Views of health care professionals on the implementation of preoperative advance care planning in older patients with head and neck cancer: Q methodology.

Objective: To investigate the views of health care professionals in a head and neck surgical department toward the implementation of advance care planning prior to surgery for older patients with head and neck cancer. Method: Q methodology was used to explore and analyze participants' views by combining quantitative and qualitative methods. Participants were asked to rank 35 Q statements generated via semi-structured interviews and a literature review and to explain the reasons for their ranking in subsequent interviews. The data was then analyzed and used to develop a factor series to illustrate participants' views. Results: This study surveyed 15 health care professionals, including eight doctors and seven nurses. The views of health care professionals toward preoperative implementation of advance care planning discussions were varied and could be categorized into three types: defending the autonomy of patients, patients' knowledge and the Chinese traditional cultural context hinder the implementation of preoperative advance care planning, and lack of confidence in performing preoperative advance care planning. Conclusions: Although the health care professionals in the head and neck surgical department in this study recognized the benefits of preoperative discussions regarding advance care planning, patients' knowledge level, traditional Chinese values, inadequate capacity among health care professionals, and unsound legal policies have caused these professionals to have misgivings about preoperative counseling and discussing advance care planning with patients. Further studies should be conducted, and strategies to overcome barriers to discussions of preoperative advance care planning should be developed.

Interleukin-2/anti-interleukin-2 complex attenuates inflammation in a mouse COPD model by expanding CD4+ CD25+ Foxp3+ regulatory T cells.

BACKGROUND AND PURPOSE: Chronic, nonspecific inflammation of the alveoli and airways is an important pathological feature of chronic obstructive pulmonary disease (COPD), while sustained inflammatory reactions can cause alveolar damage. Regulatory T cells (Tregs) inhibit inflammation, whereas the interleukin-2/anti-interleukin-2 complex (IL-2C) increases the number of Tregs; however, whether the IL-2C has a therapeutic role in COPD remains unknown. Therefore, this study investigated whether IL-2C alleviates lung inflammation in COPD by increasing the number of Tregs. EXPERIMENTAL APPROACH: A mouse COPD model was created by exposing mice to lipopolysaccharides (LPS) and cigarette smoke (CS), and the effects of IL-2C treatment on COPD were evaluated. The number of Tregs in the spleen and lung, pulmonary pathological changes, and inflammatory damage were examined through flow cytometry, histopathology, and immunofluorescence, respectively. KEY RESULTS: IL-2C increased the number of Treg cells in the spleen and lungs after exposure to CS and LPS, reduced the number of T helper 17 (Th17) cells in lung tissue, and improved the Th17/Treg balance. IL-2C decreased the number of inflammatory cells and reduced the levels of pro-inflammatory cytokines IL-6, TNF-α, IL-1ß, CCL5, KC, and MCP-1 in bronchoalveolar lavage fluid and serum. IL-2C significantly reduced the pathological scores for lung inflammation, as well as decreased airway mucus secretion and infiltration of neutrophils and macrophages in the lungs. The depletion of Tregs using anti-CD25 antibodies eliminated the beneficial effects of IL-2C. CONCLUSIONS AND IMPLICATIONS: IL-2C is a potential therapeutic agent for alleviating excessive inflammation in the lungs of patients with COPD.

MiR-23a-5p alleviates chronic obstructive pulmonary disease through targeted regulation of RAGE-ROS pathway.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and represents the third leading cause of death worldwide. This study aimed to investigate miRNA regulation of Receptor for Advanced Glycation End-products (RAGE), a causal receptor in the pathogenesis of cigarette smoke (CS)-related COPD, to guide development of therapeutic strategies. METHODS: RAGE expression was quantified in lung tissue of COPD patients and healthy controls, and in mice with CS-induced COPD. RNA-sequencing of peripheral blood from COPD patients with binding site prediction was used to screen differentially expressed miRNAs that may interact with RAGE. Investigation of miR-23a-5p as a potential regulator of COPD progression was conducted with miR-23a-5p agomir in COPD mice in vivo using histology and SCIREQ functional assays, while miR-23a-5p mimics or RAGE inhibitor were applied in 16-HBE human bronchial epithelial cells in vitro. RNA-sequencing, ELISA, and standard molecular techniques were used to characterize downstream signaling pathways in COPD mice and 16-HBE cells treated with cigarette smoke extract (CSE). RESULTS: RAGE expression is significantly increased in lung tissue of COPD patients, COPD model mice, and CSE-treated 16-HBE cells, while inhibiting RAGE expression significantly reduces COPD severity in mice. RNA-seq analysis of peripheral blood from COPD patients identified miR-23a-5p as the most significant candidate miRNA interaction partner of RAGE, and miR-23a-5p is significantly downregulated in mice and cells treated with CS or CSE, respectively. Injection of miR-23a-5p agomir leads to significantly reduced airway inflammation and alleviation of symptoms in COPD mice, while overexpressing miR-23a-5p leads to improved lung function. RNA-seq with validation confirmed that reactive oxygen species (ROS) signaling is increased under CSE-induced aberrant upregulation of RAGE, and suppressed in CSE-stimulated cells treated with miR-23a-5p mimics or overexpression. ERK phosphorylation and subsequent cytokine production was also increased under RAGE activation, but inhibited by increasing miR-23a-5p levels, implying that the miR-23a-5p/RAGE/ROS axis mediates COPD pathogenesis via ERK activation. CONCLUSIONS: This study identifies a miR-23a-5p/RAGE/ROS signaling axis required for pathogenesis of COPD. MiR-23a-5p functions as a negative regulator of RAGE and downstream activation of ROS signaling, and can inhibit COPD progression in vitro and in vivo, suggesting therapeutic targets to improve COPD treatment.

The impact of core self-evaluation on school adaptation of high school students after their return to school during the COVID-19 pandemic: the parallel mediation of positive and negative coping styles.

Background: To explore the direct effect of core self-evaluation and the indirect effects of positive and negative coping styles on school adaptation of high school students after their return to school during the COVID-19 pandemic. Methods: The Core Self-Evaluation Scale, Simple Coping Style Scale, and School Adaptation Questionnaire were used for the psychometric analysis of 500 high school students (229 males and 271 females) one month after their return to school. The bootstrap method was applied for mediation analysis. Results: A positive correlation was noted between core self-evaluation and school adaptation (r = 0.56), and the predictive effect was significant (ß = 0.43). Core self-evaluation positively predicted positive coping styles, which positively predicted school adaptation, while core self-evaluation negatively predicted negative coping styles, which negatively predicted school adaptation. Positive and negative coping styles played a significant mediating role between core self-evaluation and school adaptation. The mediating effect included the indirect effects generated by two pathways: core self-evaluation → positive coping style → school adaptation (95% CI [0.08-0.19]) and core self-evaluation → negative coping style → school adaptation (95% CI [0.03-0.11]). Conclusion: There is a positive association between the core self-evaluation and school adaptation of high school students after their return to school during the COVID-19 pandemic. It may directly or indirectly affect the school adaptation of high school students after their return to school through positive or negative coping styles. After returning to school, educators should guide students to view themselves positively, cultivate healthy core self-evaluation, and enable them to have good school adaptation.

Pharmacological therapy for stable chronic obstructive pulmonary disease.

In recent years, emphasis has shifted from preventing and treating chronic obstructive pulmonary disease (COPD) to early prevention, early treatment, and disease stabilization, with the main goal of improving patients' quality of life and reducing the frequency of acute exacerbations. This review summarizes pharmacological therapies for stable COPD.

Psychological resilience and cognitive reappraisal mediate the effects of coping style on the mental health of children.

Introduction: This study explored the effects of coping style and two potential intermediately factors (cognitive reappraisal and psychological resilience) on the mental health of middle school students during the normalization of epidemic prevention and control in China. Methods: Answers on questionnaires designed to assess coping style, cognitive reappraisal, psychological resilience, and mental health among 743 middle school students (386 boys, 357 girls, 241 first graders, 235 second graders, and 267 third graders) were analyzed using structural equation modeling. Results: The results showed that coping style, cognitive reappraisal, and psychological resilience directly predicted mental health. The negative effect of a negative coping style on mental health was significantly stronger than the positive effect of a positive coping style. Coping style affected mental health through the independent mediating effects of cognitive reappraisal and psychological resilience and through their chain mediation. Discussion: The use of positive coping styles by most students led to greater cognitive reappraisal, strengthened psychological resilience, and thus few mental health problems. These findings provide empirical evidence and may guide educators in the prevention and intervention of mental health problems among middle school students.

Outdoor particulate matter exposure affects metabolome in chronic obstructive pulmonary disease: Preliminary study.

Introduction: The metabolomic changes caused by airborne fine particulate matter (PM2.5) exposure in patients with chronic obstructive pulmonary disease (COPD) remain unclear. The aim of this study was to determine whether it is possible to predict PM2.5-induced acute exacerbation of COPD (AECOPD) using metabolic markers. Methods: Thirty-eight patients with COPD diagnosed by the 2018 Global Initiative for Obstructive Lung Disease were selected and divided into high exposure and low exposure groups. Questionnaire data, clinical data, and peripheral blood data were collected from the patients. Targeted metabolomics using liquid chromatography-tandem mass spectrometry was performed on the plasma samples to investigate the metabolic differences between the two groups and its correlation with the risk of acute exacerbation. Results: Metabolomic analysis identified 311 metabolites in the plasma of patients with COPD, among which 21 metabolites showed significant changes between the two groups, involving seven pathways, including glycerophospholipid, alanine, aspartate, and glutamate metabolism. Among the 21 metabolites, arginine and glycochenodeoxycholic acid were positively associated with AECOPD during the three months of follow-up, with an area under the curve of 72.50% and 67.14%, respectively. Discussion: PM2.5 exposure can lead to changes in multiple metabolic pathways that contribute to the development of AECOPD, and arginine is a bridge between PM2.5 exposure and AECOPD.

Integrated analysis of mRNA and long noncoding RNA profiles in peripheral blood mononuclear cells of patients with bronchial asthma.

BACKGROUND: Bronchial asthma is a heterogeneous disease with distinct disease phenotypes and underlying pathophysiological mechanisms. Long non-coding RNAs (lncRNAs) are involved in numerous functionally different biological and physiological processes. The aim of this study was to identify differentially expressed lncRNAs and mRNAs in patients with asthma and further explore the functions and interactions between lncRNAs and mRNAs. METHODS: Ten patients with asthma and 9 healthy controls were enrolled in this study. RNA was isolated from peripheral blood mononuclear cells. We performed microarray analysis to evaluate lncRNA and mRNA expression. The functions of the differentially expressed mRNAs were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. A global signal transduction network was constructed to identify the core mRNAs. An lncRNA-mRNA network was constructed. Five mRNAs showing the greatest differences in expression levels or high degrees in the gene-gene functional interaction network, with their correlated lncRNAs, were validated by real-time quantitative polymerase chain reaction. RESULTS: We identified 2229 differentially expressed mRNAs and 1397 lncRNAs between the asthma and control groups. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified many pathways associated with inflammation and cell survival. The gene-gene functional interaction network suggested that some core mRNAs are involved in the pathogenesis of bronchial asthma. The lncRNA-mRNA co-expression network revealed correlated lncRNAs. CXCL8, FOXO3, JUN, PIK3CA, and G0S2 and their related lncRNAs NONHSAT115963, AC019050.1, MTCYBP3, KB-67B5.12, and HNRNPA1P12 were identified according to their differential expression levels and high degrees in the gene-gene network. CONCLUSIONS: We identified the core mRNAs and their related lncRNAs and predicted the biological processes and signaling pathways involved in asthma.

Short-term exposure to fine particulate matter and genome-wide DNA methylation in chronic obstructive pulmonary disease: A panel study conducted in Beijing, China.

Background: Fine particulate matter (PM2.5) is a crucial risk factor for chronic obstructive pulmonary disease (COPD). However, the mechanisms whereby PM2.5 contribute to COPD risk have not been fully elucidated. Accumulating evidence suggests that epigenetics, including DNA methylation, play an important role in this process; however, the association between PM2.5 exposure and genome-wide DNA methylation in patients with COPD has not been studied. Objective: To evaluate the association of personal exposure to PM2.5 and genome-wide DNA methylation changes in the peripheral blood of patients with COPD. Methods: A panel study was conducted in Beijing, China. We repeatedly measured and collected personal PM2.5 data for 72 h. Genome-wide DNA-methylation of peripheral blood was analyzed using the Illumina Infinium Human Methylation BeadChip (850 k). A linear-mixed effect model was used to identify the differentially methylated probe (DMP) associated with PM2.5. Finally, we performed a functional enrichment analysis of the DMPs that were significantly associated with PM2.5. Results: A total of 24 COPD patients were enrolled and 48 repeated DNA methylation measurements were associated in this study. When the false discovery rate was < 0.05, 19 DMPs were significantly associated with PM2.5 and were annotated to corresponding genes. Functional enrichment analysis of these genes showed that they were related to the response to toxic substances, regulation of tumor necrosis factor superfamily cytokine production, regulation of photosensitivity 3-kinase signaling, and other pathways. Conclusion: This study provided evidence for a significant relationship between personal PM2.5 exposure and DNA methylation in patients with COPD. Our research also revealed a new biological pathway explaining the adverse effects of PM2.5 exposure on COPD risk.

Exposure Response Relationship of Acute Effects of Air Pollution on Respiratory Diseases - China, 2013-2018.

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Short-term exposure to air pollutants has been associated with chronic obstructive pulmonary disease (COPD) and asthma, which needs continuous observation. WHAT IS ADDED BY THIS REPORT?: This study uses the longest time series data so far from 2013 to 2018 and adds additional data analysis for ozone (O3) to existing studies. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: This study suggests that air pollutants have certain acute effects on outpatient and hospital admission of patients with COPD and asthma, which can be combined with the disease diagnosis and treatment guidelines to guide clinical practice.

Adverse effects of short-term personal exposure to fine particulate matter on the lung function of patients with chronic obstructive pulmonary disease and asthma: a longitudinal panel study in Beijing, China.

Fine particulate matter (PM2.5) is an important environmental factor affecting human health. However, most studies on PM2.5 and health have used data from fixed monitoring sites to assess PM2.5 exposure, which may have introduced misleading information on the exposure-response relationship. We aimed to assess the effect of short-term personal PM2.5 exposure on lung function in patients with chronic obstructive pulmonary disease (COPD) and asthma. To achieve this, we conducted a longitudinal panel study among 37 COPD patients and 45 asthma patients from Beijing, China. The COPD group and the asthma group completed 148 and 180 lung function tests, respectively. We found that in COPD patients, for every 10-µg/m3 increase in PM2.5 exposure at lag2, the FEV1, FVC and DLco decreased by -0.014 L (95% CI -0.025, -0.003), -0.025 L (95% CI -0.050, -0.003) and -0.089 mmol/min/kPa (95% CI -0.156, -0.023), respectively. There was also a decrease of -0.023 L/s (95% CI -0.042, -0.003) and -0.017 L/s (95% CI -0.032, -0.002) in MMEF at lag3 and lag03, respectively. In the asthma group, every 10-µg/m3 increase in PM2.5 exposure led to a reduction of -0.012 L (95% CI -0.023, -0.001), -0.042 L (95% CI -0.081, -0.003) and -0.061 L/s (95% CI -0.116, -0.004) in the FEV1, FVC and PEF at lag3, respectively. Our findings suggest that PM2.5 exposure may primarily affect both airway function and lung diffusion function in COPD patients, and airway function in asthma patients.

Air pollution and chronic obstructive pulmonary disease.

There is considerable epidemiological evidence indicating that air pollution has adverse effects on human health and is closely related to respiratory diseases, including chronic obstructive pulmonary disease (COPD). These effects, which can be divided into short- and long-term effects, can manifest as an exacerbation of existing symptoms, impaired lung function, and increased hospitalization and mortality rates. Long-term exposure to air with a high concentration of pollutants may also increase the incidence of COPD. The combined effects of different pollutants may become more complex in the future; hence, there is a need for more intensive research on specific at-risk populations, and formulating corresponding protective strategies is crucial. We aimed to review the epidemiological evidence on the effect of air pollution on COPD, the possible pathophysiological mechanisms underlying this effect, as well as protective measures against the effects of air pollutants in patients with COPD.

Identification and Bioinformatic Analysis of Circular RNA Expression in Peripheral Blood Mononuclear Cells from Patients with Chronic Obstructive Pulmonary Disease.

Purpose: Circular RNAs (circRNAs) regulate other RNA transcripts by competing for shared microRNAs, which play roles in the pathogenesis of many diseases, including chronic obstructive pulmonary disease (COPD). However, the role of circRNAs in COPD remains unknown. This study aimed to investigate the expression profile and the role of circRNAs in COPD. Patients and Methods: Twenty-one COPD patients and twenty-one normal controls were recruited. Total RNAs were collected from peripheral blood mononuclear cells (PBMCs) of each participant. CircRNAs and protein-coding mRNAs were profiled by microarray and systematically compared between patients with COPD and control subjects. The top differentially expressed circRNAs and mRNAs were validated by quantitative real-time PCR (RT-qPCR). Functional analysis identified pathways relevant to the pathogenesis of COPD. Next, the circRNA target pathway network, the circRNA-miRNA-mRNA network (ceRNA network) and functional ceRNA regulatory modules were constructed. Results: In total, 2132 circRNAs and 2734 protein-coding mRNAs were differentially expressed (|fold change| >1.5 and P-value <0.05) in COPD patients. Six out of nine selected RNAs were confirmed by RT-qPCR validation. Our functional analysis suggested that immune imbalances and inflammatory responses play roles in the pathogenesis of COPD. The ceRNA network highlighted the differentially expressed circRNAs and their related miRNAs and mRNAs in COPD. In the circRNA target pathway network and functional ceRNA regulatory modules, hsa_circRNA_0008672 appeared in the top three KEGG pathways (NOD-like receptor signaling pathway, natural killer cell mediated cytotoxicity and Th17 cell differentiation) and may act as the miRNA sponge regulating the hsa_circRNA_0008672/miR-1265/MAPK1 axis. Conclusion: Our findings demonstrate critical roles of the circRNAs in COPD molecular etiology. The data support a plausible mechanism that circRNAs may be involved in the development of COPD by affecting the immune balance. Moreover, the hsa_circRNA_0008672/miR-1265/MAPK1 axis may contribute to the pathogenesis of COPD, warranting further investigation.

Chitinase 3-like 1 polymorphisms and risk of chronic obstructive pulmonary disease and asthma in a Chinese population.

BACKGROUND: Chitinase 3-like 1 (CHI3L1) plays an important role in airway inflammation and tissue remodeling; however, its pathogenic role in lung diseases remains unclear. In the present study, we investigated whether CHI3L1 polymorphisms are associated with the risk of chronic obstructive pulmonary disease (COPD) and asthma in a Chinese population. METHODS: We detected seven single nucleotide polymorphisms in CHI3L1 among 361 patients and 527 age- and sex-matched control subjects. We analysed genotype and allele distributions using Stata software (StataCorp,CollegeStation,TX,USA). We used haplotype disease analysis and haplotype phenotype analysis to assess the relationship between seven polymorphisms and the risk of COPD and asthma. RESULTS: The results showed significant differences between controls and patients with COPD/asthma in the genotype distributions of the polymorphism rs4950928. Additionally, significant differences were observed in the genotype and allele distributions of rs10399805 and rs10399931 between COPD patients and controls. Moreover, the frequencies of haplotype G-G-T-G-T-C-G, G-G-T-G-T-C-C and G-A-T-G-T-C-G (alleles of rs12141494, rs7542294, rs880633, rs10399805, rs10399931, rs946261 and rs4950928, respectively) were significantly higher in patients with COPD. Consideration of the haplotypes of these seven single nucleotide polymorphisms in CHI3L1 in asthma patients revealed a significant association with homocysteine levels (p < 0.001). CONCLUSIONS: Our findings suggest that the CHI3L1 polymorphisms rs4950928, rs10399805 and rs10399931 can be used as genetic markers for predicting COPD and asthma risk in the Chinese population.

Association of RAGE gene multiple variants with the risk for COPD and asthma in northern Han Chinese.

Clinical and experimental data have shown that the receptor for advanced glycation end products (RAGE) is implicated in the pathogenesis of respiratory disorders. In this study, we genotyped five widely-evaluated variants in RAGE gene, aiming to assess their association with the risk for chronic obstructive pulmonary disease (COPD) and asthma in northern Han Chinese. Genotypes were determined in 105 COPD patients, 242 asthma patients and 527 controls. In single-locus analysis, there was significant difference in the genotype distributions of rs1800624 between COPD patients and controls (p=0.022), and the genotype and allele distributions of rs1800625 differed significantly (p=0.040 and 0.016) between asthma patients and controls. Haplotype analysis revealed that haplotype T-A-G-T (allele order: rs1800625, rs1800624, rs2070600, rs184003) was significantly associated with a reduced COPD risk (OR=0.32, 95% CI: 0.06-0.60), and haplotype T-A-A-G was significantly associated with a reduced asthma risk (OR=0.19, 95% CI: 0.04-0.96). Further haplotype-phenotype analysis showed that high- and low-density lipoprotein cholesterol and blood urea nitrogen were significant mediators for COPD (psim=0.041, 0.043 and 0.030, respectively), and total cholesterol was a significant mediator for asthma (psim=0.009). Taken together, our findings indicate that RAGE gene is a promising candidate for COPD and asthma, and importantly both disorders are genetically heterogeneous.