symptomatic AS at our center between January 2015 and December 2022. All patients underwent a comprehensive transthoracic echocardiographic evaluation and right heart catheterization prior to the procedure. PH was classified into: no PH, isolated post-capillary PH (IpcPH), and combined pre- and post-capillary PH (CoPH). Follow-up time was defined as the time from the procedure to the last documented contact with the patient (alive) or to the time of documented death. All-cause mortality at two years was the primary endpoint.

eTAPSE/PAPs showed a moderately positive correlation with pulmonary vascular resistance (Spearman's Rho = 0.52; p = 0.025) and was associated with CoPH (odds ratio 1.29, 95% confidence interval 1.10-1.30). ROC curve analysis showed that eTAPSE/PAPs discriminated presence of CoPH with an AUC of 0.740. The optimal cut-off value was 0.29 mm/mmHg (sensitivity 72%, specificity 60%). During follow-up, 157 deaths were recorded. Kaplan-Meier curves showed a significant difference in overall mortality at 2 years when patients were stratified according to eTPASE/PAPs ratio value of 0.29 (log rank = 4.94, p = 0.026).

The eTAPSE/PAPs ratio identifies patients with symptomatic AS undergoing TAVR with higher risk of CoPH. These patients can benefit from an RHC to refine pre-operative risk assessment.

This study employed evidence mapping to systematically summarize clinical research on TCM for treating chronic obstructive pulmonary disease(COPD) in recent five years, aiming to characterize the distribution characteristics and methodological quality of the evidence, thereby providing an evidence-based reference for optimizing clinical decision-making and guiding future research directions. A computerized search was conducted in CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and the Cochrane Library for literature on TCM for COPD, with the search period spanning from January 2020 to October 2025. The focus was on both the stable phase and acute exacerbation of COPD. Evidence characteristics were presented comparatively using a combination of text and charts. A total of 962 articles were ultimately included. Publication volume in this field has shown a fluctuating downward trend in recent five years. The predominant study type was randomized controlled trial(RCT), with sample sizes in interventional studies mostly concentrated between 61 and 120 cases. The treatment regimen in experimental groups primarily involved TCM combined with western medicine. The intervention durations were mainly 3 months for stable phase of COPD and 2 weeks for acute exacerbation of COPD, involving 50 and 48 classical formulas, and 48 and 32 Chinese proprietary medicines, respectively. The primary TCM syndrome distributions were lung-kidney deficiency syndrome for stable phase of COPD and phlegm-heat obstruction in the lung for acute exacerbation of COPD. Outcome indicators covered categories such as lung function indices, clinical efficacy evaluations, serological markers, and TCM syndrome scores. Most RCTs exhibited issues such as unclear allocation concealment and insufficient application of blinding. The overall quality of systematic reviews was relatively low. TCM demonstrates unique advantages in the treatment of COPD. However, the overall quality of the existing relevant literature is variable and requires improvement. Future research needs to further standardize study designs to enhance the scientific rigor and methodological quality of clinical studies and improve the methodological standards of systematic reviews. This will provide higher-level evidence-based medical evidence for TCM in treating COPD, supporting its standardized clinical application and promotion.

This study aimed to investigate the therapeutic effect of Maiwei Yangfei Decoction(MWYF) on pulmonary fibrosis and its underlying mechanisms. Seventy-two C57BL/6J mice were randomly divided into a blank group, a model group, a low-dose MWYF group, a medium-dose MWYF group, a high-dose MWYF group, and a pirfenidone group. A pulmonary fibrosis model was established by intratracheal instillation of bleomycin. The blank group and the model group were administered double-distilled water daily, while the MWYF groups received corresponding concentrations of MWYF, and the positive control group was given pirfenidone. The severity of pulmonary fibrosis was assessed through Micro-CT scans, histopathological staining of lung tissues, and the expression of collagen Ⅰ and collagen Ⅲ. Network pharmacology combined with transcriptomics analysis was used to explore the anti-fibrotic mechanism of MWYF, which was further validated through in vivo experiments. The results showed that MWYF reduced pulmonary fibrotic lesions, improved inflammation and fibrosis scores, and downregulated the protein expression of collagen Ⅰ and collagen Ⅲ. Network pharmacology and transcriptomics suggested that the anti-fibrotic effect of MWYF was associated with cellular senescence and the p53 signaling pathway. In vivo experiments demonstrated that MWYF significantly reduced senescence-associated β-galactosidase(SA-β-Gal) activity in lung tissues, downregulated the expression of key senescence-related proteins p53, p21, and p16, and decreased cellular senescence, with the high-dose group showing the most pronounced effects. Collectively, these findings demonstrated that MWYF attenuated bleomycin-induced pulmonary fibrosis in mice, likely by suppressing cellular senescence via modulation of the p53 signaling pathway.