Associations between comorbidities and annual incidence plus frequency of asthma exacerbation hospitalisation during the past year: data from CARN study.

PURPOSE: While asthma comorbidities are associated with higher health care utilisation, lower quality of life and poorer asthma control, the impact of asthma comorbidities on hospitalisation for asthma exacerbation (H-AX) remains less recognised. We aim to analyse the impact of asthma comorbidities on H-AX. METHODS: Based on a national survey on asthma control and disease perception (CARN 2015 study), we analysed the impact of comorbidities on annual incidence and frequency of H-AX in China. Information on demographic characteristics, asthma comorbidities and annual incidence and frequency of H-AX were presented in this study. RESULTS: Among 3875 ambulatory asthma patients, 75.9% (2941/3875) had comorbidities, and 26.4% (1017/3858) experienced H-AX during past year. After adjusting for confounding factors such as demographic data, smoking status and asthma control, COPD [OR = 2.189, 95% CI (1.673, 2.863)] and coronary heart disease [OR = 1.387, 95% CI (1.032, 1.864)] were associated with higher annual incidence, while allergic rhinitis [OR = 0.692, 95% CI (0.588, 0.815)] was associated with lower annual incidence, of H-AX. In terms of frequency, allergic rhinitis [OR = 1.630, 95% CI (1.214, 2.187)], COPD [OR = 1.472, 95% CI (1.021, 2.122)] and anxiety [OR = 2.609, 95% CI (1.051, 6.477)] showed statistically significant correlation with frequent H-AX. CONCLUSIONS: COPD and coronary heart disease were associated with higher annual incidence, while allergic rhinitis was associated with lower annual incidence of H-AX. Allergic rhinitis, COPD and anxiety were associated with frequent H-AX. Comorbidities may have an important role in the risk and frequency of annual hospitalisations due to asthma exacerbation. The goal of asthma control should rely on a multi-disciplinary treatment protocol.

Asthma Management Using the Mobile Asthma Evaluation and Management System in China.

PURPOSE: As stated in the Global Initiative for Asthma, there are still some asthmatic patients who have not achieved asthma control. Mobile is a useful tool for asthma management. We aimed to compare the advantages of mobile management with traditional management in improving adherence and control of asthma. METHODS: In this prospective, multicentre, randomized, controlled and parallel-group study, we enrolled patients with poor adherence and uncontrolled asthma at 32 hospitals in 28 provinces in China. Patients were randomly assigned to the mobile management or traditional management groups for 12 months. The primary endpoint was the proportion of patients with good adherence (Medication Adherence Report Scale for Asthma [MARS-A] score ≥ 45) for 6 months. This study is registered at ClinicalTrials.gov (NCT02917174). RESULTS: Between April 2017 and April 2018, 923 patients were eligible for randomization (mobile group, n = 461; traditional group, n = 462). Dropout was 84 (18.2%) in the mobile management group and 113 (24.4%) patients in the traditional management group. The proportion of patients with good adherence was significantly higher in the mobile management group than in the traditional management group (66.0% vs. 58.99%, P = 0.048). The mobile management group showed higher mean MARS-A score (at 1, 6, 9, and 12 months) and asthma control test scores (at 6 and 9 months), and lower total lost rate to follow-up within 12 months than the traditional management group. CONCLUSIONS: Mobile asthma management can improve adherence and asthma control compared to traditional management. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02917174.

Atypical Pathogen Distribution in Chinese Hospitalized AECOPD Patients: A Multicenter Cross-Sectional Study.

Purpose: The proportion of atypical pathogens in patient with AECOPD within mainland China is unknown. The objectives of this study were to determine the distribution of atypical pathogens among Chinese patients with AECOPD, to evaluate the clinical characteristics of different atypical pathogen infections, and to compare different detection methods for atypical pathogens. Patients and Methods: Specimens were collected from patients with AECOPD from March 2016 to November 2018 at eleven medical institutions in eight cities in China. Double serum, sputum, and urine samples were obtained from 145 patients. Serological and nucleic acid tests were used to assess for Mycoplasma pneumonia and Chlamydia pneumoniae; serological, urinary antigen, and nucleic acid tests were applied to detect Legionella pneumophila. The clinical characteristics of atypical pathogen-positive and -negative groups were also compared. Results: The overall positivity rate for Mycoplasma pneumoniae was 20.69% (30/145), with the highest rate being 20.00% (29/145) when determined by passive agglutination.The overall positive rates for Chlamydia pneumoniae and Legionella pneumophila were 29.66% (43/145) and 10.34% (15/145), respectively. The most common serotype of Legionella pneumophila was type 6. The maximum hospitalized body temperature, ratio of eosinophils, C-reactive protein (CRP) level, and procalcitonin (PCT) level of the Mycoplasma pneumoniae-positive group were significantly higher than those of the Mycoplasma pneumoniae-negative group. Patients in the Chlamydia pneumoniae-positive group smoked more, had higher proportions of comorbidities and frequent aggravations in the previous two years than those in the Chlamydia pneumoniae-negative group. Furthermore, the forced expiratory volume in one second to forced vital capacity (FEV1/FVC) ratio assessment of lung function was higher, and the concentration of arterial blood bicarbonate (HCO3-) was lower in the Legionella pneumophila-positive group than in the Legionella pneumophila-negative group. Conclusion: Overall, atypical pathogens play an important role in AECOPD. Regarding the testing method, serological testing is a superior method to nucleic acid testing.

Efficacy and safety of tratinterol hydrochloride tablets in bronchial asthma: a randomized double-blind and multicenter clinical trial.

PURPOSE: The aim of this study was to investigate the efficacy and safety of tratinterol hydrochloride in bronchial asthma (BA) treatment. METHODS: Patients enrolled in this study were distributed randomly into a treatment group (tratinterol hydrochloride) and an active control group (procaterol hydrochloride) and were treated for 2 weeks after running-in. The end points were changes in pulmonary function and clinical symptoms after administration. Safety indices were physical examinations, laboratory testing and spontaneous reporting. FINDINGS: We enrolled 732 subjects, -365 in the treatment group and 367 in the active control group. Forced expiratory volume (FEV1), significantly increased in both group after treatment (P < 0.05). Least-squares (LS) means were -0.03/in the full-analysis set (FAS) and -0.02 in the per-protocol set (PPS) set, and 95% confidence intervals (CIs) for these sets were -0.09 to 0.03 and -0.08 to 0.04, respectively. Forced expiratory volume (FVC), morning peak expiratory flow (PEF) and asthma scores were significantly different with pretreatment (P < 0.05). There was no difference in asymptomatic days or frequency of relief medicine use (P > 0.05). No serious adverse events occurred. IMPLICATIONS: Tratinterol hydrochloride was effective, safe and not inferior to procaterol hydrochloride in treating BA.

Effects of ACEI and ARB on COVID-19 patients: A meta-analysis.

BACKGROUND: The clinical use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) in patients with COVID-19 infection remains controversial. Therefore, we performed a meta-analysis on the effects of ACEI/ARB on disease symptoms and laboratory tests in hypertensive patients infected with COVID-19 virus and those who did not use ACEI/ARB. METHODS: We systematically searched the relevant literatures from Pubmed, Embase, EuropePMC, CNKI, and other databases during the study period of 31 December 2019 (solstice, 15 March 2020), and analyzed the differences in symptoms and laboratory tests between patients with COVID-19 and hypertension who used ACEI/ARB drugs and those who did not. All statistical analyses were performed with REVMAN5.3. RESULTS: We included a total of 1808 patients with hypertension diagnosed with COVID-19 in six studies. Analysis results show that ACEI/ARB drugs group D-dimer is lower (SMD = -0.22, 95%CI: -0.36 to -0.06), and the chances of getting fever is lower (OR = 0.74, 95%CI: 0.55 to 0.98). Meanwhile, laboratory data and symptoms were not statistical difference, but creatinine tends to rise (SMD = 0.22, 95% CI: 0.04 to 0.41). CONCLUSION: We found that the administration of ACEI/ARB drugs had positive effect on reducing D-dimer and the number of people with fever. Meanwhile it had no significant effect on other laboratory tests (creatinine excepted) or symptoms in patients with COVID-19, while special attention was still needed in patients with renal insufficiency.

Hospitalization Due to Asthma Exacerbation: A China Asthma Research Network (CARN) Retrospective Study in 29 Provinces Across Mainland China.

PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients. METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed. RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%). CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.

Amaryllidaceae alkaloids from Crinum latifolium with cytotoxic, antimicrobial, antioxidant, and anti-inflammatory activities.

Four novel and potently bioactive Amaryllidaceae alkaloids, 4,8-dimethoxy-cripowellin C (1), 4,8-dimethoxy-cripowellin D (2), 9-methoxy-cripowellin B (3), and 4-methoxy-8-hydroxy-cripowellin B (4), together with one known alkaloid, cripowellin C (5) were isolated from the 95% EtOH extract of the bulbs of Crinum latifolium. Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR as well as spectroscopy high resolution mass spectrometry. All isolates were in vitro evaluated for their cytotoxic activity against seven lung cancer cell lines, in addition to antimicrobial activity for eight bacteria, scavenging potential using ABTS·+ and DPPH test, and anti-inflammatory activity for Cox-1 and Cox-2 which had not previously been tested for crinane-type alkaloids with the cleavage between C-1 and C-13. Consequently, alkaloids 1-5 exhibited potent cytotoxicity against all of seven tested tumor cell lines with (IC50 < 30 nM). Alkaloids 3 and 4 displayed the significant antimicrobial activity with IC50 values <0.50 mM and antioxidant activity in the ABTS·+ and DPPH test. Additionally, Alkaloids 1-5 exhibited comparable inhibition of Cox-1 (>64%) and Cox-2 (>90%) with positive control.

Correction to: MiR-760 suppresses non-small cell lung cancer proliferation and metastasis by targeting ROS1.

In the original article the authors list and the credit to the corresponding authors were not complete.

MiR-760 suppresses non-small cell lung cancer proliferation and metastasis by targeting ROS1.

MicroRNAs (miRNAs) have been shown to be critical regulators in many types of tumors. The aim of our study was to investigate the role of miR-760 in non-small cell lung cancer (NSCLC). We demonstrated that the expression of miR-760 was downregulated in NSCLC tissues compared with the adjacent normal tissues. We also demonstrated that the expression of miR-760 was downregulated in the NSCLC cell lines. Overexpression of miR-760 suppressed the NSCLC cell proliferation, cell cycle, and migration. Moreover, we identified that ROS1 was a direct target of miR-760 in the NSCLC cell. Elevated expression of miR-760 suppressed ROS1 expression in the NSCLC cell. We also demonstrated that the expression of ROS1 was higher in the NSCLC tissues than in the adjacent lung tissues. MiR-760 expression level was reversely associated with the expression level of ROS1 in the NSCLC tissues. In summary, we showed that miR-760 suppressed the NSCLC cell proliferation, cell cycle, and migration through regulating the ROS1 expression. These data suggested that miR-760 may act as a tumor suppressor gene in the NSCLC partly through regulating ROS1 expression.

LncRNA PICART1 suppressed non-small cell lung cancer cells proliferation and invasion by targeting AKT1 signaling pathway.

LncRNAs play significant roles in various cell biological processes. In the present study, we demonstrated that PICART1 expression was down-regulated in non-small cell lung cancer (NSCLC) tissues. Lower expression level of PICART1 was associated with advanced stage. In addition, PICART1 expression was down-regulated in NSCLC cell lines. Overexpression of PICART1 inhibited NSCLC cell growth and induced cell cycle arrest at G2/M phase. Elevated expression of PICART1 suppressed NSCLC cell colony formation and cell invasion. Ectopic expression of PICART1 promoted the expression of epithelial marker E-cadherin while suppressed the mesenchymal marker expression such as N-cadherin and Snail and Vimentin. Furthermore, PICART1 overexpression suppressed AKT phosphorylation and c-Myc expression while inhibited the p21 expression in NSCLC cell. AKT phosphorylation was involved in PICART1 mediated suppression of cell growth and invasion. These results suggested that overexpression of PICART1 suppressed cell growth and invasion partly through regulating AKT signaling pathway in NSCLC.

Randomized, Multicenter Clinical Study of Tratinterol Hydrochloride Tablets for the Treatment of Bronchial Asthma.

PURPOSE: The aim of this study was to determine the efficacy and safety profile of tratinterol hydrochloride tablets in the treatment of bronchial asthma. METHODS: This multicenter, randomized, double-blind clinical research study was completed at 6 centers in the People's Republic of China from March 2009 to June 2010, and a randomized trial of procaterol hydrochloride tablets produced by Otsuka Pharmaceutical Co Ltd was conducted. The study was approved by the Medical Ethics Committee of the First Hospital of China Medical University. The clinical trial registration number is 2007L04263. FINDINGS: A total of 223 patients were selected for this study, with 112 patients in the treatment group and 111 in the control group. The lung function of the 2 groups after treatment significantly increased in all (P < 0.05); however, there was no significant difference in the changes between the 2 groups (P > 0.05). The occurrence of related adverse events at varying degrees in the control group was higher than in the treatment group. IMPLICATIONS: It is safe and effective to use tratinterol hydrochloride tablets to treat bronchial asthma.

RNA interference targeting enhancer of polycomb1 exerts anti-tumor effects in lung cancer.

BACKGROUND AND AIM: Lung cancer is one of leading malignant tumor worldwide with a high mortality rate. A new therapy target, enhancer of polycomb1 (EPC1) knocked down by short hairpin RNA (shRNA) interference technology, for lung cancer was established to investigate its effects on lung cancer in present study. METHODS: RNA interference technology was applied to down-regulate the expression of EPC1 by specific-shRNA with lentivirus vector in neoplastic human alveolar basal epithelial cells (A549 cells). The survival rate and apoptosis were respectively measured by MTT and Flow Cytometry to evaluate the effects of shRNA EPC1 on cells. Mice xenografts of HCT116 cells with shRNA EPC1 were also established to assess the effect on tumor growth. The levels of AKT and p65 were detected by western blotting. RESULTS: The down-regulation of EPC1 by specific-shRNA with lentivirus vector was significantly decreased the survival rate and apoptosis of A549 cells, and the tumors in EPC1 shRNA transfection group had a significant lower size and weight compared with the ones with control shRNA. The protein expression of p-AKT and p65 was reduced by EPC1 shRNA in both in vitro and in vivo experiments. CONCLUSION: Silencing EPC1 by shRNA technology had the inhibition effects on cell proliferation and tumor growth in lung cancer, which provided a new potential target for treatment of cancers.

Effects of arsenic trioxide (As(2)O(3)) on airway remodeling in a murine model of bronchial asthma.

We investigated the effects of arsenic trioxide (As(2)O(3)) as a possible approach for preventing airway remodeling in a murine model of bronchial asthma induced by ovalbumin (OVA) challenge. Forty Balb/c mice were randomly assigned to 1 of 4 groups (10 mice/group) as follows: controls (challenged with sterile saline inhalation only); OVA-challenged, no treatment; OVA-challenged, treated with dexamethasone; and OVA-challenged, treated with As(2)O(3). All mice were sensitized by intraperitoneal injection with 10% OVA at 2 weeks prior to saline or OVA inhalation challenge. Challenges were for 8 weeks. After OVA challenge, typical asthma-like morphology changes in the bronchi and lung tissues were observed by hematoxylin-eosin staining and pulmonary function indices were reduced compared with controls. Changes in pulmonary indices and lung tissues were similar in the dexamethasone and As(2)O(3) groups and were in between those of the untreated and control groups. Compared with the untreated group, transforming growth factor ß1, vascular endothelial growth factor, and matrix metalloproteinase-9 protein levels and mRNA expression were decreased in lung tissues of the dexamethasone and As(2)O(3) groups. Our results suggest that steroids and As(2)O(3) can inhibit airway remodeling in chronic asthma by mechanisms related to inhibiting the expression of the 3 aforementioned mediators.

[Expressions of and the effect of smoking on vascular endothelial growth factor and induced nitric oxide synthase in lung tissues of chronic obstructive pulmonary disease patients].

OBJECTIVE: To investigate the expressions of and the effect of smoking on vascular endothelial growth factor (VEGF) and induced nitric oxide synthase (iNOS) in lung tissues of chronic obstructive pulmonary disease (COPD) patients. METHODS: The peripheral lung tissues were obtained from 46 patients with lung carcinoma. They were divided into three groups according to their habit of smoking and lung function, 19 smokers with moderate COPD, 12 smokers and 15 nonsmokers with normal lung function. The expression of VEGF and iNOS was detected by immunohistochemistry. RESULTS: Expressions of VEGF and iNOS were increased in lung tissues of smokers without COPD (1.50 +/- 0.39, 1.45 +/- 0.41) compared with nonsmokers without COPD (1.18 +/- 0.33, 1.09 +/- 0.41) (each P < 0.05), and were significantly increased in lung tissues of smokers with moderate COPD (2.19 +/- 0.51, 2.39 +/- 0.45) compared with nonsmokers without COPD (each P < 0.01). The expression of VEGF in lung tissues was significantly correlated with the expression of iNOS (r = 0.78, P < 0.01), but was inversely correlated with FEV(1) (r = -0.67, P < 0.01). CONCLUSIONS: Expressions of VEGF and iNOS were upregulated in lung tissues of smokers and patients with moderate COPD. Overexpression of iNOS and VEGF may participate in the mechanism of airway and vascular remodeling, and airflow limitation in COPD.

Unravelling the hidden heterogeneities of diffuse large B-cell lymphoma based on coupled two-way clustering.

BACKGROUND: It becomes increasingly clear that our current taxonomy of clinical phenotypes is mixed with molecular heterogeneity. Of vital importance for refined clinical practice and improved intervention strategies is to define the hidden molecular distinct diseases using modern large-scale genomic approaches. Microarray omics technology has provided a powerful way to dissect hidden genetic heterogeneity of complex diseases. The aim of this study was thus to develop a bioinformatics approach to seek the transcriptional features leading to the hidden subtyping of a complex clinical phenotype. The basic strategy of the proposed method was to iteratively partition in two ways sample and feature space with super-paramagnetic clustering technique and to seek for hard and robust gene clusters that lead to a natural partition of disease samples and that have the highest functionally conceptual consensus evaluated with Gene Ontology. RESULTS: We applied the proposed method to two publicly available microarray datasets of diffuse large B-cell lymphoma (DLBCL), a notoriously heterogeneous phenotype. A feature subset of 30 genes (38 probes) derived from analysis of the first dataset consisting of 4026 genes and 42 DLBCL samples identified three categories of patients with very different five-year overall survival rates (70.59%, 44.44% and 14.29% respectively; p = 0.0017). Analysis of the second dataset consisting of 7129 genes and 58 DLBCL samples revealed a feature subset of 13 genes (16 probes) that not only replicated the findings of the important DLBCL genes (e.g. JAW1 and BCL7A), but also identified three clinically similar subtypes (with 5-year overall survival rates of 63.13%, 34.92% and 15.38% respectively; p = 0.0009) to those identified in the first dataset. Finally, we built a multivariate Cox proportional-hazards prediction model for each feature subset and defined JAW1 as one of the most significant predictor (p = 0.005 and 0.014; hazard ratios = 0.02 and 0.03, respectively for two datasets) for both DLBCL cohorts under study. CONCLUSION: Our results showed that the proposed algorithm is a promising computational strategy for peeling off the hidden genetic heterogeneity based on transcriptionally profiling disease samples, which may lead to an improved diagnosis and treatment of cancers.

[Coexpression and clinical significance of multi-drug resistance factors in lung cancer].

BACKGROUND: To study the levels of expression, coexpression, and clinical significancer of four multidrug resistance factors in lung cancer. METHODS: The P glycoprotein (P-gp), multidrug-resistance-associated protein (MRP), lung resistance protein (LRP), glutathione S-transferase (GST-π) of 60 lung cancer patients were detected by using immunohistochemical method. RESULTS: The positive rate of the drug resistance factor was 53.3% (32/60), 63.3% (38/60), 70.0% (42/60), and 80.0% (48/60) for P-gp, MRP, LRP, and GST-π respectively. Patients with NSCLC had significantly higher expression of the drug resistance factors than those with SCLC. On the other hand, no relationship was observed between the expression of drug resistance factors and TNM stage and cell differentiation. The coexpression rate was as follows: P-gp+MRP, 41.6% ; P-gp+LRP, 35.0%; MRP+LRP, 53.3%; MRP+GST-π, 50.0%; LRP+GST-π, 58.3%; P-gp+GST-π, 45.0%; P-gp+MRP+LRP+GST-π, 20.0%. Among them, a relationship was detected between P-gp and MRP ( rs =0.756, P < 0.01), between P-gp and LRP ( rs =0.686, P < 0.01), between MRP and LRP ( rs =0.669, P < 0.01), between MRP and GST-π( rs =0.546, P < 0.01), between LRP and GST-π ( rs =0.848, P < 0.01), between P-gp and LRP ( rs =0.689, P < 0.01), and between P-gp and GST-π ( rs = 0.535 , P < 0.01). CONCLUSIONS: The MDR in lung cancer patients is affected by various multidrug resistance factors. The drug resistance factors' expression is related to histology, but not to TNM stage and cell differentiation.

[Arsenic trioxide induced apoptosis and expression of p53 and bcl-2 genes in human small cell lung cancer cells].

OBJECTIVE: To study the arsenic trioxide (As(2)O(3)) induced apoptosis in a human small cell lung cancer cell line (NeI-H cells) and its possible mechanisms. METHODS: Apoptotic cells were detected by the TUNEL method. The expression of p53 and bcl-2 was analyzed with immunohistochemical staining. RESULTS: NeI-H cells showed the sub-G(1) peak after treatment with As(2)O(3) (0.5 micromol/L, 1.0 micromol/L, and 2.0 micromol/L) for 72 hours. The ratio of apoptotic cells increased with the increasing concentrations of the drug and the time of culture. Immunohistochemical staining of NeI-H cells showed increased expression of p53, but decreased expression of bcl-2 with the increasing concentrations of the drug. CONCLUSION: The anti-carcinogenic effect of As(2)O(3) is due to the induction of cell apoptosis. Up-regulation of the p53 gene and down-regulation of the bcl-2 gene may be an underlining mechanism.