Efficacy of N-acetylcysteine on idiopathic or postinfective non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis protocol.

INTRODUCTION: Non-cystic fibrosis (non-CF) bronchiectasis is a chronic pulmonary disorder that causes destruction and permanent dilatation of the airways, resulting in excessive sputum production, repeated infection and inflammation. A need for high-quality and specialised care has been highlighted in recent years. N-acetylcysteine (NAC) is a widely used mucolytic agent in respiratory diseases that not only possesses a property to enhance secretion clearance, but also exhibits antioxidant and anti-inflammatory effects. However, the efficacy and safety of NAC are not well described in idiopathic or postinfective non-CF bronchiectasis. OBJECTIVE: This study aims to evaluate the efficacy and safety of NAC in patients with idiopathic or postinfective non-CF bronchiectasis. METHODS AND ANALYSIS: PubMed/Medline, Embase, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials will be searched from inception to 1 March 2022 for eligible randomised controlled trials that investigating the effects of NAC on exacerbations, health-related quality of life, lung functions, sputum volume and colour, inflammation markers, exercise capacity and adverse events in patients with idiopathic or postinfective non-CF bronchiectasis, with ongoing trials being identified by searches on the websites of Chinese Clinical Trial Registry and ClinicalTrials.gov. Two independent reviewers will identify eligible studies, two will fulfil the data extraction and three will perform the quality appraisal. To generate more accurate analyses, the Grading of Recommendations Assessment, Development and Evaluation will be used to grade the evidence. χ2 test and I2 statistic will be used to assess heterogeneity. Subgroup analyses and meta-regression will be used to explore potential sources of heterogeneity. The potential publication bias will be examined using funnel plots. ETHICS AND DISSEMINATION: No research ethics approval is required in this study because it is a systematic review. The results of this study are expected to be disseminated through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: CRD42021239438.

Eosinopenia as a biomarker for antibiotic use in COPD exacerbations: protocol for a retrospective hospital-based cohort study.

INTRODUCTION: The acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has a seriously negative impact on patients' healths condition and disease progression. Bacterial infection is closely related to AECOPD, and antibiotics are frequently used in clinical practice. The lack of specific biomarkers for rational antibiotics use always leads to antibiotics abuse in chronic obstructive pulmonary disease (COPD) flare-ups. Eosinopenia has been considered to be related to increased bacterial load of potentially pathogenic organisms at the onset of COPD exacerbations. Therefore, this study aims to investigate whether eosinopenia could be used as a reference for the use of antibiotics in AECOPD. METHODS AND ANALYSIS: In this study, a hospital-based retrospective cohort design will be adopted to analyse the clinical data of inpatients who are primarily diagnosed with AECOPD in West China Hospital of Sichuan University from 1 January 2010 to 31 December 2020. Relevant data will be extracted from the Clinical Big Data Platform for Scientific Research in West China Hospital, including demographic characteristics, blood eosinophil count, procalcitonin, C reactive protein, microbial cultivation, antibiotics use, length of hospital stay, non-invasive ventilation use, intensive care unit transfer and mortality, etc. The collected data will be described and inferred by corresponding statistical methods according to the data type and their distributions. Multiple binary logistic regression models will be used to analyse the relationship between blood eosinophil count and bacterial infection. The antibiotics use, and patient morbidity and mortality will be compared between patients with or without eosinopenia. ETHICS AND DISSEMINATION: This study has been approved by the Biomedical Ethics Review Board of West China Hospital of Sichuan University (Approval No. 2020-1056). And the research results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2000039379.

Neural-specific distribution of transmembrane protein TMEM240 and formation of TMEM240-Body.

Mutation in TMEM240 is suggested to cause SCA21, but the specific mechanism has not been clarified. The subcellular localization, specific biological function, and corresponding mechanism of action of TMEM240 have also not been delineated. In this study, the mRNA and protein expression of TMEM240 were assessed using qPCR and western blotting, respectively. Live cell imaging was used to establish the sub-cellular location of TMEM240, and electron microscopy was used to determine the morphology and distribution of TMEM240 in the cell. TMEM240 was specifically expressed in the neurons. Exogenous TMEM240 formed a multilayered cell structure, which we refer to as TMEM240-Body (T240-Body). T240-Body was separated and purified by centrifugation and filtration. An anchor protein His-tagged-GFP-BP on Ni-NTA agarose was used to pull down T240-GFP binding proteins. Both the N-terminal and the C-terminal of TMEM240 were confirmed to be inside the T240-Body. Co-localization experiments suggested that peroxisomes might contribute to T240-Body formation, and the two transmembrane regions of TMEM240 appear to be essential for formation of the T240-Body. Emerin protein contributed to formation of T240-Body when combined with TMEM240. Overall, this study provides new insights into TMEM240, which inform future research to further our understanding of its biological function.

Regulator of G protein signaling 5 (RGS5) inhibits sonic hedgehog function in mouse cortical neurons.

Regulator of G protein signaling 5 (RGS5) acts as a GTPase-activating protein (GAP) for the Gαi subunit and negatively regulates G protein-coupled receptor signaling. However, its presence and function in postmitotic differentiated primary neurons remains largely uncharacterized. During neural development, sonic hedgehog (Shh) signaling is involved in cell signaling pathways via Gαi activity. In particular, Shh signaling is essential for embryonic neural tube patterning, which has been implicated in neuronal polarization involving neurite outgrowth. Here, we examined whether RGS5 regulates Shh signaling in neurons. RGS5 transcripts were found to be expressed in cortical neurons and their expression gradually declined in a time-dependent manner in culture system. When an adenovirus expressing RGS5 was introduced into an in vitro cell culture model of cortical neurons, RGS5 overexpression significantly reduced neurite outgrowth and FM4-64 uptake, while cAMP-PKA signaling was also affected. These findings suggest that RGS5 inhibits Shh function during neurite outgrowth and the presynaptic terminals of primary cortical neurons mature via modulation of cAMP.