Osteosarcoma (OS) is a prevalent primary malignant bone tumor that lacks effective therapeutic interventions. Artesunate (ART) has been proved to have remarkable treatment effects on severe malaria and anti‐tumor properties. This study aimed to investigate the anti‐OS effects and underlying mechanisms of ART. The potential mechanisms of ART‐mediated anti‐OS activity were analyzed by using RNA sequencing, iron accumulation, lipid peroxidation, western blotting, and small interfering RNA (siRNA) transfection. In vivo, a xenograft mice model was adopted to explore the anticancer effect of ART. The present study revealed that ART significantly suppressed OS cell proliferation. Subsequent results suggested that ART exerted anti‐OS activity mainly through the ferroptosis pathway. ART decreased the GSH/GSSG ratio, xCT and GPX4 expression, while increasing MDA and lipid peroxidation, which were reversed by Fer‐1, DFO, 3‐MA, and NCOA4 silencing. Mechanistically, ART upregulated the expression of TFR and DMT1, and triggered ferritinophagy by upregulating the expression of NCOA4, which increased Fe ²⁺ accumulation and triggered ferroptosis. In addition, cytoplasmic iron further activated Mfrn2‐mediated transportation of cytoplasmic free iron into the mitochondria, resulting in mitochondrial iron overload, eventually leading to lipid peroxidation and ferroptosis. Furthermore, in an OS xenograft mouse model, administration of ART inhibited tumor growth by ferroptosis. Collectively, our findings indicated that ART has the potential anti‐OS capacity through NCOA4‐mediated ferritinophagy, which might shed light on the future of OS therapy.

Osteosarcoma (OS) is a prevalent primary malignant bone tumor which lacks effective therapeutic interventions. Ferroptosis is a new form of programmed cell death characterized by iron-dependent accumulation of lethal lipid oxidation, which provides a potential alternative intervene for the OS treatment. Shikonin is the major bioactive component extracted from the roots of lithospermum erythrorhizon which is also known as “Zicao” in traditional Chinese medicine, has been proved to have exhibits remarkable anti-tumor properties in several cancers. However, whether ferroptosis participated in the shikonin mediated anti-OS activity still remains to be clarified. Herein, we provide evidence that shikonin possesses the capability to induce the ferroptosis, and elucidate the underlying mechanisms in the treatment of OS. In the present study, it was found that shikonin significantly suppressed OS cells proliferation and blocked the cell cycle progression in vitro. Subsequent results revealed that shikonin could trigger ferroptosis in OS cells by promoting the Fe²⁺ accumulation, reactive oxygen species and lipid peroxidation formation, malondialdehyde production and mitochondrial damage. Further study showed that the effects of OS cell proliferation and death caused by shikonin could be successfully reversed by ferroptosis inhibitor ferrostatin-1, indicating that ferroptosis participated in the shikonin mediated anti-OS activity. Mechanistically, shikonin physically interacted with Nrf2, a critical regulator of ferroptosis, and influenced Nrf2 stability via inducing ubiquitin degradation, which suppressed the expression of Nrf2 downstream targets xCT and GPX4, and led to stimulating ferroptosis. Collectively, our findings indicated that shikonin induced OS cells ferroptosis through Nrf2/xCT/GPX4 regulatory axis, which might shed light on exploiting shikonin as a promising candidate for the future OS therapy.

Background: Spinal tuberculosis (STB) and Brucella spondylitis (BS) are the two most common infectious diseases of the spine. Despite overlapping clinical features, their immunopathological mechanisms remain poorly defined. Methods: We performed integrated transcriptomic profiling of infected nucleus pulposus tissues from STB and BS patients, combining single-cell RNA sequencing (STB n=3; BS n=3) with bulk RNA sequencing (STB n=7; BS n=5). Single-cell analysis resolved immune heterogeneity and T-cell subset architecture, whereas bulk RNA-seq defined global transcriptional signatures. Cross-platform integration identified concordant differentially expressed genes and shared pathways. AUCell was applied to quantify T-cell functional programmes. Pseudotime trajectory reconstruction, regulon inference, and cell-cell communication analyses were performed to delineate immune circuit differences. Results: A total of 67,274 high-quality cells were analysed, identifying nine major cell populations, with T cells as a dominant immune component. STB tissues were enriched in inflammatory cells, including monocytes/macrophages, neutrophils, and osteoclasts, whereas BS showed higher proportions of B and T cells. In STB, CD4 T cells were skewed toward IL26-CD4 T, Cytotoxic CD4 T, Proliferating CD4 T, and Treg subsets, while CD8 T cells were enriched in IFNG-AS1-CD8 T and exhaustion-like populations, reflecting sustained IFN-driven activation with proliferative and apoptotic stress. In contrast, BS exhibited expansion of GZMB-CTLs and IFNG-CTLs subsets, consistent with a focused cytotoxic programme with preserved memory features. Integrated single-cell and bulk analyses demonstrated convergence of overlapping genes on TCR, NF-κB, cytokine signalling, and osteoclast differentiation pathways. Functional scoring and pseudotime analysis indicated broader Th1/Th17 activation and progression toward terminal exhaustion in STB, whereas BS T cells maintained intermediate effector–memory states. Regulatory network analysis revealed a STAT1/IRF-dominated interferon axis in STB and an IRF4/EOMES/RFX3-centred effector–memory programme in BS. Cell-cell communication mapping showed an MHC-II-CD4 axis predominating in STB and an MHC-I-CD8 axis in BS. Despite divergent immune circuits, both conditions converged on osteoclast differentiation pathways, suggesting immune–bone metabolic coupling as a shared mechanism of vertebral destruction. Conclusions: STB and BS exhibit pathogen-specific T-cell immune circuits that converge on a common osteo-immune pathway, providing mechanistic insight and potential targets for host-directed therapy.

Epidemiological and clinical analyses of Brucellar spondylitis (BS) are crucial for public health authorities to enhance disease surveillance and optimize case management strategies. However, clinical epidemiological research on BS remains limited. This study analyzed the clinical and epidemiological characteristics of hospitalized BS patients at a hospital in Ningxia, aiming to provide evidence to support region-specific strategies for BS prevention and control. We retrospectively collected demographic profiles, epidemiological characteristics, clinical presentations, laboratory/imaging findings, therapeutic regimens, and prognostic outcomes of BS inpatients admitted to the orthopedic department of a hospital in Ningxia from January 2012 to December 2023. A total of 821 patients with BS were included, consisting of 564 males (68.7%; 564/821) and 257 females (31.3%; 257/821), with a median age of 55 years (range: 18–88 years). Among all patients (n = 821), 466 (56.76%) were agricultural or pastoral workers, and 578 (70.4%) had a documented history of contact with cattle or sheep. Low back pain was the most common presenting symptom, reported in 779 cases (94.88%; 779/821). The combined positive rate of the Rose Bengal Plate Test (RBPT) and the Standard Agglutination Test (SAT) in serological testing was 90.99% (747/821). Blood cultures were performed in 618 patients, of whom 217 (35.11%; 217/618) yielded positive results. Imaging examinations revealed that the lumbar spine was the most frequently involved region (59.81%; 491/821), with the L4–L5 segment being the most commonly affected (20.83%; 171/821). Single-segment involvement was observed in 668 patients (81.37%; 668/821), single-vertebra involvement in 44 patients (5.36%; 44/821), and multi-segment or trans-segment involvement in 109 patients (13.28%; 109/821). Of the 465 patients who underwent surgical treatment, the most common procedure was posterior fixation combined with lesion debridement, performed in 215 cases (46.24%; 215/465). Among the 754 patients who completed follow-up, the most frequently used antibiotic regimen was doxycycline plus rifampicin (60.05%; 493/754). Relapse occurred in 26 patients during follow-up (3.45%; 26/754). Brucellar spondylitis in Ningxia exhibits a temporal pattern aligned with regional brucellosis trends. Strengthening imaging-based diagnosis, clinical evaluation, and targeted follow-up of high-risk populations may help reduce recurrence and improve disease control. Not applicable.

Background: Bone metastases of lung cancer (BMLC) severely diminish patients’ quality of life due to bone-related events, and the lack of clear guidelines globally regarding medical and surgical treatment significantly reduces patient survival. While knowledge about BMLC has grown exponentially over the past two decades, a comprehensive and objective bibliometric analysis remains absent.Methods: A comprehensive bibliometric analysis was conducted on relevant literature on BMLC extracted from the Web of Science database from 2004 to 2023 by Biblioshiny, VOSviewer, Scimago Graphica, CiteSpace, and Microsoft Office Excel Professional Plus 2016 software. 936 papers related to BMLC were extracted from the Web of Science Core Collection (WoSCC). The number of publications, countries, institutions, global collaborations, authors, journals, keywords, thematic trends, and cited references were then visualized. Finally, the research status and development direction in the last 20 years were analyzed.Results: This study included a total of 936 papers on BMLC from 2004 to 2023. There has been a steady increase in global publications each year, peaking in 2021. China had the highest number of publications, followed by Japan and the United States. Additionally, China had the most citations with an H-index of 35, while the US followed with an H-index of 34, highlighting their significant contributions to the field. “Frontiers in Oncology” had the highest number of publications. CiteSpace analysis identified “lung cancer,” “bone metastasis,” and “survival” as the top high-frequency keywords, encapsulating the core research focus. Keyword clustering analysis revealed six main clusters representing the primary research directions. Burst analysis of keywords showed that “skeletal complications” had the highest burst intensity from 2005 to 2013, while recent research trends include “immunotherapy” and “denosumab,” with bursts from 2021 to 2023. Trend topic analysis indicated that “non-small cell lung cancer,” “immunotherapy,” and “immune checkpoint inhibitors” represent the cutting-edge research directions in this field.Conclusion: This article reveals the current status and trend of research on BMLC, which is increasing worldwide. China and the United States have contributed the most, but international cooperative research on BMLC should be strengthened. The pathogenesis, early prevention, and individualized treatment of BMLC need to be strengthened for further study, and immunotherapy is the next hotspot of lung cancer bone metastasis research.

Objective: This study aims to investigate the treatment strategies for lumbar brucellar spondylitis by comparing the outcomes of pure pharmacological treatment with diseased intervertebral fixation fusion, with or without lesion clearance.Methods: A total of 157 patients with lumbar brucellar spondylitis were categorized into three groups: Group A (52 cases) received pure pharmacological treatment, Group B (53 cases) underwent posterior vertebral fixation fusion, and Group C (52 cases) received posterior (or anterior) lesion clearance followed by posterior vertebral fixation fusion. Clinical data were analyzed, and the efficacy of the three treatment methods was evaluated.Results: The surgical groups showed better outcomes at various time points compared to the pharmacological treatment group (P < 0.05). The pure fixation group outperformed the lesion clearance fusion group during the perioperative period (P < 0.05). The ESR, CRP, ODI scores, imaging evaluation and complications of the lesion clearance followed by fixation group were all better than those of the other two groups (P < 0.05). Surgical treatment groups showed no statistically significant difference in VAS scores (P > 0.05), and both were superior to the pharmacological treatment group. There were no statistically significant differences in clinical efficacy among the three groups at the last follow-up.Conclusion: Surgical treatment achieves early recovery goals compared to pharmacological treatment for brucellar spondylitis. However, individualized treatment principles should guide surgical decisions to select the most suitable approach for patients.