First Affiliated Hospital of Chinese PLA General Hospital

Cisplatin (Cis) is widely recognized as the cornerstone of osteosarcoma (OS) chemotherapy. However, its clinical effectiveness remains limited by poor drug delivery efficiency, severe adverse effects, and emerging chemoresistance. To overcome these limitations, a triple-drug co-delivery system (NP3) is designed, encapsulating Cis prodrug (Cis(IV)), curcumin (Cur), and manganese ions within reactive oxygen species (ROS)-responsive nanoparticles (NPs). NP3 efficiently accumulated at tumor sites and rapidly released its therapeutic payload upon endocytosis, triggered by abundant intracellular ROS. After NP3 degradation, Cis in combination with Cur induced significant DNA damage. This DNA debris subsequently activated the cGAS-STING pathway, enhancing tumor immunogenicity. Additionally, manganese ions functioned as immune adjuvants, further amplifying cGAS-STING activation. Consequently, NP3 promoted dendritic cell (DC) maturation, enhanced the infiltration of CD8+ T-cells, and concurrently decreased the infiltration of immunosuppressive cells. In an OS mouse model, combining NP3 with anti-PD-L1 treatment markedly improved both tumor suppression and immune system activation. RNA sequencing analysis demonstrated that NP3 synergistically promoted tumor regression by concurrently inducing pro-apoptotic signaling and immune responses. In conclusion, this study presents an innovative therapeutic strategy combining targeted chemotherapy delivery with robust antitumor metalloimmunotherapy, offering a promising therapeutic approach for OS.

Sophora tonkinensis radix et rhizoma is a medicinal herb traditionally used to treat inflammatory diseases and various types of cancer, previous phytochemistry studies have identified abundant alkaloids and flavonoids as the major bioactive components with anti-inflammatory, anti-tumor, hepatoprotective and immunomodulatory pharmacological effects, but their effects on Tumor-associated macrophages (TAMs) and the tumor immune microenvironment have not been systematically explored. This work aimed to establish whether a standardized extract of Sophora tonkinensis (STE) can halt IL-4-driven M2 macrophage polarization, reprogram established M2-like tumor-associated macrophages toward a pro-inflammatory M1-like phenotype, and clarify the underlying molecular mechanisms and in vivo efficacy of these immunomodulatory actions. Bone-marrow-derived macrophages (BMDMs) were polarized to an M2 phenotype and subsequently treated with STE. Expression of the M1/M2 markers Arg-1, CD206, iNOS, and CD86 in these macrophages was quantified by immunoblotting, qPCR, and flow cytometry. The impact of STE-pretreated M2-conditioned medium on the proliferation, migration, and invasion of Hepa 1-6 cells was then examined. H22 cells were subcutaneously inoculated into Balb/c mice to assess STE's effects on the macrophage landscape within the tumor immune microenvironment and to evaluate its antitumor efficacy. STE dose-dependently suppressed IL-4-induced Arg-1 and CD206 while up-regulating iNOS and CD86, indicating a blockade of M2 polarization and a shift toward an M1 signature. Mechanistically, STE markedly increased JAK1 and STAT1 phosphorylation. Functionally, it potently inhibited invasion and migration of Hepa 1-6 cells. In tumor-bearing mice, robust suppression of tumor growth was accompanied by a pronounced reduction in M2-like TAMs and a reciprocal increase in M1-like macrophages within the tumor microenvironment. STE reprograms TAMs via the JAK1/STAT1 axis and exhibits robust antitumor activity, underscoring its promise as a natural, macrophage-targeted immunotherapeutic that warrants further investigation for integration into cancer treatment strategies.

ObjectiveAcne conglobata (AC) is a severe inflammatory skin condition with limited therapeutic options that can provide rapid and sustained remission. This retrospective cohort study aimed to evaluate the clinical efficacy and safety of a combination therapy of twice-weekly red-blue light-emitting diode (LED) phototherapy with a shortened 4-week course of oral minocycline, compared to a conventional polypharmacy regimen for AC.MethodsWe analyzed clinical data from 28 outpatients diagnosed with AC. The study group (n = 15) received LED phototherapy (640 nm red and 460 nm blue light) and oral minocycline (100 mg/day for 4 weeks). The control group (n = 13) was treated with a heterogeneous conventional regimen, including oral isotretinoin and/or extended minocycline (8 weeks) plus topical agents. Efficacy outcomes, including Symptom Score Reduction Index (SSRI), Global Acne Grading System (GAGS), and Pruritus Visual Analog Scale (P-VAS), were assessed by blinded dermatologists at baseline and over 8 weeks. Safety and tolerability were also evaluated.ResultsBaseline characteristics were comparable between groups. The LED-minocycline combination resulted in significantly superior and more rapid clinical improvement. At week 8, 100% of patients in the study group achieved cure (SSRI ≥90%), versus 0% in the control group (p < 0.001). The mean SSRI in the study group was 92.1 ± 2.37% compared to 23.1 ± 4.35% in the control group (p < 0.001). The study group also showed significantly lower post-treatment GAGS scores (7.01 ± 2.01 vs. 9.03 ± 2.36, p = 0.022) and P-VAS scores (1.2 ± 0.6 vs. 4.8 ± 1.1, p < 0.001). Adverse events were mild and transient, with no significant difference in the incidence of skin irritation between groups (93.3% vs. 84.6%, p = 0.583).ConclusionCombining red-blue LED phototherapy with a 4-week course of minocycline is a rapid, highly effective, and safe therapeutic strategy for AC, outperforming conventional polypharmacy while halving the duration of systemic antibiotic exposure. Despite the inherent limitations of a retrospective design, these findings support the integration of LED therapy to optimize the management of severe acne.

Effective survival analysis is essential for identifying optimal preventive treatments within smart healthcare systems and leveraging digital health advancements; however, existing prediction models face limitations, primarily relying on ensemble classification techniques with suboptimal performance in both target detection and predictive accuracy. To address these gaps, this paper proposes a multimodal framework that integrates enhanced facial feature detection and temporal predictive modeling. For facial feature extraction, this study developed a lightweight face-region convolutional neural network (FRegNet) specialized in detecting key facial components, such as eyes and lips in clinical patients that incorporates a residual backbone (Rstem) to enhance feature representation and a facial path aggregated feature pyramid network for multi-resolution feature fusion; comparative experiments reveal that FRegNet outperforms state-of-the-art target detection algorithms, achieving average precision (AP) of 0.922, average recall of 0.933, mean average precision (mAP) of 0.987, and precision of 0.98–significantly surpassing other mask region-based convolutional neural networks (RCNN) variants, such as mask RCNN-ResNeXt with AP of 0.789 and mAP of 0.957. Based on the extracted facial features and clinical physiological indicators, this study proposes an enhanced temporal encoding-decoding (ETED) model that integrates an adaptive attention mechanism and a gated weighting mechanism to improve predictive performance, with comparative results demonstrating that the ETED variant incorporating facial features (ETEncoding-Decoding-Face) outperforms traditional models, achieving an accuracy of 0.916, precision of 0.850, recall of 0.895, F1 of 0.884, and area under the curve (AUC) of 0.947–outperforming gradient boosting with an accuracy of 0.922, but AUC of 0.669, and other classifiers in comprehensive metrics. The results confirm that the multimodal dataset (facial features + physiological indicators) significantly enhances the prediction accuracy of the seven-day survival conditions of patients. Correlation analysis reveals that chronic health evaluation and mean arterial pressure are positively correlated with survival, while temperature, Glasgow Coma Scale, and fibrinogen are negatively correlated.

A systematic quality control (QC) inspection system is very important to standardize migraine management. This study assesses the impact of the QC inspections on center operations, guideline adherence, and patient outcomes for an established national tiered headache care network in china, hoping to identify the key improvements that inform national care optimization strategies. A multi-center cross-sectional study was conducted in China. Lead physicians from 103 headache centers completed a structured electronic questionnaire covering headache consultation capacity, migraine treatment status, comorbidity and disability assessment, and comprehensive management. Centers were stratified by QC inspection status (29 inspected, 74 non-inspected), and outcomes were compared using nonparametric tests. Centers had a median of 4 [IQR: 3-5] headache specialists operating 4 [IQR: 2-6] half-day weekly headache clinics. Migraine accounted for 40% of the caseload, with chronic migraine and conventional acute drugs resistant migraine comprising approximately 40%. The most frequently recommended acute medications were rimegepant, ibuprofen, and acetaminophen; leading preventive medications included flunarizine, topiramate, and CGRP receptor antagonists. Non-pharmacological therapies were recommended by over 50% of specialists, yet patient uptake was less than 10%. QC-inspected centers operated significantly more clinic sessions per week (median 6 [4–8] vs. 3.5 [2–5] half-days, p = 0.0082), had higher rates of headache diary use (30% [20%–50%] vs. 20% [10%–40%], p = 0.0315), and demonstrated better follow-up rates for medication overuse headache (80% [50%–80%] vs. 50% [15%–80%], p = 0.0131) and higher rates of headache control (70% [50%–85%] vs. 60% [40%–80%], p = 0.0496). These centers also prescribed fewer Chinese patent medicines, and used more evidence-based preventive agents (e.g. galcanezumab, amitriptyline, p < 0.05), and conducted more continuing medical education sessions for physicians (median 5 [IQR: 4-10] vs. 3 [IQR: 2-5] per year, p = 0.0044). Headache centers in China generally provide guideline-adherent care for migraine cases, although access to specific therapies remains limited. QC inspections are associated with improved operational capacity, standardized management, and increased use of evidence-based treatments. Enhancing QC inspections, expanding access to advanced therapies, and strengthening physician and patient education are essential to further optimize China’s headache care network.

Stress is a non-specific systemic response to internal or external challenges. Recent studies show that stress can disrupt iron metabolism and that iron dyshomeostasis is implicated in many diseases-particularly within the nervous system, where iron distribution and regulation intersect tightly with oxidative stress and inflammation. Activation of the hypothalamic-pituitary-adrenal (HPA) axis by stress can upregulate hepatic hepcidin and reprogram systemic iron fluxes, leading to functional iron deficiency and, in the brain, reduced iron availability, which affects myelination and neurotransmitter metabolism. Conversely, iron dyshomeostasis also contributes to neurodegenerative pathology. In this review, we synthesize recent evidence of how stress reprograms brain iron distribution and regulation, and we outline the mechanistic links between stress-induced iron dysregulation and neurological pathology. We also discuss the therapeutic implications (such as iron-chelation strategies) and highlight the three-way interplay among stress, iron metabolism, and neurodegeneration. These insights suggest that managing iron homeostasis may offer new therapeutic avenues for stress-related neural disorders.

BackgroundThis study aimed to explore the impact of T helper 17 (Th17)/regulatory T (Treg) cells imbalance and inflammatory factors (IL-1b, IL-18, and TNF-a) on sagittal balance in patients with thoracolumbar kyphosis due to ankylosing spondylitis (AS) following vertebral column decancellation (VCD), to clarify the predictive efficacy of the Th17/Treg ratio and IL-1b, IL-18, and TNF-a in post-operative sagittal imbalance.MethodsA total of 134 AS patients undergoing VCD were enrolled and categorised into an imbalance group (46 cases) and a balance group (88 cases), depending on post-operative sagittal balance. Measurements of the Th17/Treg ratio and inflammatory factor levels were conducted at three time points: preoperatively (T0), 24 hours postoperatively (T1), and 4 weeks postoperatively (T2). These data were analysed alongside sagittal parameters (SVA, PI-LL, and PT) to assess their correlations and predictive potential.ResultsAt 4 weeks after surgery, the imbalance group showed significantly elevated Th17/Treg ratios and higher levels of IL-1b, IL-18, and TNF-a compared to the balance group (P<0.05). Th17/Treg ratios and inflammatory factors (IL-1b, IL-18, TNF-a) showed significant positive correlations with SVA, PI-LL, and PT (P<0.05). Notably, the combined assessment of Th17/Treg ratio and inflammatory factors sagittal imbalance had a sensitivity of 52.17% and specificity of 90.91 (P<0.001).ConclusionsThe findings suggest that Th17/Treg imbalance and excessive expression of IL-1b, IL-18, and TNF-a are strongly linked to postoperative sagittal imbalance in AS patients. These biomarkers may serve as valuable early predictors for assessing surgical outcomes.

BackgroundMesenchymal stem cells (MSCs) exhibit therapeutic potential for ulcerative colitis (UC) due to their immunomodulatory, homing, and tissue repair capabilities, but clinical efficacy is constrained by heterogeneity. Induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) exhibit superior stem cell properties compared to traditional MSCs, with CD146+ MSCs exhibiting enhanced biological characteristics. Nevertheless, the biological properties of CD146+iMSCs, as well as their therapeutic potential in UC, remain unclear.MethodsCD146+ subpopulations were isolated from iMSCs and umbilical cord-derived MSCs (UCMSCs) using magnetic beads sorting. The surface markers, proliferation capacity, differentiation potential, and regulatory effects on macrophage polarization were analyzed. Dextran sulfate sodium (DSS) - induced UC mouse models were established and treated with CD146+iMSCs. Body weight, disease activity index (DAI), colon length, and histopathological damage were evaluated. Peripheral immune cells and cytokines were analyzed by flow cytometry and ELISA. Transcriptome sequencing of colon tissues was performed and jointly analyzed with GEO datasets to identify the mechanisms of CD146+iMSCs’ therapeutic efficacy in UC through differential gene expression profiling, protein-protein interaction network, functional enrichment analysis, and immune infiltration assessment. The core mechanisms were validated in vitro and vivo.ResultsCD146+ iMSCs exhibited similar morphology and macrophage polarization regulatory capacity to CD146+UCMSCs, with superior proliferation and differentiation potential. CD146+ iMSCs significantly ameliorated UC symptoms (weight, DAI), reduced colon damage, decreased IL-6/TNF-α, and restored immune balance. Integrated analysis of colon transcriptome sequencing data and GEO datasets revealed the pivotal role of the IL-17 signaling pathway in the therapeutic effects of CD146+iMSCs. CD146+iMSCs effectively suppressed IL-17 expression both in cell inflammation models and colon tissues, downregulated nine hub genes, and inhibited macrophage polarization via the cGAS-STING axis.ConclusionCD146+iMSCs exhibited advantages in proliferative and differentiation capabilities. They could ameliorate UC by suppressing IL-17 expression, downregulating HUB genes, and modulating macrophage polarization through the cGAS-STING axis.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13287-025-04695-7.