ABSTRACT
BACKGROUND@#Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts.@*METHODS@#We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models.@*RESULTS@#The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749).@*CONCLUSIONS@#The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR 1800018895.
Subject(s)
Humans , Aged , Sarcopenia/diagnosis , Deep Learning , Aging , Algorithms , BiomarkersABSTRACT
Objective@#To detect the effect and regulatory mechanism of human ether à go-go related gene 1 (Herg 1) knockdown on the proliferation and invasion of osteosarcoma (OS).@*Methods@#We constructed a recombinant adenovirus vector (Ad5-Herg1-shRNA) expressing short hair RNA (shRNA) against Herg1 and tested the knockdown efficiency. Then, the effects of Herg 1 knockdown on the proliferation, growth and invasion of osteosarcoma were measured by using cell counting kit-8 (CCK-8), wound healing assay, Transwell assay and xenograft model of nude mice, respectively. Tandem affinity purification, mass spectrometry and dual luciferase reporter assay were used to find out the molecules interacted with Herg1. Western blot was used to detect the expressions of large tumor suppressor gene (LATS1), p-LATS1, Yes-associated protein (YAP) and p-YAP in cells after infection of Ad5-Herg1-shRNA.@*Results@#Compared to Ad5-control-shRNA, Ad5-Herg1-shRNA dramatically inhibited the expression of Herg1 in OS cells. The result of CCK8 array demonstrated that 143B cell vitalities of Ad5-Herg1-shRNA1 and Ad5-Herg1-shRNA2 group were (65.47±3.90)% and (79.90±1.52)%, significantly lower than (100.00±6.14)% of Ad5-control-shRNA group. Meanwhile, U2OS cell vitality of Ad5-Herg1-shRNA1 and Ad5-Herg1-shRNA2 group were (69.69±1.36)% and (76.72±2.75)%, significantly lower than (100.00±3.01)% of Ad5-control-shRNA group (all P<0.001). The results of wound healing array showed that 143B cell migration rates of Ad5-Herg1-shRNA1 and Ad5-Herg1-shRNA2 group were (33.03±2.88)% and (36.47±4.16)%, significantly lower than (97.78±2.28)% of Ad5-control-shRNA group. Meanwhile, U2OS cell migration rates of Ad5-Herg1-shRNA1 and Ad5-Herg1-shRNA2 group were (68.07±0.90)% and (73.97±1.25)%, significantly lower than (96.50±1.12)% of Ad5-control-shRNA group (all P<0.001). The results of Transwell showed that 143B cell invasion numbers of Ad5-Herg1-shRNA1 and Ad5-Herg1-shRNA2 group were 36.50±12.15 and 44.83±7.62, significantly lower than 195.33±19.68 of Ad5-control-shRNA group. Meanwhile, U2OS cell migration rates of Ad5-Herg1-shRNA1 and Ad5-Herg1-shRNA2 group were 21.83±7.99 and 22.85±7.08, significantly lower than 83.33±12.36 of Ad5-control-shRNA group (all P<0.001). The results of xenograft model of OS showed that the tumor volume and weight of Ad5-Herg1-shRNA group were significantly smaller than of Ad5-control-shRNA group after 14 days and 5 weeks of inoculation, respectively (P<0.001). Moreover, knockdown of Herg1 inhibited the metastasis of OS cells. In mechanism, Herg1 protein interacted with NF2 protein. Knockdown of Herg1 significantly suppressed the expression levels of LATS1 and YAP protein, and promoted the phosphorylation of LATS1 and YAP in OS cells (all P<0.001).@*Conclusion@#Our findings suggest that Herg1 participates in the proliferation and motility of OS cells and may serve as a potential therapeutic target for osteosarcoma patients.
ABSTRACT
Objective To observe the effect of advanced oxidation protein products (AOPPs) on articular and synovial in a rabbit model of osteoarthritis (OA).Methods 48 male New Zealand rabbits were randomly divided into 3 groups:AOPPs group,PBS group and sham-operated group.OA model were created in AOPPs group and PBS group by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx).then intra-articular injection of 1 ml AOPPs or PBS were performed once every other day in AOPPs group and PBS group,respectively.In sham-operated group,the anterior cruciate ligament was just exposed without transection,and then the incision was sutured.All rabbits were saerificed after 4 and 8 weeks of intervention,respectively.Results The India ink seore of 4 and 8 weeks were 4.19±0.60,5.75±0.60 in AOPPs group,and 1.06±0.18,1.38±0.60 in sham-operated group,2.50±0.46、3.06±0.62 in PBS group,respectively.In addition,the differences were statistically significant among the three groups.The Mankin score of 4 and 8 weeks were 8.19±0.70,11.94±0.90 in AOPPs group,and 0.75±0.53,1.06± 0.73 in sham-operated group,4.25± 1.46、4.50±0.89 in PBS group,respectively.The differences were statistically significant among the three groups.Meanwhile,the protein expression level of matrix metalloproteinases (MMP)-3 on synovial at 4 and 8 weeks in AOPPs group were 1.006±0.080,1.098±0.088;0.065±0.006,0.053±0.011 in sham-operated group;and 0.552±0.024,0.839±0.084 in PBS group,respectively.The proteiu expression level of MMP-13 on synovial at 4 and 8 weeks in AOPPs group were 0.966±0.080,1.621 ±0.041;0.101±0.022,0.367±0.033 in sham-operated group;and 0.564±0.030,1.322±0.085 in PBS group,respectively.The differences were statistically significant among the three groups at two times.Conclusion AOPPs participate in the occurrence and development of artieular cartilage by upregulating the protein expression of MMP-3 and MMP-13 on synovial.