The expression and function of programmed death-ligand 1 and related cytokines in neutrophilic asthma.

BACKGROUND: Programmed death-ligand 1 (PD-L1) is an important immune checkpoint inhibitor. Recent studies suggest that the PD-L1-mediated pathway may be a promising target in allergic asthma. However, the mechanism by which PD-L1 represses neutrophilic asthma (NA) remains unclear. In this study, we examined correlations between the expression of PD-L1 and the production of T helper cell type 1 (Th1), T helper cell type 2 (Th2), and T helper cell type 17 (Th17) cells in pediatric patients with NA and a mouse model. METHODS: The clinical samples of 26 children with asthma and 15 children with a bronchial foreign body were collected over a period of 12 months by the Children's Hospital of Soochow University. An experimental mouse model of asthma was established to study NA. An enzyme-linked immunoassay (ELISA) was used to assess soluble PD-L1 (sPD-L1) and cytokines [e.g., interleukin (IL)-4, IL-6, interferon gamma (IFN-γ), IL-17 and granulocyte-macrophage colony-stimulating factor (GM-CSF)] in bronchoalveolar lavage fluid (BALF). RESULTS: NA patients had significantly higher levels of sPD-L1, IL-6, IL-17, and GM-CSF in their BALF than non-NA and control patients (P<0.05). In a murine model of asthma, the positive rate and fluorescence intensity of PD-L1 in the NA group and the immunoglobulin G (IgG)-treated NA group were higher than in the PD-L1 antibody (Ab)-treated NA group and the phosphate-buffered saline (PBS) control group (P<0.05). In the plasma and the BALF of the NA group and the IgG-treatment NA group, the levels of IL-17, IL-4, tumor necrosis factor alpha (TNF-α), and granulocyte colony-stimulating were higher than those in the PBS control group (P<0.05). The histopathological examination of lung tissues from all mice groups showed that a large number of inflammatory cells were found around the airway in the NA group and the IgG-treatment group. CONCLUSIONS: PD-L1 may contribute to the Th17/IL-17 immune response, which is associated with neutrophilic inflammation and asthma. A PD-L1 blockade reduces pulmonary neutrophils and mucus production.

Update on thyroid ultrasound: a narrative review from diagnostic criteria to artificial intelligence techniques.

OBJECTIVE: Ultrasound imaging is well known to play an important role in the detection of thyroid disease, but the management of thyroid ultrasound remains inconsistent. Both standardized diagnostic criteria and new ultrasound technologies are essential for improving the accuracy of thyroid ultrasound. This study reviewed the global guidelines of thyroid ultrasound and analyzed their common characteristics for basic clinical screening. Advances in the application of a combination of thyroid ultrasound and artificial intelligence (AI) were also presented. DATA SOURCES: An extensive search of the PubMed database was undertaken, focusing on research published after 2001 with keywords including thyroid ultrasound, guideline, AI, segmentation, image classification, and deep learning. STUDY SELECTION: Several types of articles, including original studies and literature reviews, were identified and reviewed to summarize the importance of standardization and new technology in thyroid ultrasound diagnosis. RESULTS: Ultrasound has become an important diagnostic technique in thyroid nodules. Both standardized diagnostic criteria and new ultrasound technologies are essential for improving the accuracy of thyroid ultrasound. In the standardization, since there are no global consensus exists, common characteristics such as a multi-feature diagnosis, the performance of lymph nodes, explicit indications of fine needle aspiration, and the diagnosis of special populations should be focused on. Besides, evidence suggests that AI technique has a good effect on the unavoidable limitations of traditional ultrasound, and the combination of diagnostic criteria and AI may lead to a great promotion in thyroid diagnosis. CONCLUSION: Standardization and development of novel techniques are key factors to improving thyroid ultrasound, and both should be considered in normal clinical use.

Ultrasound in neonatal lung disease.

Lung diseases in neonates can be life-threatening condition and may result in respiratory failure and death. Chest X-ray is a traditional diagnostic technique that results in radiation exposure to patients. Lung ultrasound is a user-friendly imaging technique that has been increasingly used in clinical practice in recent years and presents the advantages of real-time imaging and without radiation. Here we review the sonographic appearances of common neonatal lung diseases and present demonstration of typical cases.

Application of molecular imaging technologies in antitumor drug development and therapy.

Molecular imaging enables noninvasive characterization, quantification and visualization of biological and pathological processes in vivo at cellular and molecular level. It plays an important role in drug discovery and development. The skillful use of molecular imaging can provide unique insights into disease processes, which greatly aid in identifications of target. Importantly, molecular imaging is widely applied in the pharmacodynamics study to provide earlier endpoints during the preclinical drug development process, since it can be applied to monitor the effects of treatment in vivo with the use of biomarkers. Herein, we reviewed the application of molecular imaging technologies in antitumor drug development process ranging from identification of targets to evaluation of therapeutic effect.

The compromised inflammatory response to bacterial components after pediatric cardiac surgery is associated with cardiopulmonary bypass-suppressed Toll-like receptor signal transduction pathways.

PURPOSE: Cardiopulmonary bypass (CPB) during pediatric cardiac surgery often elicits a systemic inflammatory response followed by a compromised immune response, which has been attributed to the morbidity of postoperative infection; however, the underlying mechanism(s) has not yet been fully elucidated. We hypothesized that CPB inhibits the activation of Toll-like receptor (TLR) signal transduction pathways, thereby causing an immunosuppressive state after pediatric cardiac surgery. METHODS: We examined 20 children with congenital heart disease undergoing pediatric cardiac surgery. RESULTS: Cardiopulmonary bypass differentially affected lipopolysaccharide (LPS)- or bacterial lipoprotein (BLP)-stimulated ex vivo production of proinflammatory and anti-inflammatory cytokines, with significantly diminished tumor necrosis factor α, interleukin (IL) 1ß, IL-6, and IL-8, but substantially enhanced IL-10 production. Consistent with the reduced inflammatory response, CPB strongly inhibited LPS- or BLP-activated TLR signal transduction pathways in monocytes with down-regulated expression of CD14, TLR4, and TLR2 and with suppressed phosphorylation of nuclear factor κB p65, p38, and extracellular signal-regulated kinase 1/2. CONCLUSIONS: These results indicate that CPB during pediatric cardiac surgery causes substantially reduced production of inflammatory cytokines in response to bacterial component LPS or BLP stimulation, which is associated with CPB-induced suppression of TLR-mediated signal transduction pathways. This reduced inflammatory response after CPB in children with congenital heart disease may predispose them to an increased risk of postoperative infection.