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.

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.

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.

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.

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.

Clinical risk factors for mortality of hospitalized patients with COVID-19: systematic review and meta-analysis.

BACKGROUND: New evidence from retrospective cohort studies on risk of death from COVID-19 infection became available. We aimed to systematically review the clinical risk factors for fatal outcome of COVID-19. METHODS: We performed meta-analysis, using PubMed, EMBASE and Cochrane databases from December 1 2019 to June 10 2020. The meta-analysis summarized clinical, laboratory, radiological features, and complications of non-survivors with confirmed COVID-19. In addition, a fixed- or random-effects model was adopted based on the heterogeneity among studies. We also used funnel-plot with Egger's tests to screen potential publication bias. RESULTS: In total, twenty studies with 15,408 COVID-19 cases were included in our meta-analysis. Male, current smoking, and older age were associated with in-hospital death. Patients aged 60 years or over had the highest pooled ORs [OR 4.94 (2.89, 8.44)]. Non-survivors were more likely to have diabetes, hypertension, cardiovascular disease (CVD), respiratory disease, or chronic kidney disease (CKD). Respiratory disease had the highest pooled ORs [OR 2.55 (2.14, 3.05)]. Dyspnea [OR 3.31 (1.78, 6.16); I2 : 83%] and fatigue [OR 1.36 (1.07, 1.73); I2 : 0%] were associated with increased risk of death. Increased white blood cell count, decreased lymphocyte and platelet counts, were also associated with increased risk of death. Biomarkers of coagulation function, inflammation, liver and kidney function, cardiac and muscle injury were also elevated in nonsurvivors. CONCLUSIONS: Male, current smoking patients aged 60 years or over might face a greater risk of in-hospital death and the comorbidities such as diabetes, hypertension, CVD, respiratory disease, and CKD could also influence the prognosis of the COVID-19. Clinical feature such as dyspnea and fatigue could imply the exacerbation and even death. Our findings highlighted early markers of mortality which were beneficial to identify fatal COVID-19.

Chronic intermittent hypoxia promoted lung cancer stem cell-like properties via enhancing Bach1 expression.

BACKGROUND: An adverse role for obstructive sleep apnea (OSA) in cancer aggressiveness and mortality has recently emerged from clinical and animal studies, and the reasons have not been fully determined. Cancer stem cells (CSCs) are regarded as the main cause of carcinoma metastasis. So far, the relationship between OSA and lung CSCs has not been explored. METHOD: In the present study, we established an orthotopic mouse model of primary lung cancer and utilized chronic intermittent hypoxia (CIH) exposure to mimic OSA status. RESULTS: We observed that CIH endows lung cancer with greater metastatic potential, evidenced by increased tumor growth, tumor seeding, and upregulated CSC-related gene expression in the lungs. Notably, the transcription factor BTB and CNC homology 1 (Bach1), a key factor in responding to conditions of oxidative stress, is increased in lung cancer after CIH exposure in vitro and in vivo. Meanwhile, exposing lung cancer cells to CIH promoted cell proliferation, clonal diversity, induced stem-like cell marker expression, and gave rise to CSCs at a relatively higher frequency. Furthermore, the increase of mitochondrial ROS (mtROS) and CSC-marker expression induced by CIH exposure was abolished in Bach1 shRNA-treated lung cancer cells. CONCLUSIONS: Our results indicated that CIH promoted lung CSC-like properties by activating mtROS, which was partially mediated by Bach1.

Benzo(a)pyrene induces MUC5AC expression through the AhR/mitochondrial ROS/ERK pathway in airway epithelial cells.

OBJECTIVES: Benzo(a)pyrene (BaP) is a ubiquitous air pollutants, and BaP exposure leads to a risk of respiratory diseases. The oversecretion of airway mucus and high expression of mucin 5AC (MUC5AC) are associated with common respiratory disorders caused by air pollution. We aimed to investigate the effect of BaP on MUC5AC expression, especially the mechanisms by which BaP induces MUC5AC gene expression. METHODS: The human airway epithelial cell NCI-H292 was used to test the effects of BaP on the expression of MUC5AC in vitro. MUC5AC mRNA and protein expression were assessed with real-time quantitative PCR, immunochemistry, and western blotting. A luciferase assay was conducted to detect the activity of the promoter. The total cellular ROS and mitochondrial ROS were measured by corresponding probes. Small-interfering RNAs were used for gene silencing. AhR-overexpressing cell lines were constructed by transfection with AhR overexpression lentivirus. RESULTS: We found that BaP stimulation upregulated the MUC5AC mRNA and protein levels and activated the ERK pathway. Suppressing ERK with U0126 (an ERK inhibitor) or knocking down ERK with siRNA decreased BaP-induced MUC5AC expression. The luciferase activity transfected with the MUC5AC promoter and cAMP-response element (CRE) was increased after BaP treatment, whereas CREB siRNA suppressed the BaP-induced overexpression of MUC5AC. In addition, BaP increased mitochondrial ROS production, and Mito-TEMP, a mitochondrial ROS inhibitor, inhibited BaP-induced MUC5AC expression and ERK activation. BaP increased the mRNA levels of CYP1A1 and CYP1B1, while Alizarin, a CYP1s inhibitor, suppressed the effects of BaP, including the MUC5AC overexpression, ERK activation and mitochondrial ROS generation. BaP induced the translocation of aryl hydrocarbon receptor (AhR) from the cytoplasm to the nucleus. SiRNA-mediated knockdown or chemical inhibition of AhR decreased the BaP-induced expression of MUC5AC, while the overexpression of AhR significantly enhanced the BaP-induced expression of MUC5AC. ITE, an endogenous AhR ligand, also upregulated the mRNA and protein expression of MUC5AC. Furthermore, resveratrol treatment inhibited the BaP-induced MUC5AC overexpression, AhR translocation, mitochondrial ROS production and ERK pathway activation. CONCLUSION: Here, we highlighted the crucial role of AhR/mitochondrial ROS/ERK pathway activation in BaP-induced MUC5AC overexpression and identified resveratrol as a promising drug to reduce BaP-induced MUC5AC overexpression.

Assessment of knowledge, attitude, and practice towards pulmonary rehabilitation among COPD patients: A multicenter and cross-sectional survey in China.

BACKGROUND: Pulmonary rehabilitation (PR) has been recognized to be an evidence-based treatment recommended for chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate COPD patients' knowledge, attitudes and practices towards PR in China. METHODS: 1138 COPD patients from 13 hospitals were enrolled in this cross-sectional study. A questionnaire designed based on an official statement was completed by the participants. Effects of PR in patients were investigated. RESULTS: Mean score of the knowledge portion was only 7.76, while 46.22% of the participants believed they needed PR. Attendance rate was 24.69%. Financial conditions and hospitalization were contributing factors for scores, attendance rate, and belief in demands for PR therapy. Severe pulmonary function impairment indicated more demands for PR (OR = 0.18) and higher uptake rate (OR = 0.30). There was a weak correlation between smoking status (rho = -0.060), diagnosis year (rho = 0.094), frequency of exacerbations (rho = 0.059) and grades. High CAT score is a facilitator for attitudes towards PR (OR = 0.022). 93.24% of patients claimed that their exercise tolerance improved with PR therapy. The improvements were positively associated with needs (rho = 0.20), family support (rho = 0.22), grades (rho = 0.18), and monthly income of the family (rho = 0.14), but negatively correlated with age (rho = -0.16), exacerbations (rho = -0.15), and CAT score (rho = -0.13). CONCLUSIONS: This study suggested poor perception, disbelief in the need for PR, and limited uptake of PR among COPD patients in China, and revealed the significant factors involved. The findings of this study may assist health professionals in developing targeted strategies to promote PR and improve access and uptake of PR.

Epigallocatechin­3­gallate inhibits self­renewal ability of lung cancer stem­like cells through inhibition of CLOCK.

Circadian rhythm plays an important role in diverse physiological processes. Abnormal expression of circadian rhythm genes is associated with increased risk of disease, including different types of cancer. The cancer stem cell (CSC) hypothesis suggests that there is a small subset of stem­like cells within tumors that are responsible for tumor initiation. However, the biological effect of circadian rhythm on CSCs remains largely unknown. Studies have highlighted that the circadian rhythm protein CLOCK controls key aspects of various diseases. In the present study, lung cancer stem­like cells were successfully enriched using a sphere formation assay. Next, it was observed that CLOCK mRNA and protein expression levels in the A549 and H1299 sphere cells were notably increased compared with those in the corresponding parental cells. In addition, flow cytometry was performed to isolate CD133+ cells and, consistently, CLOCK expression was also found to be markedly upregulated in CD133+ lung cancer cells. Subsequently, to determine the effect of CLOCK on lung cancer stem cells in detail, CLOCK was knocked down using targeted short inhibiting RNA and the results demonstrated that the sphere­forming ability of the A549 and H1299 cell lines was reduced. In addition, CSC­like properties, including the expression of CD133, CD44, sex determining region Y­box 2, Nanog and octamer­binding transcription factor 4, were markedly decreased in the A549 and H1299 sphere cells following knockdown of CLOCK. Epigallocatechin­3­gallate (EGCG), a green tea polyphenol, has been reported to be a potential anticancer phytochemical. EGCG was found to repress CLOCK expression in A549 and H1299 sphere cells. In addition, EGCG also decreased the ratio of CD133+ cells. The Wnt/ß­catenin pathway was notably inactivated by the knockdown of CLOCK in A549 and H1299 sphere cells. Subsequently, using a xenograft model, it was demonstrated that EGCG suppressed the CSC­like characteristics of lung cancer cells by targeting CLOCK. In conclusion, the present study demonstrated that EGCG inhibited the self­renewal ability of lung cancer stem­like cells by targeting CLOCK.

The Construction of Primary Screening Model and Discriminant Model for Chronic Obstructive Pulmonary Disease in Northeast China.

Objective: The diagnosis of chronic obstructive pulmonary disease (COPD) is challenging, especially in the primary institution which lacks spirometer. To reduce the rate of COPD missed diagnoses in Northeast China, which has a higher prevalence of COPD, this study aimed to establish efficient primary screening and discriminant models of COPD in this region. Patients and Methods: Subjects from Northeast China were enrolled from December 2017 to April 2019 from The First Hospital of China Medical University. Pulmonary function tests and questionnaire were given to all participants. Using illness or no illness as the goal for screening models and disease severity as the goal for discriminant models, multivariate linear regression, logical regression, linear discriminant analysis, K-nearest neighbor, decision tree and support vector machine were constructed through R language and Python software. After comparing effectiveness among them, the most optimal primary screening and discriminant models were established. Results: Enrolled were 232 COPD patients (124 GOLD I-II and 108 GOLD III-IV) and 218 normal controls. Eight primary screening models were established. The optimal model was Y = -1.2562-0.3891X4 (education level) + 1.7996X5 (dyspnea) + 0.5102X6 (cooking fuel grade) + 1.498X7 (smoking index) + 0.8077X9 (family history)-0.5552X11 (BMI) + 0.538X13 (cough with sputum) + 2.0328X14 (wheezing) + 1.3378X16 (farmers) + 0.8187X17 (mother's smoking exposure history during pregnancy)-0.389X18 (kitchen ventilation) + 0.6888X19 (childhood heating). Six discriminant models were established. The optimal model was decision tree (the optimal variables: dyspnea (x5), cooking fuel grade (x6), second-hand smoking index (x8), BMI (x11), cough (x12), cough with sputum (x13), wheezing (x14), farmer (x16), kitchen ventilation (x18), and childhood heating (x19)). The code was established to combine the discriminant model with computer technology. Conclusion: Many factors were related to COPD in Northeast China. Stepwise logistic regression and decision tree were the optimal screening and discriminant models for COPD in this region.

Pulmonary Function Influences the Performance of Berlin Questionnaire, Modified Berlin Questionnaire, and STOP-Bang Score for Screening Obstructive Sleep Apnea in Subjects with Chronic Obstructive Pulmonary Disease.

Purpose: The co-existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) has been described as the overlap syndrome. The objective of the study is to investigate the performance of Berlin Questionnaire (BQ), modified Berlin Questionnaire (MBQ), and STOP-Bang score in screening overlap syndrome from COPD subjects and investigate how pulmonary function interferes with questionnaire scoring. Subjects and Methods: Among 116 COPD subjects included in this study, 62 were overlap syndrome subjects and 54 were COPD subjects without OSA. Subjects included were asked to fill out the questionnaires to collect demographic characteristics of subjects and questionnaire scores of BQ, MBQ, and STOP-Bang; perform pulmonary function test to confirm their COPD diagnosis; and perform polysomnography. Results: AUC (area under the curve) of BQ, MBQ, and STOP-Bang score in screening OSA among patients with COPD was 0.71 (0.64-0.79), 0.75 (0.67-0.83), and 0.72 (0.64-0.80). In COPD subjects without OSA, FEV1%pred was statistically associated with the misdiagnosis of BQ (P= 0.0091), MBQ (P= 0.0143), and STOP-Bang (P= 0.0453). In patients with overlap syndrome, FVC%pred affected the risk of misdiagnosis of the three questionnaires (BQ: P= 0.0413; MBQ: P= 0.0150; STOP-Bang: P= 0.0241). BMI and neck circumferences (NC) were negatively correlated with FEV1%pred (BMI: P= 0.0454; NC: P= 0.0230) and FVC%pred (BMI: P= 0.0042; NC: P= 0.0367) in overlap subjects. In contrast, BMI was positively correlated with FEV1/FVC (P= 0.0141) and FEV1%pred (P= 0.0391) in COPD subjects without OSA. Conclusion: BQ, MBQ, and STOP-Bang score performed well in COPD subjects for screening OSA. The diagnosis of the three questionnaires was more accurate in subjects with lower FEV1%pred or FVC%pred value. Pulmonary function might exert influence on the diagnosis efficacy of the three questionnaires through BMI and neck circumference.

Necessity of personal sampling for exposure assessment on specific constituents of PM2.5: Results of a panel study in Shanghai, China.

Many epidemiological studies have evaluated the health risks of ambient fine particulate matter (PM2.5). However, few studies have investigated the potential exposure misclassification caused by using ambient PM2.5 concentrations as proxy for individual exposure to PM2.5 in regions with high-level of air pollution. This study aimed to compare the differences between personal and ambient PM2.5 constituent concentrations, and to predict the personal exposure of sixteen PM2.5 constituents. We collected 141 72-h personal exposure filter samples from a panel of 36 healthy non-smoking college students in Shanghai, China. We then used the liner mixed effects models to predict personal constituent-specific exposure using ambient observations and several possible influencing factors including time-activity patterns, temporal variables, and meteorological conditions. The final model of each component was further evaluated by determination coefficient (R2) and root mean square error (RMSE) from leave-one-out-cross-validation (LOOCV). We observed ambient concentrations were higher than personal concentrations for all PM2.5 components except for Mn, Fe, Ca, and V. Especially, ambient NH4+, As, and NO3- concentrations were 3.65, 5.65 and 7.33-fold higher than their corresponding personal concentrations, respectively. The ambient level was the strongest predictor of their corresponding personal PM2.5 components with the highest marginal R2 (RM2: 0.081 ~ 0.901), meteorological conditions (RM2: 0.000 ~ 0.357), time-activity pattern (RM2: 0.000 ~ 0.083) and temporal indicators (RM2: 0.031 ~ 0.562) were also important predictors. Our final models predicted at least 50% of the variance of all personal PM2.5 constituents and even over 90% for K, Pb, and SO42-. LOOCV analysis showed that R2 and RMSE ranged from 0.251 to 0.907 and 0.000 to 0.092 µg/m3, respectively. Our results showed that ambient concentration of most PM2.5 constituents along with time-activity patterns, temporal variables, and meteorological conditions, could adequately predict personal exposure concentration. Prediction models of individual PM2.5 constituent may help to improve the accuracy of exposure measurement in future epidemiological studies.

Effects of non-invasive ventilation in subjects undergoing cardiac surgery on length of hospital stay and cardiac-pulmonary complications: a systematic review and meta-analysis.

BACKGROUND: Cardiac surgery often leads to pulmonary complications. Non-invasive ventilation (NIV) is a mechanical ventilation modality that may help to prevent the pulmonary complications, and the role of the prophylactic use of NIV in patients after cardiac surgery remains controversial. METHODS: We searched PubMed, Embase, Web of Science and Cochrane Central for randomized controlled trials comparing the use of NIV (continues positive airway pressure or bi-level positive airway pressure) with standard treatment in post-cardiac surgery subjects without language restriction. Two investigators screened the eligible studies up to July, 2019. Meta-analysis using random effect model or fixed effect model was conducted for pulmonary complications, mortality, rate of reintubation and cardiac complications, and mean difference (MD) or standard mean difference for length of hospital stay and length of ICU stay. RESULTS: We included nine randomized controlled trails with 830 subjects. The use of NIV failed to reduce the risk of pulmonary complications, including atelectasis [risk rate (RR) 0.60; 95% confidence interval (CI): 0.28 to 1.28, P=0.19] and pneumonia (RR 0.27; 95% CI: 0.05 to 1.64, P=0.16). However, it has shortened the length of ICU stay (MD -1.00 h, 95% CI: -1.38 to -0.63, P<0.00001) and the length of hospital stay (MD -1.00 d, 95% CI: -1.12 to -0.87, P<0.00001). NIV also failed to reduce the rate of reintubation (RR 0.68; 95% CI: 0.21 to 2.26, P=0.53) or the risk of cardiac complications (RR 0.81; 95% CI: 0.59 to 1.13, P=0.22). CONCLUSIONS: The prophylactic use of NIV immediately in post-cardiac subjects who underwent cardiac surgery might be able to shorten the length of hospital stay and the length of ICU stay, but it has no significant effect on pulmonary complications, rate of reintubation or cardiac complications.

Bach1-induced suppression of angiogenesis is dependent on the BTB domain.

The transcription factor Bach1 impairs angiogenesis after ischemic injury by suppressing Wnt/ß-catenin signaling; however, the specific domains responsible for the anti-angiogenic effects of Bach1 remain unclear. This study determined the role of the BTB domain of Bach1 in ischemic angiogenesis. Bach1 is highly expressed in circulating endothelial cells from acute myocardial infarction patients and is the early induction gene after ischemia. Mice were treated with adenoviruses coding for GFP (AdGFP), Bach1 (AdBach1), or a Bach1 mutant lacking the BTB domain (AdBach1-ΔBTB) after surgically induced hind-limb ischemia. Measures of blood-flow recovery, capillary density, and the expression of vascular endothelial growth factor (VEGF) and heme oxygenase-1 (HO-1) were significantly lower and ROS levels were higher in the AdBach1 group, but not in AdBach1-ΔBTB animals. Furthermore, transfection with AdBach1, but not AdBach1-ΔBTB, in human endothelial cells was associated with significant declines in 1) capillary density and hemoglobin content in the Matrigel-plug assay, 2) proliferation, migration, tube formation, and VEGF and HO-1 expression in endothelial cells. Bach1 binds directly with TCF4, and this interaction is mediated by residues 81-89 of the Bach1 BTB domain and the N-terminal domain of TCF4. Bach1, but not Bach1-ΔBTB, also co-precipitated with histone deacetylase 1 (HDAC1), while the full-length HDAC1 proteins, but not HDAC1 mutants lacking the protein-interaction domain, co-precipitated with Bach1. Collectively, these results demonstrate that the anti-angiogenic activity of Bach1 is crucially dependent on molecular interactions that are mediated by the protein's BTB domain, and this domain could be a drug target for angiogenic therapy.

LncRNA SNHG3 is activated by E2F1 and promotes proliferation and migration of non-small-cell lung cancer cells through activating TGF-ß pathway and IL-6/JAK2/STAT3 pathway.

Recently, long noncoding RNAs (lncRNAs) have been widely reported to play pivotal roles in the regulation of human cancers. Although the oncogenic property of lncRNA small nucleolar RNA host gene 3 (SNHG3) has been revealed in a variety of cancers, functions and regulatory mechanism of SNHG3 in non-small-cell lung cancer (NSCLC) remain to be investigated. In this study, we detected the upregulated expression of SNHG3 in NSCLC tissues as well as cells through quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. Using Kaplan-Meier analysis, we determined that a high-level of SNHG3 was associated with a low overall survival rate of patients with NSCLC. Through gain and loss of function experiments, we demonstrated that SNHG3 had a significantly positive effect on NSCLC cell proliferation and migration. Mechanistic investigations revealed that SNHG3 was a predicted direct transcriptional target of E2F1. We observed that the transcriptional activation of SNHG3 could be induced by E2F1. To explore the mechanism, rescue experiments were carried out, which revealed that the cotreatment with SB-431542, JSI-124, or JSI-124 + SB-431542 rescued the effects brought by the overexpression of SNHG3 on NSCLC cell proliferation, migration, and epithelial-mesenchymal transition process. Our results suggested that E2F1 activated SNHG3 and promoted cell proliferation and migration in NSCLC via transforming growth factor-ß pathway and interleukin-6/janus-activated kinase 2/signal transducer and activator of transcription 3 pathway, which implied that SNHG3 may be a biomarker for the treatment of patients with NSCLC.

The acute effects of fine particulate matter constituents on circulating inflammatory biomarkers in healthy adults.

BACKGROUND: Systemic inflammation is considered one of the key mechanisms in the development of cardiovascular diseases induced by fine particulate matter (PM2.5) air pollution. However, evidence concerning the effects of various PM2.5 constituents on circulating inflammatory biomarkers were limited and inconsistent. OBJECTIVES: To evaluate the associations of short-term exposure to a variety of PM2.5 constituents with circulating inflammatory biomarkers. METHODS: We conducted a panel study from May to October 2016 among 40 healthy adults in Shanghai, China. We monitored the concentrations of 27 constituents of PM2.5. We applied linear mixed-effect models to analyze the associations of PM2.5 and its constituents with 7 inflammatory biomarkers, and further assessed the robustness of the associations by fitting models adjusting for PM2.5 mass and/or their collinearity. Benjamini-Hochberg false discovery rate was used to correct for multiple comparisons. RESULTS: The associations of PM2.5 were strongest at lag 0 d with tumor necrosis factor-α (TNF-α), at lag 1 d with interleukin-6, interleukin-8, and interleukin-17A, at lag 02 d with monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1). After correcting for multiple comparisons in all models, Cl-, K+, Si, K, As, and Pb were significantly associated with interleukin-8; SO42- and Se were marginally significantly associated with interleukin-8; SO42-, As, and Se were marginally significantly associated with TNF-α; and Si, K, Zn, As, Se, and Pb were marginally significantly associated with MCP-1. CONCLUSIONS: Our results suggested that some constituents (SO42-, Cl-, K+, and some elements) might be mainly responsible for systemic inflammation triggered by short-term PM2.5 exposure.

The acute effects of ultraviolet radiation exposure on solar dermatitis in Shanghai, China.

Ultraviolet radiation (UVR) has long been considered associated with solar dermatitis, but the associations have not been well quantified. To depict the full-range exposure-response association between daily UVR exposures and daily outpatient visits of solar dermatitis. We collected the daily number of outpatient visits of solar dermatitis and monitored hourly ground data of UVR (the sum of A- and B-band) from 1 January 2013 to 31 December 2017 in Shanghai, China. The data were analyzed using the time-series approach, in which overdispersed generalized additive model was used and time trends and weather conditions were controlled for. During the study period, we recorded a total of 15,051 outpatient visits of solar dermatitis. There was a consistently increasing risk of solar dermatitis associated with stronger UVR without a discernible threshold. The effects occurred on the present day, increased to the largest at lag 1 or 2 days, and attenuated to the null at lag 5 days or more. A unit (w/m2) increase in daily maximum-hour UVR was associated with 1.70% (95%CI: 1.19%, 2.20%) increase of outpatient visits of solar dermatitis. Stronger effects occurred among the young people, females, and in the warm season. The risks of solar dermatitis due to UVR exposure would be overestimated if ambient temperature was not adjusted. This study provides quantitative epidemiological estimates for the positive associations between short-term exposure to UVR and increased risks of solar dermatitis. The associations were more prominent among young people, females, and in warm seasons.