PO-014 The effects of HIIT on ROS-AMPK- PGC-1α pathway in skeletal muscle and VO2max of ageing Wistar rats.

Objective To observe the 16 weeks of HIIT intervention on SOD,ROS and its related factors AMPK and oxidation capacity PGC-1α expression and the influence of the VO2max and its change rule in the process of the natural aging rats, To explore the correlation between the expression of ROS, AMPK and PGC-1αand the change of VO2max; Furthermore, it provides a theoretical basis for HIIT to delay the reduction of aerobic capacity in skeletal muscle ageing. Methods 58 male wistar rats(age：32 weeks) were selected and randomly divided into quiet group (C) and HIIT intervention group (H). All rats were fed in the barrier environment. Each group of rats entered the animal laboratory for a week of adaptive feeding and exercise. VO2max was tested and observed every two weeks in each group. Rats of group C don't exercise, group H at a rate of 50%, 70% and 90% VO2max corresponding alternation of 50 min/day, 5 days/week, for 16 weeks of exercise intervention, and according to the VO2max test results the exercise intensity. Both groups of rats in the intervention of 8 weeks, 16 weeks after the end of the 24 hours of materials, stripping rats soleus, SOD and content of ROS was tested by multifunctional enzyme mark, using western blot test the expression of AMPK and PGC-1α. VO2max, SOD, ROS test results and AMPK, PGC-1α, and relative expression data were analyzed using SPSS for one way ANOVA. Results The cardiopulmonary endurance of rats in group C and group H showed a decreasing trend in group C and group H during HIIT intervention, but the decrease trend in group H was slower than that in group C. 2. During 16 weeks aging , SOD expression of group C in the process of rendering first rise after falling, and expressed in 8 weeks SOD content was significantly lower than base value (P < 0.05), 16 weeks group C SOD levels higher than the base state. After 16 weeks of intervention, the expression of SOD in group H was relatively flat in the first 8 weeks, and the trend was in 8-16 weeks, and was significantly lower than 8 weeks in 16 weeks (P < 0.05). 3.The ROS content was significantly higher than basic state in 8 weeks and 16 weeks in the intervention process (P<0.05), and the ROS content was significantly higher than 8 weeks (P<0.05) at 16 weeks. The ROS content of group C and group H was significantly higher than that in the group at 8 weeks (P < 0.05). 4.The AMPK content in group C was significantly lower than that of the basic value (P<0.05), and the AMPK content in group H was significantly higher than that in group C (P<0.05). 5.After the intervention of 16 weeks, the content of PGC-1α in group C and group H showed a decrease trend and significantly lower than the basic value (P<0.05), but the content of group H was significantly higher than that of group C (P<0.05). 6.The changes of AMPK, PGC-1α and cardiopulmonary endurance were the same in all groups during the intervention. Conclusions 1.16 weeks of HIIT can effectively delay the decrease of SOD content in the aging rats, thus inhibiting the accumulation of ROS in the body. 2.16 weeks of HIIT intervention can effectively delay the expression of VO2max and AMPK and PGC-1α in aging rats. 3.16 weeks HIIT may delay the decrease of AMPK-PGC1 protein expression by inhibiting the accumulation of skeletal muscle ROS in the aging rats, thus inhibiting the decrease of VO2max

PO-082 16-Week high intensity interval training does not alter LKB1 and AMPKα protein in Rats Liver

Objective Liver, as one of the most important organs involved in lipids and glucose metabolism, yet no study has examined the response of liver kinase B1 (LKB1) and AMP-activated protein kinase α(AMPKα) signaling after high intensity interval training. This study aims to evaluate the effect of 16-week high intensity interval training intervention on the expression of LKB1、AMPKα in liver of aging rats. Methods 8 -month-old male Wistar rats（n=40）were randomly divided into control group (C) and HIIT group (H). Group H with 70%-90%-50%VO2max intensity training for 50min/ day, 5 days / week, lasted for 16 weeks. Rats were killed on 0, 8 and 16 weeks. We examined the protein expression of LKB1 and AMPKα in liver. Proteins were analyzed by western blot analysis. Data are mean±SD; for ANOVA, p<0.05 was significant. Results The AMPKα levels in group C and group H increased with time and there was no significant difference between the groups. The content of LKB1 in group C and group H both increased first and then decreased, but there was no significant difference between the groups. Conclusions 16-week high intensity interval training intervention had no effect on LKB1, AMPKα protein expression in aging rats

Lack of association between the CALM1 core promoter polymorphism (-16C/T) and susceptibility to knee osteoarthritis in a Chinese Han population

<p>Abstract</p> <p>Background</p> <p><it>CALM1 </it>gene encodes calmodulin (CaM), an important and ubiquitous eukaryotic Ca²⁺-binding protein. Several studies have indicated that a deficient CaM function is likely to be involved in the pathogenesis of osteoarthritis (OA). Using a convincing genome-wide association study, a Japanese group has recently demonstrated a genetic association between the <it>CALM1 </it>core promoter polymorphism (-16C/T transition SNP, rs12885713) and OA susceptibility. However, the subsequent association studies failed to provide consistent results in OA patients of differently selected populations. The present study is to evaluate the association of the -16C/T polymorphism with knee OA in a Chinese Han population.</p> <p>Methods</p> <p>A case-control association study was conducted. The polymorphism was genotyped in 183 patients who had primary symptomatic knee OA with radiographic confirmation and in 210 matched controls. Allelic and genotypic frequencies were compared between patients and control subjects.</p> <p>Results</p> <p>No significant difference was detected in genotype or allele distribution between knee OA and control groups (all <it>P </it>> 0.05). The association was also negative even after stratification by sex. Furthermore, no association between the -16C/T SNP genotype and the clinical variables age, sex, BMI (body mass index) and K/L (Kellgren/Lawrence) score was observed in OA patients.</p> <p>Conclusion</p> <p>The present study suggests that the CALM1 core promoter polymorphism -16C/T is not a risk factor for knee OA susceptibility in the Chinese Han population. Further studies are needed to give a global view of this polymorphism in pathogenesis of OA.</p

Therapeutic Potential of Exosomes in Tendon and Tendon–Bone Healing: A Systematic Review of Preclinical Studies

Exosomes have been proven to play a positive role in tendon and tendon–bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes in tendon and tendon–bone healing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic and comprehensive review of the literature was performed on 21 January 2023. The electronic databases searched included Medline (through PubMed), Web of Science, Embase, Scopus, Cochrane Library and Ovid. In the end, a total of 1794 articles were systematically reviewed. Furthermore, a “snowball” search was also carried out. Finally, forty-six studies were included for analysis, with the total sample size being 1481 rats, 416 mice, 330 rabbits, 48 dogs, and 12 sheep. In these studies, exosomes promoted tendon and tendon–bone healing and displayed improved histological, biomechanical and morphological outcomes. Some studies also suggested the mechanism of exosomes in promoting tendon and tendon–bone healing, mainly through the following aspects: (1) suppressing inflammatory response and regulating macrophage polarization; (2) regulating gene expression, reshaping cell microenvironment and reconstructing extracellular matrix; (3) promoting angiogenesis. The risk of bias in the included studies was low on the whole. This systematic review provides evidence of the positive effect of exosomes on tendon and tendon–bone healing in preclinical studies. The unclear-to-low risk of bias highlights the significance of standardization of outcome reporting. It should be noted that the most suitable source, isolation methods, concentration and administration frequency of exosomes are still unknown. Additionally, few studies have used large animals as subjects. Further studies may be required on comparing the safety and efficacy of different treatment parameters in large animal models, which would be conducive to the design of clinical trials

The predictive value of [18F]FDG PET/CT radiomics combined with clinical features for EGFR mutation status in different clinical staging of lung adenocarcinoma

Abstract Background This study aims to construct radiomics models based on [18F]FDG PET/CT using multiple machine learning methods to predict the EGFR mutation status of lung adenocarcinoma and evaluate whether incorporating clinical parameters can improve the performance of radiomics models. Methods A total of 515 patients were retrospectively collected and divided into a training set (n = 404) and an independent testing set (n = 111) according to their examination time. After semi-automatic segmentation of PET/CT images, the radiomics features were extracted, and the best feature sets of CT, PET, and PET/CT modalities were screened out. Nine radiomics models were constructed using logistic regression (LR), random forest (RF), and support vector machine (SVM) methods. According to the performance in the testing set, the best model of the three modalities was kept, and its radiomics score (Rad-score) was calculated. Furthermore, combined with the valuable clinical parameters (gender, smoking history, nodule type, CEA, SCC-Ag), a joint radiomics model was built. Results Compared with LR and SVM, the RF Rad-score showed the best performance among the three radiomics models of CT, PET, and PET/CT (training and testing sets AUC: 0.688, 0.666, and 0.698 vs. 0.726, 0.678, and 0.704). Among the three joint models, the PET/CT joint model performed the best (training and testing sets AUC: 0.760 vs. 0.730). The further stratified analysis found that CT_RF had the best prediction effect for stage I–II lesions (training set and testing set AUC: 0.791 vs. 0.797), while PET/CT joint model had the best prediction effect for stage III–IV lesions (training and testing sets AUC: 0.722 vs. 0.723). Conclusions Combining with clinical parameters can improve the predictive performance of PET/CT radiomics model, especially for patients with advanced lung adenocarcinoma

Transfer learning–based PET/CT three-dimensional convolutional neural network fusion of image and clinical information for prediction of EGFR mutation in lung adenocarcinoma

Abstract Background To introduce a three-dimensional convolutional neural network (3D CNN) leveraging transfer learning for fusing PET/CT images and clinical data to predict EGFR mutation status in lung adenocarcinoma (LADC). Methods Retrospective data from 516 LADC patients, encompassing preoperative PET/CT images, clinical information, and EGFR mutation status, were divided into training (n = 404) and test sets (n = 112). Several deep learning models were developed utilizing transfer learning, involving CT-only and PET-only models. A dual-stream model fusing PET and CT and a three-stream transfer learning model (TS_TL) integrating clinical data were also developed. Image preprocessing includes semi-automatic segmentation, resampling, and image cropping. Considering the impact of class imbalance, the performance of the model was evaluated using ROC curves and AUC values. Results TS_TL model demonstrated promising performance in predicting the EGFR mutation status, with an AUC of 0.883 (95%CI = 0.849–0.917) in the training set and 0.730 (95%CI = 0.629–0.830) in the independent test set. Particularly in advanced LADC, the model achieved an AUC of 0.871 (95%CI = 0.823–0.919) in the training set and 0.760 (95%CI = 0.638–0.881) in the test set. The model identified distinct activation areas in solid or subsolid lesions associated with wild and mutant types. Additionally, the patterns captured by the model were significantly altered by effective tyrosine kinase inhibitors treatment, leading to notable changes in predicted mutation probabilities. Conclusion PET/CT deep learning model can act as a tool for predicting EGFR mutation in LADC. Additionally, it offers clinicians insights for treatment decisions through evaluations both before and after treatment

Using a Xenogeneic Acellular Dermal Matrix Membrane to Enhance the Reparability of Bone Marrow Mesenchymal Stem Cells for Cartilage Injury

Due to its avascular organization and low mitotic ability, articular cartilage possesses limited intrinsic regenerative capabilities. The aim of this study is to achieve one-step cartilage repair in situ via combining bone marrow stem cells (BMSCs) with a xenogeneic Acellular dermal matrix (ADM) membrane. The ADM membranes were harvested from Sprague-Dawley (SD) rats through standard decellularization procedures. The characterization of the scaffolds was measured, including the morphology and physical properties of the ADM membrane. The in vitro experiments included the cell distribution, chondrogenic matrix quantification, and viability evaluation of the scaffolds. Adult male New Zealand white rabbits were used for the in vivo evaluation. Isolated microfracture was performed in the control (MF group) in the left knee and the tested ADM group was included as an experimental group when an ADM scaffold was implanted through matching with the defect after microfracture in the right knee. At 6, 12, and 24 weeks post-surgery, the rabbits were sacrificed for further research. The ADM could adsorb water and had excellent porosity. The bone marrow stem cells (BMSCs) grew well when seeded on the ADM scaffold, demonstrating a characteristic spindle-shaped morphology. The ADM group exhibited an excellent proliferative capacity as well as the cartilaginous matrix and collagen production of the BMSCs. In the rabbit model, the ADM group showed earlier filling, more hyaline-like neo-tissue formation, and better interfacial integration between the defects and normal cartilage compared with the microfracture (MF) group at 6, 12, and 24 weeks post-surgery. In addition, neither intra-articular inflammation nor a rejection reaction was observed after the implantation of the ADM scaffold. This study provides a promising biomaterial-based strategy for cartilage repair and is worth further investigation in large animal models