【Abstract】 Objective To investigate both incidence and mechanism attributing to steroid-associated osteonecrosisof femoral head(ONFH) using an experimental protocol with a single low-dose l i popolysaccharide (LPS) injection andsubsequently three injections of high-dose methylprednisolone (MPS). Methods Twenty-five New Zealand white rabbits with body weight of (3.0 ± 0.3) kg were divided randomly into 2 groups. In treatment group, 19 rabbits received one intravenous injection of LPS (10 μg/kg); 24 hours later, three injections of 20 mg/kg of MPS were given intramuscularly at an interval of 24 hours. Additional 6 rabbits which received normal sal ine injection at the same time point were used as controls(control group). The blood samples were collected for hematological examinations before and after LPS injection, MRI was performed on bilateral hip six weeks after last MPS injection, meanwhile, bone marrow was aspirated from femoral head region to evaluate stem cell’s activity. Bilateral femoral heads were harvested to make histopathology examination. Results All animals survived throughout the experiment period except one death on the second day after LPS injection. In the histopathological examinationfor the femoral head, ONFH+ was observed in 16 rabbits (88.9%), and the lesions were mainly in the metaphysis. In ONFH+ rabbits, micro vessels fibrous thrombosis and extravascular marrow fat cell size increasing were found around necrotic bone; The femoral heads of control group had no changes. MRI accurate ratio was 93.8% (15/16). Compared to basel ine, a significant decrease in ratio of tissue plasminogen activator/plasminogen activator inhibitor 1 and activated partial thromboplatin time, and a significant increase in ratio of low-density l ipoprotein/high-density l ipoprotein were only found in ONFH+ rabbits (P lt; 0.05). Meanwhile there was a significant decrease in the number of CFU-F (8.50 ± 9.63) compared with the control (70.17 ± 7.78, P lt; 0.05). Conclusion A single low-dose LPS injection and subsequent three injections of high-dose MPS is effective on building steroid-associated ONFH model, coagulation and l ipometabol ism abnormal ity, activity degeneration of stem cell may be the key factors of ONFH.
Objective To know the basic research and the clinical application of cartilage-derived retinoic acid-sensitive protein (CD-RAP) in orthopedic and in other clinical fields. Methods The literature related to CD-RAP in basic research and clinical application were extensively reviewed. Results CD-RAP, as a protein, which is cartilage-specific,could be a marker of the joint diseases. It also can be used to monitor metastsais of melanoma. Conclusion CD-RAP test provides a new way to study repair of cartilage and metastsais of melanoma.
ObjectiveTo investigate the molecular mechanism of osteoclast differentiation induced by Staphylococcal peptidoglycan (PGN-sa). MethodsRaw264.7 cells were stimulated with PGN-sa and with PGN-sa+SC75741[a potent inhibitor of nuclear factor κB (NF-κB) activation] in a concentration of 200 ng/mL. The protein expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) was tested at 0, 1, 2, and 3 days; the proteins related to osteoclast differentiation of extracellular regulated protein kinases (ERK), p38, c-Jun N-terminal kinase (JNK), NF-κB, inhibitor of NF-κB (IκB-α), Akt, and the phosphorylation forms of p38, ERK, JNK, Akt, NF-κB were measured at 0, 5, 10, 20, 40, and 60 minutes by Western blot. In addition, Raw264.7 cells were stimulated with PGN-sa in the concentrations of 100 ng/mL (group A), 200 ng/mL (group B), 400 ng/mL (group C), and with PBS (group D) for 1, 2, and 3 days; the expression levels of tumor necrosis factor α (TNF-α), interleukin 1α (IL-1α), and IL-6 were detected by ELISA. ResultsThe results of Western blot showed that the expression of NFATc1 increased gradually with time, showing significant difference between different time points (P<0.05). However, after SC75741 was added, the expression of NFATc1 was inhibited at 2 and 3 days, showing significant difference when compared with no addition of SC75741 (P<0.001). After stimulation of PGN-sa, the expression of IkB-α decreased significantly at 5 and 10 minutes when compared with those at the other time points (P<0.001), and returned to normal at 20 minutes. Meanwhile, the expression of p-NF-κB increased significantly at 5 and 10 minutes when compared with those at the other time points (P<0.001), and returned to normal at 20 minutes; and the expression of p-NF-κB at 5 minutes was significantly higher than that at 10 minutes (P<0.001). After the addition of SC75741, there was no change in the expressions of IκB-α and p-NF-κB, showing no significant difference between different time points P>0.05). Moreover, the expressions of ERK, p38, JNK, NF-κB, Akt, p-p38, p-ERK, p-JNK, and p-Akt showed no significant change between different time points P>0.05). ELISA results showed that there were no expressions of TNF-α and IL-1α in groups A-D at different time points. The expression of IL-6 had an increasing trend with time prolonged in each group, showing significant differences between different time points (P<0.05). Moreover, at 1 day after culture, the expression of IL-6 showed no significant difference among groups P>0.05). At 2 and 3 days after culture, the expression of IL-6 in groups A-C showed an increasing trend and was significantly higher than that in group D, showing significant difference among groups (P<0.05). ConclusionPGN-sa can promote osteoclast differentiation through NF-κB signaling pathway, and IL-6 may play a role in this process.
The issue of bacterial drug resistance has remained unresolved, and in recent years, biomimetic nanostructured surfaces inspired by nature have garnered significant attention due to their bactericidal properties demonstrated through mechanical mechanisms. This article reviewed the main research progress in the field of nanostructured mechanical bactericidal surfaces, including various preparation methods for nanostructured surfaces with mechanical bactericidal properties, as well as the basic mechanisms and related physical models of the interaction between bacteria and nanostructured surfaces. In addition, the application of nanostructured surfaces in biomedicine was introduced. Finally, the article proposed the major challenges faced by mechanical bactericidal research and the future development direction.
Objective To discuss the role of heparan sulfate (HS) in bone formation and bone remodeling and summarize the research progress in the osteogenic mechanism of HS. Methods The domestic and abroad related literature about HS acting on osteoblast cell line in vitro, HS and HS composite scaffold materials acting on the ani-mal bone defect models, and the effect of HS proteoglycans on bone development were summarized and analyzed. Results Many growth factors involved in fracture healing especially heparin-binding growth factors, such as fibroblast growth factors, bone morphogenetic protein, and transforming growth factor β, are connected noncovalently with long HS chains. HS proteoglycans protect these proteins from protease degradation and are directly involved in the regulation of growth factors signaling and bone cell function. HS can promote the differentiation of stem cells into osteoblasts and enhance the differentiation of osteoblasts. In bone matrix, HS plays a significant role in promoting the formation, maintaining the stability, and accelerating the mineralization. Conclusion The osteogenesis of HS is pronounced. HS is likely to become the clinical treatment measures of fracture nonunion or delayed union, and is expected to provide more choices for bone tissue engineering with identification of its long-term safety.
ObjectiveTo explore the mechanism of volume-related mitral regurgitation (MR) from the anatomy of mitral valve.MethodsA total of 32 patients with ventricular septal defect (VSD) combined MR meeting inclusion criteria in West China Hospital from September 2018 to November 2019 were enrolled in this study. The direction relative to the cardiac axis: the deviation of the MR bundle along the left atrial wall was eccentric, otherwises it was central. There were 23 patients of VSD and eccentric MR (EMR, a VSD-EMR group), including 10 males and 13 females aged 21 (10, 56) months, and 9 patients of VSD and central MR (CMR, a VSD-CMR group), including 4 males and 5 females aged 26 (12, 87) months. Besides, 9 healthy children were enrolled in a control group, including 4 males and 5 females aged 49 (15, 72) months. All patients underwent transthoracic echocardiography (TTE) examination at 2 weeks before surgery and 6 months after surgery, respectively, The MR degree, end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), antero-posterior diameter (AP), annulus circumference (AC), commissural diameter (CD) were assessed.ResultsBefore operation, EDV, ESV, SV, AP, AC and CD in the VSD-EMR and VSD-CMR groups were significantly larger or longer than those in the control group (P<0.05); after operation, EDV, ESV, SV, AP and CD decreased compared with those before operation (P<0.05), but there was no significant difference compared with the control group (P>0.05). Compared with the control group, AC was slightly decreased (P<0.05). There was no significant difference in EF between and within groups before and after operation (P>0.05). The improvement rate of MR was 78.9% (15/19) in the VSD-EMR group and 100.0% (9/9) in the VSD-CMR group.ConclusionAfter unloading of volume, the valve structure is back to normal except AC. The improvement rate of MR in the VSD-EMR group is lower than that in the VSD-CMR group, which may indicate that the mechanism of VSD-EMR is more complicated.
ObjectiveTo review the research progress on the role and mechanism of matrix stiffness in regulating endothelial cell sprouting. MethodsThe related literature at home and abroad in recent years was extensively reviewed, and the behaviors of matrix stiffness related endothelial cell sprouting in different cell cultivation conditions were analyzed, and the specific molecular mechanism of matrix stiffness regulating related signal pathways in endothelial cell sprouting was elaborated. Results In two-dimensional cell cultivation condition, increase of matrix stiffness stimulates endothelial cell sprouting within a certain range. However, in three-dimensional cell cultivation condition, the detailed function of matrix stiffness in regulating endothelial cell sprouting and angiogenesis are still unclear. At present, the research of the related molecular mechanism mainly focuses on YAP/TAZ, and roles of its upstream and downstream signal molecules. Matrix stiffness can regulate endothelial cell sprouting by activating or inhibiting signal pathways to participate in vascularization. ConclusionMatrix stiffness plays a vital role in regulating endothelial cell sprouting, but its specific role and molecular mechanism in different environments remain ambiguous and need further study.
Lung cancer is the most threatening tumor disease to human health. Early detection is crucial to improve the survival rate and recovery rate of lung cancer patients. Existing methods use the two-dimensional multi-view framework to learn lung nodules features and simply integrate multi-view features to achieve the classification of benign and malignant lung nodules. However, these methods suffer from the problems of not capturing the spatial features effectively and ignoring the variability of multi-views. Therefore, this paper proposes a three-dimensional (3D) multi-view convolutional neural network (MVCNN) framework. To further solve the problem of different views in the multi-view model, a 3D multi-view squeeze-and-excitation convolution neural network (MVSECNN) model is constructed by introducing the squeeze-and-excitation (SE) module in the feature fusion stage. Finally, statistical methods are used to analyze model predictions and doctor annotations. In the independent test set, the classification accuracy and sensitivity of the model were 96.04% and 98.59% respectively, which were higher than other state-of-the-art methods. The consistency score between the predictions of the model and the pathological diagnosis results was 0.948, which is significantly higher than that between the doctor annotations and the pathological diagnosis results. The methods presented in this paper can effectively learn the spatial heterogeneity of lung nodules and solve the problem of multi-view differences. At the same time, the classification of benign and malignant lung nodules can be achieved, which is of great significance for assisting doctors in clinical diagnosis.
In the diagnosis of cardiovascular diseases, the analysis of electrocardiogram (ECG) signals has always played a crucial role. At present, how to effectively identify abnormal heart beats by algorithms is still a difficult task in the field of ECG signal analysis. Based on this, a classification model that automatically identifies abnormal heartbeats based on deep residual network (ResNet) and self-attention mechanism was proposed. Firstly, this paper designed an 18-layer convolutional neural network (CNN) based on the residual structure, which helped model fully extract the local features. Then, the bi-directional gated recurrent unit (BiGRU) was used to explore the temporal correlation for further obtaining the temporal features. Finally, the self-attention mechanism was built to weight important information and enhance model's ability to extract important features, which helped model achieve higher classification accuracy. In addition, in order to mitigate the interference on classification performance due to data imbalance, the study utilized multiple approaches for data augmentation. The experimental data in this study came from the arrhythmia database constructed by MIT and Beth Israel Hospital (MIT-BIH), and the final results showed that the proposed model achieved an overall accuracy of 98.33% on the original dataset and 99.12% on the optimized dataset, which demonstrated that the proposed model can achieve good performance in ECG signal classification, and possessed potential value for application to portable ECG detection devices.
Tuberculosis is a chronic infectious diseases caused by Mycobacterium tuberculosis. Its high morbidity and mortality have posed a serious threat to global public health. Matrix metalloproteinase (MMP) is a proteolytic enzyme involved in regulating extracellular matrix degradation and remodeling. MMP is highly expressed in pulmonary tuberculosis, and its expression is regulated by genes, epigenetic modifications, cellular signaling pathways, immune regulation, and cellular environment. MMP is a potential target for the treatment of pulmonary tuberculosis. Therefore, this article summarizes the expression and related mechanisms of MMP in pulmonary tuberculosis, aiming to provide a reference for the diagnosis and treatment of pulmonary tuberculosis.