[Combinational Overexpression of Foxa3 and Hnf4α Enhance the Proliferation and Prolong the Functional Maintenance of Primary Hepatocytes].

In an in vitro culture system, primary hepatocytes usually display a low proliferation capacity, accompanied with a decrease of viability and a loss of hepatocyte-specific functions. Previous studies have demonstrated that the combination introductions of certain hepatocyte-specific transcription factors are able to convert fibroblasts into functional hepatocyte-like cells. However, such combinational usage of transcription factors in primary hepatocytes culture has not yet sufficiently studied. The forkhead box protein A3 (FoxA3) and hepatocyte nuclear factor 4α (Hnf4α) are liver-enriched transcription factors that play vital roles in the differentiation, and maintenance of hepatocytes. Thus, we simultaneously overexpressed the two genes, Foxa3 and Hnf4α, in rat hepatocytes and observed that the combinational augmentation of these two transcription factors have enhanced the proliferation and stabilized the hepatocyte-specific functions of primary hepatocytes over a long-term culture period.

Duration-response association between occupational exposure and pancreatic cancer risk: meta-analysis.

BACKGROUND: Evidence is lacking on the occupational exposure time window to chemical agents related to pancreatic cancer risk. AIMS: This study performed meta-regression and meta-analysis to examine the dose-response association between occupational exposure duration to chemical agents and pancreatic cancer risk. METHODS: We searched and reviewed studies on exposure duration and pancreatic cancer in five databases (Cochrane Library, EMBASE, PubMed, ScienceDirect and Web of Science) from inception to 16 May 2022. Exposure refers to the years a worker was exposed to any chemical agent, and outcome variables were pancreatic cancer incidence and mortality. RESULTS: We identified 31 studies, including 288 389 participants. In the meta-regression, the positive dose-response association indicated pancreatic cancer risk increased slightly with every additional year of exposure duration (slope = 1.01; 95% confidence interval [CI] 1.00-1.02). Pancreatic cancer risk increased with an exposure duration of 1-10 (relative risk [RR] = 1.04; 95% CI 1.02-1.06), 11-20 (RR = 1.11; 95% CI 1.05-1.16), and 21-30 years (RR = 1.39; 95% CI 1.12-1.73). CONCLUSIONS: Pancreatic cancer risk increased as occupational exposure duration increased, with an exposure time window ranging from 1 to 30 years.

[Influencing factors of poor treatment adherence in uncontrolled asthma patients in China].

Objective: To evaluate the influencing factors of poor treatment adherence in patients with uncontrolled asthma in China. Methods: From April 2017 to April 2018, all asthma patients with uncontrolled asthma and poor compliance in 32 third-class hospitals in 28 provinces and cities of China mainland included in the "National Mobile Asthma Assessment and Management Project" were selected as the subjects. A total of 923 patients were enrolled in the study including 388 males and 535 females. By analyzing the baseline data of the patients at the initial visit when enrolled, the influencing factors of poor adherence of adult asthma was analyzed by inter-group comparison and χ2 test. Results: Poor compliance in asthma was related to the following factors: age from 59 to 68 years old, course of disease more than 20 years, low education level, non-local follow-up, having obstructive ventilation dysfunction and low awareness of the disease[P values were 0.026(t=1.20), 0.004(t=3.97), 0.001(t=4.92), 0.003(t=3.98), 0.032(t=1.22) and 0.001(t=4.99), respectively]. Totally, 243 patients (26.33%) answered all the questions about asthma correctly. Their medication adherence rating scale (MARS-A) scores were significantly higher than those who answered incompletely correctly (36.23±5.85 vs. 31.77±5.74, P=0.001). Conclusions: The adherence of adult asthma patients was affected by individual and external environment factors. Clinicians should choose individualized methods based on the characteristics of patients. Patient education should be strengthened to improve patients' awareness of the disease at the same time.

[Application of exhaled nitric oxide detection in the diagnosis, treatment and management of chronic airway diseases: current status and prospects].

Airway inflammation is the most important pathological basis of chronic airway diseases. The detection and evaluation of airway inflammation is helpful for the diagnosis, treatment and management of airway diseases. Exhaled nitric oxide is the most widely used noninvasive airway inflammation detection technique in recent years, which provides a simple and quick reference for the diagnosis and management of chronic airway diseases, but there are still some controversies and deficiencies. This paper briefly expounds the biological significance of exhaled nitric oxide and detecting technique, summarizes the clinical application and the deficiencies of exhaled nitric oxide detection. In the future, with the further researchers on technology and the accumulation of application experiences, the detection technology of exhaled nitric oxide will play a more significant role in the accurate management of chronic airway diseases.

[The value of home monitoring of exhaled nitric oxide and mobile pulmonary function in the management of asthma].

Objective: To investigate the application value of household dynamic monitoring of exhaled nitric oxide (FeNO) and pulmonary ventilation function in daily management of asthma. Methods: A total of 22 untreated patients with uncontrolled asthma who visited the Respiratory Disease Clinic of China-Japan Friendship Hospital from October 2019 to December 2020 were enrolled. Demographic characteristics, asthma history, comorbidities, asthma control test (ACT), and mini-asthma quality of life questionnaire (mini-AQLQ) were collected through face-to-face surveys. FeNO, pulmonary ventilation function, sputum eosinophil ratio and blood eosinophil count before treatment were collected through medical records. During the treatment of inhaled corticosteroids (ICS), the subjects were monitored at home for 4 weeks by FeNO analyzer and mobile electronic vital capacity at fixed time in the morning and evening. After the treatment, the above indicators were measured again to evaluate the treatment effect. Diurnal and dynamic changes of FeNO and pulmonary ventilation function monitored at home during treatment were analyzed. Results: The age of the subjects was (40±14) years, and 14 cases were female. After 4 weeks of ICS treatment, ACT score, mini-AQLQ score, forced expiratory volume at 1 second (FEV1, L) and FEV1/forced vital capacity (FVC, %) were 23±2, 5.49±1.04, 2.89±0.60 and 72.2±7.8, respectively, higher than before treatment [16±4, 4.06±0.95, 2.47±0.76 and 66.4±14.3, respectively]. FeNO [ppb (part per billion)], sputum eosinophil percentage (%) and blood eosinophil levels (×106/L) [M (Q1, Q3)] were 27 (18, 47), 2.8 (1.0, 14.0) and 255 (188, 280), respectively, lower than before treatment [80 (56, 117), 25.8 (15.0, 59.6) and 380 (283, 658)] (all P values<0.05). The level of FeNO in the morning was higher than that in the evening 2 weeks before routine monitoring (P=0.028), and no statistical difference was found in pulmonary ventilation function between day and night (P>0.05). The curve fitting of daily monitoring of FeNO and lung ventilation function showed that FeNO and lung ventilation function were gradually improved, and the effective time of treatment determined by FeNO was 3.5 (3.0, 5.3) d, which was earlier than all lung ventilation function indicators (all P values<0.05). The maximum action time of FeNO was (14.5±2.2) d, which was earlier than that of FEV1 (20.7±2.8) d (all P values<0.05), but there was no statistically difference between the maximum effect time determined by other lung ventilation function indicators (all P values>0.05). Conclusion: Household dynamic daily monitoring of FeNO and pulmonary ventilation function can be used to assess the response to ICS treatment, with FeNO being the more sensitive indicator.

[Exploring and bioinformatics analysis of differentially expressed genes in bronchial asthma].

Objective: To screen core differentially expressed genes of bronchial asthma and conduct bioinformatics analysis. Methods: Macrophage microarray data GSE22528 from asthma patients were downloaded from gene expression database (GEO). The dataset included transcriptome information from 10 human alveolar lavage fluid samples, and five of them were from allergic asthmatic subjects and five from control subjects. Differential expression genes (DEGs) were screened by R 4.0.4 software. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to select DEGs using DAVID 6.8 database. Protein interaction network (PPI) was constructed from DEGs encoded proteins using STRING online database. Cytoscape software was used to construct core modules and determine core DEGs. Results: Alveolar lavage fluid samples were all collected from Caucasian Canadians, with age range as (20, 37) and (18, 36) years, respectively, including 3 males for each group. In asthmatic patients, 449 genes were up-regulated and 47 down-regulated. GO analysis showed that the up-regulated genes in asthmatic patients were mainly involved in biological processes such as response to folded proteins, and the molecular function was focused on binding of folded proteins and growth factors. Down-regulated genes were mainly involved in biological processes such as histone deacetylation and ubiquitin-mediated protein degradation, and their molecular functions focused on histone deacetylation activity. KEGG pathway enrichment analysis showed that pathways were mainly enriched by up-regulation genes, involving Hippo signaling pathway, hypertrophic cardiomyopathy, estrogen signaling pathway, arrhythmogenic right ventricular cardiomyopathy, basal cell carcinoma, neuro-activated receptor ligand interaction, dilated cardiomyopathy and adhesion and connection signaling pathways. Two core modules were obtained by PPI analysis, and 14 core DEGs were screened out. They were pro-melanin concentrating hormone (PMCH), prepronociceptin (PNOC), Sphingosinol-1-phosphate receptor 2 (S1PR2), Sphingosinol-1-phosphate receptor 5 (S1PR5), CC-type chemokine ligand 21 (CCL21), Kelch-like protein 25 (KLHL25), ubiquitin binding enzyme E2V2 (UBE2V2), F-box protein 17 (FBXO17), taste receptor type 2 member 3 (TAS2R3), somatostatin receptor 2 (SSTR2), metabolic glutamate receptor 2 (GRM2), Lister E3 ubiquitin protein ligase 1 (LTN1), LIM domain specific protein 7 (LMO7) and ring finger protein 19A gene(RNF19A), in which LTN1 and UBE2V2 were down-regulated and the rest were up-regulated. Conclusion: DEGs was found in macrophages of asthmatic and control individuals. PMCH, PNOC, S1PR2, S1PR5 and CCL21 might be the core genes in the pathological process of asthma.

[Human bone marrow mesenchymal stem cells improve steroid resistance of human airway epithelial BEAS-2B cells in vitro].

Objective: To explore the effect of human bone marrow mesenchymal stem cells(MSC) on the steroid resistance of human airway epithelial cells. Methods: Ovalbumin (OVA)/lipopolysaccharide (LPS) were used to construct steroid resistant BEAS-2B cells, which were then co-cultured with MSC. Groups were set as follows: blank group, model group, Glucocorticoid group, MSC group, MSC+Glucocorticoid group (MSC+bud group). The expression of interleukin (IL)-8 in the cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA); the expression of reactive oxygen species (ROS) in the cells was detected by flow cytometry; the expression of glucocorticoid receptor α (GRα) and histone deacetylase 2 (HDAC2) protein in the cell was detected by Western blotting; and the expression of GRα and HDAC2 mRNA was detected by reverse transcription-polymerase chain reaction (RTPCR). Results: The expression level of IL-8 in the MSC group was significantly lower than that in the Glucocorticoid group (31.7±0.7 vs. 49.8±3.6, P<0.01). The expression of ROS in the MSC group was significantly lower than that in the Glucocorticoid group (2754±154 vs.4624±228, P<0.05). The expression level of HDAC2 mRNA in the MSC group was significantly higher than that in the Glucocorticoid group(1.749±0.005 vs. 1.283±0.098, P<0.05). The expression level of GRα mRNA in the MSC group was significantly higher than that in the Glucocorticoid group (1.623±0.079 vs.1.047±0.220, P<0.01). The expression of HDAC2 protein in the MSC group was significantly higher than that in the Glucocorticoid group (1.067±0.100 vs. 0.620±0.083, P<0.01). The expression of GRα protein in the MSC group was significantly higher than that in the Glucocorticoid group (0.834±0.053 vs. 0.579±0.017, P<0.01). ROS was positively correlated with the IL-8 expression (r=0.796, P<0.01) and negatively correlated with the HDAC2 and GRα mRNA expression (r=-0.893 3, P<0.01; r=0.931 4, P<0.01, respectively), as well as the HDAC2 and GRα Protein expression (r=-0.929 5, P<0.01;r=-0.864 3, P<0.01, respectively). Conclusions: Human MSC can improve steroid resistance of airway epithelial cells in an exocrine manner. The mechanism may be related to the down-regulation of ROS and up-regulation of HDAC2, which lead to GRα overexpression. In addition, MSC may improve the steroid resistance by reducing the expression of IL-8.

[Strengthen the management of asthma in the elderly and strive to improve the prognosis of the disease].

Asthma in the elderly is a special type of asthma, with special pathophysiology, clinical characteristics, complications and drug reaction, resulting in its diagnosis and treatment complicated, with higher morbidity and mortality. Combined with the newly published Chinese Expert Consensus on the Diagnosis and Management of Asthma in the Elderly, this paper calls for strengthening the management of asthma in the elderly, promoting relevant research, and perfecting the clinical diagnosis and treatment program suitable for the elderly asthma patients, so as to improve the level of asthma control and improve the prognosis.

[Efficacy and safety of Kangbingdu granules in the treatment of influenza: a randomized, double-blind, double-dummy, positive-drug parallel control multicenter clinical trial].

Objective: To observe the efficacy and safety of Kangbingdu granules (KBD) in the treatment of influenza. Methods: A multicenter, randomized, double-blind, double-dummy, and positive-drug parallel control trial was conducted in 27 Grade ⅢA hospitals in China and the subjects were randomly assigned to the KBD test group or the oseltamivir phosphate capsule control group at a ratio of 1∶1. 200 subjects were planned to be enrolled in each group. The experimental group was given KBD (18g each time, 3 times a day) and oseltamivir phosphate simulator orally, while the control group was given oseltamivir phosphate capsule (75 mg each time, twice a day) and KBD simulator orally for 5 days. The primary efficacy indicators included the remission time of major clinical symptoms and the time of complete defervescence. The secondary efficacy indicators included dosage of acetaminophen, the change of traditional Chinese medicine (TCM) syndrome score and the remission time of other important clinical symptoms. The efficacy of KBD in the test group and Oseltamivir phosphate control group were compared. Adverse events or adverse reactions were observed at the same time to evaluate the safety of KBD Granules. Results: A total of 393 subjects from 27 Grade ⅢA hospitals in China were enrolled. The experimental group included 195 subjects and 191 subjects (97.95%) completed the trial, While the control group included 198 subjects and 195 subjects (98.48%) completed the trial. There was no significant difference in the shedding rate and rejection rate between the two groups (P>0.05). In the Full Analysis Set (FAS), the mean age of the experimental group was (34.9±14.4) years old, with 83 males (42.78%). The mean age of the control group was (33.3±13.5) years old, with 78 males (39.59%). There were no statistically significant differences between the two groups in demographic data, physical examination, viral pathogen detection, total score of TCM syndromes and scores of each symptom at baseline (P>0.05). In the FAS, the remission time M (Q1, Q3) of major clinical symptoms was 3.0 (3.0, 4.0) days in the experimental group and 3.0 (3.0, 4.0) days in the control group, and the difference was not statistically significant (P>0.05). The time M (Q1, Q3) of complete defervescence was 34.0 (20.3, 49.0) hours in the experimental group and 36.5 (19.6, 48.8) hours in the control group, and the difference was not statistically significant (P>0.05). KBD granules had the same effect as Oseltamivir phosphate capsule (P>0.05) in terms of acetaminophen dosage, TCM syndrome effect and disappearance rate of most important clinical symptoms. Meanwhile, the disappearance rate of dizziness and chest distress on day 3 in the KBD granules group was better than that of oseltamivir phosphate capsule (P<0.05). Conclusion: KBD granules have the same efficacy as Oseltamivir Phosphate capsule in the treatment of influenza and the drug safety is good.

[Evaluation of the effectiveness of bronchial thermoplasty in patients with severe asthma in the real world two years after bronchial thermoplasty treatment].

Objective: To assess the effectiveness of bronchial thermoplasty (BT) in "real-world" patients with severe asthma at 2 years post therapy. Method: Outcomes of 70 patients with severe asthma undergoing bronchial thermoplasty from March 2014 to November 2017 in China-Japan Friendship Hospital were retrospectively analyzed two years post therapy. The scores of Asthma Control Test (ACT) and Mini Asthma Quality of Life Questionnaire (mini-AQLQ), the number of severe exacerbations, emergency department visits and hospitalizations for asthma symptoms in the past year, indicators of pulmonary function including forced expiratory volume in one second (FEV(1)), FEV(1) as a percentage of predicted value (FEV(1)%pred) and FEV(1)/forced vital capacity (FEV(1)/FVC), maintenance asthma medications, the cost of asthma drugs and the total annual cost of asthma treatment were evaluated and analyzed before and 2 years after BT therapy, and the subjective assessment about effectiveness of BT were given by the patients. Results: Before and 2 years after BT, the numbers of subjects suffering severe exacerbations in the past year were 70 (100%) and 37 (52.9%), and the numbers of total severe exacerbations were 575 and 162 respectively. The numbers of patients having emergency department visits due to asthma exacerbation were 46 (65.7%) and 9 (12.9%), and the numbers of emergency department visits were 186 and 19 respectively. The numbers of patients hospitalized due to asthma exacerbation were 43 (61.4%) and 16 (22.9%), and the numbers of total hospitalizations were 124 and 24, respectively. The rate of severe exacerbation, emergency department visit and hospitalization were significantly reduced two years after the treatment by 71.9%, 88.9% and 83.3% (all P<0.001). The scores of ACT and mini-AQLQ were significantly increased [22 (21, 24) vs 17 (13, 19), (5.57±0.89) vs (3.83±0.92); both P<0.001]. Two years after BT, 4 patients (5.7%) were weaned off inhaled corticosteroids (ICS) and long-acting ß(2)-agonist (LABA), while 14 patients (37.8%) were weaned off oral corticosteroid (OCS), with daily dose of ICS and OCS significantly decreased (both P<0.05). The proportion of patients treated with montelukast sodium and theophylline was also significantly reduced after BT (40.0% vs 81.4%, 27.1% vs 71.4%; both P<0.001). In addition, the indicator of FEV(1), FEV(1)%pred and FEV(1)/FVC ratio were all greatly improved two years after the treatment [2.27 (1.84, 2.82) vs 2.10 (1.70, 2.61) L, (76.8±19.5)% vs (72.5±19.8)%, (66.3±13.6)% vs (63.8±13.0)%; all P<0.05]. The annual cost for asthma drug and asthma treatment after BT were significantly decreased (P<0.001). Fifty-nine patients (84.3%) subjectively assessed the treatment as effective. Conclusion: The bronchial thermoplasty in "real-world" patients with severe asthma could significantly improve the asthma control, lung function and quality of life, and reduce severe exacerbations, emergency department visits and hospitalizations for asthma symptoms, while the maintenance asthma medications, the cost of asthma drugs and the total annual cost of asthma treatment are significantly decreased.

[Experts consensus for the diagnosis, treatment, and prevention of coronavirus disease 2019 in the elderly].

Coronavirus disease 2019 (COVID-19) can cause great damage to the elderly patients and lead to high mortality. The clinical presentations and auxiliary examinations of the elderly patients with COVID-19 are atypical, due to the physiological ageing deterioration and basal pathological state. The treatment strategy for the elderly patients has its own characteristics and treatment protocol should be considered accordingly. To improve the diagnosis, treatment, and prevention of COVID-19 in the elderly, the Expert Committee of Geriatric Respiratory and Critical Care Medicine, China Society of Geriatrics established the "Expert consensus for the diagnosis, treatment, and prevention of coronavirus disease 2019 in the elderly" . We focused on the clinical characteristics and key points for better treatment and prevention of COVID-19 in the elderly. (1) For diagnosis, atypical clinical presentation of COVID-19 in the elderly should be emphasized, which may be complicated by underlying disease. (2) For treatment, strategy of multiple disciplinary team (mainly the respiratory and critical care medicine) should be adopted and multiple systemic functions should be considered. (3) For prevention, health care model about integrated management of acute and chronic diseases, in and out of hospital should be applied.

[An epidemiological survey on clinical features, self-management and cognitive level of elderly asthmatics in China].

Objective: To investigate the prevalence of asthma among the elderly people in China and to analyze the clinical features, self-management and cognitive level of elderly asthma patients. Methods: According to the multi-stage random cluster sampling methods, a total of 164 215 subjects were visited by a questionnaire in the last epidemiology survey from eight provinces (Beijing, Shanghai, Guangdong, Liaoning, Henan, Shanxi, Jiangsu, Sichuan provinces) and seven regions (north, northeast, southern china, east, south, southwest and northwest) in China from February 2010 to August 2012. 2 034 were diagnosed as asthma. The elderly patients aged ≥65 years were selected from the 2 034 asthma patients. The clinical characteristics, comorbidities, the status of asthma control and self-management and insights of the disease in elderly asthma patients were analyzed. Results: Among the 2 034 asthma patients, 584 (28.7%) were elderly asthmatics aged ≥65 years old and 1 450 (71.3%) were<65 years old. In the elderly asthma group, Early-onset asthma accounted for 439 (75.2%) and 145 (24.8%) were late-onset. The common clinical manifestations of elderly asthma patients were: chest distress 395 (67.6%), wheezing 304 (52.1%), cough 298 (51.0%). Common comorbidities of elderly asthmatics were: chronic obstructive pulmonary disease 144 (24.7%), allergic rhinitis 122(20.9%), gastroesopheal reflux disease (GERD) 114(19.5%), allergic conjunctivitis 86 (14.7%), eczema 82 (14.0%), chronic bronchitis 76 (13.0%). The Asthma Control Test (ACT) scores of elderly asthmatics and non-elderly asthmatics were (18.5±3.2) and (21.7±3.4) respectively. There was a significant difference between the two groups (P=0.042). Of the elderly asthmatics, only 13 (2.2%) patients monitored daily using a peak flow meter. 93 (15.9%) patients aware that asthma was characterized by chronic airway inflammation. 64 (11.0%) asthmatics understood that the treatment goal. Conclusions: The clinical manifestations of elderly asthmatics are atypical, especially paroxysmal wheezing. Asthma in elderly people causes more comorbidities and mortality. The self-management and cognitive level of patients with asthma needs to be improved.

[Effects of bronchial thermoplasty on airway remodeling, asthma control and quality of life in patients with severe asthma].

Objective: To investigate the effects of bronchial thermoplasty (BT) on airway remodeling, asthma control and quality of life in patients with severe asthma. Methods: From January to September 2019, 11 patients with severe asthma were recruited from China Japan Friendship Hospital to receive BT treatment. The treatment was performed over three sessions separated by 3-week intervals. The right lower lobe, the left lower lobe and the bilateral upper lobes were treated respectively. In this study, patients' self-control method was used. The timepoint before the first BT treatment was defined as pre-treatment group, and the timepoint before the third treatment was defined as post-treatment group. Histological staining was used to detect the airway remodeling of the left lower lobe in two groups, including the mass of airway smooth muscle (ASM) and collagen in airway wall, and the thickness of basement membrane. The cell classification of bronchoalveolar lavage fluid (BALF) from the left lower lobe and peripheral blood, total serum IgE, asthma control test (ACT), mini asthma quality of life questionnaire (miniAQLQ) and the forced expiratory volume in 1 second expressed as percent predicted (FEV(1)%pred) were evaluated in the two groups. The correlation was analyzed between airway remodeling and asthma control and quality of life. Results: Effects of BT in post-treatment group, compared with pre-treatment group: the mass of ASM and collagen in airway wall was significantly decreased [(9.8±2.5)% vs (25.8±7.7)%, (12.9±4.0)% vs (17.4±5.6)%] (both P<0.05), while basement membrane thickness was not significantly different (P>0.05); the percentage of eosinophils in BALF and peripheral blood, and total serum IgE were not significantly different (all P>0.05); ACT score and miniAQLQ score were significantly increased [(23.1±1.8) vs (13.8±6.2) points, (5.3±1.3) vs (3.6±1.5) points] (both P<0.05), while FEV(1)% pred was not statistically different (P>0.05). The mass of ASM was negatively correlated with ACT score (r=-0.712), miniAQLQ score (r=-0.557) and FEV(1)%pred (r=-0.477), while the mass of collagen was negatively correlated with ACT score (r=-0.549) and miniAQLQ score (r=-0.639) (all P<0.05). Conclusion: BT treatment could improve airway remodeling, asthma control and quality of life in patients with severe asthma; besides, the reduction of remodeling is related to the improvements of asthma control and quality of life.

[A survey on clinical characteristics and risk factors of severe asthma in China].

Objective: To investigate the clinical characteristics and risk factors of severe bronchial asthma in Chinese people over 14 years old. Methods: According to the multi-stage random cluster sampling methods, a total of 164 215 subjects were visited by a questionnaire in the epidemiology survey from eight provinces (Beijing, Shanghai, Guangdong, Liaoning, Henan, Shanxi, Jiangsu, Sichuan provinces) located in seven regions (north, northeast, east, central China, south, southwest and northwest) of China from February 2010 to August 2012. A total of 2 034 were diagnosed as asthma. The clinical characteristics and related risk factors of patients with severe asthma in China were analyzed. Results: Among all asthma patients, 560 were newly diagnosed, accounting for 27.5% (560/2 034) and the percentage of previously confirmed patients was 72.5% (1 474/2 034). A total of 145 were eligible for severe asthma, accounting for 9.8% (145/1 474) of previously confirmed asthmatics and 7.1% (145/2 034) of all asthmatics. 83.5% (121/145) severe asthmatics had at least one trigger factor. Correlation analysis showed that the risk factors of severe asthma were: smoking (OR=1.543, 95%CI: 1.250-1.814), obesity (OR=2.186, 95%CI: 1.972-2.354), petting (OR=2.135, 95%CI: 1.904-2.283), combined with allergic rhinitis (OR=3.456, 95%CI: 2.721-4.326), gastroesophageal reflux disease (OR=1.842, 95%CI: 1.682-2.140), bronchiectasis (OR=1.665, 95%CI: 1.347-1.912) or chronic obstructive pulmonary disease (OR=1.312, 95%CI: 1.171-1.694). Conclusions: The most common comorbidities in severe asthmatics in China are allergic rhinitis and gastroesophageal reflux disease. The risk factors of severe asthma include obesity, allergic rhinitis, gastroesophageal reflux disease, chronic obstructive pulmonary disease, bronchiectasis, smoking and petting.

[Effect of artesunate on airway responsiveness and airway inflammation in asthmatic mice].

Objective: To observe the effects of artesunate on airway responsiveness and airway inflammation in asthmatic mice. Methods: Thirty female BALB/c mice aged 6-8 weeks were randomly divided into control group, asthma group and artesunate group. In the asthma group and the artesunate group, the mice were sensitized by intraperitoneal injection of 20 µg of ovalbumin (OVA) and 0.2 ml of aluminum hydroxide suspension (2 mg) on day 0 and 14, respectively, and 1% OVA 10 ml dissolved in sterile phosphate (PBS) buffer was aerosolized for 30 min from the 21st to 28th day. The control group was sensitized with 0.2 ml of 2 mg suspension of aluminum hydroxide on day 0 and 14, and aerosolized by 10 ml of sterile PBS from the 21st to 28th day. Before the challenge, the artesunate group was intraperitoneally injected with 0.2 ml of artesunate. Artesunate was replaced with the same amount of normal saline in the control group and the asthma group. The mice were treated after 24 hours of last stimulation. The airway responsiveness of mice was measured by airway intubation and the changes of airway resistance and compliance were observed. Bronchoalveolar lavage fluid (BALF) was classified by cytology, and pathological changes of left lung tissue were observed and scored. Results: The airway resistance of the three groups increased and the lung compliance decreased with the increase of methacholine (Ach) concentration. The airway resistance and lung compliance of the three groups were different under the same concentration (P<0.05). The airway resistance of the artesunate group at Ach 6.25, 12.5, 25, 50, 100 mg/ml was lower than that of the asthma group at the same concentration [(1.01±0.48) vs (1.30±0.22), (1.06±0.44) vs (1.70±0.31), (1.30±0.64) vs (2.66±0.79), (1.82±0.55) vs (3.38±1.35), (2.49±0.85) vs (4.07±1.34) cmH(2)O·s(-1)·ml(-1)(1 cmH(2)O=0.098 kPa); t=3.862, 7.376, 9.113, 7.051, 6.685, all P<0.05]; the degree of lung compliance decrease at the concentration of Ach 3.125, 6.25, 12.5, 25, 50, 100 mg/ml was lower than that of the asthma group at the same concentration [(3.89±0.55)×10(-2) vs (3.07±0.63)×10(-2), (3.61±0.52)×10(-2) vs (3.04±0.58)×10(-2), (3.48±0.38)×10(-2) vs (2.78±0.57)×10(-2), (3.09±0.52)×10(-2) vs (1.73±0.62)×10(-2), (2.32±0.60)×10(-2) vs (1.29±0.54)×10(-2), (1.87±0.59)×10(-2) vs (1.15±0.44)×10(-2) ml/cmH(2)O; t=-6.295, -4.921, -6.533, -11.135, -8.48, -6.319, all P<0.05]. The proportion of eosinophils in artesunate group in BALF was significantly lower than that in asthma group [(16.63±8.58)% vs (40.44±12.94)%; t=4.336, P<0.05]. In the asthma group, the inflammatory cells infiltration of the bronchi and the perivascular area, the bronchial epithelial edema and degeneration can be observed, and the artesunate could reduce the infiltration of inflammatory cells around the bronchus and blood vessels, and the mucus secretion was also reduced in the artesunate group. Conclusion: Artesunate can improve airway hyperresponsiveness and airway inflammation in asthmatic mice and has a certain therapeutic effect on asthma.

[The clinical characteristics and airway inflammatory phenotypes in 35 patients with severe asthma].

Objective: To analyze the clinical features and airway inflammatory phenotypes in patients with severe asthma. Methods: Patients with severe asthma were recruited in this cross-sectional study in our center. History of asthma, blood and sputum samples, and respiratory function were tested and recorded. The phenotypes of inflammation in airway were evaluated. Results: A total of 35 asthmatic patients with the mean age 41.4 years were involved in this study from January 2013 to December 2013. The disease duration were (14.3±13.6) years with mostly male in China-Japan Friendship Hospital. Thirteen patients reported the history of smoking. Twenty-one patients had the complications such as allergic rhinitis, followed by chronic rhinosinusitis of 11 cases, nasal polyp of 7 cases, gastroesophageal reflux disease of 5. The forced expiratory volume in one second/predicted value ratio (FEV(1)%pred) in 29 patients was lower than 80%.Twenty-one participants did not react in bronchial reversibility test. Sixteen patients were administrated with oral cortical steroids (OCS). The average annual cost per patient was 22 thousand RMB. Sixteenrefractory asthmatics were diagnosed as eosinophilic asthma. Conclusions: The clinical features associated with severe asthma include male gender, smoking, persistent airway limitation. Systemic use of corticosteroids is common and treatment costs are high. The eosinophilic asthma is the main inflammatory phenotype in patients with severe asthma.

Upregulated miRNA-1236-3p in osteosarcoma inhibits cell proliferation and induces apoptosis via targeting KLF8.

OBJECTIVE: To elucidate the regulatory effect of miRNA-1236-3p on the cellular behaviors of osteosarcoma (OS) cells, and to provide novel hallmarks and therapeutic targets for the diagnosis, treatment, and prognosis of OS. PATIENTS AND METHODS: Relative level of miRNA-1236-3p in OS tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Regulatory effects of miRNA-1236-3p on the proliferative ability of HOS and U-2OS cells were evaluated by cell counting kit-8 (CCK-8) assay. Through flow cytometry, the potential influences of miRNA-1236-3p on cell cycle progression and apoptosis of OS cells were examined. Subsequently, the dual-luciferase reporter gene assay was conducted to explore the binding of KLF8 (Krüppel-like factor 8) to miRNA-1236-3p. Regulatory effects of KLF8 on cellular behaviors of OC cells were also evaluated. RESULTS: MiRNA-1236-3p was downregulated in OS tissues relative to controls. Meanwhile, miRNA-1236-3p was lowly expressed in OS with worse TNM stage or distant metastasis. The overexpression of miRNA-1236-3p in HOS and U-2OS cells suppressed the proliferative ability, arrested the cell cycle in the G0/G1 phase and induced apoptosis. Conversely, miRNA-1236-3p knockdown obtained the opposite trends. KLF8 was verified to bind to miRNA-1236-3p, and its expression was negatively regulated by miRNA-1236-3p in OS cells. A series of functional experiments displayed the oncogenic role of KLF8 in OS. CONCLUSIONS: MiRNA-1236-3p is downregulated in OS tissues and cell lines. The overexpression of miRNA-1236-3p suppresses the proliferative ability and induces apoptosis of OS cells via downregulating KLF8.

[Distribution of airway inflammation phenotype in patients with bronchial asthma and its correlation with control level].

Objective: To investigate the distribution of airway inflammation phenotypes in patients with bronchial asthma and its correlation with asthma control level. Methods: Patients who met GINA 2017 asthma diagnostic criteria from October 2017 to April 2018 in respiratory outpatient department of China-Japan Friendship Hospital were included. The clinical data of non-acute asthma patients were prospectively collected, including general data, asthma control level, pulmonary function, induced sputum cell classification, serum total IgE, exhaled nitric oxide (FeNO), blood cell classification. The correlation between phenotype distribution of airway inflammation and airway inflammation markers (eosinophils in sputum, FeNO, blood eosinophil, serum IgE) and asthma control was analyzed by correlation analysis. The correlation between sputum eosinophil level and FeNO, blood eosinophil count, serum total IgE, forced expiratory volume in one-second (FEV(1)) predicted (FEV(1)%pred) was analyzed by correlation analysis too. Results: A total of 97 asthmatic patients were enrolled. There were 38 males (39.2%) and 59 females (60.8%), aged (48±14) (range 22 to 80). Control level of asthma:13 cases (13.4%) were controlled, 39 cases(40.2%) were partially controlled and 45 cases (46.4%) were uncontrolled. The phenotypes of airway inflammation were eosinophilic 51 cases (52.6%), neutrophilic 9 cases (9.3%), mixed 35 cases (36.1%) and paucigranulocytic 2 cases (2.1%). There was no significant correlation between airway inflammation phenotype distribution, airway inflammation markers and asthma control level (P>0.05). Sputum eosinophil level was positively correlated with FeNO level in controlled and uncontrolled patients (r=0.420, P=0.008 and r=0.325, P=0.031); sputum eosinophil level was positively correlated with blood eosinophil level in uncontrolled asthma patients (r=0.328, P=0.037). There was no significant correlation between sputum eosinophil level and FEV(1)%pred (P>0.05). Conclusions: Eosinophil type is the dominant type of airway inflammation in asthmatic patients, and there is no significant correlation between airway inflammation and asthma control level. At present, airway inflammation cannot be used to assess asthma control level.