Comparison of elastic stable intramedullary nailing versus Kirschner wires in treatment of pediatric radial neck fractures.

Purpose: The aim of the study was to compare the different internal fixations between elastic stable intramedullary nailing and Kirschner wires in treatment of angulated radial neck fractures. Methods: We retrospectively reviewed the patients with radial neck fracture without associated injuries who underwent surgery approach in our department during April 2011-March 2020. There were 62 patients meeting all the criteria with complete clinical data, with median age of 7.5 (IQR 5.8-9.5) years, 34 males and 28 females. The preoperative fracture pattern was assessed according to the Judet classification system. Depending on the materials implanted and fixation strategy, the patients could be divided into a Kirschner wire group and an elastic stable intramedullary nailing group. Final functional outcomes of patients were assessed by the Mayo Elbow Performance Score and Tibone-Stoltz functional evaluation classification. Results: The Kirschner wire group included 37 patients, with 4.8 years median follow-up. The elastic stable intramedullary nailing group included 25 patients with 5.9 years median follow-up. There were no significant differences in gender, age, Judet classification, average operative time, Mayo Elbow Performance Score, Tibone-Stoltz classification, or length of hospital stay between groups. However, the time to union in the Kirschner wire group was significantly shorter than that in the elastic stable intramedullary nailing group (p < 0.05). Both groups achieved satisfactory functional and cosmetic results. Conclusion: In the management of pediatric radial neck fractures, both elastic stable intramedullary nailing and Kirschner wire internal fixation have shown equivalent therapeutic results, leading to satisfactory functional outcomes. The selection of the internal fixation approach can be influenced by the patient's fracture characteristics and the surgeon's preferences. Level of evidence: Level III; Retrospective Comparison; Treatment Study.

A novel targeted iron oxide nanocarrier for inhibiting M2-type macrophages in the tumor microenvironment.

Background: Tumor-associated macrophages (TAMs) are vital to the tumor microenvironment. They are classified as antitumor M1-type or protumor M2-type macrophages. M2-type macrophages accumulate in the tumor stroma and are related to poor prognosis. Iron oxide nanoparticles are used as drug delivery vehicles because of the structure of carboxyl groups on their surface and their ability to be easily phagocytosed by macrophages. Aim: The signal transducer and activator of transcription 6 (STAT6) signaling pathway controls M2 macrophage polarization, but the STAT6 signaling pathway inhibitor AS1517499 lacks efficient targeting in vivo. Thus, our study aimed to block the polarization of TAMs to M2-type macrophages. Methods and Material: We used ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) as drug carriers coated with the STAT6 signaling pathway inhibitors AS1517499 and CD163 monoclonal antibodies to synthesize the targeted nanocomplex AS1517499-USPION-CD163 utilizing the carbodiimide method. Then, we determined its physicochemical properties, including hydrodynamic size distribution, ultrastructure, iron concentration, protein content and activity of the CD163 monoclonal antibody, AS1517499 content, and selectivity for M2-type macrophages, and its biological applications. Results: The hydrodynamic size distribution was stable (average size = 95.37 nm). Regarding biological applications, the targeted nanocomplex selectively inhibited M2-type macrophages. Conclusions: The targeted nanocomplex AS1517499-USPION-CD163 showed high selectivity for M2-type macrophages. Therefore, iron oxide nanoparticles targeting TAMs may be an effective approach to TAM therapy.

MMP-9 secreted by M2-type macrophages promotes Wilms' tumour metastasis through the PI3K/AKT pathway.

BACKGROUND: Wilms' tumour (WT) is a malignant tumour of childhood with the typical symptoms of an abdominal mass. Tumour-associated macrophages (TAMs) accumulate and imply a poor prognosis in WT, but the mechanism of how TAMs affect the prognosis has not been fully elucidated. In this study, we aimed to present the molecular mechanisms underlying the protumorigenic capacities of TAMs in WT. METHODS: TAMs were polarized into M1- and M2-type macrophages. The two types of macrophages were cocultured with SK-NEP-1 cells, and their cell viability and invasion ability were measured. Matrix metalloproteinase 9 (MMP9) expression was assessed in different types of macrophages, and the role of MMP9 in WT was explored. Then data from children diagnosed with WT in our department between February 2006 and July 2014 were retrospectively analysed, the tumour tissues were analysed to explore the distribution of MMP9. Kaplan-Meier analysis of the relationship between MMP9 expression and follow-up information was performed. RESULTS: The results showed that M2-type macrophages could improve the viability and invasive ability of SK-NEP-1 cells. MMP9 expression in M2-type macrophages was significantly higher than that in M1-type macrophages. MMP9 could activate the AKT/PI3K signalling pathway to initiate the epithelial-mesenchymal transition (EMT) process, and promote the proliferation and invasion of WT. In WT tissue, the MMP9 expression level was elevated and it was located in the tumour stroma, which was the same as M2-type macrophage location, and a high level of MMP9 predicted poor survival. CONCLUSION: M2-type macrophages facilitate tumour proliferation and metastasis by secreting MMP9 to enhance the EMT process via a PI3K/AKT dependent pathway in Wilms' tumour.

Recognition of M2 type tumor-associated macrophages with ultrasensitive and biocompatible photoelectrochemical cytosensor based on Ce doped SnO2/SnS2 nano heterostructure.

Tumor-associated macrophages (TAMs) play central roles in the regulation of tumor growth. TAMs can be differentiated into M1 and M2 types, which are responsible for the inhibition and growth of tumor tissues, respectively. Recognition of M2-TAMs is significant for the diagnosis and therapy of cancer, which is however severely limited due to the deficiency of selective and sensitive photoelectrochemical sensors. In this work, using Ce doped SnO2/SnS2 nano heterostructure as the highly sensitive platform, a photoelectrochemical sensor enabling the recognition of M2-TAMs was fabricated for the first time. By the decoration of CD163 antibody on the platform, the ultrasensitive photoelectrochemical sensor can selectively detect the CD163 protein on the surface of M2-TAMs. To our best knowledge, this is the first demonstration for recognition of M2-TAMs using photoelectrochemical method. The fabricated cytosensor has ultra-sensitive photocurrent response, applicable biological compatibility, high selectivity and relatively wide linear sensing range (5 × 101 to 1 × 105 cells/ml) with a low detection limit (50 cells/ml) for the detection of M2-TAMS. This kind of PEC cytosensor would provide a novel analysis and detection strategy for M2-TAMs.

Relationship of tumour-associated macrophages with poor prognosis in Wilms' tumour.

BACKGROUND: Wilms' tumour (WT) is the most common childhood renal tumour. Tumour-associated macrophages (TAMs) are a critical component of tumour microenvironments and contain two main subtypes, classically (M1) or alternatively (M2) activated macrophages. Evidence has revealed TAMs in predicting poor prognosis in some malignant tumours. However, the role of TAMs in WT is still unclear, and the relationship of different types of TAMs with prognosis has not been elucidated. OBJECTIVE: The aim of the study was to explore the presence of two types of TAMs in WT and analyse the relationship of TAMs with prognosis. STUDY DESIGN: Overall, 61 paediatric patients with WT underwent nephrectomy before any chemotherapy from April 2006 to March 2014. The tumour tissues were analysed by Western blot, immunohistochemistry, and immunofluorescence to explore the distribution of M1 and M2 macrophages in different stages. Kaplan-Meier analysis with regard to the relationship between the presence of TAMs and follow-up information was performed. RESULTS: In the 61 patients (44 males and 17 females), there was a median age of 19 months (IQR 13-35.5); 47 patients are still alive, 11 died, 3 were lost to follow-up. According to the National Wilms Tumor Study (NWTS)-5 guidelines, the distribution of tumour stages was as follows: stage I, 27 patients; stage II, 18 patients; and stage III, 16 patients. The Western blot analysis showed that the density of M1 and M2 macrophages in tumour tissues were significantly greater than that in adjacent normal tissues. Immunohistochemistry showed the proportion of patients with positive M1-type macrophages across different stages: stage I, 66.7% (18/27); stage II, 44.4% (8/18); and stage III, 25% (4/16) (p = 0.027). The proportion of patients with positive M2-type macrophages across different stages: stage I, 25.9% (7/27); stage II, 55.6% (10/18); and stage III, 81.3% (13/16) (p = 0.002). Kaplan-Meier analysis suggested that patients with high densities of M2-type macrophages had shorter overall survival time than those with low densities (log-rank test, p = 0.011). DISCUSSION: TAMs play a pivotal comments in the tumour microenvironment and tumorigenesis. With the progression of clinical stage, M2 macrophage densities increased greatly, and M1 macrophage density decreased. M2 macrophages represent a poor prognosis and can be utilized as a new indicator in pathological examination. CONCLUSION: There is a high density of TAMs in WT, and M2-type macrophage density increases with tumour progression and implies a poor prognosis.

The oncogenic role of GNL3 in the progression and metastasis of osteosarcoma.

BACKGROUND: GNL3 has been reported to be up-regulated in cancers and function in tumor progression, whereas the role of GNL3 in the progression of osteosarcoma remains unclear. MATERIALS AND METHODS: In this study, we blocked the expression of GNL3 by siRNA interference in osteosarcoma cell lines MG63 and U20S. CCK8, colony formation, wound-healing, Transwell, flow cytometry, and Hoechst/PI staining assays were used to examine the effects of GNL3 knockdown on cell proliferation, migration, invasion and apoptosis in MG63 and U20S cells. The relative activity of MMP9 was detected using Gelatin zymography assay. Western blot was performed to detect the expression of related proteins. RESULTS: We found that silencing of GNL3 reduced the growth, migration, and invasion abilities of MG63 and U20S cells. Moreover, silencing GNL3 triggered cell cycle arrest in MG63 and U20S cells, as well as promoted cell apoptosis. In addition, depletion of GNL3 was observed to reduce the activity of MMP9 and suppress the process of epithelial-mesenchymal transition (EMT) through up-regulation of E-cadherin and down-regulation of N-cadherin. Furthermore, we found that X-box-binding protein 1 (XBP1) could bind to GNL3 using dual-luciferase reporter assay, and XBP1 overexpression could restore the inhibitory effects on proliferation, invasion, and EMT in MG63 and U20S cells caused by GNL3 knockdown. CONCLUSION: These data suggest that GNL3 functions as an oncogene in the progression of osteosarcoma by regulation of EMT, and XBP1 is also involved in its mechanism.