Performance of the Activities and Participation component of International Classification of Functioning, Disability and Health Sleep Disorders Brief Core Set in patients with obstructive sleep apnea.

Background: Limitation of daily activities and impairment of working memory have received less attention in the clinical diagnosis and prognostic assessment of obstructive sleep apnea (OSA). In this study, the Activities and Participation component of the International Classification of Functioning, Disability and Health (ICF) Sleep Disorders Brief Core Set was evaluated for its performance in predicting impaired work ability in OSA patients. Methods: A total of 221 subjects were recruited into this cross-sectional study. ICF Sleep Disorders Brief Core Set, polysomnography, and neuropsychological tests were applied for data acquisition. Data analysis was performed by regression analysis and receiver operating characteristic (ROC) construction. Results: The scores for the component Activities and Participation were significantly different between the no OSA/OSA group, and were elevated as the severity of OSA increased. Scores were positively correlated with apnea-hypopnea index (AHI), trail making test (TMT), and negatively correlated with symbol digit modalities test (SDMT) correct. The component Activities and Participation performed better with the threshold of 4 in the prediction of impaired attention and work ability in severe OSA [AHI ≥30 events/h, bottom 10% of TMT part B (TMTb) scores as the diagnostic criteria], with area under the curve, sensitivity and specificity as 0.909, 71.43% and 96.72%, respectively. Conclusions: The Activities and Participation component of the ICF Sleep Disorders Brief Core Set could have the potential to predict the impairment of attention and work ability in OSA patients. It provides a new perspective for the identification of OSA patients' disturbances in daily activities and improving the overall assessment level.

The Identification and Clinical Value Evaluation of CYCS Related to Asthma through Bioinformatics Analysis and Functional Experiments.

Background: Asthma is one of the most common respiratory diseases and one of the largest burdens of health care resources across the world. This study is aimed at using bioinformatics methods to find effective clinical indicators for asthma and conducting experimental validation. Methods: We downloaded GSE64913 data and performed differentially expressed gene (DEG) screening. Weighted gene coexpression network analysis (WGCNA) on DEGs was applied to identify key module most associated with asthma for protein-protein interaction (PPI) analysis. According to the degree value, ten genes were obtained and subjected to expression analysis and receiver operating characteristic (ROC) analysis. Next, key genes were screened for expression analysis and immunological analysis. Finally, cell counting kit-8 (CCK-8) and qRT-PCR were also conducted to observe the influence of hub gene on cell proliferation and inflammatory cytokines. Results: From the GSE64913 dataset, 711 upregulated and 684 downregulated DEGs were found. In WGCNA, the top 10 genes in the key module were examined by expression analysis in asthma, and CYCS was determined as an asthma-related oncogene with a good predictive ability for the prognosis of asthmatic patients. CYCS is significantly associated with immune cells, such as HHLA2, IDO1, TGFBR1, and CCL18 and promoted the proliferation of asthmatic cells in vitro. Conclusion: CYCS plays an oncogenic role in the pathophysiology of asthma, indicating that this gene may become a novel diagnostic biomarker and promising target of asthma treatment.

Parasubthalamic calretinin neurons modulate wakefulness associated with exploration in male mice.

The parasubthalamic nucleus (PSTN) is considered to be involved in motivation, feeding and hunting, all of which are highly depending on wakefulness. However, the roles and underlying neural circuits of the PSTN in wakefulness remain unclear. Neurons expressing calretinin (CR) account for the majority of PSTN neurons. In this study in male mice, fiber photometry recordings showed that the activity of PSTNCR neurons increased at the transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep, as well as exploratory behavior. Chemogenetic and optogenetic experiments demonstrated that PSTNCR neurons were necessary for initiating and/or maintaining arousal associated with exploration. Photoactivation of projections of PSTNCR neurons revealed that they regulated exploration-related wakefulness by innervating the ventral tegmental area. Collectively, our findings indicate that PSTNCR circuitry is essential for the induction and maintenance of the awake state associated with exploration.

Autocrine TGF-alpha is associated with Benzo(a)pyrene-induced mucus production and MUC5AC expression during allergic asthma.

OBJECTS: Benzo(a)pyrene (BaP), an environmental pollutant, is present in high concentrations in urban smog and cigarette smoke and has been reported to promote high mucin 5AC (MUC5AC) expression. Epithelium-derived inflammatory cytokines are considered an important modulator of mucus oversecretion and MUC5AC overexpression. Here, we investigated whether the effect of BaP on MUC5AC overexpression was associated with cytokine autocrine activity in vivo and in vitro. METHODS: In vivo, BALB/c mice were treated with ovalbumin (OVA) in the presence or absence of BaP. Allergy-induced mucus production was assessed by Alcian Blue Periodic acid Schiff (AB-PAS) staining. The human airway epithelial cell line NCI-H292 was used in vitro. MUC5AC and transforming growth factor (TGF)-α mRNA levels were assessed with real-time quantitative PCR. The concentration of cytokines was measured by ELISA. The MUC5AC, p-ERK, ERK, p-EGFR and EGFR proteins were detected by Western blotting in cells or by immunohistochemistry in mouse lungs. Small-interfering RNAs were used for gene silencing. RESULTS: TGF-α was overproduced in the supernatant of NCI-H292 cells treated with BaP. Knockdown of TGF-α expression inhibited the BaP-induced increase in MUC5AC expression and subsequent activation of the EGFR-ERK signalling pathway. Knocking down aryl hydrocarbon receptor (AhR) expression or treatment with an ROS inhibitor (N-acetyl-L-cysteine) could relieve the TGF-α secretion induced by BaP in epithelial cells. In an animal study, coexposure to BaP with OVA increased mucus production, MUC5AC expression and ROS-EGFR-ERK activation in the lung as well as TGF-α levels in bronchoalveolar lavage fluid (BALF). Furthermore, the concentration of TGF-α in BALF was correlated with MUC5AC mRNA levels. Additionally, TGF-α expression was found to be positively correlated with MUC5AC expression in the airway epithelial cells of smokers. Compared with non-smoker asthma patients, TGF-α serum levels were also elevated in smoker asthma patients. CONCLUSION: Autocrine TGF-α was associated with BaP-induced MUC5AC expression in vitro and in vivo. BaP induced TGF-α secretion by activating AhR and producing ROS, which led to activation of the EGFR-ERK pathway.

Expert consensus on multi-disciplinary treatment, whole-course pulmonary rehabilitation management in patients with lung cancer and chronic obstructive lung disease.

Comorbidity of lung cancer and chronic obstructive pulmonary disease (COPD) is very common. Surgical operation is the initial treatment of lung cancer. But surgery operation will aggravate the symptoms of COPD, such as shortness of breath, chest tightness. On the other side, the COPD also increase the perioperative complications. Besides, the COPD may also influence the anti-cancer treatment and long-term survival of lung cancer patients. At present, there are guidelines for pulmonary rehabilitation (PR) of COPD or lung cancer respectively, but there is no reference expert consensus on the PR of patients with lung cancer who are comorbidity of COPD. Primary care has to satisfy the patient's complex needs holistically, and single-disease guidelines are unsuitable. In view of this, we organized experts from respiratory department, thoracic surgery department, oncology department, nursing department, etc., to write the expert consensus. We discussed the contents of the expert consensus through literature review, expert correspondence, expert meeting and discussion. This expert consensus contain five parts: introduction, respiratory assessment, timing of PR, PR strategies, perioperative PR management strategies in lung cancer patients with COPD. This expert consensus focuses on patients with COPD comorbid lung cancer and undergoing surgery operation, highlighting the concept of whole process management. For clinical medical staff, this expert consensus will promote the practice of PR in and out the hospital for this specific patient; for patients, this expert consensus is helpful to better understand PR and improve the enthusiasm of participating in PR in the whole process.

Growth differentiation factor 11 induces skeletal muscle atrophy via a STAT3-dependent mechanism in pulmonary arterial hypertension.

Skeletal muscle wasting is a clinically remarkable phenotypic feature of pulmonary arterial hypertension (PAH) that increases the risk of mortality. Growth differentiation factor 11 (GDF11), centrally involved in PAH pathogenesis, has an inhibitory effect on skeletal muscle growth in other conditions. However, whether GDF11 is involved in the pathogenesis of skeletal muscle wasting in PAH remains unknown. We showed that serum GDF11 levels in patients were increased following PAH. Skeletal muscle wasting in the MCT-treated PAH model is accompanied by an increase in circulating GDF11 levels and local catabolic markers (Fbx32, Trim63, Foxo1, and protease activity). In vitro GDF11 activated phosphorylation of STAT3. Antagonizing STAT3, with Stattic, in vitro and in vivo, could partially reverse proteolytic pathways including STAT3/socs3 and iNOS/NO in GDF11-meditated muscle wasting. Our findings demonstrate that GDF11 contributes to muscle wasting and the inhibition of its downstream molecule STAT3 shows promise as a therapeutic intervention by which muscle atrophy may be directly prevented in PAH.

Deletion of BACH1 Attenuates Atherosclerosis by Reducing Endothelial Inflammation.

BACKGROUND: The transcription factor BACH1 (BTB and CNC homology 1) suppressed endothelial cells (ECs) proliferation and migration and impaired angiogenesis in the ischemic hindlimbs of adult mice. However, the role and underlying mechanisms of BACH1 in atherosclerosis remain unclear. METHODS: Mouse models of atherosclerosis in endothelial cell (EC)-specific-Bach1 knockout mice were used to study the role of BACH1 in the regulation of atherogenesis and the underlying mechanisms. RESULTS: Genetic analyses revealed that coronary artery disease-associated risk variant rs2832227 was associated with BACH1 gene expression in carotid plaques from patients. BACH1 was upregulated in ECs of human and mouse atherosclerotic plaques. Endothelial Bach1 deficiency decreased turbulent blood flow- or western diet-induced atherosclerotic lesions, macrophage content in plaques, expression of endothelial adhesion molecules (ICAM1 [intercellular cell adhesion molecule-1] and VCAM1 [vascular cell adhesion molecule-1]), and reduced plasma TNF-α (tumor necrosis factor-α) and IL-1ß levels in atherosclerotic mice. BACH1 deletion or knockdown inhibited monocyte-endothelial adhesion and reduced oscillatory shear stress or TNF-α-mediated induction of endothelial adhesion molecules and/or proinflammatory cytokines in mouse ECs, human umbilical vein ECs, and human aortic ECs. Mechanistic studies showed that upon oscillatory shear stress or TNF-α stimulation, BACH1 and YAP (yes-associated protein) were induced and translocated into the nucleus in ECs. BACH1 upregulated YAP expression by binding to the YAP promoter. BACH1 formed a complex with YAP inducing the transcription of adhesion molecules. YAP overexpression in ECs counteracted the antiatherosclerotic effect mediated by Bach1-deletion in mice. Rosuvastatin inhibited BACH1 expression by upregulating microRNA let-7a in ECs, and decreased Bach1 expression in the vascular endothelium of hyperlipidemic mice. BACH1 was colocalized with YAP, and the expression of BACH1 was positively correlated with YAP and proinflammatory genes, as well as adhesion molecules in human atherosclerotic plaques. CONCLUSIONS: These data identify BACH1 as a mechanosensor of hemodynamic stress and reveal that the BACH1-YAP transcriptional network is essential to vascular inflammation and atherogenesis. BACH1 shows potential as a novel therapeutic target in atherosclerosis.

Identifying Obstructive Sleep Apnea Syndrome-Associated Genes and Pathways through Weighted Gene Coexpression Network Analysis.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is the most common type of sleep apnea disorder. The disease seriously affects the patient's respiratory system. At present, the prognosis of the disease is poor and there is a lack of effective treatments. Therefore, it is urgent to explore its pathogenesis and treatment methods. METHOD: We downloaded a set of expression profile data from GSE75097 related to OSAS based on the Gene Expression Omnibus (GEO) database and selected the representative differentially expressed genes (DEGs) from the sample of the GSE75097 dataset. WGCNA was used to find genes related to OSAS and obtain coexpression modules. The Gene Ontology (GO) function and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to analyze genes from key modules. Finally, Cytoscape software was used to construct a protein-protein interaction (PPI) network and analyze the hub genes. RESULT: We obtained a total of 7565 DEGs. Through WGCNA, we got four coexpression modules and the modules most related to OSAS were green-yellow, magenta, purple, and turquoise, and we screened out eight hub genes (DDX46, RNF115, COPA, FBXO4, PA2G4, NHP2L1, CDC20, and PCNA). GO and KEGG analyses indicated that the key modules were mainly enriched in tRNA modification, nucleobase metabolic process, DNA ligation, regulation of cellular component movement, basal transcription factors, Huntington disease, and vitamin digestion and absorption. CONCLUSION: These pathways and hub genes can facilitate understanding the molecular mechanism of OSAS and provide a meaningful reference for finding biological targets of OSAS treatment.

Protective effects of progesterone on pulmonary artery smooth muscle cells stimulated with Interleukin 6 via blocking the shuttling and transcriptional function of STAT3.

BACKGROUND: Sex hormone paradox is a crucial but unresolved issue in the field of pulmonary artery hypertension (PAH), and is thought to be related to different pathogenic factors. Inflammation is one of pathological mechanisms of PAH development. However, effects of sex hormones on the pulmonary vasculature under the condition of inflammation are still elusive. METHODS: Interleukin-6 (IL-6) was used as a representative inflammatory stimulator. Effects of 17ß-estradiol or progesterone on human pulmonary artery smooth muscle cells (PASMCs) were measured under the condition of IL-6. Cell functions of proliferation and migration were measured by Alarmar Blue, EdU assay, wound-healing assay and transwell chambers. We explored further mechanisms using western blot, immunofluorescence, co-immunoprecipitation, qPCR and chromatin immunoprecipitation. RESULTS: Our results revealed that IL-6 promoted the proliferation of PASMCs, but progesterone could reverse the adverse effect of IL-6. The protective effect was dependent on progesterone receptor (PGR). By interacting with signal transducer and activator of transcription 3 (STAT3), activated PGR could reduce the IL-6-induced nuclear translocation of STAT3 and prevent STAT3-chromatin binding in PASMCs, leading to the decreased transcription of downstream CCND1 and BCL2. Alternatively, progesterone slightly decreased the phosphorylation of pro-proliferative Erk1/2 and Akt kinases and upregulated the anti-proliferative pSmad1-Id1/2 axis in IL-6-incubated PASMCs. CONCLUSIONS: Progesterone played a protective role on PASMCs in the context of IL-6, by blocking the functions of STAT3. Our findings might assist in explaining the clinical phenomenon of better prognosis for women with PAH.

BTB and CNC homology 1 (Bach1) induces lung cancer stem cell phenotypes by stimulating CD44 expression.

BACKGROUND: Growing evidence suggests that cancer stem cells (CSCs) are responsible for cancer initiation in tumors. Bach1 has been identified to contribute to several tumor progression, including lung cancer. The role of Bach1 in CSCs remains poorly known. Therefore, the function of Bach1 on lung CSCs was focused currently. METHODS: The expression of Bach1, CD133, CD44, Sox2, Nanog and Oct4 mRNA was assessed using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR). Protein expression of Bach1, CD133, CD44, Sox2, Nanog, Oct4, p53, BCL2, BAX, p-p38, p-AKT1, c-Fos and c-Jun protein was analyzed by western blotting. 5-ethynyl-29-deoxyuridine (EdU), colony formation, Flow cytometry analysis and transwell invasion assay were carried out to analyze lung cancer cell proliferation, apoptosis and invasion respectively. Tumor sphere formation assay was utilized to evaluate spheroid capacity. Flow cytometry analysis was carried out to isolate CD133 or CD44 positive lung cancer cells. The relationship between Bach1 and CD44 was verified using ChIP-qPCR and dual-luciferase reporter assay. Xenograft tumor tissues were collected for hematoxylin and eosin (HE) staining and IHC analysis to evaluate histology and Ki-67. RESULTS: The ratio of CD44 + CSCs from A549 and SPC-A1 cells were significantly enriched. Tumor growth of CD44 + CSCs was obviously suppressed in vivo compared to CD44- CSCs. Bach1 expression was obviously increased in CD44 + CSCs. Then, via using the in vitro experiment, it was observed that CSCs proliferation and invasion were greatly reduced by the down-regulation of Bach1 while cell apoptosis was triggered by knockdown of Bach1. Loss of Bach1 was able to repress tumor-sphere formation and tumor-initiating CSC markers. A repression of CSCs growth and metastasis of shRNA-Bach1 was confirmed using xenograft models and caudal vein injection. The direct interaction between Bach1 and CD44 was confirmed by ChIP-qPCR and dual-luciferase reporter assay. Furthermore, mitogen-activated protein kinases (MAPK) signaling pathway was selected and we proved the effects of Bach1 on lung CSCs were associated with the activation of the MAPK pathway. As manifested, loss of Bach1 was able to repress p-p38, p-AKT1, c-Fos, c-Jun protein levels in lung CSCs. Inhibition of MAPK signaling remarkably restrained lung CSCs growth and CSCs properties induced by Bach1 overexpression. CONCLUSION: In summary, we imply that Bach1 demonstrates great potential for the treatment of lung cancer metastasis and recurrence via activating CD44 and MPAK signaling.

Serum cartilage oligomeric matrix protein is decreased in patients with pulmonary hypertension: a potential protective factor.

Cartilage oligomeric matrix protein (COMP) was a protective factor in the cardiovascular system. Previous studies showed that hypoxia led to decreased COMP in rat models of pulmonary hypertension. However, the expression pattern of COMP in the pulmonary hypertension population was unclear. A total of 35 patients newly diagnosed with pulmonary hypertension and 70 controls were enrolled in the study. Circulating COMP concentrations of serum samples were measured by enzyme-linked immunosorbent assay and were analyzed the association with multiple clinical variables. Serum COMP concentrations in the pulmonary hypertension group were significantly declined in comparison with age- and sex-matched normal controls, especially in the female subgroup. No significant difference of COMP concentrations was observed in the etiological classification, heart function classification, and risk stratification. Major hemodynamic parameters, six-minute walk distance, N-terminal pro brain natriuretic peptide, and short-term prognosis were not statistically associated with COMP. However, some echocardiography parameters, like tricuspid annular plane systolic excursion and mean right atrial pressure, were found the negative relation to COMP concentrations. In conclusion, serum COMP levels were decreased in the patients with pulmonary hypertension, which was in accordance with its known biological effects. Its association with long-term prognosis was worth further exploring.

Respiratory physicians' awareness and referral of pulmonary rehabilitation in China: a cross-sectional study.

BACKGROUND: Pulmonary rehabilitation (PR) has demonstrated physiological, symptom reducing, psychosocial, and health care savings benefits in multiple outcome areas for patients with chronic respiratory diseases. Physicians' PR awareness and PR referral practices are key in PR promotion. However, PR awareness and referral among respiratory physicians in China have rarely been studied. This study aims to explore respiratory physicians' perceptions towards PR and assess the referral of PR in China. METHODS: A self-administered questionnaire was distributed via WeChat and emails to respiratory physicians in hospitals to assess their attitudes toward and knowledge of PR and identify treatment barriers. The study was conducted from June through October 2019. RESULTS: As reported in the 520 questionnaires collected through October 2019 most respondents had heard about PR, and many had knowledge of PR practice, but relatively few had referred patients to PR before having responded to the survey. Education, region of practice, and duration of practice are significant factors that influenced the participating respiratory physicians' awareness of PR. The percentage of referral was influenced by physicians' education, region, and duration of practice. The absence of PR facilities was the main barrier to respiratory physicians' referral of patients to PR. CONCLUSIONS: Chinese respiratory physicians' awareness of PR and referral to PR remain insufficient to support the delivery of PR to patients with chronic respiratory diseases. PR training for respiratory physicians and building PR centers are necessary to remedy these conditions.

Predictors of mortality for hospitalized young adults aged less than 60 years old with severe COVID-19: a retrospective study.

BACKGROUND: To analyze the clinical characteristics and predictors for mortality of adult younger than 60 years old with severe coronavirus disease 2019 (COVID-19). METHODS: We retrospectively retrieved data for 152 severe inpatients with COVID-19 including 60 young patients in the Eastern Campus of Wuhan University affiliated Renmin Hospital in Wuhan, China, from January 31, 2020 to February 20, 2020. We recorded and analyzed patients' demographic, clinical, laboratory, and chest CT findings, treatment and outcomes data. RESULTS: Of those 60 severe young patients, 15 (25%) were died. Male was more predominant in deceased young patients (12, 80%) than that in recovered young patients (22, 49%). Hypertension was more common among deceased young patients (8, 53%) than that in recovered young patients (7, 16%). Compared with the recovered young patients, more deceased young patients presented with sputum (11, 73%), dyspnea (12, 80%) and fatigue (13, 87%). Only sputum, PSI and neutrophil counts were remained as independent predictors of death in a multivariate logistic regression model. Among ARDS patients, the recovered were administrated with corticosteroid earlier and anticoagulation. The addition of neutrophil counts >6.3×109/L to the SMART-COP score resulted in improved area under the curves. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection in young deceased patients appears to cause exuberant inflammatory responses, leading to compromised oxygen exchange, coagulation and multi-organ dysfunction. In addition, young patients with ARDS could benefit from adjuvant early corticosteroid and anticoagulation therapy. The expanded SMART-COP could predict the fatal outcomes with optimal efficiency.

Essential Genes and MiRNA-mRNA Network Contributing to the Pathogenesis of Idiopathic Pulmonary Arterial Hypertension.

Background: Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease. Owing to its high fatality rate and narrow therapeutic options, identification of the pathogenic mechanisms of IPAH is becoming increasingly important. Methods: In our research, we utilized the robust rank aggregation (RRA) method to integrate four eligible pulmonary arterial hypertension (PAH) microarray datasets and identified the significant differentially expressed genes (DEGs) between IPAH and normal samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed to analyze their functions. The interaction network of protein-protein interaction (PPI) was constructed to explore the correlation between these DEGs. The functional modules and hub genes were further identified by the weighted gene coexpression network analysis (WGCNA). Moreover, a miRNA microarray dataset was involved and analyzed to filter differentially expressed miRNAs (DE-miRNAs). Potential target genes of screened DE-miRNAs were predicted and merged with DEGs to explore a miRNA-mRNA network in IPAH. Some hub genes were selected and validated by RT-PCR in lung tissues from the PAH animal model. Results: A total of 260 DEGs, consisting of 183 upregulated and 77 downregulated significant DEGs, were identified, and some of those genes were novel. Their molecular roles in the etiology of IPAH remained vague. The most crucial functional module involved in IPAH is mainly enriched in biological processes, including leukocyte migration, cell chemotaxis, and myeloid leukocyte migration. Construction and analysis of the PPI network showed that CXCL10, CXCL9, CCR1, CX3CR1, CX3CL1, CXCR2, CXCR1, PF4, CCL4L1, and ADORA3 were recognized as top 10 hub genes with high connectivity degrees. WGCNA further identified five main functional modules involved in the pathogenesis of IPAH. Twelve upregulated DE-miRNAs and nine downregulated DE-miRNAs were identified. Among them, four downregulated DEGs and eight upregulated DEGs were supposed to be negatively regulated by three upregulated DE-miRNAs and three downregulated DE-miRNAs, respectively. Conclusions: This study identifies some key and functional coexpression modules involved in IPAH, as well as a potential IPAH-related miRNA-mRNA regulated network. It provides deepening insights into the molecular mechanisms and provides vital clues in seeking novel therapeutic targets for IPAH.

The effect of Tai Chi on the pulmonary rehabilitation of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of Tai Chi for chronic obstructive pulmonary disease (COPD) so far is unclear. The present systematic review aimed to determine the influence of Tai Chi among people with COPD. METHODS: We searched six electronic databases for relevant studies in September, 2019. The methods of standard meta-analysis were used for identifying relevant studies, quality appraisal, and synthesis. The primary outcomes were six-minute walking distance (6MWD), percentage predicted forced expiratory flow volume in the first second (%PredFEV1), and St. George's Respiratory Questionnaire (SGRQ) score. RESULTS: A total of 23 studies including 1663 participants were included in the meta-analysis. The pooled data showed that the Tai Chi group was associated with a significant improvement in 6MWD [mean difference (MD) 40.83 m, 95% CI: 32.47 to 49.19], %PredFEV1 (MD 1.67%, 95% CI: 0.41 to 2.93), SGRQ score (MD -6.57, 95% CI: -10.17 to -2.98), and Chronic Respiratory Disease Questionnaire (CRQ) (MD 1.60, 95% CI: 0.89 to 2.30) relative to the blank control population. When compared with breathing exercises, the 6MWD was significantly enhanced with Tai Chi (MD 14.15 m, 95% CI: 3.76 to 24.53). Finally, when compared with breathing and walking exercises, Tai Chi was associated with a significant improvement in 6MWD (MD 7.68 m, 95% CI: 2.28 to 13.09 m) and SGRQ score (MD -6.31, 95% CI: -9.13 to -1.48). CONCLUSIONS: Tai Chi may have the potential to reduce dyspnoea, enhance exercise capacity, and improve the quality of life in COPD patients. People with COPD may obtain benefit from practicing Tai Chi.

LncRNA NEAT1 contributes to the acquisition of a tumor like-phenotype induced by PM 2.5 in lung bronchial epithelial cells via HIF-1α activation.

The hazards of particulate matter (PM2.5) on human respiratory health have been previously reported. However, the molecular mechanisms underlying PM2.5-induced lung carcinogenesis have rarely been studied. In the present study, we explored the effects of PM2.5 on the epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like properties in lung bronchial epithelial cells. We found that exposure of PM2.5 enhanced lung bronchial epithelial cell proliferation and EMT. In addition, the expression level of CSC-like biomarkers, CD133 and CD44, was significantly elevated by PM2.5 in vitro. Nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to participate in lung cancer. Loss of NEAT1 represses the malignant transformation of BEAS-2B and HBE cells induced by PM2.5. NEAT1 interacts with microRNA (miR)-582-5p, and miR-582-5p reverses the pro-tumor effects of NEAT1 overexpression. Hypoxia-inducible factor (HIF)-1α is an important transcription factor in the pathological responses to hypoxia. HIF-1α was a predicted target for miR-582-5p, and a direct correlation between them was identified. Inhibitors of miR-582-5p rescued HIF-1α expression, which was attenuated by a lack of NEAT1. In conclusion, PM2.5 increased NEAT1 expression, which, by binding with miR-582-5p, released HIF-1α and promoted EMT and the acquisition of CSC-like characteristics.

NLRP3 Deficiency Protects Against Intermittent Hypoxia-Induced Neuroinflammation and Mitochondrial ROS by Promoting the PINK1-Parkin Pathway of Mitophagy in a Murine Model of Sleep Apnea.

Obstructive sleep apnea (OSA) associated neurocognitive impairment is mainly caused by chronic intermittent hypoxia (CIH)-triggered neuroinflammation and oxidative stress. Previous study has demonstrated that mitochondrial reactive oxygen species (mtROS) was pivotal for hypoxia-related tissue injury. As a cytosolic multiprotein complex that participates in various inflammatory and neurodegenerative diseases, NLRP3 inflammasome could be activated by mtROS and thereby affected by the mitochondria-selective autophagy. However, the role of NLRP3 and possible mitophagy mechanism in CIH-elicited neuroinflammation remain to be elucidated. Compared with wild-type mice, NLRP3 deficiency protected them from CIH-induced neuronal damage, as indicated by the restoration of fear-conditioning test results and amelioration of neuron apoptosis. In addition, NLRP3 knockout mice displayed the mitigated microglia activation that elicited by CIH, concomitantly with elimination of damaged mitochondria and reduction of oxidative stress levels (malondialdehyde and superoxide dismutase). Elevated LC3 and beclin1 expressions were remarkably observed in CIH group. In vitro experiments, intermittent hypoxia (IH) significantly facilitated mitophagy induction and NLRP3 inflammasome activation in microglial (BV2) cells. Moreover, IH enhanced the accumulation of damaged mitochondria, increased mitochondrial depolarization and augmented mtROS release. Consistently, NLRP3 deletion elicited a protective phenotype against IH through enhancement of Parkin-mediated mitophagy. Furthermore, Parkin deletion or pretreated with 3MA (autophagy inhibitor) exacerbated these detrimental actions of IH, which was accompanied with NLRP3 inflammasome activation. These results revealed NLRP3 deficiency acted as a protective promotor through enhancing Parkin-depended mitophagy in CIH-induced neuroinflammation. Thus, NLRP3 gene knockout or pharmacological blockage could be as a potential therapeutic strategy for OSA-associated neurocognitive impairment.

Prevalence and screening of specific aeroallergens in Chinese male patients with chronic obstructive pulmonary disease: A retrospective cross-sectional observational study.

INTRODUCTION: Sensitization to aeroallergens was linked to severe symptoms and frequent exacerbations in chronic obstructive pulmonary disease (COPD) patients. Elevated serum total immunoglobulin E (tIgE) level is a hallmark of allergic COPD patients. Phadiatop test exhibited high sensitivity for predicting specific aeroallergens (SAs) sensitization. However, the prevalence of aeroallergens, the value of Phadiatop test, alone or combined with tIgE, for predicting aeroallergens sensitization in male COPD patients have not been explored in China. OBJECTIVES: To explore the prevalence and predictors of aeroallergens in the context of COPD. METHODS: The predictive value of Phadiatop test for SAs sensitization in male COPD patients was analyzed via the area under receiver operating characteristic curves (AUCs). RESULTS: The top five SAs in the context of COPD were d2, mx2, i6, d1, and tx5, of which the seasonal distribution showed no significant differences. Allergic group showed higher levels of blood eosinophils, total Phadiatop IgE and tIgE than the nonallergic group (all P ≤ 0.001). The AUCs of total Phadiatop IgE and tIgE for predicting the sensitization to SAs, SAs excluding mx2 (AEM) and mx2 were ((0.921 vs. 0.879, P = 0.2522), (0.967 vs. 0.807, P = 0.0003), and (0.780 vs. 0.883, P < 0.05)) (AUCPhadiatop vs AUCtIgE ), respectively. The combined application of these two parameters (model) increased the AUC of SAs, significantly higher than the single parameter used (P < 0.05 for all). CONCLUSION: d2, mx2, i6, and d1 were the top four SAs sensitized in male COPD patients; Phadiatop test was valuable for predicting the sensitization to SAs when it was > 0.13 kAU/L.