Efficacy and safety of Yu-Ping-Feng powder for asthma in children: a protocol of systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Asthma has become the most common chronic disease in children, which seriously affects children's health and growth. Yu-Ping-Feng powder (YPFP) is widely used for the treatment of asthma in children, but there are few meta-analyses to assess the add-on effects of YPFP in children with asthma. Therefore, it is necessary to conduct a systematic review to evaluate the efficacy and safety of YPFP in the management of asthma in children. METHODS: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science and the Chinese electronic databases including China Network Knowledge Infrastructure (CNKI), Chinese Biomedicine (CBM), Chinese Scientific Journals Database (VIP), and Wan Fang Database were searched for the randomized controlled trials (RCTs) of YPFP in children with asthma based on the eligibility criteria from the date of the database inception to 28 November 2018. Two reviewers assessed the articles and extracted data from the included RCTs independently. Data will be synthesized by either the fixed-effects or random-effects model according to a heterogeneity test. We will assess the risk of bias with the Cochrane Collaboration Tool and overall quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation system (GRADE). Primary outcomes include the improvement of symptoms including breathlessness, coughing, wheezing and the frequency of asthma exacerbations. Lung function, serum IgE level, blood eosinophil count, phlegm eosinophil count and adverse events will be assessed as the secondary outcomes. We will perform the data synthesis, sensitivity analyses, and subgroup analyses in the Rev-Man version 5.3 software. A funnel plot will be established to evaluate reporting bias. RESULTS: This systematic review and meta-analysis will review and synthesis current clinical evidence of YPFP for the treatment of asthma in children. CONCLUSION: This analysis will provide high quality evidence of YPFP for the treatment of asthma in children. PROSPERO REGISTRATION NUMBER: CRD42018111223.

Human antigen R enhances the epithelial-mesenchymal transition via regulation of ZEB-1 in the human airway epithelium.

BACKGROUND: Increasing evidence suggests that human antigen R (HuR) is involved in the epithelial-mesenchymal transition (EMT) process of several diseases. However, the role of HuR in EMT in the airway epithelial cells of patients with COPD remains unclear. METHODS: BEAS-2B cells were cultured and treated with 3%CSE. Western blotting, RT-PCR and immunofluoresence were used to detect the expression of HuR, ZEB-1. RNAi was used to suppress HuR expression. Then knockdown of HuR, RT-PCR and Western blotting showed that with siHuR-1 and siHuR-3, clear suppression of HuR expression was confirmed. We chose siHuR-3, the most effective one, to proceed with subsequent experiments. Immunofluorescence analysis, western blotting were used to detect the expression of E-cadherin, vimentin, ZEB-1 and HuR. RESULTS: We show that more HuR expression is enhanced in the airways epithelium of smokers with or without COPD than controls (nonsmoker non-COPD patients). However, there was no definite correlation between HuR expression and FEV1%. Further study reveals that knockdown of HuR significantly increases the apoptosis of BEAS-2B cells and down-regulates ZEB-1 expression. CONCLUSIONS: EMT is partially enhanced through the HuR-binding proteins and its post-transcriptional regulation role in airway epithelium in COPD.

A HuR/TGF-ß1 feedback circuit regulates airway remodeling in airway smooth muscle cells.

BACKGROUND: Asthma is a worldwide health burden with an alarming prevalence. For years, asthma-associated airway injury remains elusive. Transforming growth factor ß1 (TGF-ß1) is a pleiotropic cytokine that has been shown to be involved in the synthesis of the matrix molecules associated with airway remodeling. Human antigen R (HuR), the member of the Hu RNA-binding protein family, can bind to a subset of short-lived mRNAs in their 3' untranslated regions (UTR). However, the functional roles and relevant signaling pathways of HuR in airway remodeling have not been well illustrated. Thus, we aim to explore the relationship between HuR and TGF-ß1 in platelet derived growth factor(PDGF)-induced airway smooth muscle (ASM) cells and asthmatic animal. METHODS: Cultured human ASM cells were stimulated by PDGF for 0, 6, 12 and 24 h. Western blotting, RT-PCR and immunofluoresence were used to detect the expression of HuR, TGF-ß1, α-smooth muscle actins (α-SMA) and collagen type I (Col-I). Then knockdown of HuR, flow cytomerty was used to detect the morphological change and western blotting for functionally change of ASM cells. Furthermore, the interference of TGF-ß1 and exogenous TGF-ß1 were implemented to testify the influence on HuR. A murine OVA-driven allergic model based on sensitization and challenge was developed. The inflammatory response was measured by bronchoalveolar lavage fluid (BALF), airway damage was analyzed by hematoxylin and eosin staining, airway remodeling was assessed by sirius red staining and periodic acid-schiff staining, the expression level of HuR, TGF-ß1 and α-SMA were measured by RT-PCR, western blotting and immunohistochemistry. RESULTS: Here, we found that PDGF elevated HuR expression both at mRNA and protein level in cultured ASM cells at a time-dependent manner, which was simultaneously accompanied by the enhanced expression of TGF-ß1, α-SMA and Col-I. Further study revealed that the knockdown of HuR significantly increased the apoptosis of ASM cells and dampened TGF-ß1, Col-I and α-SMA expression. However, interfering TGF-ß1 with siRNA or extra addition of TGF-ß1, HuR could restore its production as well as Col-I. Compared with normal mice stimulating with PBS, OVA-induced mice owned high amount of inflammatory cells, such as eosinophils, lymphocytes and neutrophils except macrophages. HE staining showed accumulation of inflammatory cells surrounding bronchiole and sirius red staining distinguished collagen type I and III deposition around the bronchiole. Higher abundance of HuR, TGF-ß1 and α-SMA were verified in OVA-induced mice than PBS-induced mice by RT-PCR, western blotting and immunohistochemistry. CONCLUSIONS: A HuR/TGF-ß1 feedback circuit was established to regulate airway remodeling in vivo and in vitro and targeting this feedback has considerable potential for the intervention of asthma.

Diagnostic value of (1 → 3)-ß-D-glucan in bronchoalveolar lavage fluid for invasive fungal disease: A meta-analysis.

BACKGROUND: The serum (1 â†’ 3)-ß-D-glucan (BG) assay has been approved for diagnosing invasive fungal diseases (IFDs). However, the performance of (1 â†’ 3)-ß-D-glucan assay in bronchoalveolar lavage (BAL) fluid is various among studies. The present study aimed to assess the accuracy of (1 â†’ 3)-ß-D-glucan assay in bronchoalveolar lavage fluid for the diagnosis of invasive fungal diseases by means of meta-analysis and systematic review of relevant studies. METHOD: The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (OR) and a summary receiver-operating characteristic curve of BAL-BG for diagnosing invasive fungal diseases were pooled using meta-analysis. We also performed meta-regression analysis. RESULTS: A total of 838 patients (138 with proven or probable invasive fungal diseases), included in 6 studies, were analyzed. The pooled sensitivity, specificity, PLR, NLR and diagnostic odds ratio were 0.52 (95%CI, 0.38-0.53), 0.58 (95%CI, 0.55-0.61), 1.34 (95%CI, 1.08-1.66), 0.82 (95% CI, 0.63-1.07) and 1.71 (95%CI, 1.01-2.92) respectively. The area under the summary receiver operating characteristic curve, with 95% confidence intervals was 0.61 (95%CI, 0.67-0.55). CONCLUSION: The accuracy of (1 â†’ 3)-ß-D-glucan test in bronchoalveolar lavage fluid is marginal, so that the results should not be interpreted alone but can be used as a part of full assessment with clinical features, image findings and other laboratory results for the diagnosis of invasive fungal diseases.

[mRNA-binding protein Human-antigen R regulates α-SMA expression in human bronchia smooth muscle cells].

OBJECTIVE: To investigate the role of mRNA binding protein Human-antigen R (HuR) in the over-expression of α-Smooth muscle actin (α-SMA) stimulated by Platelet-derived Growth Factor (PDGF) in cultured human bronchia smooth muscle cells. METHODS: Human bronchia smooth muscle cells cultured in vitro were divided into 0, 6, 12 and 24 h groups according to the time of PDGF treatment. Total HuR protein and total α-SMA protein expression were detected by Western blot. Total HuR mRNA and total α-SMA mRNA level were determined by quantitative real time-polymerase chain reaction. RNA interference technology was used to down-regulate HuR protein level to study the protective effect of HuR in PDGF-stimulated α-SMA protein expression. RESULTS: PDGF up-regulated the expression of HuR in a time-dependent manner. The relative expression levels of whole-cell HuR protein and mRNA in 0, 6, 12, 24 h groups were 0.23±0.09, 0.42±0.11, 0.93±0.21, 1.37±0.28; 1.00±0.00, 1.09±0.03, 1.16±0.03, 1.27±0.02 (all P<0.05). The relative expression levels of α-SMA protein and mRNA in 0, 6, 12, 24 h group also showed an increase trend marked in a time-dependent manner (1.03±0.08, 1.20±0.09, 1.39±0.11, 1.58±0.10; 1.00±0.00, 1.17±0.02, 1.23±0.02, 1.45±0.03; all P<0.05). Using RNA interference technology to down-regulate HuR protein level, there was a decrease in α-SMA protein expression. CONCLUSION: PDGF stimulation can increase the expression of HuR and α-SMA in the smooth muscle cells, and HuR protein is involved in the expression of α-SMA protein stimulated by PDGF.

[Diagnostic value of interleukin-27 in tuberculous pleural effusion].

OBJECTIVE: To explore the diagnostic value of interleukin-27 (IL-27) in tuberculous pleural effusion. METHODS: A total of 76 patients of pleural effusion treated at Shandong Provincial Hospital from March 2013 to February 2014 in accordance with the natures of effusion fluid were divided into: (1) Tuberculosis group of tuberculous pleural effusion (n = 40), including 22 males and 18 females; aged 19 to 73 years; (2) Malignant group of malignant pleural effusion (n = 36), including 20 males and 16 females; aged 33 to 78 years old; including lung cancer (n = 28), lymphoma (n = 3), esophageal (n = 1) and uncertain primary tumor site (n = 4). The effusion and serum levels of IL-27 were detected by enzyme-linked immunosorbent assay (ELISA) and the results analyzed. And the curve of receiver operating characteristic (ROC) was employed to determine the diagnostic value of IL-27 in tuberculous pleural effusion. RESULTS: The level of IL-27 was (1 402 ± 321) ng/L in tuberculous pleural effusion and it was significantly higher than those in malignant pleural effusion (556 ± 133) ng/L and sera (499 ± 88) ng/L (both P < 0.05). According to the ROC curve, the cut-off value of IL-27 was 838 ng/L in diagnosing tuberculous pleural effusion. And the rates of diagnostic sensitivity, specificity and accuracy of IL-27 were 95.0%, 97.2% and 96.1% respectively. CONCLUSIONS: Detection of pleural effusion IL-27 concentration is of great importance in the diagnosis of tuberculous pleural effusion. And it is worthy of wider clinical promotion.