Background: No prominent advancements in osteosarcoma (OS) treatment have been made in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, the lack of targeted photosensitizers for OS treatment severely limits its applications. Results: In this study, we constructed a potential theranostic nanoplatform by using (poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) encapsulating IR780 into the shell (PLGA-IR780 NPs), which were further camouflaged with human OS cell membranes from the HOS cell line (MH-PLGA-IR780 NPs). These constructed NPs showed the capacity for homologous targeting with excellent photoacoustic (PA)/fluorescence (FL) imaging ability. Benefitting from their homologous targeting capacity, MH-PLGA-IR780 NPs obviously promoted cell endocytosis in vitro and tumor accumulation in vivo, which could further improve PDT performance under near-infrared (NIR) irradiation. In addition, to their homologous targeting and PA/FL dual-mode imaging ability, MH-PLGA-IR780 NPs had advantages in penetrating deeper into tumor tissues and in real-time dynamic distribution monitoring in vivo, which laid a foundation for further clinical applications in OS. Moreover, we demonstrated that PDT guided by the constructed NPs could significantly induce HOS cells apoptosis and ferroptosis via excessive accumulation of reactive oxygen species (ROS), and further determined that the potential anticancer molecular mechanism of apoptosis was triggered by the release of cytochrome c-activated mitochondrial apoptosis (endogenous apoptosis), and that ferroptosis caused the activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and the inactivation of glutathione peroxidase 4 (GPX4), synergistically leading to excessive accumulation of Lipid-ROS and Lipid peroxides (LPOs). Concurrently, MH-PLGA-IR780 NPs-guided PDT also showed an obvious inhibitory effect on tumor growth in vivo. Conclusion: These results suggest that this homologous targeting-based theranostic nanoplatform provides an effective method to improve PDT performance in OS and contributes a new and promising approach for OS therapy. Graphical

Globally, osteosarcoma (OS) is the most prevalent form of primary bone cancer in children and adolescents. Traditional neoadjuvant chemotherapy regimens have reached a bottleneck; thus, OS survivors have unsatisfactory outcomes. Theaflavin-3,3-digallate (TF3) exhibits potent anticancer properties against many human cancers. Nevertheless, the biological effects and the underlying molecular mechanism of TF3 in human OS remain unclear. The objective of this study was to investigate the effects of TF3 on human OS cell lines and mouse xenograft models. The results showed that TF3 reduced cell viability, suppressed cell proliferation, and caused G0/G1 cell cycle arrest in both MG63 and HOS cell lines in a concentration-dependent manner. TF3 also altered the homeostatic mechanisms for iron storage in the examined cell lines, resulting in an excess of labile iron. Unsurprisingly, TF3 caused oxidative stress through reduced glutathione (GSH) exhaustion, reactive oxygen species (ROS) accumulation, and the Fenton reaction, which triggered ferroptosis and apoptosis in the cells. TF3 also induced MAPK signalling pathways, including the ERK, JNK, and p38 MAPK pathways. Furthermore, oxidative stress was shown to be the primary reason for TF3-induced proliferation inhibition, programmed cell death, and MAPK pathway activation in vitro. Moreover, TF3 exhibited markedly strong antitumour efficacy in vivo in mouse models. In summary, this study demonstrates that TF3 concomitantly plays dual roles in apoptotic and ferroptotic cell death by triggering the ROS and MAPK signalling pathways in both in vitro and in vivo models.

Despite the high prevalence of osteoarthritis (OA) in older populations, disease-modifying OA drugs (DMOADs) are still lacking. This study was performed to investigate the effects and mechanisms of the small molecular drug salicin (SA) on OA progression. Primary rat chondrocytes were stimulated with TNF-α and treated with or without SA. Inflammatory factors, cartilage matrix degeneration markers, and cell proliferation and apoptosis markers were detected at the mRNA and protein levels. Cell proliferation and apoptosis were evaluated by EdU assays or flow cytometric analysis. RNA sequencing, molecular docking and drug affinity-responsive target stability analyses were used to clarify the mechanisms. The rat OA model was used to evaluate the effect of intra-articular injection of SA on OA progression. We found that SA rescued TNF-α-induced degeneration of the cartilage matrix, inhibition of chondrocyte proliferation, and promotion of chondrocyte apoptosis. Mechanistically, SA directly binds to IRE1α and occupies the IRE1α phosphorylation site, preventing IRE1α phosphorylation and regulating IRE1α-mediated endoplasmic reticulum (ER) stress by IRE1α-IκBα-p65 signaling. Finally, intra-articular injection of SA-loaded lactic-co-glycolic acid (PLGA) ameliorated OA progression by inhibiting IRE1α-mediated ER stress in the OA model. In conclusion, SA alleviates OA by directly binding to the ER stress regulator IRE1α and inhibits IRE1α-mediated ER stress via IRE1α-IκBα-p65 signaling. Topical use of the small molecular drug SA shows potential to modify OA progression.

Objectives: This study aimed to measure the patient safety culture and the current practice of patient safety goals in China. Methods: This cross-sectional survey was conducted between November 2020 and November 2021. The 12-dimensions Hospital Survey on Patient Safety Culture questionnaire and the 14-items Survey on the Current Practice of Patient Safety Goal questionnaire were electronically distributed to 8164 healthcare providers across 26 provinces in China. Data were analyzed using descriptive statistics, correlation analysis, and multivariate linear regression. Results: A total of 8164 surveys were received, of which 7765 were valid and analyzed. The average positive response rate for the Hospital Survey on Patient Safety Culture survey was 69.68% (43.41%–91.54%). The percentage of positive responses in 5 dimensions (organizational learning, teamwork within units, feedback about error, management support for safety, and teamwork across units) was above the control limits, and 3 (nonpunitive response to error, staffing, and frequency of event reporting) were below the control limits. The average positive response rate for the Survey on the Current Practice of Patient Safety Goal survey was 96.11%. Patient safety culture was positively related to the current practice of patient safety goals (r = 0.34, P < 0.001). Conclusions: Our study concludes that although healthcare providers in China feel positively toward patient safety culture and practicably toward patient safety goals, considerable work is still needed to promote a patient safety movement.

Metastasis of osteosarcoma (OS) is an essential factor affecting the prognosis and survival of patients. The tumor microenvironment, including tumor immune-infiltrating cells (TIIC), is closely related to tumor progression. The purpose of this study was to investigate the differences between metastatic and non-metastatic immune-infiltrating cells in OS and to identify key immune-related genes. The differences in immune infiltration in OS metastasis were calculated based on the ssGSEA algorithm of 28 immuno-infiltrating cells. Weighted gene co-expression network analysis (WGCNA) and intersection analysis were used to screen immune-related modules and hubgenes. Univariate/multivariate/Lasso Cox regressions were used for models construction and signatures screening. The receiver operating characteristic (ROC) and Kaplan–Meier (K–M) curves were constructed to observe the metastases of different groups. Both internal and external data were verified. We found that macrophages and Type-2 T-helper cells were significantly decreased in patients with OS metastases. The high-risk groups obtained from multivariate/Lasso Cox models constructed with 11 immune-related hubgenes almost all underwent distant metastases within 5 years. Interestingly and importantly, two genes, MSR1 and TLR7, appeared in various models and various hubgenes, which play an anti-metastasis role and may prolong overall survival in OS. Our study may help elucidate the impact of TIIC on OS metastasis outcomes and to identify biomarkers and therapeutic targets.