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.

Objectives: . The prognostic value of the pretreatment albumin-to-alkaline phosphatase ratio (AAPR) in head and neck cancer (HNC) remains uncertain. This meta-analysis aimed to evaluate the predictive role of AAPR for survival outcomes in patients with HNC. Methods: . A comprehensive search of the Cochrane Library, PubMed, and Embase databases was conducted to identify relevant studies published up to July 30, 2024. We included studies on AAPR and survival outcomes in HNC patients. Results: . Eight studies comprising 1,737 HNC patients were analyzed using random-effects models. Lower AAPR values were significantly correlated with worse overall survival (hazard ratio [HR], 2.08), progression-free survival (HR, 2.00), and disease-free survival (HR, 2.18). Sensitivity analyses confirmed the robustness of these results, with no significant publication bias detected. Conclusion . Our findings suggest that pretreatment AAPR could serve as a valuable and cost-effective prognostic indicator in HNC, potentially aiding clinicians in risk stratification and treatment decision-making. However, additional validation studies are warranted to confirm its clinical applicability.

ObjectiveThe present study aimed to investigate alterations in white matter microstructure and spontaneous neural activity in male college smokers, and to further explore their associations with nicotine dependence. Given that adolescence and early adulthood represent critical periods for brain maturation, particularly for white matter development, understanding the neural correlates of smoking behavior during this stage is of substantial importance for both neuroscience and public health. MethodsA total of 115 male undergraduate students were initially recruited for this study. After quality control and exclusion procedures, 52 male college smokers and 42 demographically matched healthy non-smokers were included in the final analysis. All participants underwent multimodal magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI). White matter fiber tracts were reconstructed using the automated fiber quantification (AFQ) method, which enables precise identification and quantification of major fiber bundles. Eighteen major white matter tracts were segmented for each participant. Along the core trajectory of each tract, 100 equidistant nodes were sampled. Fractional anisotropy (FA) was calculated at each node to assess white matter microstructural integrity, while amplitude of low-frequency fluctuation (ALFF) was computed to evaluate spontaneous neural activity within white matter tracts. Between-group differences in FA and ALFF were assessed using two-sample t-tests, with appropriate corrections applied for multiple comparisons. Furthermore, Pearson correlation analyses were conducted to examine the relationships between imaging-derived metrics (FA and ALFF values in regions showing significant group differences) and nicotine dependence severity, as measured by the Fagerström test for nicotine dependence (FTND). ResultsCompared with healthy non-smokers, male college smokers exhibited significantly increased FA values in several white matter tracts, including the left thalamic radiation, right corticospinal tract, forceps major of the corpus callosum, left uncinate fasciculus, and right arcuate fasciculus. These findings suggest altered microstructural organization or increased directional coherence within these pathways. In addition, smokers demonstrated significantly elevated ALFF values in the forceps major, right uncinate fasciculus, and left arcuate fasciculus, indicating enhanced spontaneous neural activity in these white matter regions. Correlation analyses revealed that FA values in the left thalamic radiation and right corticospinal tract were negatively correlated with FTND scores, suggesting that higher levels of nicotine dependence were associated with reduced microstructural integrity or altered fiber organization in these regions. In contrast, ALFF values in the forceps major and right uncinate fasciculus were positively correlated with FTND scores, indicating that greater nicotine dependence was associated with increased spontaneous neural activity in specific white matter pathways. ConclusionThe present study provides evidence that male college smokers exhibit distinct alterations in both white matter microstructure and functional activity. These abnormalities are not uniformly distributed but rather localized to specific fiber tracts implicated in sensorimotor processing, interhemispheric communication, and higher-order cognitive and emotional regulation. Importantly, the observed associations between imaging metrics and nicotine dependence severity suggest that these structural and functional alterations may reflect neurobiological mechanisms underlying addiction. The combination of AFQ-based tract profiling and multimodal MRI offers a sensitive approach for detecting subtle changes along white matter pathways, highlighting its potential utility in identifying neuroimaging biomarkers of nicotine dependence. Overall, these findings indicate that smoking during early adulthood may disrupt ongoing white matter maturation, potentially leading to long-term consequences for brain function. This study provides novel insights into the neural basis of nicotine dependence and underscores the importance of early intervention and prevention strategies targeting young smokers.

OBJECTIVE To construct and evaluate a perioperative pharmaceutical care model for orthopedic joint replacement based on clinical pharmacy specialty collaboration and medication therapy management （MTM）， so as to provide a reference for improving the level of clinical rational drug use and reducing medical costs.METHODS Patients undergoing orthopedic joint replacement were taken as the research subjects. A specialized collaboration group was established， consisting of the head of the clinical pharmacy group， ward-based clinical pharmacists， and multi-specialty clinical pharmacists. The practice path， service contents，and workflow of MTM for the perioperative period of orthopedic joint replacement were clarified，and a perioperative pharmaceutical care model for orthopedic joint replacement was developed. Data of patients in the orthopedic diagnosis-related groups （DRG）-IC29 group of the department of orthopedics in Daping Hospital，Army Medical University were collected from July 2022 to June 2023 （pre-intervention， 581 cases） and from July 2023 to June 2024 （post-intervention， 843 cases）. The work-implementation indicators in the post-intervention period were counted， and the efficiency indicators and pharmaceutical management indicators were compared between the pre- and post-intervention periods. Meanwhile，200 patients were randomly selected from the pre-intervention and post-intervention groups， respectively， to evaluate the rate of rational medical orders.RESULTS From July 2023 to June 2024， the collaboration group implemented MTM for 843 patients undergoing orthopedic joint replacement via the established perioperative pharmaceutical care model. A total of 1 163 drug‑related problems （DRPs） were identified， and 79 patients with high medication‑related risks were screened out. The most common types of DRPs included （possible） adverse drug events/reactions （48.93%）， unnecessary drug therapy （21.58%）， and ineffective drug therapy （16.25%）. Among the 1 163 DRPs， 895 （76.96%） were completely resolved. Compared with the pre‑intervention period， the post‑intervention period showed reductions in average hospitalization cost per case， average drug cost per case， average length of hospital stay， proportion of drug cost， utilization rate and use intensity of antibacterial agents， and per‑capita drug cost of six main drug categories. The rate of rational medical orders increased from 78.25% to 98.11%.CONCLUSIONS The perioperative pharmaceutical care model for orthopedic joint replacement based on clinical pharmacy specialty collaboration and MTM can help pharmacists identify and resolve DRPs during the perioperative period of orthopedic joint replacement，improve the level of clinical rational drug use，and reduce treatment costs.

During orthodontic treatment, clinical monitoring of patients is a crucial factor in determining treatment success. It aids in timely problem detection and resolution, ensuring adherence to the intended treatment plan. In recent years, digital technology has increasingly permeated orthodontic clinical diagnosis and treatment, facilitating clinical decision-making, treatment planning, and follow-up monitoring. This review summarizes recent advancements in digital technology for monitoring orthodontic tooth movement, related complications, and appliance-wearing compliance. It aims to provide insights for researchers and clinicians to enhance the application of digital technology in orthodontics, improve treatment outcomes, and optimize patient experience. The digitization of diagnostic data and the visualization of dental models make chair-side follow-up monitoring more convenient, accurate, and efficient. At the same time, the emergence of remote monitoring technology allows orthodontists to promptly identify oral health issues in patients and take corresponding measures. Furthermore, the multimodal data fusion method offers valuable insights into the monitoring of the root-alveolar relationship. Artificial intelligence technology has made initial strides in automating the identification of orthodontic tooth movement, associated complications, and patient compliance evaluation. Sensors are effective tools for monitoring patient adherence and providing data-driven support for clinical decision-making. The application of digital technology in orthodontic monitoring holds great promise. However, challenges like technical bottlenecks, ethical considerations, and patient acceptance remain.

ObjectiveThe controllability changes of structural brain network were explored based on the control and brain network theory in young smokers, this may reveal that the controllability indicators can serve as a powerful factor to predict the sleep status in young smokers. MethodsFifty young smokers and 51 healthy controls from Inner Mongolia University of Science and Technology were enrolled. Diffusion tensor imaging (DTI) was used to construct structural brain network based on fractional anisotropy (FA) weight matrix. According to the control and brain network theory, the average controllability and the modal controllability were calculated. Two-sample t-test was used to compare the differences between the groups and Pearson correlation analysis to examine the correlation between significant average controllability and modal controllability with Fagerström Test of Nicotine Dependence (FTND) in young smokers. The nodes with the controllability score in the top 10% were selected as the super-controllers. Finally, we used BP neural network to predict the Pittsburgh Sleep Quality Index (PSQI) in young smokers. ResultsThe average controllability of dorsolateral superior frontal gyrus, supplementary motor area, lenticular nucleus putamen, and lenticular nucleus pallidum, and the modal controllability of orbital inferior frontal gyrus, supplementary motor area, gyrus rectus, and posterior cingulate gyrus in the young smokers’ group, were all significantly different from those of the healthy controls group (P<0.05). The average controllability of the right supplementary motor area (SMA.R) in the young smokers group was positively correlated with FTND (r=0.393 0, P=0.004 8), while modal controllability was negatively correlated with FTND (r=-0.330 1, P=0.019 2). ConclusionThe controllability of structural brain network in young smokers is abnormal. which may serve as an indicator to predict sleep condition. It may provide the imaging evidence for evaluating the cognitive function impairment in young smokers.

This comprehensive review systematically explores the multifaceted applications, inherent challenges, and promising future directions of artificial intelligence (AI) within the medical domain. It meticulously examines AI's specific contributions to basic medical research, disease prevention, intelligent diagnosis, treatment, rehabilitation, nursing, and health management. Furthermore, the review delves into AI's innovative practices and pivotal roles in clinical trials, hospital administration, medical education, as well as the realms of medical ethics and policy formulation. Notably, the review identifies several key challenges confronting AI in healthcare, encompassing issues such as inadequate algorithm transparency, data privacy concerns, absent regulatory standards, and incomplete risk assessment frameworks. Looking ahead, the future trajectory of AI in healthcare encompasses enhancing algorithm interpretability, propelling generative AI applications, establishing robust data-sharing mechanisms, refining regulatory policies and standards, nurturing interdisciplinary talent, fostering collaboration among industry, academia, and medical institutions, and advancing inclusive, personalized precision medicine. Emphasizing the synergy between AI and emerging technologies like 5G, big data, and cloud computing, this review anticipates a new era of intelligent collaboration and inclusive sharing in healthcare. Through a multidimensional analysis, it presents a holistic overview of AI's medical applications and development prospects, catering to researchers, practitioners, and policymakers in the healthcare sector. Ultimately, this review aims to catalyze the deep integration and innovative deployment of AI technology in healthcare, thereby driving the sustainable advancement of smart healthcare.

A combination of the "disease-syndrome-symptom" approach was used to study the syndrome characterization and features of dampness-heat obstruction syndrome in papain-induced knee osteoarthritis(KOA) model rats during the disease process. Forty-eight male SD rats were randomly divided into sham and model groups. The KOA model was established by injecting a mixture of papain and L-cysteine into the joint cavity on days 1, 3, and 5. During the 8 weeks following model establishment, the rats were assessed weekly for the plantar mechanical pain threshold, knee joint diameter, local skin temperature of the knee joint, weight-bearing difference between the two hind feet, and the modified Lequesne MG score of the knee joint. Samples were collected at 1, 2, 4, 6, and 8 weeks after model establishment to observe the gross lesions in cartilage and synovium. Histopathological changes in joint tissues were examined using hematoxylin-eosin, Masson's trichrome, and Senna red O-solid green staining. ELISA and immunohistochemical analysis were performed to detect the levels of interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, prostaglandin E2(PGE2), and the expression of aquaporins(AQP) 1 and 3 in serum and synovium. The results showed that the ink score of articular cartilage in the model group significantly increased from 4 to 8 weeks, the cartilage Mankin's score and the percentage of Masson-positive area in cartilage increased significantly from 1 to 8 weeks. The percentage of red-stained area for cartilage proteoglycans decreased significantly from 1 to 8 weeks. The synovitis score from 1 to 6 weeks and the percentage of blue-stained collagen fibers in the synovium from 1 to 8 weeks increased significantly, with statistically significant differences compared to the sham group. The mechanical pain threshold in the model group significantly decreased from 1 to 8 weeks, the knee joint diameter significantly increased from 1 to 6 weeks, and the local skin temperature of the knee joint, the weight-bearing difference between the two hind feet, and the modified Lequesne MG score from 1 to 5 weeks significantly increased, all with statistically significant differences compared to the sham group. The levels of IL-1β, IL-6, TNF-α, and PGE2 in serum and synovium of the model group significantly increased from 1 to 6 weeks. Serum TNF-α and PGE2, and synovial IL-1β, also significantly increased at 8 weeks. The levels of cartilage AQP1 and AQP3 significantly increased from 1 to 4 weeks, while synovial AQP1 and AQP3 increased significantly from 1 to 6 weeks, with all differences statistically significant compared to the sham group. In conclusion, papain-induced KOA rats exhibited pathological changes, including articular cartilage degeneration and synovial inflammation, within 1 week of induction. The KOA rats showed characteristics of dampness-heat obstruction syndrome, such as joint pain, swelling, elevated skin temperature, and decreased function, as well as increased inflammatory factors and AQP1、AQP3 in serum and joint tissues within 5 to 6 weeks of disease onset. These results provide an experimental model for studying the syndromes of KOA with dampness-heat obstruction syndrome.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Osteoarthritis, Knee/physiopathology* ; Disease Models, Animal ; Humans ; Interleukin-1beta/metabolism* ; Interleukin-6/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Knee Joint/pathology*

To investigate the effects of Biyan Jiedu Capsules on the proliferation and apoptosis of nasopharyngeal carcinoma cells and their molecular mechanism, nasopharyngeal carcinoma cells CNE1 and CNE2 were used. They were divided into control group(30% blank serum medium), low-(10% drug-containing serum + 20% blank serum medium), medium-(20% drug-containing serum + 10% blank serum medium), and high-(30% drug-containing serum medium) concentration group of Biyan Jiedu Capsules according to in vitro experiment. After 24 h of intervention, the effects of Biyan Jiedu Capsules on the proliferation of CNE1 and CNE2 were detected by CCK-8 assay, clonal formation experiment, and EdU staining. The effect of Biyan Jiedu Capsules on apoptosis of CNE1 and CNE2 was detected by flow cytometry. Western blot was used to detect the effect of Biyan Jiedu Capsules on the expression of X-linked apoptosis inhibitor protein(XIAP), survivin, proliferating cell nuclear antigen(PCNA), and PI3K/Akt pathway-related proteins in CNE1 and CNE2. The results showed that compared with the control group, the survival rate of CNE1 and CNE2 in the medium and high concentration groups of Biyan Jiedu Capsules could be decreased in a concentration-dependent way(P<0.05, P<0.01). At the same time, EdU staining and clonal formation experiments showed that the proliferation of CNE1 and CNE2 was significantly inhibited in the medium and high concentration groups of Biyan Jiedu Capsules(P<0.05, P<0.01). Flow cytometry showed that the apoptosis rate of CNE1 and CNE2 was significantly increased in all concentration groups of Biyan Jiedu Capsules(P<0.01), and the apoptosis rate was concentration-dependent. Western blot showed that the expressions of XIAP, survivin, PCNA, p-PI3K, and p-Akt in all concentration groups of Biyan Jiedu Capsules were significantly down-regulated(P<0.05, P<0.01). In conclusion, Biyan Jiedu Capsules can inhibit the proliferation and induce apoptosis of nasopharyngeal carcinoma cells possibly by down-regulating the PI3K/Akt signaling pathway.
Humans ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/physiopathology* ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Line, Tumor ; Drugs, Chinese Herbal/pharmacology* ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Capsules ; Carcinoma/drug therapy*

This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology. The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480, and the targets of Jiaotai Pills and depression were retrieved from online databases. STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the "compound-target-pathway" network. DAVID was used for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of the core targets. The mouse model of depression was established with chronic unpredictable mild stress(CUMS) and treated with different doses of Jiaotai Pills. The behavioral changes and pathological changes in the hippocampus were observed. UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum, from which the differential metabolites and related metabolic pathways were screened. A "metabolite-reaction-enzyme-gene" network was constructed for the integrated analysis of metabolomics and network pharmacology. A total of 34 chemical components of Jiaotai Pills were identified, and 143 core targets of Jiaotai Pills in treating depression were predicted, which were mainly involved in the arginine and proline, sphingolipid, and neurotrophin metabolism signaling pathways. The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression. In addition, Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism, sphingolipid metabolism, and porphyrin metabolism in the serum of model mice. The integrated analysis showed that arginine and proline metabolism, cysteine and methionine metabolism, and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills. In conclusion, metabolomics combined with network pharmacology clarifies the antidepressant mechanism of Jiaotai Pills, which may provide a basis for the clinical application of Jiaotai Pills in treating depression.
Animals ; Drugs, Chinese Herbal/chemistry* ; Depression/genetics* ; Mice ; Network Pharmacology ; Metabolomics ; Male ; Disease Models, Animal ; Humans ; Protein Interaction Maps/drug effects* ; Antidepressive Agents