Cathepsin B (CB) is involved in the turnover of proteins and has various roles in maintaining the normal metabolism of cells. In our recent study, CB is increased in the muscles of polymyositis/dermatomyositis (PM/DM). However, the role of CB in interstitial lung disease (ILD) has not been reported. ILD is a frequent complication of PM/DM, which is the leading cause of death in PM/DM. It carries high morbidity and mortality in connective tissue diseases, characterized by an overproduction of inflammatory cytokines and induced fibrosis, resulting in respiratory failure. The etiology and pathogenesis of ILD remain incompletely understood. This study investigated whether treatment with CA-074Me, a specific inhibitor of CB, attenuates ILD in PM. CB expression, inflammation, and fibrosis were analyzed in the lung tissues from patients with PM/DM. The animal model of PM was induced in guinea pigs with Coxsackie virus B1 (CVB1). CA-074Me was given 24 h after CVB1 injection for 7 consecutive days. At the end of the experiment, the animals were killed and lung tissues were collected for the following analysis. Inflammation, fibrosis and apoptosis cells, and cytokines were assessed by histological examinations and immunohistochemical analyses, western blot analysis and transferasemediated dUTP nick-end labeling assay. In patients with PM/DM, the protein levels of CB were significantly elevated in lung tissues compared with healthy controls, which correlated with increases in inflammation and fibrosis. Similarly, the expression of CB, inflammation and fibrosis, CD8 þ T cell, CD68 þ cell, tumor necrosis factor-alpha, transforming growth factor-beta1 infiltrations, and apoptotic cell death were significantly increased in lung tissues of the guinea-pig model of CVB1-induced PM. These changes were attenuated by the administration of CA-074Me. In conclusion, this study demonstrates that PM/DM increases CB expression in lung tissues and inhibition of CB reduces ILD in a guinea-pig model of CVB1-induced PM. This finding suggests that CB may be a potential therapeutic target for ILD.
This study aimed to determine the antibiotic resistance and molecular epidemiology of Haemophilus influenzae isolated from children with acute respiratory infection in Chongqing, China. To this end, 1967 H. influenzae isolates from 2006 to 2009 were analysed regarding β-lactamase production and antibiotic resistance. Ninety-nine β-lactamase-producing H. influenzae isolates from 2010 were analysed for antibiotic resistance and promoter regions of bla(TEM) (-1) . β-lactamase production was found in 35.8% (705/1967) of the strains. All ninety-nine β-lactamase-producing strains from 2010 were of the TEM-1 type as determined by PCR but did not produce the predicted 1075 bp product. According to PCR-SSCP and DNA sequencing, the promoter regions of bla(TEM) (-1) were categorized into 6 genotypes as SSCP1 (Pdel), SSCP2 (Pa/Pb), SSCP3 (P4), SSCP4 (Prpt.b), SSCP5 (2Prpt) and SSCP6 (P3.b). The Pdel, Pa/Pb and Prpt.b were common promoters of bla(TEM) (-1) for H. influenzae isolated from children in Chongqing. Strains with Prpt.b were more resistant to ampicillin (AMP) than strains with Pdel, Pa/Pb and P4 (p < 0.05). Therefore, bla(TEM-1) β-lactamase is the main mechanism for resistance of H. influenzae to ampicillin in Chongqing. Furthermore, the Prpt.b promoters may be related to the high resistance of H. influenzae to AMP.
Background: Identification of malignancy in small breast nodules can be difficult using conventional methods, especially in patients with dense breast tissue. Advanced imaging techniques, including contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE), could be used in conjunction with the Breast Imaging Reporting and Data System (BI-RADS) classification to characterize these nodules more effectively. This retrospective study aimed to evaluate the use of CEUS and SWE for the differentiation of benign from malignant small (≤ 2 cm) breast nodules.Methods: We reviewed the medical records and imaging data of 302 patients who underwent evaluation for 305 small breast nodules from November 2015 to December 2019. The BI-RADS classification values of the nodules and the results of CEUS and SWE were retrospectively analyzed; the diagnostic efficacy of these techniques was evaluated by comparison of the pathology results. Receiver operating characteristic (ROC) curves were analyzed based on the CEUS patterns and shear-wave velocity values of the nodules. The sensitivity, specificity, positive and negative predictive values, accuracies of BI-RADS, CEUS, SWE, and a combination of all three methods for identifying benign and malignant small breast nodules were investigated.Results: CEUS was effective at diagnosing malignant nodules when at least two out of nine suspicious features were present. ROC analysis revealed that the best cut-off value for SWE was at 3.7 m/s. For the diagnosis of benign breast nodules, the BI-RADS classification was reduced by one level when both, CEUS and SWE were used, and remained unchanged when either one, CEUS or SWE was used; the highest and lowest levels were of category 5 and 3, respectively. Furthermore, when using the combined method, 75.8% (91/120) of small breast nodules with a BI-RADS category 4A classification avoided the need for coarse needle biopsies.Conclusions: CEUS and SWE can be used as auxiliary methods for clarifying BI-RADS classification of the breast nodules, and a combination of these techniques may provide more diagnostic efficacy for identifying malignancy in small breast nodules.Trial registration: Retrospectively registered.
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