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Adrenalectomy is the first line of treatment in unilateral aldosterone-producing adenoma. Whether adrenalectomy should be performed using a cortex-sparing technique (partial adrenalectomy) or total adrenalectomy remains debatable. Therefore, this meta-analysis aims to evaluate the safety and effectiveness of partial adrenalectomy (PA) to total adrenalectomy (TA) by comparing perioperative and functional outcomes. A systematic search was performed across Pubmed, Embase, Web of Science, Cochrane Library database for RCTs and non-RCTs comparing PA and TA on unilateral aldosterone-producing adenoma. The main outcomes analyzed were the perioperative and postoperative effectiveness. In addition, weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals of continuous and dichotomous variables are presented. Two RCTs and 5 non-RCTs trials, including 834 patients were identified and included in the meta-analysis. PA was associated with statistically significant shorter hospital stay (WMD - 0.51 days, 95% CI - 0.87, - 0.14; p = 0.007), shorter operative time (WMD - 15.54 min, 95% CI - 25.12, - 5.97; p = 0.001) and lower overall complications (OR 0.52, 95% CI 0.32, 0.85; p = 0.009) compared to TA. There was no statistical significance in postoperative effectiveness, including postoperative blood pressure, potassium, hypokalemia, ARR and renin between TA and PA. PA seems to have advantages over TA. The surgical outcomes were comparable in TA and PA. The hospital stay, operative time and overall complications may be reduced. When technically feasible, PA might be considered as a better treatment for unilateral aldosterone-producing adenoma.

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 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.

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

Citrate has a prominent role as a substrate in cellular energy metabolism. Recently, citrate has been shown to drive inflammation. However, the role of citrate in lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains unclear. Here, we aimed to clarify whether extracellular citrate aggravated the LPS-induced ALI and the potential mechanism. Our findings demonstrated that extracellular citrate aggravated the pathological lung injury induced by LPS in mice, characterized by up-regulation of pro-inflammatory factors and over-activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in the lungs. In vitro, we found that citrate treatment significantly augmented the expression of NLRP3 and pro-IL-1β and enhanced the translocation of NF-κB/p65 into the nucleus. Furthermore, extracellular citrate plus adenosine-triphosphate (ATP) significantly increased the production of reactive oxygen species (ROS) in primary murine macrophages. Inhibiting the production of ROS with a ROS scavenger N-acetyl-L-cysteine (NAC) attenuated the activation of NLRP3 inflammasome. Altogether, we conclude that extracellular citrate may serve as a damage-associated molecular pattern (DAMP) and aggravates LPS-induced ALI by activating the NLRP3 inflammasome.

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

Prohibitin is an evolutionarily conserved and ubiquitously expressed protein in eukaryocyte. It mediate many important roles in cell survival, apoptosis, autophagy and senescence. In the present study, we aimed to explore the role of prohibitin in cigarette smoke extract (CSE)-induced apoptosis of human pulmonary microvascular endothelial cells (HPMECs). For this purpose, HPMECs were trasfected with prohibitin and challenged with CSE. Our results showed that CSE exposure inhibited prohibitin expression in a dose-dependent manner in HPMECs. Overexpression of prohibitin could protect cell from CSE-induced injury by inhibiting CSE-induced cell apoptosis, inhibiting reactive oxygen species (ROS) production, increase mitochondrial membrane potential, increase the content of mitochondrial transcription factor A (mtTFA), IKKα/β phosphorylation and IκB-α degradation. CSE decreases prohibitin expression in endothelial cells and restoration of prohibitin expression in these cells can protect against the deleterious effects of CSE on mitochondrial and cells. We identified prohibitin is a novel regulator of endothelial cell apoptosis and survival in the context of cigarette smoke exposure.

Arachidonic acid can be metabolized to prostaglandins and epoxyeicosatrienoic acids (EETs) by cyclooxygenase-2 (COX-2) and cytochrome P450 (CYP), respectively. While protective EETs are degraded by soluble epoxide hydrolase (sEH) very fast. We have reported that dual inhibition of COX-2 and sEH with specific inhibitor PTUPB shows anti-pulmonary fibrosis and renal protection. However, the effect of PTUPB on cecal ligation and puncture (CLP)-induced sepsis remains unclear. The current study aimed to investigate the protective effects of PTUPB against CLP-induced sepsis in mice and the underlying mechanisms. We found that COX-2 expressions were increased, while CYPs expressions were decreased in the liver, lung, and kidney of mice undergone CLP. PTUPB treatment significantly improved the survival rate, reduced the clinical scores and systemic inflammatory response, alleviated liver and kidney dysfunction, and ameliorated the multiple-organ injury of the mice with sepsis. Besides, PTUPB treatment reduced the expression of hypoxia-inducible factor-1α in the liver, lung, and kidney of septic mice. Importantly, we found that PTUPB treatment suppressed the activation of NLRP3 inflammasome in the liver and lung of septic mice. Meanwhile, we found that PTUPB attenuated the oxidative stress, which contributed to the activation of NLRP3 inflammasome. Altogether, our data, for the first time, demonstrate that dual inhibition of COX-2 and sEH with PTUPB ameliorates the multiple organ dysfunction in septic mice.

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global adult population, and no effective pharmacological treatment has been found. Products of arachidonic acid metabolism have been developed into a novel therapy for metabolic syndrome and diabetes. It has been demonstrated that protective actions of a novel dual cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) inhibitor, PTUPB, on the metabolic abnormalities. Here, we investigated the effects of PTUPB on hepatic steatosis in high-fat diet (HFD)-induced obese mice, as well as in hepatocytes in vitro. We found that PTUPB treatment reduced body weight, liver weight, liver triglyceride and cholesterol content, and the expression of lipolytic/lipogenic and lipid uptake related genes (Acc, Cd36, and Cidec) in HFD mice. In addition, PTUPB treatment arrested fibrotic progression with a decrease of collagen deposition and expression of Col1a1, Col1a3, and α-SMA. In vitro, PTUPB decreased palmitic acid-induced lipid deposition and downregulation of lipolytic/lipogenic genes (Acc and Cd36) in hepatocytes. Additionally, we found that PTUPB reduced the production of pro-inflammatory cytokines and suppressed the NLRP3 inflammasome activation in HFD mice and hepatocytes. In conclusion, dual inhibition of COX-2/sEH attenuates hepatic steatosis by inhibiting the NLRP3 inflammasome activation. PTUPB might be a promising potential therapy for liver steatosis associated with obesity.

Epoxyeicosatrienoic acids (EETs) derived from arachidonic acid exert anti-inflammation effects. We have reported that blocking the degradation of EETs with a soluble epoxide hydrolase (sEH) inhibitor protects mice from lipopolysaccharide (LPS)-induced acute lung injury (ALI). The underlying mechanisms remain essential questions. In this study, we investigated the effects of EETs on the activation of nucleotide-binding domain leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3) inflammasome in murine macrophages. In an LPS-induced ALI murine model, we found that sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl), TPPU, profoundly attenuated the pathological injury and inhibited the activation of the NLRP3 inflammasome, characterized by the reduction of the protein expression of NLRP3, ASC, pro-caspase-1, interleukin precursor (pro-IL-1β), and IL-1β p17 in the lungs of LPS-treated mice. In vitro, primary peritoneal macrophages from C57BL/6 were primed with LPS and activated with exogenous adenosine triphosphate (ATP). TPPU treatment remarkably reduced the expression of NLRP3 inflammasome-related molecules and blocked the activation of NLRP3 inflammasome. Importantly, four EETs (5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET) inhibited the activation of NLRP3 inflammasome induced by LPS + ATP or LPS + nigericin in macrophages in various degree. While the inhibitory effect of 5,6-EET was the weakest. Mechanismly, EETs profoundly decreased the content of reactive oxygen species (ROS) and restored the calcium overload in macrophages receiving LPS + ATP stimulation. In conclusion, this study suggests that EETs inhibit the activation of the NLRP3 inflammasome by suppressing calcium overload and ROS production in macrophages, contributing to the therapeutic potency to ALI.

Background: There is currently no recognized discharge criteria for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). In clinical work, pulmonologists determine whether a patient can be discharged considering the patient self-reported health status and some measurements which are related to the health status of AECOPD patients. Various measurements have been used to evaluate health status in patients with AECOPD, including lung function, fractional exhaled nitric oxide (FENO), blood gas analysis, COPD Assessment Test (CAT) and modified Medical Research Council test (mMRC). However, which one is most closely related to the patient self-reported health status remains unknown. Methods: Patients with AECOPD were assessed at two visits: on admission and on day 7. The above measurements were tested at each visit. At the second visit, the patients were asked to report the health status according to a five-point Likert scale ranging from 1 to 5, representing ‘much better’, ‘slightly better’, ‘no change’, ‘slightly worse’ and ‘much worse’. Based on patients self-reported outcome, we defined the responders as those patients who reported “much better,” or “slightly better”, non-responders were those who reported ‘no change,’ ‘slightly worse’ or ‘much worse’. Results: 55 patients were recruited into analysis. FENO and CAT could change sensitively based on different health status, except failing to differentiate the patients between those who reported ‘slightly better’ and ‘no changes’. The changes in predicted percentage of forced expiratory volume in 1 s (FEV1%) didn’t change significantly between ‘no change’ group and ‘slightly better or much better’ group, it could only identify the ‘slightly worse’ patients. Although mMRC and blood gas analysis (PaO2, PaCO2) changed significantly after treatment, they didn’t reflect sensitively the evolution of health status. Among these measurements, the changes in CAT was best correlated with the evolution of health status (Rho=0.81), followed by FENO and FEV1%, the rho was 0.59 and -0.42, respectively. Conclusion: It’s reasonable to monitor CAT and FENO during exacerbation stage, the use of lung function and mMRC to evaluate the evolution of patients’ reported health status of patients with AECOPD is limited. Registry number: ChiCTR-ROC-16009087 (http://www.chictr.org.cn/).

Vasoactive intestinal peptide (VIP) is a neuropeptide that exerts anti-inflammatory functions. We have reported that VIP mediated by lentivirus attenuates acute lung injury (ALI) in lipopolysaccharide (LPS)-induced murine model. However, the exact role of VIP in uncontrolled inflammation during ALI is largely unknown. Accumulating evidence indicates that the NLRP3 inflammasome has a critical role during ALI. In this study, we investigated the effects of VIP on the activation of NLRP3 inflammasome during the development of ALI in mice. Seven days after the intratracheal injection of VIP-lentivirus, a murine ALI model was induced by intratracheal injection of LPS. VIP-lentivirus significantly reduced the expression of NLRP3 inflammasome components in lung tissue, including NLRP3, pro-caspase-1, pro-IL-1β, and pro-IL-18. VIP-lentivirus also inhibited the formation of caspase-1 p10 and the maturation of IL-1β and IL-18. In vitro, exogenous VIP pre-treatment inhibited the priming of NLRP3 inflammasome in murine primary peritoneal macrophages, indicated by down-regulation of expression of NLRP3 inflammasome components. VIP pre-treatment effectively prevented the LPS-induced degradation of I-κB and the synthesis of the downstream of NF-κB, including TNF-α and IL-17A. Furthermore, VIP pre-treatment pronouncedly suppressed the autoproteolysis of caspase-1 and the secretion of IL-1β and IL-18 induced by LPS plus ATP in macrophages. In addition, VIP inhibited the generation of reactive oxygen species in macrophages by decreasing NOX1 and NOX2 expression. These findings illustrate one mechanism that VIP attenuates ALI induced by LPS through inhibiting the activation of the NLRP3 inflammasome and encourage further studies assessing the therapeutic potential of VIP to ALI.

Objective. Allergic asthma is a chronic inflammatory disease, which seriously affects the life quality of patients, especially children. Alanylglutamine is a nutritional supplement with potential protective and anti-inflammatory effects, but its function in allergic asthma remains elusive. In this study, we focused on the investigations of the roles and functional mechanism of Alanylglutamine in asthma. Methods. Ovalbumin (OVA) induction was utilized to establish a mouse asthma model. 16S rDNA sequencing was performed to compare the diversity of intestinal microorganisms under different treatments. Gas chromatography was utilized to screen the intestinal microbe-short-chain fatty acids in the stool. The lung tissue was extracted to determine signaling pathways, including AMPK, NF-κB, mTOR, STAT3, IKKβ, TGF-β, and IL-1β through Western blot or RT-qPCR. Results. It was observed that Alanylglutamine reduced the cytokine in OVA-induced allergic asthma mice. H&E staining showed obvious pneumonia symptoms in the asthma group, while Alanylglutamine alleviated the inflammatory infiltration. Alanylglutamine reversed gut microbiota compositions in OVA-induced allergic asthma mice and enhanced the butyric acid level. The protective role of Alanylglutamine may be associated with the gut microbiota-butyric acid-GPR43 pathway in asthma mice. In contrast to the OVA group, Alanylglutamine activated the protein expression of P-AMPK/AMPK and inhibited the protein expression of P-mTOR/mTOR, P-P65/P65, P-STAT3/STAT3, P-IKKβ/IKKβ, TGF-β, and IL-1β, with similar effects from butyric acid. Conclusion. The results indicated that Alanylglutamine might be beneficial for asthma, and its effect was achieved through the regulation on microbiota and the derived metabolites. The therapeutic effects might be associated with AMPK, NF-κB, mTOR, and STAT3 signaling pathways. These findings will help identify effective therapeutic direction to alleviate allergic inflammation of the lungs and airways.

Gluconic metabolic reprogramming, immune response, and inflammation are intimately linked. Glycolysis involves in the pathologic progress in acute and chronic inflammatory diseases. However, the involvement of glycolysis in the acute lung injury (ALI) is still unclear. This study investigated the role of glycolysis in an animal model of ALI. First, we found that lactate content in serum was remarkably increased in ALI patients and a murine model induced by intratracheal administration of lipopolysaccharide (LPS). The key proteins involving in glycolysis were robustly elevated, including HK2, PKM2, and HIF-1α. Intriguingly, inhibition of glycolysis by 2-deoxyglucose (2-DG) pronouncedly attenuated the lung tissue pathological injury, accumulation of neutrophil, oxidative stress, expression of proinflammatory factors in the lung of ALI mice induced by LPS. The 2-DG treatment also strongly suppressed the activation of the NOD-like receptor (NLR) family and pyrin domain-containing protein 3 (NLRP3) inflammasome. Furthermore, we investigated the role of glycolysis in the inflammatory response of primary murine macrophages activated by LPS in vitro. We found that the 2-DG treatment remarkably reduced the expression of proinflammatory factors induced by LPS, including tumor necrosis factor-α messenger RNA (mRNA), pro-interleukin (IL)-1β mRNA, pro-IL-18 mRNA, NLRP3 mRNA, caspase-1 mRNA, and IL-1β protein. Altogether, these data provide a novel link between gluconic metabolism reprogramming and uncontrolled inflammatory response in ALI. This study suggests glycolytic inhibition as an effective anti-inflammatory strategy in treating ALI.

Background: The Clinical COPD Questionnaire (CCQ) has been suggested by the Global Initiative of Chronic Obstructive Lung Disease (GOLD) as a comprehensive symptom measurement tool, which helps to classify patients in order to direct pharmacological treatment. Therefore, it is essential to understand its determinants. Objectives: To identify the determinants of the overall CCQ score and scores of its 3 subdomains among chronic obstructive pulmonary disease (COPD) patients from China. Methods: A total of 1,241 COPD patients in the outpatient department of the Second Xiangya Hospital in China were recruited. Basic information and clinical data were collected. Differences in the GOLD categories based on Modified Medical Research Council Dyspnea Scale (mMRC), COPD Assessment Test (CAT), and CCQ were compared. Multiple linear regression analyses were performed to evaluate determinant factors of the total CCQ and subdomain scores. Results: The total CCQ and/or separate domain scores significantly differed with sex, age, BMI, smoking status, biomass fuel exposure, exacerbation frequency, mMRC, CAT, and GOLD grades and groups. Subjects with asthma-COPD overlap (ACO) had worse health status based on CCQ than those with COPD alone. As for the 16 subgroups based on GOLD 2017, statistical differences in the total CCQ and functional domain scores were found among subgroups 1A–4A, 1B–4B, and 1D–4D. The mMRC classified much more patients into more symptom groups than CAT and CCQ. No significant difference was observed in the GOLD categories between the CAT and CCQ (cut point = 1.5). Multiple linear regression analysis showed that smoking status, underweight, ACO, post-bronchodilator FEV1% predicted Conclusions: The classification of COPD produced by mMRC, CAT, and CCQ was not identical. Smoking status, underweight, ACO, post-bronchodilator FEV1% predicted

Background Several studies have shown a relationship between psoriasis and erectile dysfunction (ED), but a meta-analysis of the data has not been performed. Aim To conduct a comprehensive meta-analysis of existing evidence to quantify and compare the risk of ED with psoriasis. Methods A systematic literature search was conducted using MEDLINE, EMBASE, Cochrane databases, and Google Scholar. We calculated pooled odds ratios (OR), standardized mean difference (SMD), and 95% CI. Outcomes Outcome measures included characteristics of included studies, association between psoriasis and ED risk, and association for adjusted-for-covariates studies between psoriasis and ED risk. Results In total, 9 studies with 36,242 psoriasis patients and 1,657,711 controls (participants without psoriasis) met inclusion criteria and showed that there was statistically significant association between psoriasis and ED risk (OR 1.35; 95% CI 1.29–1.41; P < .00001; I2 = 44%). A significant association for adjusted-for-covariates studies between psoriasis and ED risk was also observed (OR 1.22; 95% CI 1.08–1.37; P = .002; I2 = 43.8%). It revealed the International Index of Erectile Function-5 score was statistically significantly lower in the psoriasis group than controls (SMD −3.09; 95% CI −4.81 to −1.37; P = .0004; I2 = 77%). A subgroup analysis was performed to potentially explain heterogeneity. It examined the main potential sources of inter-study variance including variance sample sizes and different assessment tools for ED. Clinical Translation The risk of ED in psoriasis patients should also be assessed by physicians. Conclusions This study is a well-designed and comprehensive meta-analysis to examine the relationship between psoriasis and risk of ED. However, the included studies are mostly cross-sectional or have small sample cohorts, which could bring bias and heterogeneity into the analysis. Our findings support the hypothesis that psoriasis is associated with an increased risk of ED. Furthermore, additional prospective cohort studies are needed to elucidate these relationships and to advance knowledge in this field.

Zijing Zhou,1–3 Aiyuan Zhou,1–3 Yiyang Zhao,1–3 Jiaxi Duan,1–3 Ping Chen1–3 1Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China; 2Research Unit of Respiratory Disease, Central South University, Changsha, China; 3Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, China Background: Both the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) were recommended as comprehensive symptom measures by the Global Initiative for Chronic Obstructive Lung disease. The main objective of this work was to compare the evalua­tion of symptom severity with the CAT and the CCQ and find a cutoff value of the CCQ for the Chinese clinical population. Methods: Patients diagnosed with stable COPD in the outpatient department who completed the CAT and CCQ were enrolled from November 2015 to December 2016. Scores of 0–10, 11–20, 21–30, and 31–40 represent low, medium, high, and very high impact level, respectively, by CAT. Scores of the CCQ can be considered as acceptable (CCQ

Vasoactive intestinal peptide (VIP) is an intrapulmonary neuropeptide with multi-function, including anti-fibrosis. However, the exact role of VIP in pulmonary fibrosis has not been documented. Here, we investigated the protective effect of VIP against pulmonary fibrosis in a murine model induced by bleomycin (BLM). We found that the overexpression of VIP mediated by the adenoviral vector significantly attenuated the lung tissue destruction, reduced the deposition of the extracellular matrix, and inhibited the expression of alpha-smooth muscle actin (α-SMA) in the lungs of mice received BLM. Mechanismly, we found that VIP significantly suppressed the transforming growth factor-beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) and inhibited the matrix-producing ability of alveolar epithelial cells in vitro. Furthermore, we found that TGF-β1 depressed the autophagy and an autophagy inductor partly reversed the TGF-β1-induced EMT in alveolar epithelial cells. The impaired autophagy was also observed in the lungs of BLM-treated mice, which was restored by VIP treatment. And VIP treatment enhanced autophagy in TGF-β1-stimulated alveolar epithelial cells, contributing to its anti-EMT effect. In summary, our data, for the first time, show that VIP attenuates BLM-induced pulmonary fibrosis in mice with anti-EMT effect through restoring autophagy in alveolar epithelial cells. This study provides a possibility that inhaled long-acting VIP may be an anti-fibrotic drug in the treatment of pulmonary fibrosis.

In recent times, Gold nanoparticles (AuNPs) synthesized from plant extracts and their anticancer activity have attracted significant attention. We report the green approach for the synthesis of AuNPs using extract from Abies spectabilis plant. In this study, the reaction parameters were optimized to control the size of the nanoparticle, which was confirmed by Transmission Electron microscopy (TEM). Various characterization technique such as SAED pattern, UV visible spectroscopy, EDX, FTIR, and AFM were employed to analyze the synthesized AuNPs obtained from A. spectabilis plant extract. Furthermore, we investigated the anticancer activities using T24 cell lines. Interestingly, the results of extensive screening on the applications of newly synthesized AuNPs were tested for their cytotoxicity effects on anticancer activity against T24 cells by MTT assay. The cell apoptosis was studied using TUNEL, DAPI, caspase activity, cell invasion and migration. Nanoparticles at different concentrations ranging from 1 to 25 μg/ml exhibited a dose dependent cytotoxicity for 24 h. Condensation and DNA fragmentation are characteristic of apoptosis by DAPI, TUNEL staining, and the significant up regulations of Beclin-1, Bax and caspase 3, whereas the expressions of anti-apoptotic Bcl-2 and Bid were down regulated. However, this study, therefore attempts to report the synthesis, characterization, and anticancer activity of gold nanoparticles of A. spectabilis plant extract beneficial for cancer therapeutics.

In this study, allergic rhinitis (AR) disease targets and Xiang Ju tablet-associated targets were determined through the use of databases for the identification of putative therapeutic targets and then combined. After the production of a putative therapeutic target interaction network for Xiang Ju tablets against AR, topological analysis was used to determine the core targets of Xiang Ju tablets in AR treatment. For all putative therapeutic targets, analyses of biological function and pathway enrichment were performed to optimize the biological processes and key signaling pathways of Xiang Ju tablets in AR treatment. The top 5 therapeutic targets of Xiang Ju tablets in AR treatment were identified and included CXCL8, IL1B, IL6, IL10, and TNF. The biological processes, molecular functions, and cell composition related to the use of Xiang Ju tablets in AR treatment were predominantly associated with cytokine production, regulation of protein secretion, and regulation of peptide secretion; cytokine activity, cytokine receptor binding, and receptor ligand activity; and platelet alpha granule lumen, collagen-containing extracellular matrix, and platelet alpha granule. In addition, the top 64 key signaling pathways were identified.

Highlights • NLRP3 inflammasome inhibition reduces TREM-1 expression in the lungs of mice with ALI. • Activation of NLRP3 inflammasome up-regulates TREM-1 expression in murine macrophages via HMGB1 and IL-18. • NLRP3 inflammasome activation induces TREM-1 expression, contributing to the inflammatory network in the lungs of ALI mice., NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome and triggering receptor expressed on myeloid cells-1 (TREM-1) are considered critical orchestrators of the inflammatory response in acute lung injury (ALI). However, few assumptions are based on the relationship between them. Here, we investigated the effect of NLRP3 inflammasome activation on the TREM-1 expression in lipopolysaccharide (LPS)-induced ALI and macrophages. We found that inhibition of the NLRP3 inflammasome reduced the TREM-1 expression and pathological lung injury in mice with ALI. Then, primary murine macrophages were used to dissect the underlying mechanistic events of the activation NLRP3 inflammasome involved in the TREM-1 expression. Our results demonstrated that the conditioned medium (CM) from NLRP3 inflammasome-activated-macrophages up-regulated the TREM-1 expression in macrophages, while this effect was reversed by an NLRP3 inflammasome inhibitor MCC950. Furthermore, neutralizing antibodies anti-IL-18 and anti-HMGB1 reduced the TREM-1 expression induced by NLRP3 inflammasome activation. Mechanistically, we found that CM from NLRP3 inflammasome-activated-macrophages increased the level of inhibitor κB kinase protein phosphorylation (p-IκBα) and reactive oxygen species (ROS) content, and promoted IκBα protein degradation in macrophages. While the inhibition of nuclear factor kappa-B (NF-κB) and scavenging ROS eliminated the up-regulation of TREM-1 induced by the NLRP3 inflammasome activation in macrophages. In summary, our study confers NLRP3 inflammasome as a new trigger of TREM-1 signing, which allows additional insight into the pathological of the inflammatory response in ALI.

Supplemental Digital Content is available in the text, Background: Several studies have shown a relationship between psoriasis and hypertension, but no meta-analysis has been restricted to studies that adjusted for confounders. The aim of the study was to estimate the association between psoriasis and hypertension with adjustment for covariates. Methods: A systematic literature search in the MEDLINE, Embase, Cochrane databases, and Google Scholar was conducted to identify relevant studies which reported the association of psoriasis with the risk of hypertension published up to November 2018 in English. Data analysis was performed with Stata V.12, and Begg adjusted rank correlation test and Egger regression asymmetry test were used to detect publication bias. Results: A total of 16 adjusted-for-covariates studies, involving 50,291 cases with hypertension in 255,132 psoriasis patients and 76,547 cases with hypertension in 814,631 controls (no psoriasis), were included in this meta-analysis. The results indicated that psoriasis was associated with an increased risk of hypertension compared to those without psoriasis, and the prevalence of hypertension in severe psoriasis patients was higher than that in mild psoriasis patients, and the risk of hypertension in psoriasis patients was higher than that in nonpsoriasis patients in Europe and Asia. Conclusion: We conducted this meta-analysis using the adjusted-for-covariates odds ratio, demonstrating that psoriasis was associated with an increased risk of hypertension compared to those without psoriasis.

Metallic nanoparticles were extensively examined to explore their impending exploitations over pharmaceutical purposes. Current work attempting to explores the cytotoxic capacity of zinc oxide (ZnO) nanoparticles besides to human melanoma cell line (A375). Viability of cells was resoluted, and the promising cytotoxicity potential was exhibited by zinc oxide nanoparticles. Cellular adhesion and morphology was determined by propidium iodide assay. Characterization studies like UV-Spectroscopy, X-ray diffraction (XRD) investigation, transmission electron microscope (TEM), energy dispersive X-ray (EDX) Spec, and Fourier transform infrared (FT-IR) examination confirms the accessibility of measurement, form and volume. The mRNA expression of apoptotic genes like caspase 3, 8 and 9 was elevated followed by the exposure to ZnO nanoparticles and it was narrowly proved that ZnO nanoparticles stimulates the apoptotic cell necrosis at the transcriptional stage. Cardiospermum halicacabum down regulated the apoptotic gene expressions. Reactive oxygen species (ROS) accumulation was augmented at concentration reliant mode, that changed normalize numerous indicator pathways and manipulate the kinetic cellular actions. ZnO nanoparticle synthesized Cardiospermum halicacabum might persuades programmed cell necrosis via elevated ROS levels in cells. CH-ZnONPs was further stimulates the markers of apoptosis and aggravates necrosis of cancerous cells, toxicity to cells, and accretion of ROS. With sourced on above whole data, this might accomplished that CH-ZnONPs amalgamated Cardiospermum halicacabum appreciably possessed a toxicity to human melanoma cells (A375) via provoking the apoptotic cell necrosis, entailed feasible efficacy of CH-ZnONPs besides malignancy management.

Background and aims: Various prediction indices based on the single time point observation have been proposed in chronic obstructive pulmonary disease (COPD), but little was known about disease trajectory as a predictor of future exacerbations. Our study explored the association between disease trajectory and future exacerbations, and validated the predictive value of the modified and simplified short-term clinically important deterioration (CID). Methods: This study was a multicenter, prospective observational study. Patients with COPD were recruited into our study and followed up for 18 months. The modified CID (CID-C) was defined as a decrease of 100 mL in forced expiratory volume in 1 second (FEV1), or suffering exacerbations, or increase of 2 units in COPD Assessment Test (CAT) during the first 6 months follow-up. Simplified CID was defined when excluding CAT from the CID-C model. Results: A total of 127 patients were enrolled in our final analysis. Compared with patients without exacerbations during the period of the 6th to the 18th month, patients with exacerbations were more likely to have frequent short-term exacerbations in the first 6 months (2.14 versus 0.21, p Conclusion: Disease trajectory, including both the CID-C and the Simplified CID had significant predictive value for future exacerbations. The reviews of this paper are available via the supplemental material section.

Aiyuan Zhou,1–3 Zijing Zhou,1–3 Yating Peng,1–3 Yiyang Zhao,1–3 Jiaxi Duan,1–3 Ping Chen1–3 1Department of Respiratory Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; 2Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China; 3Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China Background: The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) questionnaire is a short patient-completed questionnaire, which is used to assess the health status of patients with stable COPD. However, whether it is a good tool to evaluate the response to treatment in acute exacerbation of COPD (AECOPD) has been less studied.Methods: The patients were assessed at two visits, at admission and on the seventh day. Anthropometric variables were collected at admission. CAT and lung function were measured twice at the above time points. At the second visit, the health status of the patients were divided into five groups based on a 5-point Likert scale, ranging from 1 to 5, which represents “much better,” “slightly better,” “no change,” “slightly worse,” and “much worse.” Responders were those who reported “much better” or “slightly better,” and nonresponders were those who claimed “no change,” “worse,” or “much worse.”Results: In total, 225 patients were recruited. The average CAT score at admission was 24.82±7.41, which declined to 17.41±7.35 on the seventh day. There were 81.33% responders, whose improvement in CAT score (9.37±5.24) was much higher than that of the nonresponders (−1.36±4.35). A moderate correlation was observed between the changes in CAT score and improvement in FEV1, FEV1%, and the length of hospital stay. There was a strong correlation between the changes in CAT score and health status. A 3.5-unit improvement in the CAT score, with highest area under the curve, was the cutoff to differentiate responders from nonresponders.Conclusion: The evolution of CAT scores during exacerbation can provide useful information to assess the health status of patients with AECOPD. A 3.5-unit improvement in CAT score is the best cutoff to differentiate between patients who have a response or no response to treatment, which offers a convenient and easy way for clinicians to monitor the health status of patients with an AECOPD. Keywords: COPD, acute exacerbation, CAT, curative effect

BACKGROUND:Pneumoconiosis may play an important role in the development of chronic obstructive pulmonary disease (COPD), and the complication of COPD may impose a heavy burden of illness. METHODS:The study was conducted in Hunan Province in China from December 1, 2015, to December 1, 2016. Consecutive underground male pneumoconiosis patients employed for at least 1year were recruited from the Hunan Occupational Disease Prevention Institute. Patient information, respiratory symptoms and clinical data were collected using a structured questionnaire. The diagnosis of COPD were assessed using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Logistic regression analyses were conducted to examine the clinical and demographic risk factors of COPD among pneumoconiosis patients. RESULTS:The prevalence of COPD in our sample of pneumoconiosis patients was 18.65% (119/638). In pneumoconiosis patients with and without smoking history, the prevalence of COPD was 19.32 and 16.77%. Compared with non-COPD patients, those with COPD are older in age, have longer exposure time, have lower body mass index (BMI), have a higher smoking index and have worse pulmonary function (all p

Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived from the cytochrome P450 (CYP450) epoxygenases, are mainly metabolized by soluble epoxide hydrolase (sEH) to their corresponding diols. EETs but not their diols, have anti-inflammatory properties and inhibition of sEH might provide protective effects against inflammatory fibrosis. We test the effects of a selected sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), on bleomycin-induced pulmonary fibrosis (PF) in mice. A mouse model of PF was established by intratracheal injection of bleomycin and TPPU was administered for 21days after bleomycin injection. We found TPPU treatment improved the body weight loss and survival rate of bleomycin-stimulated mice. Histological examination showed that TPPU treatment alleviated bleomycin-induced inflammation and maintained the alveolar structure of the pulmonary tissues. TPPU also decreased the bleomycin-induced deposition of collagen and the expression of procollagen I mRNA in lung tissues of mice. TPPU decreased the transforming growth factor-β1 (TGF-β1), interleukin-1β (IL-1β) and IL-6 levels in the serum of bleomycin-stimulated mice. Furthermore, TPPU inhibited the proliferation and collagen synthesis of mouse fibroblasts and partially reversed TGF-β1-induced α-smooth muscle actin expression. Our results indicate that the inhibition of sEH attenuates bleomycin-induced inflammation and collagen deposition and therefore prevents bleomycin-induced PF in a mouse model.

Calcifying fibrous pseudotumor (CFP) is a rare benign soft tissue lesion. We herein present an extremely rare case of CFP of the adrenal gland. A 32-year-old male patient presented to our hospital with a tumor-like lesion in the area of the left adrenal gland detected by ultrasound during a routine check-up several days prior. Contrast-enhanced magnetic resonance imaging examination revealed a solitary, well-circumscribed mass, in close proximity to the medial arterial branch of the left adrenal gland. Histological examination revealed that the tumor consisted of sheets of varying amount of inflammatory cell infiltration; interstitial fibrosis and psammomatous calcifications were also observed. To the best of our knowledge, this is the third case of CFP occurring in the adrenal gland in the published literature. We herein report the findings of this case and review the two previously reported cases of CFP of the adrenal gland with valuable information.

Pulmonary fibrosis is a life-threatening disease characterized by progressive dyspnea and worsening of pulmonary function. No effective therapeutic strategy for pulmonary fibrosis has been established. Aucubin is a natural constituent with a monoterpene cyclic ring system. The potency of aucubin in protecting cellular components against inflammation, oxidative stress, and proliferation effects is well documented. In this study, we investigated the protective effect of aucubin against pulmonary fibrosis in mice. A mouse model of pulmonary fibrosis was established by intratracheal injection of bleomycin (BLM), and aucubin was administered for 21 days after BLM injection. We found that aucubin decreased the breathing frequency and increased the lung dynamic compliance of BLM-stimulated mice detected by Buxco pulmonary function testing system. Histological examination showed that aucubin alleviated BLM-induced lung parenchymal fibrotic changes. Aucubin also reduced the intrapulmonary collagen disposition and inflammatory injury induced by BLM. In addition, aucubin reduced the expression of pro-fibrotic protein transforming growth factor (TGF)-β1 and α-smooth muscle actin (α-SMA) of pulmonary fibrosis mice induced by BLM. Furthermore, the effect of aucubin on the proliferation and differentiation of fibroblast was investigated in vitro. Aucubin inhibited the mRNA and protein expression of Ki67 and proliferating cell nuclear antigen (PCNA) induced by TGF-β1 and reduced the cell proliferation in a murine fibroblast cell NIH3T3. Aucubin also reduced the collagen syntheses and α-SMA expression induced by TGF-β1 in fibroblast. Our results indicate that aucubin inhibits inflammation, fibroblast proliferation, and differentiation, exerting protective effects against BLM-induced pulmonary fibrosis in a mouse model. This study provides an evidence that aucubin may be a novel drug for pulmonary fibrosis.

Acute lung injury (ALI) is a condition resulting from direct or indirect lung injury associated with high mortality and morbidity. The phenotype of macrophages in lung contributes to the pathological progress of ALI. Calcitonin gene-related peptide (CGRP) is one of the most abundant neuropeptides in lung, and attenuates lipopolysaccharide (LPS)-induced ALI in rats. However, the exact effect of CGRP on the activation of macrophages remains unknown. Here we investigate the effect of CGRP on the macrophages activation and inflammation in murine macrophages in vitro. We found that LPS increased the expression of CGRP in a LPS-induced ALI murine model and LPS-stimulated murine macrophages. Although CGRP didn't alter the expression of tumor necrosis factor-α (a marker of pro-inflammatory phenotype of macrophages, M1 macrophages) or Arginase 1 (Arg1, a marker of M2 macrophages) in non-differentiated macrophages, CGRP significantly reduced the NLRP3 and pro-IL-1β mRNA expression induced by LPS, as well as NLRP3 protein and IL-1β secretion induced by LPS+ATP in macrophages in vitro. On the other hand, CGRP dramatically enhanced the Arg1 expression and activity induced by IL-4 in the time- and dose-dependent manners. CGRP also promoted the expression of markers of M2 macrophages (IL-10, Fizz1 and Mrc1) induced by IL-4 in murine macrophages. These effects of CGRP were also observed in primary murine peritoneal macrophages. In addition, we found that CGRP regulated macrophages polarization partially through calmodulin, PKC and PKA pathways. Specifically, CGRP could inhibit the degradation of I-κB induced by LPS, and enhance the phosphorylation of STAT6 induced by IL-4 in macrophages. In conclusion, our results indicate that CGRP regulates macrophage polarization and inhibits inflammation in murine macrophages.

Acute lung injury (ALI) is characterized by rapid alveolar injury, vascular leakage, lung inflammation, neutrophil accumulation, and induced cytokines production leading to lung edema. The mortality rate of patients suffering from ALI remains high. Epoxyeicosatrienoic acids (EETs) are cytochrome P450-dependent derivatives of polyunsaturated fatty acid with antihypertensive, profibrinolytic, and anti-inflammatory functions. EETs are rapidly hydrated by soluble epoxide hydrolase (sEH) to their less potent diols. The aim of this study was to investigate the role of sEH inhibitor trifluoromethoxyphenyl propionylpiperidin urea (TPPU) and EETs in lipopolysaccharide (LPS)-induced ALI of mice. Our studies revealed that inhibition of sEH with TPPU attenuated the morphological changes in mice, decreased the neutrophil infiltration to the lung, pro-inflammatory cytokine levels (IL-1β and TNF-α) in serum and bronchoalveolar lavage fluid (BALF), and alveolar capillary leakage (lung wet/dry ratio and total protein concentration in BALF). TPPU improved the survival rate of LPS-induced ALI. In addition, in vitro experiments revealed that both TPPU and EETs (11,12-EET and 14,15-EET) suppressed the expression of IL-1β and TNF-α, and LDH release in RAW264.7 cells. These results indicate that EETs play a role in dampening LPS-induced acute lung inflammation, and suggest that sEH could be a valuable candidate for the treatment of ALI.

Objectives: To provide a systematic review and meta-analysis of studies comparing ureterolithotripsy (URS) with percutaneous nephrolithotripsy (PCNL) or laparoscopic ureterolithotomy (LU) techniques for the management of large proximal ureteral stones (diameter greater than 10 mm). Methods: A literature search was performed using PubMed, EMBASE, EBSCO, Web of Science, and Cochrane Library to identify suitable studies until November 2016. We used weighted mean difference to measure operative time and hospital stay, OR to measure stone free rate (SFR), and complication rate. Subgroup analyses were assessed for heterogeneity. Results: Fourteen publications strictly met our eligibility criteria of which 7 were randomized control studies (RCTs) and 7 non-RCTs. Meta-analysis of extractable data showed that LU and PCNL had higher SFR than URS. URS led to a similar hospital stay like that of LU. However, it had a shorter operative time and lower complication rate than LU. When we compared URS with PCNL, we found a shorter hospital stay in the URS group. However, there was no significant difference in terms of the operative time and complication rate between URS and PCNL. Conclusion: URS should be considered standard therapy for treating large proximal ureteral stones.

Headache is a common problem among the population, many factors may impact the headache characteristics and medical consultation behaviors in different age groups. The purpose of this study was to evaluate the clinical characteristics and the diagnosis and treatment status of headaches in elderly patients hospitalized in a gerontologic department. Consecutive patients hospitalized in the Department of Gerontology eligible for this study were registered. All the patients underwent a comprehensive evaluation of their whole health status, performed by three gerontologists initially. Then headache was evaluated by two physicians experienced in headache studies. Headache diagnosis was made according to the criteria of the second edition of the International Classification of Headache Disorders. In this study, 20% of the participants reported at least one headache attack in the previous year. Sixty percent of the migraineurs and 79·7% of the tension type headache (TTH) patients reported bilateral pain. Throbbing/pulsating and tightness/pressing were the most frequently described pain quality by the migraineurs and TTH patients, respectively. The migraineurs reported the most severe pain (P0·001). The frequency of headache attacks was not significantly different in the three subgroups (P = 0·053). About 76·2% of the migraineurs, 68·8% of the TTH, and 80% of the other type headache patients had consulted a physician for their headaches in the previous year. Taking acute analgesics for headache was more common in migraineurs (P0·001). The results showed that headache remained under-recognized and under-treated in the geriatrics department.

Acute lung injury (ALI) is associated with high mortality and uncontrolled inflammation plays a critical role in ALI. TREM-1 is an amplifier of inflammatory response, and is involved in the pathogenesis of many infectious diseases. NLRP3 inflammasome is a member of NLRs family that contributes to ALI. However, the effect of TREM-1 on NLRP3 inflammasome and ALI is still unknown. This study aimed to determine the effect of TREM-1 modulation on LPS-induced ALI and activation of the NLRP3 inflammasome. We showed that LR12, a TREM-1 antagonist peptide, significantly improved survival of mice after lethal doses of LPS. LR12 also attenuated inflammation and lung tissue damage by reducing histopathologic changes, infiltration of the macrophage and neutrophil into the lung, and production of the pro-inflammatory cytokine, and oxidative stress. LR12 decreased expression of the NLRP3, pro-caspase-1 and pro-IL-1β, and inhibited priming of the NLRP3 inflammasome by inhibiting NF-κB. LR12 also reduced the expression of NLRP3 and caspase-1 p10 protein, and secretion of the IL-1β, inhibited activation of the NLRP3 inflammasome by decreasing ROS. For the first time, these data show that TREM-1 aggravates inflammation in ALI by activating NLRP3 inflammasome, and blocking TREM-1 may be a potential therapeutic approach for ALI.

Triggering receptors expressed on myeloid cell-1 (TREM-1) is a superimmunoglobulin receptor expressed on myeloid cells. TREM-1 amplifies the inflammatory response. Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived from the cytochrome P450 enzyme, have anti-inflammatory properties. However, the effects of EETs on TREM-1 expression under inflammatory stimulation remain unclear. Therefore, inhibition of soluble epoxide hydrolase (sEH) with a highly selective inhibitor [1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea, TPPU] was used to stabilize EETs. LPS was intratracheally injected into mice to induce pulmonary inflammation, after TPPU treatment for 3 h. Histological examination showed TPPU treatment-alleviated LPS-induced pulmonary inflammation. TPPU decreased TREM-1 expression, but not DAP12 or MyD88 expression. Murine peritoneal macrophages were challenged with LPS in vitro. We found that TPPU reduced LPS-induced TREM-1 expression in a dose-dependent manner, but not DAP12 or MyD88 expression. TPPU also decreased downstream signal from TREM-1, reducing pro-inflammatory cytokine TNF-α and IL-1β mRNA expression. Furthermore, TPPU treatment inhibited IkB degradation in vivo and in vitro. Our results indicate that the inhibition of sEH suppresses LPS-induced TREM-1 expression and inflammation via inhibiting NF-kB activation in murine macrophage.

To present a systematic review to assess efficacy and safety of tramadol for premature ejaculation.A literature search was performed using the Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded. Literature reviewed included meta-analyses and randomized and nonrandomized prospective studies. End points included intravaginal ejaculation latency time (in minutes), adverse events, and patient-reported outcome assessments. We used mean difference to measure intravaginal ejaculation latency time and odds ratio to measure adverse events rates. These odds ratios were pooled using a random or fixed effects model and were tested for heterogeneity. We used the Cochrane Collaboration's Review manager (RevMan) 5.1 software for statistical analysis.We identified 7 publications that strictly met our eligibility criteria. Meta-analysis of extractable data showed that tramadol was associated with a 3-minute intravaginal ejaculation latency time increasing (mean difference 2.77 minutes; 95% CI 1.12-4.47; P = .001) and significantly more patients with adverse events rates compared with placebo (odds ratio 2.89; 95% CI 1.88-4.43; P.0001). There were no differences between the tramadol and the paroxetine of intravaginal ejaculation latency time (mean difference -0.44; 95% CI -5.07 to 4.18; P = .85). In addition, patients saw significantly greater improvement in patient-reported outcome.In this diverse population, tramadol is an effective and safety pharmacologic therapy for premature ejaculation.

Male pattern baldness (MPB) has been associated with an increased risk of prostate cancer (PC) as well as benign prostatic hyperplasia (BPH). We performed a meta-analysis to quantitatively determine the level of risk of PC and BPH in individuals with baldness.A systematic literature search was conducted using several databases. We calculated pooled odds ratios (OR) and 95% CIs.In total, 17 studies comprising 68,448 participants were eligible for the meta-analysis and showed that MPB is associated with an increased risk of aggressive PC (OR = 1.59; 95% CI: 1.36-1.86; P0.001) as well as BPH (OR = 1.26; 95% CI: 1.05-1.51; P = 0.01). There was statistically significant association between vertex baldness and PC (OR = 1.18; 95% CI: 1.05-1.32; P = 0.006). No statistically significant association between vertex, frontal plus vertex hair loss pattern, and BPH were identified.MPB is associated with an increased risk of PC and BPH. Despite our findings, further studies, preferably prospective cohort studies, are required to better elucidate these relationships and to advance knowledge in this field.

Objective: To present a systematic review assessing the efficacy and safety of mirabegron for overactive bladder (OAB). Materials and Methods: A literature search was performed using the Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded. The literature reviewed included meta-analyses, randomized and nonrandomized prospective studies. We utilized mean difference (MD) to measure the mean number of incontinence episodes and the mean number of micturitions, and OAB questionnaire (OAB-q) and odds ratio (OR) to measure adverse events rates. We used the Cochrane Collaboration's Review Manager 5.1 software for statistical analysis. Results: We identified six publications that strictly met our eligibility criteria. Meta-analysis of extractable data showed that mirabegron was more effective than placebo in treating OAB despite different drug dosages in the efficacy end points: mean number of incontinence episodes per 24 h (MD -0.54; 95% CI -0.63, -0.45; p = 0.001), mean number of micturitions per 24 h (MD -0.55; 95% CI -0.63, -0.47; p = 0.001), OAB-q (MD -4.49; 95% CI -6.27, -2.71; p = 0.001) and adverse events (OR 0.99; 95% CI 0.83, 1.19; p = 0.92). When compared to tolterodine, mirabegron was more effective in terms of mean number of incontinence episodes per 24 h (MD -0.25; 95% CI -0.43, -0.06; p = 0.009). However, there were no differences between mirabegron and tolterodine in mean number of micturitions per 24 h (MD -0.17; 95% CI -0.35, 0.01; p = 0.07) and OAB-q (MD -1.09; 95% CI -2.51, 0.33; p = 0.13). Mirabegron also had a lower adverse reaction rate (OR 0.9; 95% CI 0.8, 1.0; p = 0.04). Conclusions: In this diverse population, mirabegron was an effective and safe pharmacologic therapy for OAB.