Effect of fracture risk in inhaled corticosteroids in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: The fracture risk of patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids is controversial. And some large-scale randomized controlled trials have not solved this problem. The purpose of our systematic review and meta-analysis including 44 RCTs is to reveal the effect of inhaled corticosteroids on the fracture risk of COPD patients. METHODS: Two reviewers independently retrieved randomized controlled trials of inhaled corticosteroids or combinations of inhaled corticosteroids in the treatment of COPD from PubMed, Embase, Medline, Cochrane Library, and Web of Science. The primary outcome was a fracture event. This study was registered at PROSPERO (CRD42022366778). RESULTS: Forty-four RCTs were performed in 87,594 patients. Inhaled therapy containing ICSs (RR, 1.19; 95%CI, 1.04-1.37; P = 0.010), especially ICS/LABA (RR, 1.30; 95%CI, 1.10-1.53; P = 0.002) and triple therapy (RR, 1.49; 95%CI, 1.03-2.17; P = 0.04) were significantly associated with the increased risk of fracture in COPD patients when compared with inhaled therapy without ICSs. Subgroup analyses showed that treatment duration ≥ 12 months (RR, 1.19; 95%CI, 1.04-1.38; P = 0.01), budesonide therapy (RR, 1.64; 95%CI., 1.07-2.51; P = 0.02), fluticasone furoate therapy (RR, 1.37; 95%CI, 1.05-1.78; P = 0.02), mean age of study participants ≥ 65 (RR, 1.27; 95%CI, 1.01-1.61; P = 0.04), and GOLD stage III(RR, 1.18; 95%CI, 1.00-1.38; P = 0.04) were significantly associated with an increased risk of fracture. In addition, budesonide ≥ 320 ug bid via MDI (RR, 1.75; 95%CI, 1.07-2.87; P = 0.03) was significantly associated with the increased risk of fracture. CONCLUSION: Inhalation therapy with ICSs, especially ICS/LABA or triple therapy, increased the risk of fracture in patients with COPD compared with inhaled therapy without ICS. Treatment duration, mean age of participants, GOLD stage, drug dosage form, and drug dose participated in this association. Moreover, different inhalation devices of the same drug also had differences in risk of fracture.

Exosome microRNA-125a-5p derived from epithelium promotes M1 macrophage polarization by targeting IL1RN in chronic obstructive pulmonary disease.

BACKGROUND: The interplay between airway epithelium and macrophages plays a pivotal role in Chronic Obstructive Pulmonary Disease (COPD) pathogenesis. Exosomes, which transport miRNA cargo, have emerged as novel mediators of intercellular communication. MicroRNA-125a-5p (miR-125a-5p) has been implicated in macrophage polarization.This study aims to investigate the role of exosomal miR-125a-5p in the dysfunctional epithelium-macrophage cross-talk in cigarette smoke (CS)-induced COPD. METHODS: In cell models, THP-1 monocytic cells were differentiated into macrophages (M0). Human bronchial epithelial cells treated with CS extract (CSE) were co-cultured with M0. Exosomes were isolated from culture media using commercial kits and characterized using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Exosomes labeled with PKH26 red fluorescent cell linker kits were incubated with macrophages. Luciferase reporter assay was used to confirm the target gene of miR-125a-5p. In mouse experiments, inhibiting miR-125a-5p was utilized to examine its role in macrophage polarization. Furthermore, the underlying mechanism was explored. RESULTS: In vitro results indicated that CSE treatment led to upregulation of miR-125a-5p in HBE cells, and exosomes contained miR-125a-5p. PKH26-labeled exosomes were internalized by macrophages. Co-culture experiments between bronchial epithelial cells and miR-125a-5p mimic resulted in significant increase in M1 macrophage markers (TNF-α, iNOS-2, IL-1ß) and decrease in M2 markers (IL-10 and Arg-1). In COPD mouse models, miR-125a-5p inhibitor reduced levels of TNF-α, IL-1ß, and IL-6. Luciferase assays revealed that miR-125a-5p inhibitors enhanced the relative luciferase activity of IL1RN. Mechanistic experiments demonstrated that HBE-derived exosomes transfected with miR-125a-5p mimics promoted upregulation of MyD88, TRAF6, p65, iNOS-2, and downregulation of Arg-1. CONCLUSION: This study suggests that exosomal miR-125a-5p may act as a mediator in the cross-talk between airway epithelium and macrophage polarization in COPD. Exosomal miR-125a-5p targeting IL1RN may promote M1 macrophage polarization via the MyD88/NF-κB pathway.

[The preliminary study on creating the differential templates of the skeletal profiles for Shanghainese with normal occlusion in early permanent dentition].

OBJECTIVE: To establish the differential templates of the skeletal profiles for Shanghainese with normal occlusion in early permanent dentition. METHODS: 71 lateral cephalometric radiographs of subjects with normal occlusion in early permanent dentition, aged from 11 - 15 years (37 females and 34 males) were traced. 23 skeletal landmarks were identified on the tracings, which afterwards were scanned on the computer. An x-y coordinate system was established: the tracing superimposed on sella rotated 7 degrees down from the sella-nasion line as the x axis and the vertical line through sella perpendicular to the x axis as the y axis. A special length/depth ratio was designed. The length/depth ratio of each graph were calculated. Steiner analysis was applied to check the difference between genders. RESULTS: There was no difference between genders. The tracings were divided into three categories: short face, normal face and long face according to the mean and standard deviation of the ratio. The three types of tracings were superimposed on the x axis with sella registered. Three templates were created. CONCLUSIONS: The differences were apparent when the three templates were superimposed.

[Morphologic characteristics of anterior crossbite in early permanent dentition reviewed by superimposition on the template].

PURPOSE: To establish a computer-processing module to first, eliminate the factors which mislead the diagnosis of anterior crossbite and second, superimpose the individual tracing on the template to review the patient's morphologic characteristics. METHODS: First, the module would process the following steps:1.to create three templates; 2.to move the functional-shift-mandible posteriorly; 3.to standardize the potential of vertical dimension;4.to select a suitable template for superimposition; 5.to standardize the sizes of individual graph and template. Second, the module would process the five-step superimpositions: 1. X axis was superimposed and S were registered to measure the distances between Ptm points and Ar points on X axis; 2. X axis was paralleled and Ptm were registered to measure the distance between A points on X axis; 3. X axis was paralleled and A points were registered to measure the difference of anterior area between the mandibular graphs; 4.mandibular planes were superimposed and Po was registered to show the mandibular form variation; 5. Ar-Gn lines were superimposed and Ar was registered to measure the difference between the mandibular graphs. RESULTS: The module which could complete these steps was produced. With its help, the individual graph could be diagnosed with the position of maxilla and mandible, the amounts of maxillary discrepancy and jaws' dysplasia, the mandibular form and size variation. CONCLUSIONS: The module could eliminate the factors which mislead the diagnosis and review the morphologic characteristics of anterior crossbite in early permanent dentition.

[Study of fluoride released from fluoride-releasing adhesives].

OBJECTIVE: To study the fluoride release ability of two kinds of fluoride-releasing composite resin adhesives made in China. METHODS: Test samples of fluoride-releasing composite resin adhesives I and II were prepared, and fluoride ion concentrations were measured with a No.720 fluoride ion-sensitive electrode. RESULTS: Fluoride ions were released from both of the fluoride-releasing composite resin adhesives. The concentration declined sharply after first 24 hours and maintained at a low level for about 21 days. The initial fluoride ions concentration of adhesive II was higher than adhesive I. CONCLUSION: Both of the fluoride-releasing composite resin adhesives had the ability of releasing fluoride. Adhesive II seemed better.