Osteosarcoma (OS), chondrosarcoma (CS), and Ewing sarcoma (ES) represent primary malignant bone tumors and pose significant challenges in oncology research and clinical management. Conventional research methods, such as two-dimensional (2D) cultured tumor cells and animal models, have limitations in recapitulating the complex tumor microenvironment (TME) and often fail to translate into effective clinical treatments. The advancement of three-dimensional (3D) culture technology has revolutionized the field by enabling the development of in vitro constructed bone tumor models that closely mimic the in vivo TME. These models provide powerful tools for investigating tumor biology, assessing therapeutic responses, and advancing personalized medicine. This comprehensive review summarizes the recent advancements in research on 3D tumor models constructed in vitro for OS, CS, and ES. We discuss the various techniques employed in model construction, their applications, and the challenges and future directions in this field. The integration of advanced technologies and the incorporation of additional cell types hold promise for the development of more sophisticated and physiologically relevant models. As research in this field continues to evolve, we anticipate that these models will play an increasingly crucial role in unraveling the complexities of malignant bone tumors and accelerating the development of novel therapeutic strategies.
Bone Neoplasms/pathology* ; Humans ; Osteosarcoma/pathology* ; Tumor Microenvironment ; Sarcoma, Ewing/pathology* ; Chondrosarcoma/pathology* ; Animals ; Cell Culture Techniques/methods* ; Cell Culture Techniques, Three Dimensional/methods* ; Cell Line, Tumor

Background and aims:Radiofrequency ablation(RFA)is the first-line treatment for early-stage hepato-cellular carcinoma(HCC).However,recurrence after curative RFA remains a significant challenge for HCC patients.Although RFA induces an immune response,the anti-tumor effect is often limited by the immunosuppressive tumor microenvironment.Enhancing anti-tumor immunity is essential to improve treatment efficacy and prevent recurrence.In this study,we explore the efficacy and underlying mechanisms of the combination of RFA and anti-PD-1 in suppressing abscopal and recurrent tumors.Methods:We established a bilateral subcutaneous HCC mouse model and performed complete RFA on the right-flank tumor.Anti-PD-1 or anti-IgG was administered post-RFA.Tumor growth,immune cell profiles,and molecular pathways were assessed using flow cytometry,immunohistochemistry staining,RNA-sequencing,and Western blot.Chemokines released by the tumor were detected by ELISA.An in vivo tumor rechallenge experiment was performed after a complete tumor regression to evaluate the immune memory induced by the RFA+anti-PD-1 treatment.Results:RFA combined with anti-PD-1 significantly suppressed abscopal tumor growth and prolonged survival.Compared with RFA monotherapy,the infiltration of CD8+T cells and dendritic cells was sig-nificantly increased in the combined treatment group,while PMN-MDSCs were markedly reduced.Mechanistically,the chemokine signaling pathway and JAK-STAT signaling pathway were activated in the tumor of the RFA+anti-PD-1 group with upregulation of CXCL10 to recruit CD8+T cells.In addition,the combination therapy induced durable immune memory that inhibited rechallenge tumor outgrowth.Conclusions:Our study discovered that RFA combined with anti-PD-1 induced anti-tumor immunity to inhibit abscopal tumors and durable immune memory to prevent recurrence,suggesting RFA+anti-PD-1 as a potential therapeutic strategy for multifocal HCC and preventing recurrence.

ObjectiveTo investigate the effects of Shegan Mahuangtang and its pungent and bitter Chinese herbs on the expression of transient receptor potential vanilloid-1 （TRPV1） and bitter taste receptor 14 （TAS2R14） in the lung tissue of the rat model of cold asthma. MethodSeventy SD rats were randomized into 7 groups： normal， model， Shegan Mahuangtang， pungent Chinese herbs， bitter Chinese herbs （6.43 g·kg^-1）， dexamethasone （0.5 g·kg^-1）， and Guilong Kechuanning （10 g·kg^-1）. The rat model of cold asthma was established by intraperitoneal injection and subcutaneous injection of 10% ovalbumin （OVA） and aluminium hydroxide in the limbs， combined with 2% OVA atomization and cold （2-4 ℃） stimulation. The rats were treated with corresponding drugs by gavage and atomization， and the normal and model groups were treated with the same amount of normal saline for 3 weeks. After the last excitation， airway inflammation and cell proliferation were observed by hematoxylin-eosin （HE）， periodic acid-Schiff （PAS）， and Masson staining of the lung tissue. The levels of interleukin-5 （IL-5）， tumor necrosis factor-α （TNF-α）， thymic stromal lymphopoietin （TSLP）， and transforming growth factor-β₁ （TGF-β₁） in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. The expression of TRPV1 and TAS2R14 was detected by immunofluorescence. The expression of TRPV1， TAS2R14， phospholipase Cβ₂ （PLCβ₂）， B-cell lymphoma-2 （Bcl-2）， and α-smooth muscle actin （α-SMA） in the lung tissue was determined by Western blot. ResultCompared with the normal group， the model group showed decreased water intake， food intake， and body weight， increased airway inflammatory cell infiltration， goblet cell proliferation， tissue fibrosis and collagen deposition， elevated levels of IL-5， TNF-α， TSLP， and TGF-β₁ in the serum （P<0.01）， upregulated expression of TRPV1， PLCβ₂， and α-SMA， and downregulated expression of TAS2R14 and Bcl-2 （P<0.05， P<0.01）. Compared with model group， Shecgan Mahuangtang， pungent Chinese herbs， and bitter Chinese herbs increased the water intake， food intake， and body weight， reduced the inflammatory cell infiltration and goblet cell proliferation， alleviated tissue fibrosis and collagen deposition， lowered the levels of IL-5， TNF-α， TSLP， and TGF-β₁ in the serum （P<0.01）， downregulated the expression of TRPV1， PLCβ₂， and α-SMA， and upregulated the expression of TAS2R14 and Bcl-2 （P<0.05， P<0.01）. ConclusionShegan Mahuangtang and its pungent and bitter Chinese herbs can reduce OVA-induced airway inflammation， downregulate the expression of TRPV1， PLCβ₂， and α-SMA， and upregulate the expression of TAS2R14 and Bcl-2 in asthmatic rats. Moreover， bitter Chinese herbs outperformed pungent Chinese herbs， and the combination of them enhanced the therapeutic effect. It is suggested that Shegan Mahuangtang and its pungent and bitter Chinese herbs may ameliorate the OVA-induced airway inflammation by inhibiting TRPV1 and activating TAS2R14.

ObjectiveBased on network pharmacology and molecular docking techniques， the mechanism of essential oil from Chimonanthus nitens leaves （CLO） in the treatment of acute lung injury （ALI） was predicted， and a rat model of ALI was established to verify the mechanism of CLO. MethodThe composition of CLO was determined by gas chromatography-mass spectrometry （GC-MS）. The component targets were obtained from PharmMapper and SwissTargetPrediction databases， ALI-related targets were obtained from GeneCards， Online Mendelian Inheritance in Man （OMIM） and DisGeNET， cross-over analysis with differential expressed genes （DEGs） of ALI obtained from Gene Expression Omnibus （GEO） on the Venny 2.1.0 platform yielded potential anti-ALI targets of CLO. Protein-protein interaction （PPI） analysis of potential targets was carried out by STRING 11.5. The tissue expression profiles of potential targets were obtained from the National Center for Biotechnology Information （NCBI） and the target tissue distribution maps were constructed. Potential targets were analyzed for Gene Ontology （GO） function and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment by RStudio 4.0.0 software. Composition-target-pathway network was constructed by Cytoscape 3.9.1 software， and key components and pathways were screened out and verified by molecular docking. ALI model was established by lipopolysaccharide （LPS） induction， levels of interleukin （IL）-6 and tumor necrosis factor （TNF）-α in serum of rats were measured， the expression levels of IL-17 protein in the lung tissue of ALI rats were analyzed by immunohistochemistry. ResultA total of 19 components of CLO were identified by GC-MS， and 18 potential targets were obtained by target screening. After PPI analysis， 15 target proteins with interaction relationship were obtained， further analysis showed that they were highly expressed in lung and thymus. The network diagram of component-target-pathway was analyzed to obtain the key components， including bornyl acetate， linalool， elemol， geranyl isobutyrate， and the core targets of matrix metalloproteinase 13 （MMP13）， S100 calcium binding protein A9 （S100A9）， spleen tyrosine kinase （SYK）， as well as the main signaling pathways， such as IL-17 and TNF. The results of molecular docking showed that the key components were stably bound to MMP13 and S100A9 of IL-17 signaling pathway. The results of pharmacological experiment confirmed that CLO could significantly inhibit the expression of IL-6 and TNF-α in serum of ALI rats， and decrease the expression of IL-17 protein in lung tissue of ALI rats. ConclusionCLO can achieve the therapeutic effect on ALI and protect lung tissue， the mechanism may be related to the decrease of the expression of IL-6 and TNF-α in serum and the inhibition of the activation of IL-17 signaling pathway in lung tissue of ALI rats.

According to the infection characteristics of batches of patients with extensive burns in dust explosion, the article focused on the concept and mode of whole-range fine management.Based on the characteristics and rules of infection prevention in bat-ches of patients with extensive burns, the measurement and examination of infection management were refined, the infection monitoring indexes were designed scientifically, the infection prevention scheme and monitoring table were formulated.By early and whole-range intervention of infection prevention, quantitative evaluation, fine management and precise control at different times, all levels of infec-tion management teams could fully serve their purposes in order to realize effective infection prevention.