Objective. Protein tyrosine kinases regulate osteoarthritis (OA) progression by activating a series of signal transduction pathways. However, the roles of protein tyrosine phosphatases (PTPs) in OA remain obscure. This study was undertaken to identify specific PTPs involved in OA and investigate their underlying mechanisms.Methods. The expression of 107 PTP genes in human OA cartilage was analyzed based on a single-cell sequencing data set. The enzyme activity of the PTP SH2 domain-containing phosphatase 2 (SHP-2) was detected in primary chondrocytes after interleukin-1β (IL-1β) treatment and in human OA cartilage. Mice subjected to destabilization of the medial meniscus (DMM) and IL-1β-stimulated mouse primary chondrocytes were treated with an SHP-2 inhibitor or celecoxib (a drug used for the clinical treatment of OA). The function of SHP-2 in OA pathogenesis was further verified in Aggrecan-Cre ERT ;SHP2 flox/flox mice. The downstream protein expression profile and dephosphorylated substrate of SHP-2 were examined by tandem mass tag labeling-based global proteomic analysis and stable isotope labeling with amino acids in cell culture-labeled tyrosine phosphoproteomic analysis, respectively.Results. SHP-2 enzyme activity significantly increased in human OA samples with serious articular cartilage injury and in IL-1β-stimulated mouse chondrocytes. Pharmacologic inhibition or genetic deletion of SHP-2 ameliorated OA progression. SHP-2 inhibitors dramatically reduced the expression of cartilage degradation-related genes and simultaneously promoted the expression of cartilage synthesis-related genes. Mechanistically, SHP-2 inhibition suppressed the dephosphorylation of docking protein 1 and subsequently reduced the expression of uridine phosphorylase 1 and increased the uridine level, thereby contributing to the homeostasis of cartilage metabolism.Conclusion. SHP-2 is a novel accelerator of the imbalance in cartilage homeostasis. Specific inhibition of SHP-2 may ameliorate OA by maintaining the anabolic-catabolic balance.
The accuracy of defects detection for logistics packaging box is a critical factor to ensure the quality of goods under edge computing environment. Now, there are few works on this issue. This paper designs an image acquisition process system and then proposes a novel approach in addressing logistics packaging box defect detection (LPDD) on the basis of support vector machine (SVM). Firstly, this paper designs a new mean denoising template and Laplace sharpening template, which are more suitable for logistics packaging based on image preprocessing, image enhancement and other relevant technical theories. Then in the stage of noise removal, this paper proposes an improved morphological method and a gray morphological edge detection algorithm. The edge defect detection of a gray image is carried out by combining the above two methods. Hence, LPDD extracts the features of logistics packaging box by using scale-invariant feature transform (SIFT) algorithm and designs SVM classifiers to classify the logistics package defects. This paper uses a large number of samples to train, learn and test the designed SVM classifier. The simulation results show that the proposed LPDD method can accurately detect two common types of defects in logistics packaging boxes with higher accuracy and less computational costs, which meets the requirements of manufacturers on the classification and recognition of defects in machine vision detection system. INDEX TERMS Package defects, logistics packaging box, support vector machine (SVM).
Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rarely seen in clinical practice, and its treatment strategies and prognosis are still a subject of debate. To ascertain the characteristics of and prognosis for HCC with BDTT, 49 patients with HCC with BDTT were studied out of 763 consecutive patients with HCC who underwent surgical treatment from July 2004 to May 2018. The clinical characteristics of and prognosis for those 49 patients were reviewed and analyzed retrospectively. Of the 49 patients, 25 underwent radical resection, 7 underwent thrombectomy through a choledochotomy, and 17 underwent palliative internal and external bile duct drainage. Results indicated that patients who underwent a radical resection had a better prognosis than patients in the other two groups, with a median survival of 19 months vs. 8 months and 3 months (p < 0.001). Moreover, the preoperative bilirubin level (p = 0.025), intraoperative blood loss (p = 0.006), tumor size (p = 0.005), and the presence of portal and hepatic vein tumor thrombi (p = 0.021) were significant prognostic factors associated with long-term survival for patients who underwent radical resection in this study. Radical resection should be performed with adequate preoperative preparation for patients with HCC with BDTT in whom surgery is not contraindicated.
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