ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group， a model group， and groups with different doses of Erjingwan （8，16，32 g·kg^-1）. The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum samples of mice， and biochemical tests were conducted to quantify the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione （GSH） in the serum. The protein and mRNA levels of SIRT1， Nrf2， B-cell lymphoma （Bcl-2）， and Bcl-2-associated X protein （Bax） were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultsAfter 4 weeks of drug intervention， the model group exhibited significant reductions in body weight and grip strength （P0.01） compared with the control group. Compared with the model group， all doses of Erjingwan increased the body weight in mice at week 8 （P0.01） and grip strength from week 6 （P0.01）. HE staining revealed clear muscle fiber structure in the control group， muscle fiber rupture and atrophy in the model group， and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group， collagen fiber proliferation and severe fibrosis in the model group， and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group （P0.01）. After intervention， the low-dose Erjingwan group exhibited a decreased TNF-α level （P0.05）， while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels （P0.01）. Biochemical assays revealed that the model group had decreased SOD and GSH levels （P0.01） and an increased MDA level （P0.01） compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels （P0.01） and decreases in MDA level （P0.01）， compared with the model group. WB and Real-time PCR results showed that compared with the control group， the model group presented down-regulated protein and mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 in the muscle tissue （P0.01） and up-regulated protein and mRNA levels of Bax （P0.01）. Compared with the model group， Erjingwan at different doses up-regulated the protein levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01） and down-regulated the protein and mRNA levels of Bax （P0.01） in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 （P0.05， P0.01）， and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01）. ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells， improved the antioxidant capacity， and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway， inflammatory response， and apoptosis network.

ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group， a model group， and groups with different doses of Erjingwan （8，16，32 g·kg^-1）. The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum samples of mice， and biochemical tests were conducted to quantify the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione （GSH） in the serum. The protein and mRNA levels of SIRT1， Nrf2， B-cell lymphoma （Bcl-2）， and Bcl-2-associated X protein （Bax） were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultsAfter 4 weeks of drug intervention， the model group exhibited significant reductions in body weight and grip strength （P0.01） compared with the control group. Compared with the model group， all doses of Erjingwan increased the body weight in mice at week 8 （P0.01） and grip strength from week 6 （P0.01）. HE staining revealed clear muscle fiber structure in the control group， muscle fiber rupture and atrophy in the model group， and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group， collagen fiber proliferation and severe fibrosis in the model group， and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group （P0.01）. After intervention， the low-dose Erjingwan group exhibited a decreased TNF-α level （P0.05）， while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels （P0.01）. Biochemical assays revealed that the model group had decreased SOD and GSH levels （P0.01） and an increased MDA level （P0.01） compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels （P0.01） and decreases in MDA level （P0.01）， compared with the model group. WB and Real-time PCR results showed that compared with the control group， the model group presented down-regulated protein and mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 in the muscle tissue （P0.01） and up-regulated protein and mRNA levels of Bax （P0.01）. Compared with the model group， Erjingwan at different doses up-regulated the protein levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01） and down-regulated the protein and mRNA levels of Bax （P0.01） in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 （P0.05， P0.01）， and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01）. ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells， improved the antioxidant capacity， and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway， inflammatory response， and apoptosis network.

Heparin-binding protein (HBP) is a pro-inflammatory granule protein released by activated neutrophils, known for its role in modulating vascular permeability and its pathological significance in infectious diseases. In recent years, HBP has garnered attention due to its immune-activating effects in contexts such as sepsis, acute lung injury and organ transplantation. It has been proposed as a potential biomarker for early detection of infection and inflammation. While preliminary progress has been made in animal studies, clinical evidence remains limited. Therefore, this article focuses on the mechanism of action of HBP in transplantation-related complications, explores its potential pathways for predicting infection risk, mediating ischemia-reperfusion injury and rejection, and evaluates the feasibility of intervention strategies such as neutralizing antibodies, heparin derivatives and albumin. The pivotal role of HBP in regulating inflammatory responses post-transplant may offer a novel target for postoperative infection monitoring and personalized therapeutic interventions.

Chronic heart failure （CHF） is a major global public health problem， and myocardial infarction is one of its main causes. The mouse model of heart failure induced by coronary artery ligation is widely used in the study of CHF， while the TCM syndrome attributes of this model have not yet been clarified. According to the theory of correspondence between prescriptions and syndromes， the method of syndrome identification by prescription efficacy is an important means of current syndrome research of animal models. This method deduces the syndrome characteristics of animal models through prescription efficacy. Taking the four basic syndrome elements of Qi， blood， Yin and Yang as the classification reference， this study used coronary artery ligation to construct a mouse model of CHF and treated the model with four representative TCM injections with the effects of replenishing Qi， warming Yang， nourishing Yin， and activating blood and enalapril. Echocardiography， tongue color parameters， histopathology， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and cardiac troponin Ⅰ （cTnⅠ） levels， and systematically explored the TCM syndrome attributes of this model. The results showed that the coronary ligation model presented an obvious cardiac function decline， myocardial fibrosis， infarct size expansion， and purple dark tongue， which were consistent with the basic syndrome characteristics of blood stasis in CHF. Danhong injection had significant effects of improving the cardiac function， alleviating myocardial fibrosis， and reducing serum NT-proBNP and cTnⅠ levels. Huangqi Injection and Shenfu injection can improve the cardiac function and tongue color parameters， with limited effects. The effect of Shenmai injection group was not obvious. This study verifies that the established model conforms to blood stasis syndrome through the method of syndrome identification by prescription efficacy， which provides an experimental basis for the study of TCM syndrome mechanism of CHF.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective: To explore the latent profiles of psychological help seeking intentions among adolescents in Wuhan, and to investigate their association with non suicidal self injury (NSSI), in order to provide a theoretical basis for constructing an early intervention system for adolescents NSSI. Methods: From October to December 2022, a convenient sampling method was used to select 3 975 students from grades 7 to 12 in Wuhan. A self administered questionnaire assessed psychological help seeking intentions, followed by a post survey interview using the Ottawa Self injury Inventory to evaluate NSSI behaviors. Latent profile analysis(LPA) was used to explore the potential categories of help seeking intentions in adolescents. Multinomial Logistic regression was used to analyze factors associated with the latent profiles of help seeking intentions and multiple Logistic regression was used to analyze the association between latent profiles of help seeking intentions and NSSI. Results: Based on latent profile analysis, four latent profiles of help seeking intentions in adolescents were identified, namely overall low, moderate, and high help seeking group, as well as family/friendfocused help seeking group, accouting for 14.1%, 20.9%, 43.1% and 21.8%, respectively. Multinomial Logistic regression analysis showed that compared to senior high school students, junior high school students were more willing to seek help from family and friends ( OR =1.56); compared to males, females were more likely to exhibit moderate help seeking intentions( OR =1.37); students with extroverted or balanced personalities were more likely to exhibit high level help seeking intentions( OR =1.50, 1.49); students with average or good family economic status, better parental relationships, and adequate mental health knowledge were more likely to exhibit moderate and high level help seeking intentions( OR =1.59, 2.02; 1.80, 2.64; 1.44, 1.55; 1.34, 1.58) (all P <0.05). Students with moderate or severe family dysfunction were less likely to seek help from family and friends or to exhibit moderate and high level help seeking intentions( OR =0.51, 0.60, 0.25; 0.22, 0.27, 0.06, all P <0.01). Students whose parents exhibited stigma towards mental illness were less likely to show high level help seeking intentions( OR= 0.78 , P <0.05). Multivariable Logistic regression analysis results indicated that compared to the overall low help seeking intentions group, reduced risk of NSSI was observed among students in the overall moderate and overall high groups, as well as in the family/friend focused help seeking group( OR =0.73, 0.60, 0.70, all P <0.05). Conclusions Active psychological help seeking intentions can reduce NSSI behaviors in adolescents. Interventions should focus on improving family support environment to enhance adolescents intentions to seek psychological help.

ObjectiveTo investigate the effects of Anmeidan （AMD） on protein expression of the ephrin type-A receptor 4 （EphA4）/ephrinA3 signaling pathway and synaptic structural function in an aged sleep deprivation model. MethodsSeventy-two 18-month-old aged mice were randomly divided into a blank group， a model group， AMD high-， medium-， and low-dose groups （26.26， 13.13， 6.565 g·kg^-1·d^-1， respectively）， and a melatonin group （1.3 mg·kg^-1·d^-1）， with 12 mice in each group. Cognitive function was assessed using the novel object recognition test. Hematoxylin-eosin （HE） staining was used to observe cell number and morphology in hippocampal tissues， and Nissl staining was performed to examine cellular structure and quantify Nissl bodies. Transmission electron microscopy was used to observe synaptic ultrastructure， with emphasis on changes in synaptic morphology and structure. Western blot was employed to detect the expression levels of EphA4， ephrinA3， brain-derived neurotrophic factor （BDNF）， glutamate aspartate transporter （GLAST）， glutamate transporter-1 （GLT-1）， growth-associated protein 43 （GAP43）， postsynaptic density protein 95 （PSD95）， and synaptophysin （SYN） in hippocampal tissues. Immunofluorescence double labeling was performed to co-stain EphA4 and ephrinA3 with glial fibrillary acidic protein （GFAP） and neuronal nuclei antigen （NeuN）， respectively， to observe the colocalization of target proteins with neurons and astrocytes. ResultsCompared with the blank group， the model group exhibited increased exploration time of familiar objects （P<0.01）， while exploration time of novel objects and the recognition index were decreased （P<0.01）. The number of neurons in the CA1， CA3， and dentate gyrus （DG） regions of the hippocampus was reduced， Nissl bodies were decreased， and synaptic structures were damaged. Protein expression levels of BDNF， GLAST， GLT-1， GAP43， PSD95， and SYN in hippocampal tissues were decreased， whereas the expression levels of EphA4， ephrinA3， and GFAP were increased. Compared with the model group， the AMD low-， medium-， and high-dose groups and the melatonin group showed increased exploration time of novel objects and higher novel object recognition indices （P<0.01）， along with significantly reduced exploration time of familiar objects （P<0.01）. Neuronal damage in the CA1 and DG regions was ameliorated， the number of Nissl bodies in the CA1 region was increased， and organelle and synaptic structural damage was alleviated. Protein expression levels of BDNF， GLAST， GLT-1， GAP43， PSD95， and SYN were increased， and protein expression levels of EphA4， ephrinA3， and GFAP were decreased （P<0.05，P<0.01）. ConclusionAMD can regulate protein expression of the EphA4/ephrinA3 signaling pathway in an aged sleep deprivation model， enhance synaptic protein expression， and improve neuronal synaptic damage.

Angiogenesis， as a core mechanism for maintaining tissue perfusion and repairing ischemic injury， plays a crucial role in ischemic diseases such as coronary heart disease and peripheral arterial disease. Traditional Chinese medicine（TCM）， with its advantages of multi-target and synergistic regulation， provides a unique perspective for therapeutic angiogenesis. Based on this， this article intends to delve into the synergistic effects of key signaling pathways， including vascular endothelial growth factor（VEGF）/VEGF receptor（VEGFR）， Notch， phosphoinositide 3-kinase/ protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR）， and angiopoietin/endothelial TEK tyrosine kinase（Ang/Tie2）， and elucidate the driving mechanisms of endothelial cell metabolic reprogramming and exosome-mediated intercellular communication within this process. Based on existing literature， it summarizes the microenvironment-dependent and bidirectional regulatory characteristics of natural active components of TCM（such as terpenes， tanshinones， and flavonoids） on angiogenesis. Furthermore， it systematically discusses how classical TCM formulas achieve blood vessel formation and functional maturation by protecting the neurovascular units， recruiting pericytes， and remodeling the microenvironment. Current evidence highlights the advantages of multi-target synergy and temporal regulation in TCM， but also reveals challenges such as high heterogeneity and a lack of functional evaluations and high-quality clinical trials. Future efforts should integrate multi-omics to decipher network mechanisms， optimize formula compatibility， and conduct multicenter studies to promote the development of innovative preparations. This review highlights the academic value of TCM in angiogenesis， provides an evidence base for treating ischemic diseases， and supports multidisciplinary integration and innovation.

Copper is an essential trace element in the human body, extensively involved in key physiological and biochemical processes such as antioxidant defense, energy metabolism, neural signaling, and immune regulation. In recent years, increasing research has focused on the potential role of copper dyshomeostasis in the development of chronic diseases. Studies indicate that abnormal copper levels, particularly elevated free copper, may increase the risk of cardiovascular disease, neurodegenerative disorders, diabetes, and cancer by inducing oxidative stress, impairing mitochondrial function, and disrupting immune regulation. Concurrently, copper homeostasis abnormalities have been demonstrated to be closely associated with increased all-cause mortality and accelerated aging. This systematic review comprehensively examined physiological functions, metabolic pathways, and environmental exposure characteristics of copper. It emphasized the epidemiological and mechanistic links between copper metabolism disorders and multiple chronic diseases, while exploring the potential applications of copper ion transporters and chelating agents in disease intervention. This work provides scientific evidence for the prevention, control, and precision treatment of copper-related chronic diseases.

Organoid-on-a-chip technology represents a promising interdisciplinary advancement that merges two cutting-edge biomedical platforms: stem cell-derived organoids and microfluidics-based organ-on-a-chip systems. Organoids are self-organizing three-dimensional (3D) cell cultures that mimic the key structural and functional features of in vivo organs. However, traditional organoid culture systems are often static, lacking dynamic environmental cues and suffering from limitations such as batch-to-batch variability, low stability, and low throughput. Organ-on-a-chip platforms, by contrast, utilize microfluidic technologies to simulate the dynamic physiological microenvironment of human tissues and organs, enabling more controlled cell growth and differentiation. By integrating the advantages of organoids and organ-on-a-chip technologies, organoid-on-a-chip systems transcend the limitations of conventional 3D culture models, offering a more physiologically relevant and controllable in vitro platform. In organoid-on-a-chip systems, stem cells or pre-formed organoids are cultured in micro-engineered environments that mimic in vivo conditions, enabling precise control over fluid flow, mechanical forces, and biochemical cues. Specifically, these platforms employ advanced strategies including bio-inspired 3D scaffolds for structural support, precise spatial cell patterning via 3D bioprinting, and integrated biosensors for real-time monitoring of metabolic activities. These synergistic elements recreate complex extracellular matrix signals and ensure high structural fidelity. Based on structural complexity, organoid-on-a-chip systems are classified into single-organoid and multi-organoid types, forming a trajectory from unit biomimicry to systemic simulation. Single-organoid chips focus on highly biomimetic units by integrating vascular, immune, or neural functions. Multi-organoid chips simulate inter-organ crosstalk and systemic homeostasis, advancing complex disease modeling and PK/PD evaluation. This emerging technology has demonstrated broad application potential in multiple fields of biomedicine. Organoid-on-a-chip systems can recapitulate organ developmentin vitro, facilitating research in developmental biology. They mimic organ-specific physiological activities and mechanisms, showing promising applications in regenerative medicine for tissue repair or replacement. In disease modeling, they support the reconstruction of models for neurodegenerative, inflammatory, infectious, metabolic diseases, and cancers. These platforms also enable in vitro drug testing and pharmacokinetic studies (ADME). Patient-derived chips preserve genetic and pathological features, offering potential for precision medicine. Additionally, they reduce species differences in toxicology, providing human-relevant data for environmental, food, cosmetic, and drug safety assessments. Despite progress, organoid-on-a-chip systems face challenges in dynamic simulation, extracellular matrix (ECM) variability, and limited real-time 3D imaging, requiring improved materials and the integration of developmental signals. Current bottlenecks also include the high technical threshold for automation and the lack of standardized validation frameworks for regulatory adoption. Meanwhile, the concept of a “human-on-a-chip” has been proposed to mimic whole-body physiology by integrating multiple organoid modules. This approach enables systemic modeling of drug responses and toxicity, with the potential to reduce animal testing and revolutionize drug development. Future advancements in bio-responsive hydrogels and flexible biosensors will further empower these platforms to bridge the gap between bench-side research and personalized clinical interventions. In conclusion, organoid-on-a-chip technology offers a transformative in vitro model that closely recapitulates the complexity of human tissues and organ systems. It provides an unprecedented platform for advancing biomedical research, clinical translation, and pharmaceutical innovation. Continued development in biomaterials, microengineering, and analytical technologies will be essential to unlocking the full potential of this powerful tool.