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Abstract Objectives N6-Methyladenosine (m6A) modification plays a vital role in lung disorders. However, the potential of m6A in neonatal Bronchopulmonary Dysplasia (BPD) has not been reported. This study aimed to investigate the roles of METTL3 in BPD. Methods BPD models were established by hyperoxia in vivo and in vitro. Histological analysis was determined using HE staining. Gene expression was determined using Western blotting, qRT-PCR, and immunofluorescence. The release of IL-1β and IL-18 was detected using ELISA. The m6A sites of ATG8 were predicted by SCRAPM and verified by MeRIP assay. The location of GSDMD and ATG8 was determined by FISH assay. The interaction between ATG8 and GSDMD was detected using Coimmunoprecipitation (Co-IP). Cell pyroptosis was determined using flow cytometry and TUNEL assays. Results METTL3 was overexpressed in BPD, which was accompanied by an increase in m6A levels. Interestingly, METTL3 suppressed hyperoxia-mediated damage and pyroptosis in BEAS-2B cells and promoted cell autophagy. METTL3-mediated m6A modification of ATG8 suppressed its expression and disrupted the interaction between ATG8 and GSDMD. However, autophagy inhibition induced pyroptosis in BEAS-2B cells. In vivo assays showed that METTL3-mediated autophagy inhibition induced a decrease in the radial alveolar count and an increase in the mean linear intercept and promoted cell pyroptosis. Conclusion In conclusion, METTL3-mediated cell pyroptosis promotes BPD by regulating the m6A modification of ATG8. This may provide new insight into the development of BPD.
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Objective:To determine the influences of structural changes after valgus impacted femoral neck fracture on hip range of motion (ROM) so as to provide evidence for clinical judgment of whether reduction is necessary or not in the internal fixation of such fractures.Methods:1. 3D reconstructions of the CT hip scans were performed for the 73 patients who had been treated at Department of Orthopaedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University for valgus impacted femoral neck fractures from January 2019 to April 2019.The femoral neck-shaft angle, anteversion angle, femoral offset, axial alpha angle, lateral center edge angle (LCEA), anterior center edge angle (ACEA) and center displacement were measured and compared between the affected and healthy sides to determine the influences of the fracture on the above indexes. 2. Hip motions (flexion and MIR-90°) were simulated on bilateral sides to determine the influences of structural changes after fracture on hip ROM using stepwise regression and Logistic regression. 3. The distribution of femoral-acetabular contact points on the femoral side was observed in simulation of hip flexion to detect the potential area for femoracetabular impingement (FAI) induced by the fracture displacement.Results:1. The valgus impacted femoral neck fractures had significant influences on femoral neck-shaft angle, anteversion angle, femoral offset and axial alpha angle. Compared with the healthy side, on average, the femoral neck-shaft angle increased by 5.1°, anteversion angle decreased by 6.5°, femoral offset decreased by 8.2 mm and axial alpha angle increased by 9.7° on the affected side, showing significant differences ( P<0.05).The displacements of the femoral head center averaged 9.2 mm. There was no significant difference in LCEA or ACEA between the affected and healthy sides ( P>0.05). 2. Compared with the healthy side, on average, the simulated hip flexion decreased significantly by 27.0° and the hip MIR-90° decreased significantly by 20.3° on the affected side after fracture ( P<0.05). Regression analysis showed that femoral anteversion angle, ACEA and displacement of the femoral head center had a significant influence on hip ROM, especially the anteversion angle. When the anteversion angle decreased by more than 7.1°, the hip flexion would decrease by at least 20%. 3. The points of FAI distributed more widely on the fracture side. Compared with the healthy side, the impact points extended outward and upward in hip flexion and extended inwardly in hip MIR-90° on the affected side. Conclusions:After a valgus impacted femoral neck fracture, if the femoral anteversion angle has been decreased by more than 7.1°, the hip ROM can be greatly influenced and the points of FAI can be distributed more widely. Therefore, reduction should be recommended before internal fixation of the fracture.
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The high mobility group protein A2 (HMGA2) has been demonstrated as an architectural transcription factor that is associated with pathogenesis of many malignant cancers; however, its role in prostate cancer cells remains largely unknown. To explore whether HMGA2 participates in the development and progression of prostate cancer, small interfering RNA (siRNA) targeted on human HMGA2 was transfected to suppress the HMGA2 expression in prostate cancer PC3 and DU145 cells, and then the cellular biology changes after decreased the expression of HMGA2 was examined. Our results showed that knockdown of HMGA2 markedly inhibited cell proliferation; this reduced cell proliferation was due to the promotion of cell apoptosis as the Bcl-xl was decreased, whereas Bax was up-regulated. In addition, we found that HMGA2 knockdown resulted in reduction of cell migration and invasion, as well as repressed the expression of matrix metalloproteinases (MMPs) and affected the occurrence of epithelial-mesenchymal transition (EMT) in both cell types. We further found that decreased HMGA2 expression inhibited the transforming growth factor-β (TGF-β)/Smad signalling pathway in cancer cells. In conclusion, our data indicated that HMGA2 was associated with apoptosis, migration and invasion of prostate cancer, which might be a promising therapeutic target for prostate cancer.
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Objective To study the feasibility of using digital volume correlation (DVC) method to track displacement and deformation of lung tumor and chest during the period of respiration. Methods A DVC algorithm suitable for tracking 3D movement of tissues in chest was proposed. The 4D CT imaging technique was adopted to acquire images of a patient with lung cancer during one complete respiration stage. The inhalation was set as the initial stage for reference, to determine the locations of lung cancer and chest. Four specified regions of both the tumor and chest at the initiation of inhalation stage were selected. The corresponding 3D displacement of lung in the following 5 inhalation phase stages, i.e. 20%, 40% 60%, 80% and 100% as well as 3D displacement of chest in 100% inhalation phase stage were analyzed by DVC software. Results The displacement and deformation error of tumor was within 1 mm, while that of chest was within 0.5 mm. The maximum displacement of tumor presented itself along the vertical direction of human body during respiration, while that of chest at the end of inhalation stage appeared along the front and back direction of human body. Conclusions DVC methods can be potentially used to detect displacement and deformation of body tissues such as lung tumor and chest during the respiratory cycle. This study provides references for noninvasive, non X-ray, real-time image-guided radiation therapy for lung cancer based on DVC method.
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<p><b>OBJECTIVE</b>To investigate whether ω-6 polyunsaturated fatty acid promotes colon carcinogenesis through downregulation of P53-dependent growth inhibition.</p><p><b>METHODS</b>Colon carcinogenesis was induced by injection of azoxymethane (AOM) intraperitoneally. Experimental animals were randomly divided into four groups, receiving regular diet and intraperitoneal injection of normal saline(control group), high ω-6 polyunsaturated fatty acid diet with intraperitoneal injection of normal saline(Corn oil group), regular diet with intraperitoneal injection of AOM(AOM group), or high ω-6 polyunsaturated fatty acid diet with intraperitoneal injection of AOM (Corn oil+AOM group). Aberrant crypt focis (ACFs) were observed after methylene blue staining and enumerated. Colonic mucosa PCNA and P53 expressions were assessed by RT-PCR and Western blotting, and location of P53 in the colon crypt focis was determined by immunohistochemical staining.</p><p><b>RESULTS</b>Amounts of ACFs was 1.2±0.3 in the control group, 1.3±0.4 in the Corn oil group, 41.0±4.8 in the AOM group, and 73.3±9.9 in the Corn oil+AOM group, the differences were statistically significant(P<0.05). The expression of P53 in normal crypt focis was higher than that in ACFs. High ω-6 polyunsaturated fatty acid dietary significantly promoted AOM-induced colon PCNA expression, and enhanced AOM-mediated P53 inhibition in colon mucosa.</p><p><b>CONCLUSION</b>High ω-6 polyunsaturated fatty acid diet can enhance AOM-induced inhibition of P53 in colon mucosa, resulting in overexpression of PCNA, formation of ACF, and carcinogenesis in the colon.</p>
Subject(s)
Animals , Male , Rats , Colon , Metabolism , Fatty Acids, Unsaturated , Intestinal Mucosa , Metabolism , Proliferating Cell Nuclear Antigen , Metabolism , Rats, Sprague-Dawley , Tumor Suppressor Protein p53 , MetabolismABSTRACT
Objective To investigate and assess the clinical effect of treatment of children′s fractures at distal radial or radial-ulna through incision and Kirschner wire′s interior fixation without coursing epiphysis.Methods The treatment of children′s fractures at distal radial or radial-ulna in our hospital between 1996 and 2005 were reviewed,91 cases via Kirsehner-wire′s internal fixation were dealt.According to the way of placing Kirschner wire,the patients were divided into 2 groups.Group A of 53 cases eschewing epiphysis and passed bone-cortex.Group B of 38 cases got intramedullary fixation and passed epiphysis for 38 cases.After 6-100 months′ follow-up investigation,the 2 groups were comporred by analyzing statistics and the number of cases which involved repeatedly setting of Kirschner wire during operation,anatomical restoration,replacement,Kirschner-wire moving,infection,wrist′s dysfunction and bridge between the epiphysis.Results The fractures in both groups were recovering well.Besides,both were at the low rate of repeated replacement,Kirschner wire moving and infection.However,there were significant differences on repeated setting of Kirschner wire during operation,wrist′s dysfunction and bridge between the epiphysis,of which group B were higher than those in group A.Conclusions While the children′s fractures at distal radial or radial-ulna will be reduced by incision and fixing with Kirschner wire,the way of eschewing epiphyses and passing bone-cortex is better because it accords with anatomic character of children.It can not only fix reliably and bring satisfying clinical treatment effect,but also cause little complication.Thus,it is superior to the way of intramedullary fixation and passed epihysis.