Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets.

Osteosarcoma (OS) has a high recurrence rate, disability rate, mortality and metastasis, it brings great economic burden and psychological pressure to patients, and then seriously affects the quality of life of patients. At present, the treatment methods of OS mainly include radiotherapy, chemotherapy, surgical therapy and neoadjuvant chemotherapy combined with limb salvage surgery. These treatment methods can relieve the clinical symptoms of patients to a certain extent, and also effectively reduce the disability rate, mortality and recurrence rate of OS patients. However, because metastasis of tumor cells leads to new complications, and OS cells become resistant with prolonged drug intervention, which reduces the sensitivity of OS cells to drugs, these treatments still have some limitations. More and more studies have shown that traditional Chinese medicine (TCM) has the characteristics of "multiple targets and multiple pathways," and can play an important role in the development of OS through several key signaling pathways, including PI3K/AKT, Wnt/ß-catenin, tyrosine kinase/transcription factor 3 (JAK/STAT3), Notch, transforming growth factor-ß (TGF-ß)/Smad, nuclear transcription factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nuclear factor E2-related factor 2 (Nrf2), Hippo/YAP, OPG/RANK/RANKL, Hedgehog and so on. In this paper, the signaling pathways of cross-interference between active ingredients of TCM and OS were reviewed, and the development status of novel OS treatment was analyzed. The active ingredients in TCM can provide therapeutic benefits to patients by targeting the activity of signaling pathways. In addition, potential strategies for targeted therapy of OS by using ferroptosis were discussed. We hope to provide a unique insight for the in-depth research and clinical application of TCM in the fields of OS growth, metastasis and chemotherapy resistance by understanding the signaling crosstalk between active ingredients in TCM and OS.

Dynamic computed tomography manifestations of simulated wooden foreign bodies in blood-saline mixtures with variable concentrations and retention times.

Diagnosing wooden foreign bodies (WFBs) using computed tomography (CT) is often missed, leading to adverse outcomes. This study aims to reduce misdiagnoses by exploring the density variation of blood-saline mixtures in ex vivo models. Twenty Cunninghamia lanceolata sticks, selected as WFB models, were randomly assigned to five groups: a control group (saline) and four experimental groups immersed in blood-saline mixtures with varying concentrations. The samples were then placed in a constant-temperature water bath at 36.8 °C. CT scans were performed in the lowest and highest density areas, and the volume of the low-density areas was measured at the post-processing workstation. Finally, the effects of time and concentration on imaging were analyzed, and fitting curves were generated. The blood-saline mixture concentration and time significantly affected the CT number in the three areas. WFB images changed dynamically over time, with two typical imaging signs: the bull's-eye sign on the short axis images and the tram line sign on the long axis images. Fitting curves of the CT number in the lowest density areas with different concentrations can quantify imaging changes. The CT number of the lowest density areas increased with time, following a logarithmic function type, while the CT number of the highest density areas exhibited a fast-rising platform type. The volume of the low-density areas decreased over time. The time of damage caused by WFBs and the influence of varying blood and tissue fluid contents at the damaged site should be considered in the diagnosis. Imaging changes from multiple CT scans at different times can aid in diagnosis.

[Expression of Ras-Associated Protein 1 in the Vascular Endothelium of Bone Tissue with Non-Traumatic Osteonecrosis of Femoral Head].

Objective: To investigate the difference in the expression of Ras-associated protein 1 (Rap1) in necrotic and healthy areas of non-traumatic osteonecrosis of femoral head (NONFH) patients. Methods: Femoral head tissue samples from 30 cases of NONFH and 30 cases of traumatic osteonecrosis of the femoral head (TONFH) were collected after hip replacement surgery, respectively. No significant difference of Association Research Circulation Osseous (ARCO) staging was found between the NONFH and the TONFH groups ( Z=-0.769, P=0.442). In the NONFH group, 8 patients were ARCO stage IIIb, 10 were stage IV, and 12 were stage V, while in the TONFH ground, 11 patients were ARCO stage IIIb, 9 were stage IV, and 10 were stage V. There were 19 males and 11 females in the NONFH group, with an average age of 49.6 yr. (26-69 yr.), and 16 males and 14 females in the TONFH group, with an average age of 54.2 yr. (37-68 yr.). There was no significant difference in gender or age between the two groups ( P>0.05). Specimens were collected from different bone areas, including those from the necrotic areas (area A) and the healthy areas (area B) of the NONFH group, and those from the healthy areas (area B') of the TONFH group, i.e., the control group. Western blot and quantitative real-time reverse transcription PCR (qRT-PCR) were used to analyze the different expression of Rap1, vascular endothelial growth factor (VEGF) protein, phosphoinositide 3-kinase (PI3K), and Akt protein and their corresponding mRNA in the three areas of bone tissue. HE staining and immunohistochemisty staining were done in order to observe the morphological changes of each area. Results: Western blot results indicated that there was no statistical difference in the relative expression of Rap1, VEGF, PI3K, and Akt proteins ( P>0.05). The relative expressions of Rap1, VEGF, PI3K, and Akt proteins in the area A were lower than those in the area B and the difference was statistically significant ( P<0.05). qRT-PCR results showed that the relative expressions of Rap1, VEGF, PI3 K and Akt mRNA in area A were lower than those of area B, and a statistical difference was found ( P<0.05). The relative expression of the mRNA of Rap1, VEGF , PI3 K and Akt in area B and area B' were not significantly different ( P>0.05). HE staining and immunohistochemisty staining showed that chondrocytes decreased in the necrotic area (area A) of NONFH, chondrocytes nucleus disappeared, subchondral bone trabeculae were broken, bone trabeculae thickened, and empty bone lacunae appeared. Granulation tissues composed of new capillaries and fibrous cells have proliferated and crawled around the necrotic area. Positive expressions of the Rap1, VEGF, PI3K and Akt proteins in area A were weaker than those of the normal area. In addition, there were positive expressions of Rap1, PI3K and Akt on the trabecular bone of both area A and area B at similar intensity of expression. There were strong positive expressions of Rap1, VEGF, PI3K and Akt on the intima of arterioles and venules, and on the peripheral stromal cell membrane, but the positive expression in area A was significantly lower than that in area B. However, the positive expression positions and intensity of all indicators were similar in area B and area B'. Conclusion: The necrosis in NONFH may be related to vascular endothelial damages caused by the inhibition of the Rap1-PI3K/Akt signaling pathways and the subsequent decline in the protein expression.

Value of MR diffusion imaging in hepatic fibrosis and its correlations with serum indices.

AIM: To compare apparent diffusion coefficient (ADC) values on diffusion-weighted imaging (DWI) of hepatic fibrosis patients with those of healthy controls and to identify their correlations with serum indices of liver fibrosis. METHODS: Hyaluronic acid (HA), laminin (LN), type III procollagen (PCIII), and collagen type IV (IV-C) were measured in 54 hepatic fibrosis patients and 23 normal controls, and ADC values were determined on DWI at different b values (b = 300, 500, 700 s/mm(2)). Correlations between serum indices and ADC values at different liver fibrosis stages were examined, and each index variation of liver fibrosis in different stages were compared, and correlation analysis of each index and the staging of liver fibrosis carried out, and the correlation of each index performed. RESULTS: With progressive liver fibrosis, HA, PCIII, and IV-C levels increased (P < 0.01). As the b value increased, the ADC value decreased gradually with the hepatic fibrosis stages. In different groups with b values of 500 s/mm(2) and 700 s/mm(2), the ADC value decreased significantly as liver fibrosis progressed (P < 0.01). With b values of 500 s/mm(2) and 700 s/mm(2), there were negative correlations between ADC and LN, PCIII, HA, and IV-C. This pattern was observed only for HA and IV-C at a b value of 300 s/mm(2). CONCLUSION: Serum indices of liver fibrosis and ADC values are useful for diagnosing liver fibrosis, with some correlations among them.