Search

Necroptosis is the major cause of death in alveolar epithelial cells (AECs) during acute lung injury (ALI). Here, we report a previously unrecognized mechanism for necroptosis. We found an accumulation of mitochondrial citrate (citratemt) in lipopolysaccharide (LPS)-treated AECs because of the downregulation of Idh3α and citrate carrier (CIC, also known as Slc25a1). shRNA- or inhibitor–mediated inhibition of Idh3α and Slc25a1 induced citratemt accumulation and necroptosis in vitro. Mice with AEC-specific Idh3α and Slc25a1 deficiency exhibited exacerbated lung injury and AEC necroptosis. Interestingly, the overexpression of Idh3α and Slc25a1 decreased citratemt levels and rescued AECs from necroptosis. Mechanistically, citratemt accumulation induced mitochondrial fission and excessive mitophagy in AECs. Furthermore, citratemt directly interacted with FUN14 domain-containing protein 1 (FUNDC1) and promoted the interaction of FUNDC1 with dynamin-related protein 1 (DRP1), leading to excessive mitophagy-mediated necroptosis and thereby initiating and promoting ALI. Importantly, necroptosis induced by citratemt accumulation was inhibited in FUNDC1-knockout AECs. We show that citratemt accumulation is a novel target for protection against ALI involving necroptosis.

Portable interfaced robot arms equipped with mobile user interactions are significantly being utilized in modern world. The application of teaching robotics is being used in challenging pandemic situation but it is still challenging due to mathematical formulation. This article utilizes the augmented reality (AR) concept for remote control-based human-robot interaction using the Bluetooth correspondence. The proposed framework incorporates different modules like a robot arm control, a regulator module and a distant portable smartphone application for envisioning the robot arm points for its real-time relevance. This novel approach fuses AR innovation into portable application which permit the continuous virtual coordination with actual physical platform. The simulation yields effective outcomes with 96.94% accuracy for testing stage while maintaining error and loss values of 0.194 and 0.183 respectively. The proposed interface gives consistent results for teaching application in real time changing environment by outperforming existing methods with an accuracy improvement of 13.4

Background Necroptosis of macrophages is a necessary element in reinforcing intrapulmonary inflammation during acute lung injury (ALI). However, the molecular mechanism that sparks macrophage necroptosis is still unclear. Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor expressed broadly on monocytes/macrophages. The influence of TREM-1 on the destiny of macrophages in ALI requires further investigation. Methods TREM-1 decoy receptor LR12 was used to evaluate whether the TREM-1 activation induced necroptosis of macrophages in lipopolysaccharide (LPS)-induced ALI in mice. Then we used an agonist anti-TREM-1 Ab (Mab1187) to activate TREM-1 in vitro. Macrophages were treated with GSK872 (a RIPK3 inhibitor), Mdivi-1 (a DRP1 inhibitor), or Rapamycin (an mTOR inhibitor) to investigate whether TREM-1 could induce necroptosis in macrophages, and the mechanism of this process. Results We first observed that the blockade of TREM-1 attenuated alveolar macrophage (AlvMs) necroptosis in mice with LPS-induced ALI. In vitro, TREM-1 activation induced necroptosis of macrophages. mTOR has been previously linked to macrophage polarization and migration. We discovered that mTOR had a previously unrecognized function in modulating TREM-1-mediated mitochondrial fission, mitophagy, and necroptosis. Moreover, TREM-1 activation promoted DRP1Ser616 phosphorylation through mTOR signaling, which in turn caused surplus mitochondrial fission-mediated necroptosis of macrophages, consequently exacerbating ALI. Conclusion In this study, we reported that TREM-1 acted as a necroptotic stimulus of AlvMs, fueling inflammation and aggravating ALI. We also provided compelling evidence suggesting that mTOR-dependent mitochondrial fission is the underpinning of TREM-1-triggered necroptosis and inflammation. Therefore, regulation of necroptosis by targeting TREM-1 may provide a new therapeutic target for ALI in the future.

Objectives Platycarya strobilacea Sieb. et Zucc. is the dry infructescence of P. strobilacea, a Juglandaceae plant and is a traditional Chinese medicine with great development potential and utilization value. This study summarizes the research progress on the traditional uses, botany, phytochemistry, extraction methods, pharmacology and toxicology of Platycarya strobilacea Sieb. et Zucc., and provides potential therapeutic uses and drug development prospects for this plant. Key findings Phytochemical studies showed that this plant mainly contains volatile constituents, phenols, terpenoids and a carbohydrate. The pharmacological activity of Platycarya strobilacea Sieb. et Zucc. includes antibacterial and anti-inflammatory effects, anti-tumour effects and antioxidant effects. This plant is especially effective in the treatment of allergic rhinitis and chronic sinusitis. Summary In this review, the phytochemistry and pharmacological effects of Platycarya strobilacea Sieb. et Zucc. are described in detail, which will have guiding significance for the future development of this drug.

The triggering receptor expressed on myeloid cells-1 (TREM-1) is a pro-inflammatory immune receptor potentiating acute lung injury (ALI). However, the mechanism of TREM-1-triggered inflammation response remains poorly understood. Here, we showed that TREM-1 blocking attenuated NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome activation and glycolysis in LPS-induced ALI mice. Then, we observed that TREM-1 activation enhanced glucose consumption, induced glycolysis, and inhibited oxidative phosphorylation in macrophages. Specifically, inhibition of glycolysis with 2-deoxyglucose diminished NLRP3 inflammasome activation of macrophages triggered by TREM-1. Hypoxia-inducible factor-1α (HIF-1α) is a critical transcriptional regulator of glycolysis. We further found that TREM-1 activation facilitated HIF-1α accumulation and translocation to the nucleus

Background There is a large gap in the treatments for patients with COPD according to the Global Initiative for COPD (GOLD) recommendations. Determining the situation of therapies in the real world is necessary. This study aimed to characterize the real-world practical therapies of COPD and prognosis of patients after treatment for 1 year. Methods This study was a multicenter prospective observational study performed using a database set up by the Second Xiangya Hospital of Center South University. Detailed usage information for pharmacotherapies and nonpharmacotherapies for patients was collected, as well as the consistency of recommendations and patient adherence. Moreover, the effect of therapies after 1 year was calculated by comparing lung function and symptoms. Results Ultimately, 4,796 patients with COPD from 12 hospitals in China were eligible. LAMA (39.1%), LAMA + LABA/ICS (39.0%) and LABA/ICS (14.4%) were the top three inhalants. We found that 42.7% of Group A patients, 61.6% of Group B patients and 30% of Group C patients were following inappropriate therapy, especially overuse of ICS. Only 3.9% (95% CI 2.4, 5.4) of patients used oxygen therapy, and 1.8% (95% CI 1.5, 2.3) used noninvasive positive pressure ventilation at home. Among these patients, 33.2% had poor adherence. A total of 452 patients completed 1 year of follow-up. After 1 year of treatment, the lung function of FEV1/FVC decreased (P=0.001) and the mMRC score increased (P 0.05). Conclusion This study highlights a significant discrepancy between recommendations for managing patients with COPD in GOLD report, and in real-world clinical practice in China. Over-prescription of ICS and under-prescription of nonpharmacologic therapy were common. The adherence to treatment of patients was poor, and the real-life treatment effectiveness was unsatisfactory. More attention should be paid to the implementation of recommendations and standardized administration of therapies.

Background: Arachidonic acid (ARA) metabolites are involved in the pathogenesis of epithelial-mesenchymal transformation (EMT). However, the role of ARA metabolism in the progression of EMT in pulmonary fibrosis (PF) has not been fully elucidated. The purpose of this study was to investigate the role of cytochrome P450 oxidase (CYP)/ soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) metabolic disorders of ARA in EMT during PF.Methods: A signal intratracheal injection of bleomycin (BLM) was given to induce PF in C57BL/6J mice. A COX-2/sEH dual inhibitor PTUPB was used to establish the function of CYPs/COX-2 dysregulation to EMT in PF mice. In vitro experiments, murine alveolar epithelial cells (MLE12) and human alveolar epithelial cells (A549) were used to explore the roles and mechanisms of PTUPB on transforming growth factor (TGF)-β1-induced EMT. Results: PTUPB treatment reversed the increase of mesenchymal marker molecule α-smooth muscle actin (α-SMA) and the loss of epithelial marker molecule E-Cadherin in lung tissue of PF mice. In vitro, COX-2 and sEH protein levels were increased in TGF-β1-treated alveolar epithelial cells (AECs). PTUPB decreased the expression of α-SMA and restored the expression of E-cadherin in TGF-β1-treated AECs, accompanied by reduced migration and collagen synthesis. Moreover, PTUPB attenuates TGF-β1-Smad2/3 pathway activation in AECs via Nrf2 antioxidant cascade.Conclusion: PTUPB inhibits EMT in AECs via Nrf2-mediated inhibition of the TGF-β1-Smad2/3 pathway, which holds great promise for the clinical treatment of PF.

Background and Objectives Long non-coding RNAs (lncRNAs) play an important role in the pathogenesis of many diseases, including cancer, pulmonary fibrosis and chronic obstructive pulmonary disease (COPD). In this study, we intended to identify the differentially expressed lncRNAs and the role of HOXA cluster antisense RNA 2 (HOXA-AS2) in patients with COPD. Methods We analyzed lncRNA profiles of three non-COPD and seven COPD patients' lungs via microarray and then validated the expression of the top differentially expressed lncRNAs by using real-time polymerase chain reaction (PCR). To identify the mechanism of HOXA-AS2 during COPD pathogenesis and endothelial cell proliferation, we knocked down and overexpressed HOXA-AS2 with siRNA and lentivirus transfection approach in human pulmonary microvascular endothelial cells (HPMECs). Results Among 29,150 distinct lncRNA transcripts, 353 lncRNAs were significantly (≥2-fold change and P

Background Fractional exhaled nitric oxide (FENO) has been shown to be a marker of airway inflammation in various pulmonary diseases, including chronic obstructive pulmonary disease (COPD). In this study, we assessed the FENO level in patients with acute exacerbations of COPD (AECOPD) and analyzed the predictive value of the FENO level for treatment response. Methods Demographic data were collected at admission. FENO, lung function, blood gases, COPD Assessment Test (CAT), and modified Medical Research Council (mMRC) scores were measured at admission and on day 7. At the second visit, the patients were asked to report their health status; scores ranged from 1 to 5, representing "much better", "slightly better", "no change", "slightly worse", and "much worse", respectively. The treatment response was evaluated based on the patient's reported health status (responders were those who reported much better and slightly better) and lung function (responders were those who presented an increase in FEV1 over 200 mL). Results A total of 182 patients were recruited into the analysis. The FENO level positively correlated with an increase in FEV1 and FEV1% (r = 0.291, p < 0.001 and r = 0.205, p = 0.005, respectively), but negatively correlated with a decrease in the COPD Assessment Test (CAT) score (r = -0.197, p = 0.008) and patient-reported health status (rho = -0.408, p

Purpose Chronic obstructive pulmonary disease (COPD), usually caused by tobacco smoking, is increased in China. Smoking cessation is the first step in COPD management. Data on predictors of smoking cessation are sparse in COPD patients in China. We aim to find the differences in the clinical characteristics between ex-smokers and current smokers with COPD to determine the factors related to smoking cessation. Patients and methods From outpatient departments of 12 hospitals in Hunan and Guangxi provinces, a total of 4331 patients were included. Information on demographic and sociological data, lung function, and modified Medical Research Council (mMRC) dyspnea scale scores were recorded. Patients were divided into an ex-smokers group and a current smokers group based on whether they gave up smoking. A logistic regression analysis was performed to analyze the factors associated with smoking cessation. Results Of the total, the mean age was 62.9±8.5 years, and 47.3% were ex-smokers. Compared with the current smokers, the ex-smokers were older, and had heavier dyspnea, more severe airflow limitation, fewer pack-years, shorter smoking duration, and a higher proportion of Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups C and D. The logistic regression model showed that smoking cessation was negatively correlated with widowhood, years of smoking, and forced expiratory volume in 1 second (FEV1), but was positively correlated with age, education level, amount smoked, mMRC score, GOLD grades, and GOLD groups. Conclusion Among patients with COPD, more than half still smoked. In the group of patients who quit smoking, many of them quit rather late in age after they had significant symptoms. Several predictors of smoking cessation were identified, indicating that ex-smokers differ substantially from continuing smokers. This should be taken into account in smoking-cessation interventions.

The purposes of this study were to: (1) study the prevalence of pain in patients with mild-to-very severe chronic obstructive pulmonary disease (COPD) in China; (2) compare the differences in pain characteristics between stable COPD and acute exacerbation of COPD (AECOPD); (3) explore the clinical associations with pain in those with COPD. This cross-sectional study was conducted in China from October 24, 2017, to January 11, 2019. A face-to-face interview was conducted to collect data. The Chinese version of the brief pain inventory (BPI-C) was applied to investigate the pain characteristics in patients with COPD. Of the 901 patients in this study, 226 (25.1%) patients reported pain problems. The prevalence of pain in patients with mild to very severe COPD was 32.9%, 23.9%, 25.2%, and 23.5%, respectively (

Rationale: Dysregulation of arachidonic acid (ARA) metabolism results in inflammation; however, its role in acute lung injury (ALI) remains elusive. In this study, we addressed the role of dysregulated ARA metabolism in cytochromes P450 (CYPs) /cyclooxygenase-2 (COX-2) pathways in the pathogenesis of lipopolysaccharide (LPS)-induced ALI in mice. Methods: The metabolism of CYPs/COX-2-derived ARA in the lungs of LPS-induced ALI was investigated in C57BL/6 mice. The COX-2/sEH dual inhibitor PTUPB was used to establish the function of CYPs/COX-2 dysregulation in ALI. Primary murine macrophages were used to evaluate the underlying mechanism of PTUPB involved in the activation of NLRP3 inflammasome in vitro. Results: Dysregulation of CYPs/COX-2 metabolism of ARA occurred in the lungs and in primary macrophages under the LPS challenge. Decrease mRNA expression of Cyp2j9, Cyp2j6, and Cyp2j5 was observed, which metabolize ARA into epoxyeicosatrienoic acids (EETs). The expressions of COX-2 and soluble epoxide hydrolase (sEH), on the other hand, was significantly upregulated. Pre-treatment with the dual COX-2 and sEH inhibitor, PTUPB, attenuated the pathological injury of lung tissues and reduced the infiltration of inflammatory cells. Furthermore, PTUPB decreased the pro-inflammatory factors, oxidative stress, and activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in LPS-induced ALI mice. PTUPB pre-treatment remarkably reduced the activation of macrophages and NLRP3 inflammasome in vitro. Significantly, both preventive and therapeutic treatment with PTUPB improved the survival rate of mice receiving a lethal dose of LPS. Conclusion: The dysregulation of CYPs/COX-2 metabolized ARA contributes to the uncontrolled inflammatory response in ALI. The dual COX-2 and sEH inhibitor PTUPB exerts anti-inflammatory effects in treating ALI by inhibiting the NLRP3 inflammasome activation.

Background Uncontrolled inflammation is an important factor in the occurrence and development of acute lung injury (ALI). Fibroblast growth factor-inducible 14 (Fn14), a plasma membrane-anchored receptor, takes part in the pathological process of a variety of acute and chronic inflammatory diseases. However, the role of Fn14 in ALI has not yet been elucidated. This study aimed to investigate whether the activation of Fn14 exacerbated lipopolysaccharide (LPS)-induced ALI in mice. Methods In vivo, ALI was induced by intratracheal LPS-challenge combined with/without Fn14 receptor blocker aurintricarboxylic acid (ATA) treatment in C57BL/6J mice. Following LPS administration, the survival rate, lung tissue injury, inflammatory cell infiltration, inflammatory factor secretion, oxidative stress, and NLRP3 inflammasome activation were assessed. In vitro, primary murine macrophages were used to evaluate the underlying mechanism by which Fn14 activated the NLRP3 inflammasome. Lentivirus was used to silence Fn14 to observe its effect on the activation of NLRP3 inflammasome in macrophages. Results In this study, we found that Fn14 expression was significantly increased in the lungs of LPS-induced ALI mice. The inhibition of Fn14 with ATA downregulated the protein expression of Fn14 in the lungs and improved the survival rate of mice receiving a lethal dose of LPS. ATA also attenuated lung tissue damage by decreasing the infiltration of macrophages and neutrophils, reducing inflammation, and suppressing oxidative stress. Importantly, we found that ATA strongly inhibited the activation of NLRP3 inflammasome in the lungs of ALI mice. Furthermore, in vitro, TWEAK, a natural ligand of Fn14, amplified the activation of NLRP3 inflammasome in the primary murine macrophage. By contrast, inhibition of Fn14 with shRNA decreased the expression of Fn14, NLRP3, Caspase-1 p10, and Caspase-1 p20, and the production of IL-1β and IL-18. Furthermore, the activation of Fn14 promoted the production of reactive oxygen species and inhibited the activation of Nrf2-HO-1 in activated macrophages. Conclusions Our study first reports that the activation of Fn14 aggravates ALI by amplifying the activation of NLRP3 inflammasome. Therefore, blocking Fn14 may be a potential way to treat ALI.

Our study aimed to compare the predictive value of the COPD Assessment Test (CAT) score at baseline and short-term change in CAT for future exacerbations in chronic obstructive pulmonary disease (COPD) patients. This was a multicentre prospective study. Patients with COPD were recruited into the study and followed up for one year. CAT score and exacerbation in the previous year were collected at baseline. Change in CAT was defined as CAT score changing between baseline and the 6-month follow-up. Exacerbation was recorded during the one-year follow-up from 0th to 12th month. A total of 536 patients were enrolled for final analysis. The mean baseline CAT score was 14.5 ± 6.6 and the median (IQR) change in CAT was −2 (8). On Cox regression analysis, baseline CAT score, change in CAT and history of exacerbation were independent risk factors for exacerbation in the one-year follow-up. Compared with the r value of correlation between baseline CAT score and frequency of exacerbations during the one-year follow-up (r = 0.286, p < .001), that correlation between the change in CAT and frequency of exacerbations during follow-up was higher (r = 0.421, p < .001). The receiver operating characteristic (ROC) curves showed that change in CAT had a better predictive capacity for future exacerbation than baseline CAT (0.789 versus 0.609, p = .001). The ROC showed that change in CAT also had a better predictive capacity for future exacerbation than exacerbation in the previous year (0.789 versus 0.689, p = .011). The correlation between baseline CAT score and future exacerbation was weak, however, the correlation between change in CAT and future exacerbation was moderate. Change in CAT in the short term had a better predictive value for future exacerbations of COPD than baseline CAT and exacerbation in the previous year.

Antibiotic resistance genes (ARGs), as emerging environmental contaminants, are becoming a threat to human health. In this study, the combined processes of powdered activated carbon (PAC)/biological PAC (BPAC)–ultrafiltration (UF) were adopted to reduce the levels of ARGs in secondary effluents from a wastewater treatment plant. The removal of dissolved organic carbon (DOC) and the change of normalized flux in the UF process were investigated. In addition, the structural characteristics of the microorganisms of the BPAC were analyzed. The results showed that the appropriate dosage of PAC and BPAC was 40 mg/L. At this dosage, PAC/BPAC–UF combined processes could effectively remove the ARGs in secondary effluents by 1.26–2.69-log and 1.55–2.97-log, respectively; and the removal rates of DOC would be 60.7% and 54.1%, respectively. Relative to the direct UF, the membrane fluxes of the two combined processes were increased by 15.6% and 25.1%, respectively. Significant removal correlations were found between ARGs, intI1, DOC and 16SrDNA. These results revealed that the PAC/BPAC–UF combined process might play a promising role in ARG reduction in secondary effluents from wastewater treatment plants.

Arachidonic acid (ARA) metabolites are involved in the pathogenesis of epithelial-mesenchymal transformation (EMT). However, the role of ARA metabolism in the progression of EMT during pulmonary fibrosis (PF) has not been fully elucidated. The purpose of this study was to investigate the role of cytochrome P450 oxidase (CYP)/soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) metabolic disorders of ARA in EMT during PF.A signal intratracheal injection of bleomycin (BLM) was given to induce PF in C57BL/6 J mice. A COX-2/sEH dual inhibitor PTUPB was used to establish the function of CYPs/COX-2 dysregulation to EMT in PF mice.PTUPB treatment reversed the increase of mesenchymal marker moleculePTUPB inhibits EMT in AECs

Background: Arachidonic acid (ARA) metabolites are involved in the pathogenesis of epithelial-mesenchymal transformation (EMT). However, the role of ARA metabolism in the progression of EMT in pulmonary fibrosis (PF) has not been fully elucidated. The purpose of this study was to investigate the role of cytochrome P450 oxidase (CYP)/ soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) metabolic disorders of ARA in EMT during PF.Methods: A signal intratracheal injection of bleomycin (BLM) was given to induce PF in C57BL/6J mice. A COX-2/sEH dual inhibitor PTUPB was used to establish the function of CYPs/COX-2 dysregulation to EMT in PF mice. In vitro experiments, murine alveolar epithelial cells (MLE12) and human alveolar epithelial cells (A549) were used to explore the roles and mechanisms of PTUPB on transforming growth factor (TGF)-β1-induced EMT. Results: PTUPB treatment reversed the increase of mesenchymal marker molecule α-smooth muscle actin (α-SMA) and the loss of epithelial marker molecule E-Cadherin in lung tissue of PF mice. In vitro, COX-2 and sEH protein levels were increased in TGF-β1-treated alveolar epithelial cells (AECs). PTUPB decreased the expression of α-SMA and restored the expression of E-cadherin in TGF-β1-treated AECs, accompanied by reduced migration and collagen synthesis. Moreover, PTUPB alleviated the activation of the TGF-β1-Smad2/3 pathway induced by TGF-β1 in AECs.Conclusion: PTUPB inhibits TGF-β1-induced EMT via inhibition of the TGF-β1-Smad2/3 pathway, which holds great promise for the clinical treatment of PF.

Yating Peng,1– 3 Jiaxi Duan,1– 3 Xin Li,4 Yuqin Zeng,1– 3 Zijing Zhou,1– 3 Minghua Deng,1– 3,5 Ruoyun Ouyang,1– 3 Yan Chen,1– 3 Shan Cai,1– 3 Ping Chen1– 3 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, People’s Republic of China; 3Hunan Centre for Evidence-Based Medicine, Changsha, Hunan, People’s Republic of China; 4Division of Occupational Lung Disease, Hunan Prevention and Treatment Institute for Occupational Diseases, Changsha, Hunan, People’s Republic of China; 5Department of Respiratory, PLA Rocket Force Characteristic Medical Center, Beijing, People’s Republic of ChinaCorrespondence: Ping Chen Email pingchen0731@csu.edu.cnBackground: Pneumoconiosis has high prevalence of chronic obstructive pulmonary disease (COPD), respiratory morbidity, and mortality.Objective: The aim of the present study was to examine patient characteristics and adherence to inhaled therapy among pneumoconiosis with COPD in a real-world clinical setting.Methods: A cohort of pneumoconiosis patients with COPD prescript with at least one type of long-acting inhaled drug was followed for adherence for 2 years. Demographic and COPD-related characteristics were collected in baseline.Results: In baseline, after adjusting for age, dust exposure duration positively correlated with number of acute exacerbation (AE) frequency in the last year. There were close associations among COPD Assessment Tool (CAT) score, modified Medical Research Council Dyspnea Scale (mMRC) grade, number of AE, and pre-FEV1 value. Of 296 participants originally recruited, 213 participants finished the 2-year follow-up for adherence. 122 (57.28%) were non-adherent to inhaled therapy. The most common reason for non-adherence was “relief of symptoms after short-term controller medication use” (53.28%). Patients who were non-adherent reported higher body mass index (BMI), less AE events in the last year, higher pre-FEV1 value, higher post-FEV1 value and low CAT, mMRC scores compared to adherent in baseline. High pre-FEV1 value (OR = 1.04, CI = 1.018– 1.064) and low mMRC scores (OR = 0.406, CI = 0.214– 0.771) were risk factors found associated with non-adherence.Conclusion: A majority of pneumoconiosis patients complicated with COPD have suboptimal inhaled therapy adherence. Evidence-based, adherence-enhancing interventions should be targeted on less severe subjects.Keywords: adherence, inhaled therapy, pneumoconiosis, COPD

Purpose: This real-world study evaluated the effectiveness of different inhalation therapies in patients with symptomatic chronic obstructive pulmonary disease (COPD) in China and also explored the relevant factors that influence the effectiveness of inhalation therapy.Patients and Methods: We conducted a multicenter prospective longitudinal study that was carried out in 12 hospitals in China from December 2016 to June 2021. A face-to-face interview was conducted to collect data. Baseline data were collected at the first visit. Minimum clinically important difference (MCID) was defined as attaining a COPD assessment test (CAT) decrease ≥2. We mainly assessed the MCID and the incidence of exacerbations at the 6 months follow-up.Results: In 695 patients, the mean age was 62.5 ± 8.2 years, with a mean CAT score of 15.1 ± 6.0. Overall, 341 (49.1%) patients attained the MCID of CAT and the incidence of exacerbation during follow-up was 22.3%. Females were significantly more likely to attain MCID than male in COPD patients (adjusted odd ratio (aOR) = 1.93, adjusted 95% confidence interval (a95%CI) = 1.09–3.42, p = 0.024). Patients treated with LABA/LAMA or ICS/LABA/LAMA (ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist) were more likely to attain MCID than patients treated with LAMA (aOR = 3.97, a95%CI = 2.48–6.35, p < 0.001; aOR = 3.17, a95%CI = 2.09–4.80, p < 0.001, respectively). Patients treated with LABA/LAMA had a higher incidence of severe exacerbation than patients treated with ICS/LABA/LAMA (aOR = 1.95, a95%CI = 1.04–3.66, p = 0.038).Conclusion: The incidence of MCID in symptomatic COPD patients treated with inhalation therapy was nearly 50%. Patients treated with LABA/LAMA or ICS/LABA/LAMA were more likely to attain MCID than patients treated with LAMA. Patients treated with LABA/LAMA had a higher incidence of severe exacerbations than with ICS/LABA/LAMA.

Background: Differentially expressed long non-coding RNAs (lncRNA) have been reported to be involved in the proliferation and migration of keratinocyte. Potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1) was implicated in the pathogenesis of various diseases, including cancer, sepsis, diabetic cardiomyopathy, and atherosclerosis. In this study, the influence of KCNQ1OT1 on the proliferation and migration of psoriatic keratinocytes was explained. Methods: Cultured human keratinocyte cell line (HaCaT) was incubated with tumor necrosis factor-α (TNF-α). Cell viability and migration were assessed by MTT assay and wound healing, respectively. Target miRNA of KCNQ1OT1 was identified by luciferase activity and RNA immunoprecipitation (RIP) assays. Results: KCNQ1OT1 was up-regulated in TNF-α-treated HaCaT cell line, and knockdown of KCNQ1OT1 reduced viability and suppressed the migration of TNF-α-treated HaCaT cell line. KCNQ1OT1 was bound to microRNA-183-3p (miR-183-3p) and negatively regulated its expression. Over-expression of growth factor receptor binding 2-associated binding protein 1 (GAB1) counteracted with the suppressive effects of KCNQ1OT1-induced silence on the viability and migration of TNF-α-treated HaCaT cells. Conclusion: KCNQ1OT1 silence suppressed the proliferation and migration of TNF-α-treated HaCaT cells through regulation of miR-183-3p/GAB1.

Among many of the autoimmune diseases observed in patients with myasthenia gravis (MG), myocarditis is one of the most critical. The goal of this review is to systematically describe and investigate the characteristics of MG complicated with myocarditis. We identified 183 records in PubMed (MEDLINE), Web of Science, and EMBASE from 1948 to September 10, 2020. Studies were included if they presented clinical data on MG complicated with myocarditis. Of the 35 patients from 28 studies in this review, 57.14% (20/35) were males, with a mean age of 59.11 ± 15.87. Dyspnea was the most common cardiac symptom accounting for over 60% in the study. Among the 35 patients, 13 cases of myocarditis occurred concomitantly with MG and the longest interval between MG and myocarditis was 7 years. Forty percent of patients developed myocarditis caused by immune checkpoint inhibitors (ICI). Among the patients with myocarditis, over half of the patients were diagnosed by myocardial biopsy. After active immune regulation and symptomatic treatment, only 15 of 35 patients with MG complicated with myocarditis improved, 18 patients died during hospitalization, one patient died due to tumor progression and 1patient died 5 years later. The prognosis of patients with MG complicated with myocarditis is poor, and myocardial enzymes and other indexes need to be monitored for patients taking ICI drugs. Patients with dyspnea who are still not ideally treated by mechanical ventilation should be vigilant against the occurrence of MG complicated with myocarditis.

Exposure of ultraviolet (UV) radiation is the major factor from environment to cause erethema, inflammation, photoaging and skin carcinogenesis. Vicenin-2, a bioflavonoid which are isolated from several medicinal plants. The present study was demonstrated the role of vicenin-2 on UVB linked oxidative stress and photoaging signaling in human dermal fibroblasts (HDF). In this study, UVB-irradiation (100 mJ/cm2) significantly elevated the intracellular ROS levels, lipid peroxidation, DNA damage, depletion of antioxidants resulted in apoptotic HDF cells. Interestingly, HDF cells were administrated with vicenin-2, 1 h before UVB-irradiation prevents ROS generation, TBARS, apoptotic changes and DNA damage in HDF. MAPKs and MMP signaling are implicated in oxidative stress and photoaging; these signaling events are considered as photoaging and differentiation. We found that Vicenin-2 prevents over expression of MAPKs (p-ERK1, p-JNK & p-p38), AP-1 and MMPs (MMP-2, 9 & 12) in during the exposure of UVB in HDF cells. These findings conclude that vicenin-2 could be a potential bioactive ingredient to absorb UV photons and protects the dermal cells from the UVB associated oxidative stress and photoaging signaling due to sunscreen properties.

Recent relation extraction models’ architecture are evolved from the shallow neural networks to natural language model, such as convolutional neural networks or recurrent neural networks to Bert. However, these methods did not consider the semantic information in the sequence or the distance dependence problem, the internal semantic information may contain the useful knowledge which can help relation classification. Focus on these problems, this paper proposed a BERT-based relation classification method. Compare with the existing Bert-based architecture, the proposed model can obtain the internal semantic information between entity pair and solve the distance semantic dependence better. The pre-trained BERT model after fine tuning is used in this paper to abstract the semantic representation of sequence, then adopt the piecewise convolution to obtain semantic information which influence the extraction results. Compare with the existing methods, the proposed method can achieve a better accuracy on relational extraction task because of the internal semantic information extracted in the sequence. While, the generalization ability is still a problem that cannot be ignored, and the numbers of the relationships are difference between different categories. In this paper, the focal loss function is adopted to solve this problem by assigning a heavy weight to less number or hard classify categories. Finally, comparing with the existing methods, the F1 metric of the proposed method can reach a superior result 89.95% on the SemEval-2010 Task 8 dataset.

Jia-xi Duan,1,2 Wei Cheng,1,2 Yu-qin Zeng,1,2 Yan Chen,1,2 Shan Cai,1,2 Xin Li,3 Ying-qun Zhu,4 Ming Chen,5 Mei-ling Zhou,6 Li-bing Ma,7 Qi-mi Liu,8 Ping Chen1,2 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, People’s Republic of China; 3Division 4 of Occupational Diseases, Hunan Prevention and Treatment Institute for Occupational Diseases, Changsha, Hunan 410000, People’s Republic of China; 4Department of Respiratory Medicine, The Third Hospital of Changsha, Changsha, Hunan 410011, People’s Republic of China; 5Department of Respiratory Medicine, The No.1 Traditional Chinese Medicine Hospital in Changde, Changde, Hunan 415000, People’s Republic of China; 6Department of Respiratory Medicine, The First People’s Hospital of Huaihua, Huaihua, Hunan 418000, People’s Republic of China; 7Department of Respiratory Medicine, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541000, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, The Second People’s Hospital of Guilin, Guilin, Guangxi 541000, People’s Republic of ChinaCorrespondence: Ping ChenDepartment of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan 410011, People’s Republic of ChinaTel +86 731 8529 5248Email pingchen0731@csu.edu.cnPurpose: Tobacco smoking, biomass smoke, and occupational exposure are the main risk factors for chronic obstructive pulmonary disease (COPD). The present study analyzes data on exposure to these factors in a cohort of patients with COPD and assesses their differences in demographic and clinical characteristics.Patients and Methods: The cross-sectional observational study was conducted from November 2016 to December 2019. Inclusion criteria were patients aged over 40 years old with post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) < 0.7. At baseline, demographic features and exposure history were recorded. Moreover, respiratory symptoms were assessed by the COPD Assessment Test (CAT) and modified Medical Research Council scale (mMRC). A generalized linear mixed model was used to adjust for potential confounders.Results: A total of 5183 patients with COPD were included in the final analysis. The results demonstrate that exposure to tobacco combined with other risk factors resulted in significantly higher CAT scores (16.0 ± 6.7 vs 15.3 ± 6.3, P = 0.003) and more severe dyspnea (patients with mMRC ≥ 2, 71.5% vs 61.6%, P < 0.001) than exposure to tobacco alone. In addition, COPD patients with biomass smoke exposure alone had higher CAT scores than patients with only tobacco or occupational exposure (17.5 ± 6.3 vs 15.3 ± 6.3, and 15.2 ± 6.3, respectively, P < 0.05 for each comparison) and were more likely to be female and older. In addition, COPD patients who suffered from occupational exposure developed more severe dyspnea than those exposed to tobacco alone (70.8% vs 61.6%, P < 0.05), as did those exposed to biomass smoke alone (74.2% vs 61.6%, P < 0.05). This difference remained strong even after adjustment for potential confounders.Conclusion: There are significant demographic and clinical differences among COPD patients with tobacco smoking, biomass smoke, and occupational exposures.Keywords: chronic obstructive pulmonary disease, tobacco, biomass smoke, occupational exposure