Opportunistic use of lumbar computed tomography and magnetic resonance imaging for osteoporosis screening.

Compared with the healthy patients, patients with osteoporosis had a lower Hounsfield unit (HU) value and a higher vertebral bone quality (VBQ) score. Both the HU value and VBQ score can simply distinguish patients with osteoporosis (OP), with a cutoff value of HU value < 97.06 and VBQ score > 3.08. INTRODUCTION: The purpose of this study is to determine whether the opportunistic use of computed tomography (CT) or magnetic resonance imaging (MRI) is effective for identifying spine surgical patients with OP. METHODS: We retrospectively evaluated 109 lumbar spine surgery patients who received lumbar quantitative CT (QCT) and MRI. Using the area under the curve, the CT-based HU value and MRI-based VBQ score were calculated. Then, based on the QCT results, receiver operating characteristic (ROC) curves were constructed to determine the diagnostic performance of the HU value and VBQ score. RESULTS: The HU value was significantly lower in the OP group, and the VBQ score was significantly higher in the OP group. Using the area under the curve, the diagnostic performance of the HU value and VBQ score for OP were 0.959 and 0.880, respectively. The diagnostic threshold values determined with optimal sensitivity and specificity were an HU value of 97.06 and a VBQ score of 3.08. CONCLUSION: Opportunistic use of CT and MRI can simply distinguish patients with OP, which are expected to be potential alternatives to T-score for the osteoporosis screening.

Low-dose lipopolysaccharide protects nerve cells against spinal cord injury via regulating the PI3K-AKT-Nrf2 signaling pathway.

This study explored the molecular mechanism behind the protective effects from low-dose lipopolysaccharide (LPS) on an in-vitro model of spinal cord injury (SCI). For this, PC12 cells were treated with different concentrations of LPS and the cell counting kit-8 assay was used to measure the toxicity of LPS to the cells. Next, we used immunofluorescence to measure nuclear translocation of Nrf2 in PC12 cells. PC12 cells were then treated with IGF-1 (PI3K agonist) and LY294002 (PI3K inhibitor). An in-vitro model of SCI was then established via oxygen-glucose deprivation/reoxygenation. Rates of apoptosis were measured using flow cytometry and the TUNEL assay. Low-dose LPS increased the expression levels of Nrf2, p-PI3K/PI3K, and p-AKT/AKT, and facilitated nuclear translocation of Nrf2. The activation of PI3K-AKT signaling by IGF-1 significantly increased the expression of Nrf2, whereas inhibition of PI3K-AKT signaling significantly decreased the expression of Nrf2. Low-dose LPS reduced the apoptotic ratio of PC12 cells, decreased the expression levels of caspase 3 and caspase 9, and increased the expression levels of HO-1, NQO1, and γ-GCS. Low-dose LPS also reduced the rate of apoptosis and oxidative stress by activating the PI3K-AKT-Nrf2 signaling pathway. Collectively, the results indicate that PI3K-AKT-Nrf2 signaling participates in the protective effects from low-dose LPS in an in-vitro PC12 cell model of SCI.

A CIC-related-epigenetic factors-based model associated with prediction, the tumor microenvironment and drug sensitivity in osteosarcoma.

Osteosarcoma is generally considered a cold tumor and is characterized by epigenetic alterations. Although tumor cells are surrounded by many immune cells such as macrophages, T cells may be suppressed, be inactivated, or not be presented due to various mechanisms, which usually results in poor prognosis and insensitivity to immunotherapy. Immunotherapy is considered a promising anti-cancer therapy in osteosarcoma but requires more research, but osteosarcoma does not currently respond well to this therapy. The cancer immunity cycle (CIC) is essential for anti-tumor immunity, and is epigenetically regulated. Therefore, it is possible to modulate the immune microenvironment of osteosarcoma by targeting epigenetic factors. In this study, we explored the correlation between epigenetic modulation and CIC in osteosarcoma through bioinformatic methods. Based on the RNA data from TARGET and GSE21257 cohorts, we identified epigenetic related subtypes by NMF clustering and constructed a clinical prognostic model by the LASSO algorithm. ESTIMATE, Cibersort, and xCell algorithms were applied to analyze the tumor microenvironment. Based on eight epigenetic biomarkers (SFMBT2, SP140, CBX5, HMGN2, SMARCA4, PSIP1, ACTR6, and CHD2), two subtypes were identified, and they are mainly distinguished by immune response and cell cycle regulation. After excluding ACTR6 by LASSO regression, the prognostic model was established and it exhibited good predictive efficacy. The risk score showed a strong correlation with the tumor microenvironment, drug sensitivity and many immune checkpoints. In summary, our study sheds a new light on the CIC-related epigenetic modulation mechanism of osteosarcoma and helps search for potential drugs for osteosarcoma treatment.

Comparison of curative effect between OBS assisted by 3D printing and PFNA in the treatment of AO/OTA type 31-A3 femoral intertrochanteric fractures in elderly patients.

Objective: To compare and analyze the Ortho-Bridge System (OBS) clinical efficacy assisted by 3D printing and proximal femoral nail anti-rotation (PFNA) of AO/OTA type 31-A3 femoral intertrochanteric fractures in elderly patients. Methods: A retrospective analysis of 25 elderly patients diagnosed with AO/OTA type 31-A3 femoral intertrochanteric fracture was conducted from January 2020 to August 2022 at Yan'an Hospital, affiliated to Kunming Medical University. The patients were divided into 10 patients in the OBS group and 15 in the PFNA group according to different surgical methods. The OBS group reconstructed the bone models and designed the guide plate by computer before the operation, imported the data of the guide plate and bone models into a stereolithography apparatus (SLA) 3D printer, and printed them using photosensitive resin, thus obtaining the physical object, then simulating the operation and finally applying the guide plate to assist OBS to complete the operation; the PFNA group was treated by proximal femoral nail anti-rotation. The operation time, the intraoperative blood loss, Harris hip score (HHS), Oxford Hip Score (OHS), and complications were compared between the two groups. Results: The operation time and the intraoperative blood loss in the PFNA group were less than that in the OBS group, and there was a significant difference between the two groups (P < 0.05). The HHS during the 6th month using OBS was statistically higher than PFNA (P < 0.05), however, there were no significant differences in OHS during the 6th month between the OBS group and PFNA group (P > 0.05). The HHS and OHS during the 12th month in the OBS group were statistically better than in the PFNA group (P < 0.05). Conclusion: The OBS assisted by 3D printing and PFNA are effective measures for treating intertrochanteric fractures. Prior to making any decisions regarding internal fixation, it is crucial to evaluate the distinct circumstances of each patient thoroughly.

In leukemia, knock-down of the death inducer-obliterator gene would inhibit the proliferation of endothelial cells by inhibiting the expression of CDK6 and CCND1.

BACKGROUND: Endothelial cells (ECs) are a critical component of the hematopoietic niche, and the cross-talk between ECs and leukemia was reported recently. This study aimed to determine the genes involved in the proliferation inhibition of endothelial cells in leukemia. METHODS: Human umbilical vein endothelial cells (HUVEC) were cultured alone or co-cultured with K562 cell lines. GeneChip assays were performed to identify the differentially expressed genes. The Celigo, MTT assay, and flow cytometric analysis were used to determine the effect of RNAi DIDO on cell growth and apoptosis. The differently expressed genes were verified by qRT-PCR (quantitative real-time PCR) and western-blot. RESULTS: In K562-HUVEC co-cultured cell lines, 323 down-regulated probes were identified and the extracellular signal-regulated kinase 5 (ERK5) signaling pathway was significantly inhibited. Among the down-regulated genes, the death inducer-obliterator gene (DIDO) is a part of the centrosome protein and may be involved in cell mitosis. As shown in the public data, leukemia patients with lower expression of DIDO showed a better overall survival (OS). The HUVEC cells were infected with shDIDO lentivirus, and reduced expression, inhibited proliferation, and increased apoptosis was observed in shDIDO cells. In addition, the expression of Cyclin-Dependent Kinase 6 (CDK6) and Cyclin D1 (CCND1) genes was inhibited in shDIDO cells. Finally, the public ChIP-seq data were used to analyze the regulators that bind with DIDO, and the H3K4me3 and PolII (RNA polymerase II) signals were found near the Exon1 and exon2 sites of DIDO. CONCLUSION: The knock-down of DIDO will inhibit the proliferation of endothelial cells in the leukemia environment. The expression of DIDO may be regulated by H3K4me3 and the inhibition of DIDO may lead to the down-regulation of CDK6 and CCND1. However, how DIDO interacts with CDK6 and CCND1 requires further study.

A new osteonecrosis animal model of the femoral head induced by microwave heating and repaired with tissue engineered bone.

The objective of this research was to induce a new animal model of osteonecrosis of the femoral head (ONFH) by microwave heating and then repair with tissue engineered bone. The bilateral femoral heads of 84 rabbits were heated by microwave at various temperatures. Tissue engineered bone was used to repair the osteonecrosis of femoral heads induced by microwave heating. The roentgenographic and histological examinations were used to evaluate the results. The femoral heads heated at 55 degrees C for ten minutes showed low density and cystic changes in X-ray photographs, osteonecrosis and repair occurred simultaneously in histology at four and eight weeks, and 69% femoral heads collapsed at 12 weeks. The ability of tissue engineered bone to repair the osteonecrosis was close to that of cancellous bone autograft. The new animal model of ONFH could be induced by microwave heating, and the tissue engineering technique will provide an effective treatment.

Effect of mesenchymal stem cells transplantation combining with hyperbaric oxygen therapy on rehabilitation of rat spinal cord injury.

OBJECTIVE: To investigate the effect of BMSCs transplantation plus hyperbaric oxygen (HBO) on repair of rat SCI. METHODS: Seventy five male rats were divided randomly into five groups: sham, vehicle, BMSCs transplantation group, combination group, 15 rats in each group. Every week after the SCI onset, all animals were evaluated for behavior outcome by Basso-Beattle-Bresnahan (BBB) score and inclined plane test. Axon recovery was examined with focal spinal cord tissue by electron microscope at 6 weeks after the SCI onset. HE staining and BrdU staining were performed to examine the BMSCs and lesion post injury. Somatosensory evoked potential (SEP) testing was performed to detect the recovery of neural conduction. RESULTS: Results from the behavior tests from combination group were significant higher than rats which received only transplantation or HBO treatment. Results from histopathology showed favorable recovery from combination group than other treatment groups. The number of BrdU(+) in combination group were measureable more than transplantation group (P < 0.05). The greatest decrease in TNF-α, IL-1ß, IL-6, IFN-α determined by Elisa assay in combination group were evident too. CONCLUSIONS: BMSCs transplantation can promote the functional recovery of rat hind limbs after SCI, and its combination with HBO has a synergistic effect.

The effects of hyperbaric oxygen on macrophage polarization after rat spinal cord injury.

The immunoreactive responses are a two-edged sword after spinal cord injury (SCI). Macrophages are the predominant inflammatory cells responsible for this response. However, the mechanism underlying the effects of HBOT on the immunomodulation following SCI is unclear now. The present study was performed to examine the effects of hyperbaric oxygen therapy (HBOT) on macrophage polarization after the rat compressive injury of the spinal cord. HBOT was associated with significant increases in IL-4 and IL-13 levels, and reductions in TNF-α and IFN-É£ levels. This was associated simultaneously with the levels of alternatively activated macrophages (M2 phenotype: arginase-1- or CD206-positive), and decreased levels of classically activated macrophages (M1 phenotype: iNOS- or CD16/32-positive). These changes were associated with functional recovery in the HBOT-transplanted group, which correlated with preserved axons and increased myelin sparing. Our results suggested that HBOT after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, which may further promote the axonal extension and functional recovery.