Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease around the world, and pharmacotherapy is the foremost treatment method currently. In recent decades, with the rapid development of bronchoscopic interventional therapy, endoscopic physical ablation technology presents a therapeutic effect in treating COPD, with few treatment-related side effects, showing excellent application prospects in treating COPD. Since ablation techniques in this field are emerging technologies with low patient acceptance, they are not widely used in the clinical treatment of COPD. This article reviews the development process of physical ablation techniques. Moreover, their current application status and the prospects in the field of COPD treatment are also summarized and analyzed. We hope to promote the application of physical ablation in the clinical treatment of COPD and provide practical references and a theoretical basis for the clinical treatment of COPD.

Neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), cerebral ischemia, and multiple sclerosis (MS), impose an escalating global health burden and remain largely incurable. These disorders arise from multifactorial and interconnected pathological processes, such as chronic neuroinflammation, oxidative stress, protein misfolding and aggregation, demyelination, and neurovascular dysfunction. Despite substantial advances in elucidating disease-associated molecular mechanisms, current therapeutic strategies are predominantly symptomatic and fail to effectively halt or reverse disease progression. This limitation highlights the urgent need to identify endogenous regulatory molecules capable of coordinating neuronal survival, synaptic maintenance, inflammatory control, and tissue repair within the central nervous system (CNS). Pleiotrophin (PTN) is a heparin-binding, growth-associated cytokine that has emerged as a key regulator of neural development, plasticity, and regeneration. Structurally, PTN contains multiple high-affinity heparin-binding domains that facilitate interactions with extracellular matrix components and cell surface proteoglycans, enabling spatially restricted and context-dependent signaling. Through these molecular properties, PTN functions as a multifunctional organizer of neural growth, plasticity, and tissue remodeling across developmental and adult stages. Its diverse biological effects are executed through a multi-receptor signaling system that integrates extracellular cues with intracellular programs governing cellular survival, migration, and differentiation. Notably, PTN displays a highly dynamic and cell type-specific expression pattern in the central nervous system, being enriched in neural progenitor cells during development and later restricted to discrete neuronal populations, neural stem cells, and non-neuronal niche cells—including astrocytes, pericytes, and vascular endothelial cells—which serve as critical sources of PTN under physiological and pathological conditions. PTN expression is tightly regulated during development and exhibits pronounced plasticity in response to pathological stimuli. Under physiological conditions, PTN is transiently expressed during critical windows of neural growth and synaptogenesis, supporting neuron-glia interactions and myelin formation. In contrast, in pathological contexts such as amyloid β-protein (Aβ) accumulation in AD, dopaminergic neuron degeneration in PD, demyelination in MS, and ischemic brain injury, PTN expression is frequently dysregulated, suggesting an active role in disease-associated remodeling rather than a passive bystander effect. Importantly, accumulating evidence indicates that PTN exerts a dual and context-dependent influence on neurological disorders. On the one hand, aberrant PTN signaling may contribute to maladaptive responses, including sustained glial activation, dysregulated neuroinflammation, extracellular matrix remodeling, and enhanced Aβ deposition. On the other hand, PTN displays robust neuroprotective and reparative functions by promoting neuronal survival, enhancing oligodendrocyte maturation and remyelination, and stimulating post-injury angiogenesis, thereby facilitating tissue repair and functional recovery. At the mechanistic level, PTN signaling is characterized by extensive cross-talk among receptor-dependent pathways. Activation of anaplastic lymphoma kinase (ALK) triggers canonical PI3K-AKT-mTOR and MAPK cascades that support neuronal survival and axonal integrity. PTN binding to protein tyrosine phosphatase receptor type Z1 (PTPRZ1) induces conformational inhibition of its phosphatase activity, resulting in increased phosphorylation of downstream effectors such as β-catenin, Fyn, and Src, which regulate neuronal migration and synaptic stabilization. Syndecan-3 (SDC3) functions as both a co-receptor and an independent signaling mediator by capturing extracellular PTN, amplifying ALK- and PTPRZ1-dependent signaling, and directly modulating cytoskeletal dynamics through PKC and ERK pathways. In parallel, PTN interaction with αVβ3 integrin contributes to remodeling of the neurovascular niche, linking angiogenesis with neurogenesis and neural repair. From a translational perspective, therapeutic strategies targeting PTN can be broadly classified into 3 categories: direct enhancement of PTN signaling through exogenous protein supplementation or gene therapy-mediated upregulation, pharmacological modulation of PTN-associated receptor pathways and downstream signaling nodes, and exploitation of PTN as a dynamic biomarker to inform disease stratification and therapeutic responsiveness. These complementary approaches underscore the growing interest in PTN-centered interventions across a spectrum of neurological disorders. In summary, PTN functions not merely as a classical trophic factor but as a central signaling hub integrating inflammatory regulation, neural regeneration, and vascular remodeling within the CNS. This review aims to synthesize current insights into PTN’s molecular architecture, multi-receptor signaling mechanisms, and disease-specific functions, and to highlight emerging therapeutic strategies targeting PTN. By conceptualizing PTN as a dynamic modulator of neuronal resilience rather than a static biomarker, we propose that precise modulation of PTN signaling may offer promising avenues for therapeutic development in neurodegenerative and neuroinflammatory diseases.

Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang （WDD） on mice with ischemic heart disease （IHD） presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group， WDD low-dose group （WDD-L）， WDD medium-dose group （WDD-M）， WDD high-dose group （WDD-H）， and atorvastatin calcium tablet group， with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91， 17.81， 35.62 g·kg^-1， and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg^-1， twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration， the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin （HE） staining. Serum N-terminal pro-B-type natriuretic peptide （pro-BNP） content was measured by enzyme-linked immunosorbent assay （ELISA）. Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL） were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group， model serum group， WDD-L drug-containing serum group， WDD-M drug-containing serum group， and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group， the model group showed a significantly increased cardiac index （P0.01）， significantly decreased fractional shortening （FS） （P0.01）， and significantly increased left ventricular end-diastolic internal diameter （LVDD） and left ventricular end-systolic internal diameter （LVDS） （P0.01）. Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated （P0.01）， and whole-blood viscosity （BV） at high， medium， and low shear rates was significantly increased （P0.01）. Compared with the model group， the WDD groups showed significantly reduced cardiac index （P0.05， P0.01）， significantly increased FS （P0.05， P0.01）， significantly decreased LVDD and LVDS （P0.01）， markedly improved cardiomyocyte morphology， significantly reduced inflammatory infiltration， significantly decreased serum pro-BNP levels （P0.01）， and significantly decreased BV at high， medium， and low shear rates （P0.01）， with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group， TC， TG， and LDL levels were significantly increased in the model group （P0.05， P0.01）， while HDL levels were significantly decreased （P0.05）. After WDD-H treatment， TC， TG， and LDL levels were significantly reduced and HDL levels were significantly increased in mice （P0.05， P0.01）. Compared with the sham-operation group， classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group （P0.01）， whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased （P0.01）. After WDD administration， all circulating monocyte subsets in blood and bone marrow were significantly alleviated （P0.05， P0.01）， with the WDD-M group showing the optimal effect. In vitro， compared with the blank group， CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group （P0.01）， and CD36 expression was significantly upregulated on RAW264.7 cells （P0.01）. Compared with the model serum group， all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation （P0.01）. WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines （P0.05， P0.01）， with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.

ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang （WDD） on mice with ischemic heart disease （IHD） presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group， WDD low-dose group （WDD-L）， WDD medium-dose group （WDD-M）， WDD high-dose group （WDD-H）， and atorvastatin calcium tablet group， with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91， 17.81， 35.62 g·kg^-1， and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg^-1， twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration， the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin （HE） staining. Serum N-terminal pro-B-type natriuretic peptide （pro-BNP） content was measured by enzyme-linked immunosorbent assay （ELISA）. Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL） were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group， model serum group， WDD-L drug-containing serum group， WDD-M drug-containing serum group， and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group， the model group showed a significantly increased cardiac index （P<0.01）， significantly decreased fractional shortening （FS） （P<0.01）， and significantly increased left ventricular end-diastolic internal diameter （LVDD） and left ventricular end-systolic internal diameter （LVDS） （P<0.01）. Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated （P<0.01）， and whole-blood viscosity （BV） at high， medium， and low shear rates was significantly increased （P<0.01）. Compared with the model group， the WDD groups showed significantly reduced cardiac index （P<0.05， P<0.01）， significantly increased FS （P<0.05， P<0.01）， significantly decreased LVDD and LVDS （P<0.01）， markedly improved cardiomyocyte morphology， significantly reduced inflammatory infiltration， significantly decreased serum pro-BNP levels （P<0.01）， and significantly decreased BV at high， medium， and low shear rates （P<0.01）， with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group， TC， TG， and LDL levels were significantly increased in the model group （P<0.05， P<0.01）， while HDL levels were significantly decreased （P<0.05）. After WDD-H treatment， TC， TG， and LDL levels were significantly reduced and HDL levels were significantly increased in mice （P<0.05， P<0.01）. Compared with the sham-operation group， classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group （P<0.01）， whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased （P<0.01）. After WDD administration， all circulating monocyte subsets in blood and bone marrow were significantly alleviated （P<0.05， P<0.01）， with the WDD-M group showing the optimal effect. In vitro， compared with the blank group， CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group （P<0.01）， and CD36 expression was significantly upregulated on RAW264.7 cells （P<0.01）. Compared with the model serum group， all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation （P<0.01）. WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines （P<0.05， P<0.01）， with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.

Intervertebral disc degeneration (IVDD) is the predominant pathological contributor to chronic low back pain, a pervasive musculoskeletal condition affecting over 630 million people globally and imposing tremendous socioeconomic and public health burdens. The etiopathogenesis of IVDD is remarkably complex and multifactorial, involving intricate crosstalk among chronic inflammatory responses, extracellular matrix (ECM) catabolism, cellular senescence, aberrant programmed cell death (including apoptosis, pyroptosis, and ferroptosis), mitochondrial dysfunction, and oxidative damage. Compelling evidence indicates that the inflammatory microenvironment acts as a decisive driving force throughout the entire degenerative course of IVDD. Among the diverse inflammatory mediators, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) serve as core pro-inflammatory cytokines that initiate and perpetuate the degenerative cascade. These two pivotal cytokines collectively activate an array of canonical intracellular signaling pathways, including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) cascade. Such interconnected signaling networks trigger a self-reinforcing positive feedback loop, which exacerbates inflammatory reactions, disrupts the anabolic-catabolic homeostasis of the ECM, promotes oxidative stress and mitochondrial injury, induces multiple forms of disc cell death, and ultimately leads to progressive structural collapse and functional deterioration of the intervertebral disc. Conventional therapeutic strategies, dominated by nonsteroidal anti-inflammatory drugs and surgical interventions, are limited by systemic adverse reactions, suboptimal long-term efficacy, and the risk of adjacent segment degeneration. In contrast, traditional Chinese medicine (TCM) exhibits prominent advantages in the prevention and treatment of IVDD by virtue of its holistic regulation, syndrome differentiation, and multi-component, multi-target, multi-pathway pharmacological properties. This review systematically elucidates the molecular mechanisms by which inflammation-associated signaling pathways modulate disc cell fate and ECM metabolic homeostasis, and comprehensively summarizes the experimental progress over the past five years on TCM monomers and compound formulas for intervening in IVDD. Accumulating studies have confirmed that numerous natural active ingredients isolated from herbal medicines (ferulic acid, mangiferin, paeonol, astragaloside IV) and representative TCM compound prescriptions (Bushen Huoxue Formula, Shensuitongzhi Formula, Fuzi Decoction) exert synergistic protective effects by coordinately targeting core signaling hubs. These TCM agents demonstrate potent anti-inflammatory, antioxidant, anti-apoptotic, anti-pyroptotic, anti-ferroptotic, ECM-protective, and autophagy-regulating bioactivities, thereby effectively decelerating the pathological progression of IVDD. Despite remarkable progress, current investigations are still confronted by several critical limitations. Most studies are restricted to validating the regulatory effects of single TCM components on individual signaling pathways, leaving the systematic, dynamic, and synergistic mechanisms of TCM compound formulas within multi-pathway regulatory networks largely unexplored. Furthermore, clinical translation of TCM is severely hampered by the lack of efficient targeted drug delivery systems, unclear pharmacokinetic profiles, suboptimal local bioavailability, and incomplete long-term safety assessments. Therefore, future research should adopt an interdisciplinary paradigm integrating multi-omics technologies, artificial intelligence, organoid models, and organ-on-chip systems to systematically decipher the scientific basis of TCM against IVDD. Concurrently, the development of intelligent, site-specific delivery systems (hydrogels, nanoparticles, exosome-based carriers) is urgently needed to enhance the local accumulation and sustained release of TCM ingredients. By deepening mechanistic exploration and accelerating translational research, TCM is expected to evolve into safe, effective, and personalized precision therapeutic regimens for IVDD, offering novel and reliable solutions for the clinical management of chronic low back pain.

Intervertebral disc degeneration (IVDD) is the predominant pathological contributor to chronic low back pain, a pervasive musculoskeletal condition affecting over 630 million people globally and imposing tremendous socioeconomic and public health burdens. The etiopathogenesis of IVDD is remarkably complex and multifactorial, involving intricate crosstalk among chronic inflammatory responses, extracellular matrix (ECM) catabolism, cellular senescence, aberrant programmed cell death (including apoptosis, pyroptosis, and ferroptosis), mitochondrial dysfunction, and oxidative damage. Compelling evidence indicates that the inflammatory microenvironment acts as a decisive driving force throughout the entire degenerative course of IVDD. Among the diverse inflammatory mediators, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) serve as core pro-inflammatory cytokines that initiate and perpetuate the degenerative cascade. These two pivotal cytokines collectively activate an array of canonical intracellular signaling pathways, including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) cascade. Such interconnected signaling networks trigger a self-reinforcing positive feedback loop, which exacerbates inflammatory reactions, disrupts the anabolic-catabolic homeostasis of the ECM, promotes oxidative stress and mitochondrial injury, induces multiple forms of disc cell death, and ultimately leads to progressive structural collapse and functional deterioration of the intervertebral disc. Conventional therapeutic strategies, dominated by nonsteroidal anti-inflammatory drugs and surgical interventions, are limited by systemic adverse reactions, suboptimal long-term efficacy, and the risk of adjacent segment degeneration. In contrast, traditional Chinese medicine (TCM) exhibits prominent advantages in the prevention and treatment of IVDD by virtue of its holistic regulation, syndrome differentiation, and multi-component, multi-target, multi-pathway pharmacological properties. This review systematically elucidates the molecular mechanisms by which inflammation-associated signaling pathways modulate disc cell fate and ECM metabolic homeostasis, and comprehensively summarizes the experimental progress over the past five years on TCM monomers and compound formulas for intervening in IVDD. Accumulating studies have confirmed that numerous natural active ingredients isolated from herbal medicines (ferulic acid, mangiferin, paeonol, astragaloside IV) and representative TCM compound prescriptions (Bushen Huoxue Formula, Shensuitongzhi Formula, Fuzi Decoction) exert synergistic protective effects by coordinately targeting core signaling hubs. These TCM agents demonstrate potent anti-inflammatory, antioxidant, anti-apoptotic, anti-pyroptotic, anti-ferroptotic, ECM-protective, and autophagy-regulating bioactivities, thereby effectively decelerating the pathological progression of IVDD. Despite remarkable progress, current investigations are still confronted by several critical limitations. Most studies are restricted to validating the regulatory effects of single TCM components on individual signaling pathways, leaving the systematic, dynamic, and synergistic mechanisms of TCM compound formulas within multi-pathway regulatory networks largely unexplored. Furthermore, clinical translation of TCM is severely hampered by the lack of efficient targeted drug delivery systems, unclear pharmacokinetic profiles, suboptimal local bioavailability, and incomplete long-term safety assessments. Therefore, future research should adopt an interdisciplinary paradigm integrating multi-omics technologies, artificial intelligence, organoid models, and organ-on-chip systems to systematically decipher the scientific basis of TCM against IVDD. Concurrently, the development of intelligent, site-specific delivery systems (hydrogels, nanoparticles, exosome-based carriers) is urgently needed to enhance the local accumulation and sustained release of TCM ingredients. By deepening mechanistic exploration and accelerating translational research, TCM is expected to evolve into safe, effective, and personalized precision therapeutic regimens for IVDD, offering novel and reliable solutions for the clinical management of chronic low back pain.

BACKGROUND:The regulation of intestinal flora by exercise is closely related to human health,but intestinal flora involves many factors.Existing studies have lacked consistent evidence on the effect of exercise on the intestinal flora of college students. OBJECTIVE:To explore the effects of exercise on intestinal flora diversity and species composition of college students. METHODS:Through systematic search of PubMed,Web of Science,Embase,Medline,Cochrane Library,CNKI,WanFang Database and VIP database,eight empirical studies were selected and included,and semi-quantitative analysis was performed on them. RESULTS AND CONCLUSION:In terms of the species diversity of the intestinal flora,both high-intensity interval training and Tai Chi exercise significantly enhance the species diversity of intestinal flora in college students,while aerobic exercise does not have a significant effect on the enhancement of intestinal flora diversity in college students.In terms of the species composition of the intestinal flora,all three exercise modalities significantly alter the compositional structure of the intestinal flora in college students,which can increase the abundance of beneficial bacteria such as Ruminalococcus,Faecalis prevotelli,Blautia,and decrease the abundance of harmful bacteria such as Escherichia spp.Compared with high-intensity interval training,aerobic and Tai Chi exercise causes more elevated abundance of beneficial bacteria.In addition to changes in intestinal flora characteristics,exercise improves body composition,cardiorespiratory function,and executive function in college students,and these health benefits are closely linked to exercise-induced changes in intestinal flora that can produce health benefits for the body through metabolic regulation,barrier function,and neuromodulation.Although studies have confirmed the association between exercise and intestinal flora,the mechanism by which exercise affects intestinal flora has not yet been clarified,and at the same time,localizing the flora related to the host health is the key to targeting intestinal flora as a therapeutic target in the future,all of which are worthy of further attention and investigation.

BACKGROUND:Steroid-induced femoral head necrosis is mostly caused by long-term and extensive use of hormones,but its specific pathogenesis is not yet clear and needs further study. OBJECTIVE:To screen out the differential miRNAs in osteoclast exosomes after the intervention of Panax notoginseng saponins,and on this basis,to further construct an osteogenic-related ferroptosis regulatory network to explore the potential mechanism and research direction of steroid-induced osteonecrosis of the femoral head. METHODS:MTT assay was used to detect the toxic effects of different concentrations of dexamethasone and different mass concentrations of Panax notoginseng saponins on Raw264.7 cell line.Tartrate resistant acid phosphatase staining and TUNEL assay were used to detect the effects of Panax notoginseng saponins on osteoclast inhibition and apoptosis.Exosomes were extracted from cultured osteoclasts with Panax notoginseng saponins intervention.Exosomes from different groups were sequenced to identify differentially expressed miRNAs.CytoScape 3.9.1 was used to construct and visualize the regulatory network between differentially expressed miRNAs and mRNAs.Candidate mRNAs were screened by GO analysis and KEGG analysis.Finally,the differential genes related to ferroptosis were screened out,and the regulatory network of ferroptosis-related genes was constructed. RESULTS AND CONCLUSION:(1)The concentration of dexamethasone(0.1 μmol/L)and Panax notoginseng saponins(1 736.85 μg/mL)suitable for intervention of Raw264.7 cells was determined by MTT assay.(2)Panax notoginseng saponins had an inhibitory effect on osteoclasts and could promote their apoptosis.(3)Totally 20 differentially expressed miRNAs were identified from osteoclast-derived exosome samples,and 11 differentially expressed miRNAs related to osteogenesis were predicted by target mRNAs.The regulatory networks of 4 up-regulated differentially expressed miRNAs corresponding to 155 down-regulated candidate mRNAs and 7 down-regulated differentially expressed miRNAs corresponding to 238 up-regulated candidate mRNAs were constructed.(4)Twenty-four genes related to ferroptosis were screened out from the differential genes.Finally,12 networks were constructed(miR-98-5p/PTGS2,miR-23b-3p/PTGS2,miR-425-5p/TFRC,miR-133a-3p/TFRC,miR-185-5p/TFRC,miR-23b-3p/NFE2L2,miR-23b-3p/LAMP2,miR-98-5p/LAMP2,miR-182-5p/LAMP2,miR-182-5p/TLR4,miR-23b-3p/ZFP36,and miR-182-5p/ZFP36).These results indicate that Panax notoginseng saponins may regulate osteoblast ferroptosis by regulating the expression of miRNAs derived from osteoclast exosomes,thus providing a new idea for the study of the mechanism of steroid-induced femoral head necrosis.