Active terahertz modulator based on optically controlled organometal halide perovskite MAPbI2Br.

In this paper, an active terahertz modulator based on optically controlled organometal halide perovskite MAPbI2Br is proposed. The terahertz wave time-domain transmission of the MAPbI2Br/Al2O3 sample was measured by a terahertz time-domain spectrometer. Experimental results indicate that the MAPbI2Br/Al2O3 sample showed an obvious optical-power-dependent modulation effect on transmission of the terahertz wave; the maximum modulation depth of the modulator can reach 59.99% at 0.3 THz when the external pump optical power is up to 1500 mW.

A Real-Time Zanthoxylum Target Detection Method for an Intelligent Picking Robot under a Complex Background, Based on an Improved YOLOv5s Architecture.

The target recognition algorithm is one of the core technologies of Zanthoxylum pepper-picking robots. However, most existing detection algorithms cannot effectively detect Zanthoxylum fruit covered by branches, leaves and other fruits in natural scenes. To improve the work efficiency and adaptability of the Zanthoxylum-picking robot in natural environments, and to recognize and detect fruits in complex environments under different lighting conditions, this paper presents a Zanthoxylum-picking-robot target detection method based on improved YOLOv5s. Firstly, an improved CBF module based on the CBH module in the backbone is raised to improve the detection accuracy. Secondly, the Specter module based on CBF is presented to replace the bottleneck CSP module, which improves the speed of detection with a lightweight structure. Finally, the Zanthoxylum fruit algorithm is checked by the improved YOLOv5 framework, and the differences in detection between YOLOv3, YOLOv4 and YOLOv5 are analyzed and evaluated. Through these improvements, the recall rate, recognition accuracy and mAP of the YOLOv5s are 4.19%, 28.7% and 14.8% higher than those of the original YOLOv5s, YOLOv3 and YOLOv4 models, respectively. Furthermore, the model is transferred to the computing platform of the robot with the cutting-edge NVIDIA Jetson TX2 device. Several experiments are implemented on the TX2, yielding an average time of inference of 0.072, with an average GPU load in 30 s of 20.11%. This method can provide technical support for pepper-picking robots to detect multiple pepper fruits in real time.

Inhaled corticosteroids and risk of influenza in patients with asthma: a meta-analysis of randomized controlled trials.

BACKGROUND: It was reported that inhaled corticosteroids (ICS) treatment may affect local immunity and microbial community of the airway. However, whether ICS treatment increases the risk of influenza in patients with asthma remains unclear. This meta-analysis aimed to compare the risk of influenza between ICS and non-ICS treatment in patients with asthma. METHODS: PubMed, Embase, Cochrane Library and Clinical Trials.gov were searched from inception until November 2019. Randomized controlled trials (RCTs) were included that compared ICS treatment with non-ICS treatment on the risk of influenza in patients with asthma. Meta-analyses were conducted by the Peto approach and Mantel-Haenszel approach with corresponding 95% CIs. RESULTS: Nine trials involving 6486 patients were included in this meta-analysis. The risk of influenza was not different between ICS treatment and the control groups (Peto OR: 1.01, 95% CI 0.74-1.37, P = 0.95). The results of subgroup analyses based on durations (long-term and short-term treatment), doses (high-, medium- and low-dose treatment) and types (fluticasone and budesonide treatment) of ICS were consistent with the above pooled results. Moreover, subgroup analysis based on patients' age also revealed that use of ICS did not increase the risk of influenza. Results of the two meta-analysis approaches were similar. CONCLUSIONS: Use of ICS does not increase the risk of influenza in patients with asthma. This study adds to safety evidence of ICS as a regular controller treatment for patients with asthma.

Soluble P-selectin levels in patients with obstructive sleep apnea: a systematic review and meta-analysis.

PURPOSE: Obstructive sleep apnea (OSA) patients are at increased risk for cardiovascular disease, stroke, atherosclerosis, hypertension, and venous thromboembolism. Elevated soluble P-selectin (sP-selectin) levels are also associated with increased risk of above diseases. But whether sP-selectin levels in OSA patients are higher than their counterparts remain unclear, since previous studies yielded inconsistent results. Therefore, a meta-analysis is warranted. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible studies. Studies were included if they reported sP-selectin levels of both OSA patients and non-OSA controls. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to determine the effect sizes. RESULTS: Nine eligible studies were finally evaluated. When all the studies were pooled, sP-selectin levels in OSA patients were significantly higher than that in controls (SMD = 0.54, 95% CI 0.29-0.78, I2 = 66%, p < 0.0001). In the subgroup analysis based on BMI matched groups, sP-selectin levels were significantly higher in OSA patients than that in controls (SMD = 0.52, 95% CI 0.27-0.76, I2 = 23%, p < 0.0001). In the subgroup analysis stratified by blood source, either serum sP-selectin levels or plasma sP-selectin levels in OSA patients were higher than that in controls. Moderate-to-severe OSA patients had significant higher sP-selectin levels (SMD = 0.80, 95% CI 0.45-1.15, I2 = 67%, p < 0.00001), while mild OSA patients showed no significant difference with controls. CONCLUSION: The pooled results reveal that OSA patients have higher sP-selectin levels than non-OSA controls. This conclusion remains unaltered in all subgroups other than the subgroup of mild OSA patients. Additional studies are warranted to better identify the role of sP-selectin as a potential biomarker in OSA patients.

Association of tiotropium use and the risk of adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials.

BACKGROUND: Tiotropium have been recommended as first-line maintenance therapy for chronic obstructive pulmonary disease (COPD) to reduce the frequency, duration, and severity of exacerbations and improve quality of life. Recently, it was reported that tiotropium use might link to cardiovascular risk in COPD patients. But it is controversial. We aimed to clarify the associations between tiotropium use and cardiovascular risk in patients with COPD. METHODS: We searched PubMed, EMBASE, Cochrane Library, and Clinical Trials.gov to identify potentially relevant articles. We included randomized controlled trials of any inhaled tiotropium versus non-anticholinergic treatment for COPD, with reporting of cardiovascular events as an adverse event. We conducted meta-analyses by the Peto and Mantel-Haenszel approaches with corresponding 95% CIs. RESULTS: Our work included 20 RCTs with more than 27,699 subjects. Pooled results indicated that tiotropium treatment did not increase the risk of cardiovascular events (Peto OR, 0.97, 95% CI, 0.84-1.12; I2 = 0%), overall mortality (RD, 0.00, 95% CI, - 0.00-0.01; I2 = 68%), and cardiovascular mortality (Peto OR, 1.58, 95% CI, 0.92-2.74; I2 = 0%) compared with controls. Then, subgroup analysis was performed according to the type of controls. The pooled results were consistent with the above (tiotropium vs LABA: Peto OR, 0.98, 95% CI, 0.81-1.19; I2 = 17%) (tiotropium vs placebo: Peto OR, 0.92, 95% CI, 0.75-1.44; I2 = 15%). In addition, there was also no association between cardiovascular risk and duration of tiotropium treatment. CONCLUSIONS: Inhaled tiotropium does not increase the risk of cardiovascular events and cardiovascular mortality in patients with COPD.

Benefits and risks of low molecular weight heparin in patients with acute exacerbation of chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials.

BACKGROUND: Low molecular weight heparin (LMWH) is an anticoagulant that has recently been found benefit in the acute exacerbation stage of chronic obstructive pulmonary disease (COPD). But its efficacy is controversial. The objective of this paper is to compare the harm/benefit of LMWH combined with conventional therapy versus single conventional therapy in the acute exacerbation stage of COPD. METHODS: PubMed, Cochrane Library, EMBASE, CNKI, and Clinical Trials.gov were searched from inception until March 2019. Randomized control trials were included if they reported the use of LMWH for the treatment of COPD. Continuous variable data were reported as mean difference (MD), risk difference (RD), and Peto odds ratio (OR) with corresponding 95% CIs. RESULTS: Twelve RCTs (N = 1086 subjects) were included in the meta-analysis. Pooled results exhibited that LMWH treatment significantly improved the levels of arterial partial pressure of oxygen (PaO2) (MD = 4.58, 95% CI: 1.78-7.39, P = 0.001), forced expiratory volume in 1 s (FEV1) (MD = 0.19, 95% CI: 0.09-0.29, P = 0.0002), and FEV1/forced vital capacity (FVC) (MD = 10.44, 95% CI: 5.40-15.48, P < 0.0001), and significantly reduced the risk of thrombosis (RD, - 0.03; 95% CI, - 0.07 to 0.00; P = 0.05). There was a marginally but nonsignificant improvement in PaCO2 levels vs non-LMWH treatment. Moreover, pooled results exhibited that LMWH may increase the risk of hemorrhage. Subgroup analyses exhibited that LMWH treatment only was associated with a significantly increased risk of minor bleeding but not major hemorrhage. CONCLUSIONS: When compared with single conventional therapy, addition of LMWH to conventional therapy may provide more clinical benefits in the acute exacerbation stage of COPD.

Inhaled corticosteroids and risk of upper respiratory tract infection in patients with asthma: a meta-analysis.

BACKGROUND: Recent studies have suggested a possible association between respiratory infection and the use of inhaled corticosteroids (ICS). We aimed to ascertain the risk of upper respiratory tract infection (URTI) with long-term inhaled corticosteroid use among patients with asthma. METHODS: Through a comprehensive literature search of PubMed, Cochrane Library, EMBASE, and Google Scholar from inception to May 2018, we included randomized controlled trials of any ICS vs. a control treatment for asthma, with reporting of URTI as an adverse event. We conducted meta-analyses by the Peto approaches to generate summary estimates comparing ICS with non-ICS treatment on the risk of URTI. RESULTS: Seventeen trials (15,336 subjects) were included. Compared with non-ICS treatment, ICSs were associated with a significantly increased risk of URTI (Peto OR, 1.24; 95% CI 1.08-1.42; I2 = 5%, p = 0.002). Subgroup analyses were performed for different dose, both high- and low-dose ICSs were associated with a significantly increased risk of URTI (high dose: Peto OR, 1.46; 95% CI 1.05-2.03; I2 = 0%; p = 0.03) (low dose: Peto OR, 1.20; 95% CI 1.04-1.39; I2 = 25%; p = 0.01). Moreover, fluticasone was observed with an increased risk of URTI (Peto OR, 1.18; 95% CI 1.02-1.38; p = 0.03; heterogeneity: I2 = 21%) but not budesonide, low-dose fluticasone treatment was associated with a significantly higher risk of URTI but not high dose. CONCLUSIONS: This study raises safety concerns about the risk of URTI associated with ICS use in patients with asthma, but it should be further investigated.

Long-term use of inhaled corticosteroids and risk of upper respiratory tract infection in chronic obstructive pulmonary disease: a meta-analysis.

Recent studies have suggested that inhaled corticosteroids (ICS) may be associated with higher risks of tuberculosis and pneumonia in patients with COPD. However, it is not known whether ICS increases the risk of upper respiratory tract infection (URTI). Aim of this study was to explore the relationship between ICS and URTI. Through a comprehensive literature search of PubMed, EMBASE, Cochrane Library, and Google Scholar from inception to March 2016, we identified randomized controlled trials of ICS therapy lasting at least 6 months. A meta-analysis by the Peto approach was also conducted to generate summary estimates comparing ICS with non-ICS treatment on the risk of URTI. A total of 14 studies involving 19,777 subjects were considered in the meta-analysis. Compared with non-ICS treatment, ICS were associated with a significantly increased risk of URTI (Peto OR: 1.16; 95% CI: 1.05-1.29; I2 = 9%; p = .004). Subgroup analyzes were performed for different dose, high-dose ICS was associated with a significantly increased risk of URTI (Peto OR: 1.19; 95% CI: 1.05-1.34; I2 = 0%; p = .005), whereas low-dose ICS showed a non-significant increased risk of URTI (Peto OR: 1.10; 95% CI: 0.91-1.33; I2 = 0%; p = .32). Moreover, fluticasone was observed with an increased risk of URTI but not mometasone; high-dose fluticasone treatment was associated with a significantly higher risk of URTI but not low-dose. These results suggested to us that ICS use may increase the risk of URTI in patients with COPD, but it should be further investigated.

Research Advances in Molecular Mechanisms of the Invasion and Metastasis of Lung Cancer.

The basic way of invasion and metastasis of lung cancer is that the tumor cells shed in the extracellular matrix, invade the basement membrane and the surrounding tissue, infiltrate into blood flow, and then survive and transport via the blood flow. After having been extravasated, migrated and arrested in the distant site, they finally form a metastatic lesion. Some basic mechanisms are required in these steps, such as tumor stem cells, diffusion and activity of tumor cells, escaping from apoptosis, angiogenesis and lymphangiogenesis, infiltration into blood flow, circulation and exudation, and distant metastasis proliferation. A better understanding of the mechanisms of the invasion and metastasis of lung cancer will facilitate the prevention and treatment of lung cancer.

New Advances in the Diagnosis and Treatment of Allergic Bronchopulmonary Aspergillosis.

Allergic bronchopulmonary aspergillosis is one of major pulmonary fungal diseases. Although it is not a rare in clinical settings,the misdiagnosis rate is high and the treatment effectiveness remains unstable. This article reviews the recent advances in the diagnosis and treatment of this disease.

Metabolic engineering of Escherichia coli for the production of riboflavin.

BACKGROUND: Riboflavin (vitamin B2), the precursor of the flavin cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), is used commercially as an animal feed supplement and food colorant. E. coli is a robust host for various genetic manipulations and has been employed for efficient production of biofuels, polymers, amino acids, and bulk chemicals. Thus, the aim of this study was to understand the metabolic capacity of E. coli for the riboflavin production by modification of central metabolism, riboflavin biosynthesis pathway and optimization of the fermentation conditions. RESULTS: The basic producer RF01S, in which the riboflavin biosynthesis genes ribABDEC from E. coli were overexpressed under the control of the inducible trc promoter, could accumulate 229.1 mg/L of riboflavin. Further engineering was performed by examining the impact of expression of zwf (encodes glucose 6-phosphate dehydrogenase) and gnd (encodes 6-phosphogluconate dehydrogenase) from Corynebacterium glutamicum and pgl (encodes 6-phosphogluconolactonase) from E. coli on riboflavin production. Deleting pgi (encodes glucose-6-phosphate isomerase) and genes of Entner-Doudoroff (ED) pathway successfully redirected the carbon flux into the oxidative pentose phosphate pathway, and overexpressing the acs (encodes acetyl-CoA synthetase) reduced the acetate accumulation. These modifications increased riboflavin production to 585.2 mg/L. By further modulating the expression of ribF (encodes riboflavin kinase) for reducing the conversion of riboflavin to FMN in RF05S, the final engineering strain RF05S-M40 could produce 1036.1 mg/L riboflavin in LB medium at 37°C. After optimizing the fermentation conditions, strain RF05S-M40 produced 2702.8 mg/L riboflavin in the optimized semi-defined medium, which was a value nearly 12-fold higher than that of RF01S, with a yield of 137.5 mg riboflavin/g glucose. CONCLUSIONS: The engineered strain RF05S-M40 has the highest yield among all reported riboflavin production strains in shake flask culture. This work collectively demonstrates that E. coli has a potential to be a microbial cell factory for riboflavin bioproduction.

Strategies and mechanisms targeting Enterococcus faecalis biofilms associated with endodontic infections: a comprehensive review.

Enterococcus faecalis is one of the main microorganisms that infects root canals, ranking among the most prevalent microorganisms associated with endodontic treatment failure. Given its pervasive presence in persistent endodontic infections, the successful elimination of Enterococcus faecalis is crucial for effective endodontic treatment and retreatment. Furthermore, Enterococcus faecalis can form biofilms - defense structures that microbes use to fight environmental threats. These biofilms confer resistance against host immune system attacks and antibiotic interventions. Consequently, the presence of biofilms poses a significant challenge in the complete eradication of Enterococcus faecalis and its associated disease. In response, numerous scholars have discovered promising outcomes in addressing Enterococcus faecalis biofilms within root canals and undertaken endeavors to explore more efficacious approaches in combating these biofilms. This study provides a comprehensive review of strategies and mechanisms for the removal of Enterococcus faecalis biofilms.

Comparison of 6-min walk test distance vs. estimated maximum oxygen consumption for predicting postoperative pulmonary complications in patients undergoing upper abdominal surgery: a prospective cohort study.

OBJECTIVE: The present study aims to evaluate the predictive ability of estimated maximum oxygen consumption (e[Formula: see text]O2max) and 6-min walk distance (6MWD) for postoperative pulmonary complications (PPCs) in adult surgical patients undergoing major upper abdominal surgery. METHOD: This study was conducted by collecting data prospectively from a single center. The two predictive variables in the study were defined as 6MWD and e[Formula: see text]O2max. Patients scheduled for elective major upper abdominal surgery from March 2019 to May 2021 were included. The 6MWD was measured for all patients before surgery. e[Formula: see text]O2max was calculated using the regression model of Burr, which uses 6MWD, age, gender, weight, and resting heart rate (HR) to predict aerobic fitness. The patients were categorized into PPC and non-PPC group. The sensitivity, specificity, and optimum cutoff values for 6MWD and e[Formula: see text]O2max were calculated to predict PPCs. The area under the receiver operating characteristic curve (AUC) of 6MWD or e[Formula: see text]O2max was constructed and compared using the Z test. The primary outcome measure was the AUC of 6MWD and e[Formula: see text]O2max in predicting PPCs. In addition, the net reclassification index (NRI) was calculated to assess ability of e[Formula: see text]O2max compared with 6MWT in predicting PPCs. RESULTS: A total of 308 patients were included 71/308 developed PPCs. Patients unable to complete the 6-min walk test (6MWT) due to contraindications or restrictions, or those taking beta-blockers, were excluded. The optimum cutoff point for 6MWD in predicting PPCs was 372.5 m with a sensitivity of 63.4% and specificity of 79.3%. The optimum cutoff point for e[Formula: see text]O2max was 30.8 ml/kg/min with a sensitivity of 91.6% and specificity of 79.3%. The AUC for 6MWD in predicting PPCs was 0.758 (95% confidence interval (CI): 0.694-0.822), and the AUC for e[Formula: see text]O2max was 0.912 (95%CI: 0.875-0.949). A significantly increased AUC was observed in e[Formula: see text]O2max compared to 6MWD in predicting PPCs (P < 0.001, Z = 4.713). And compared with 6MWT, the NRI of e[Formula: see text]O2max was 0.272 (95%CI: 0.130, 0.406). CONCLUSION: The results suggested that e[Formula: see text]O2max calculated from the 6MWT is a better predictor of PPCs than 6MWD in patients undergoing upper abdominal surgery and can be used as a tool to screen patients at risk of PPCs.

[Risk factors for acute exacerbation of chronic obstructive pulmonary disease in patients who survived the Wenchuan earthquake].

OBJECTIVE: To investigate the major risk factors for acute exacerbations of chronic obstructive pulmonary disease (COPD) and the role of mental status in patients who survived the Wenchuan Earthquake. METHODS: A questionnaire survey was conducted in 301 COPD patients from the earthquake and non-earthquake areas in Sichuan one month, three months and 12 months after the Wenchuan Earthquake. RESULTS: A total of 269 patients with COPD completed this study, which included 133 patients earthquake area and 136 from non-earthquake area. (1) Patients from earthquake area had significant higher incidence of acute exacerbations of COPD than those from non-earthquake area 3 months (0.57 +/- 0.688 vs. 0.40 +/- 0.601) and 12 months (1.82 +/- 1.375 vs. 1.47 +/- 1.366) after the earthquake. (2) Patients from earthquake area had significant higher Modified British Medical Research Council (mMRC) grades of COPD than those from non-earthquake area 12 months (P < 0.05) after the earthquake. (3) Patients from earthquake area had significant higher prevalence of posttraumatic stress disorder (PTSD) and higher scores of Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) than those from non-earthquake area within one month and 3 months after the earthquake. The difference in PTSD prevalence remained significant 12 months after the earthquake. (4) No significant differences in the prevalence of PTSD and the scores of SAS and SDS were found within one month and 3 months after the earthquake, though significant improvements were observed 12 months after the earthquake for both participants from the earthquake and non-earthquake areas (P < 0.01). (5) Patients from earthquake area lived in worse environment than those from non-earthquake area during the first 3 months after the earthquake (P < 0.001). The living environments of both groups improved significantly 12 months later (P < 0.001). (6) Binary logistic regression showed that older age, worse pulmonary function, psychological disorder, worse living environment were risk factors of acute exacerbation of COPD after the Wenchuan Earthquake. CONCLUSION: The earthquake caused serious psychological trauma in COPD patients. Older age, worse pulmonary function, psychological disorder, worse living environment are risk factors associated with acute exacerbation of COPD. COPD patients should receive psychotherapy and better living arrangement as early as possible after serious disasters.

Diagnostic management of inpatients with a positive D-dimer test: developing a new clinical decision-making rule for pulmonary embolism.

BACKGROUND: A positive D-dimer test has high sensitivity but relatively poor specificity for the diagnosis of pulmonary embolism, causing difficulty for clinicians unskilled in pulmonary embolism diagnosis in determining whether a patient with a positive D-dimer test needs to undergo computed tomographic pulmonary angiography. OBJECTIVES: We sought to develop a new clinical decision-making rule based on a positive D-dimer result to predict the probability of pulmonary embolism and to guide clinicians in making decisions regarding the need for computed tomographic pulmonary angiography. METHODS: We conducted a prospective, multicenter study in three hospitals in China. A total of 3014 inpatients with positive D-dimer results were included. In the derivation group, we built a multivariate logistic regression model and deduced a regression equation from which our score was derived. Finally, we validated the score in an independent cohort. RESULTS: Our score included nine variables (points): chest pain (1.4), chest tightness (2.3), shortness of breath (3.6), hemoptysis (3.4), heart rate ≥100 beats/min (3.6), blood gas analysis (2.9), electrocardiogram presenting a typical S1Q3T3 pattern (4.1), electrocardiogram findings (2.4), and ultrasonic cardiogram findings (3.7). The sensitivities and specificities were 100% and 86.94%, respectively, in the derivation group and 100% and 90.82%, respectively, in the validation group. Additionally, the observed and predicted proportions of patients who underwent computed tomographic pulmonary angiography were 16.82% and 10.76%, respectively, in the derivation group and 18.72% and 11.40%, respectively, in the validation group. CONCLUSIONS: The new score can categorize inpatients with a positive D-dimer test as pulmonary embolism-likely or pulmonary embolism-unlikely, thus reducing unnecessary computed tomographic pulmonary angiography examinations.

[Effect of peroxisome proliferators activated receptor gamma and its ligand on airway mucus hypersecretion in rats].

OBJECTIVE: To explore the effect and the molecular mechanisms of peroxisome proliferators activated receptor gamma (PPAR-gamma) and its ligand on airway mucus hypersecretion. METHODS: Thirty-six Sprague-Dawley rats were randomized into the following groups: (1) Rats in the saline control group (n = 6) received normal saline inhalation; (2) Rats in the rosiglitazone control group (n = 6) received inhaled saline and oral rosiglitazone 8 mg/kg simultaneously; (3) Rats in the acrolein group (n = 6) received inhaled acronine 3.0 mg/L, 6 h/day, for 12 days; (4) Rats in the rosiglitazone intervention group (n = 18) received inhaled acrolein and oral rosiglitazone 2 mg/kg, 4 mg/kg, 8 mg/kg, respectively, as the low dose, the moderate dose and the high dose intervention groups (n = 6 each). The lung tissue sections were stained with HE for histopathological examination. The changes of airway mucus were examined with AB-PAS. Expressions of MUC5AC and PPAR-gamma protein in the bronchial epithelium were detected by immunohistochemistry. The expression of mRNA was measured with real time RT-PCR. The data were analyzed with SPSS 10.0 software. Variables were compared with One-Way ANOVA and q test. The correlations between variables were analyzed using Pearson's correlation coefficient. RESULTS: The levels of airway mucus were (60.2 +/- 9.3)%, (4.9 +/- 1.0)%, (53.3 +/- 8.5)%, (26.5 +/- 7.4)%, (12.5 +/- 3.7)% respectively in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 93.80, P < 0.01). The protein expressions of MUC5AC in the bronchial epithelium examined by immunohistochemistry were 4339 +/- 453, 1636 +/- 282, 3996 +/- 346, 3048 +/- 331, 2376 +/- 343 respectively in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 67.74, P < 0.01). The protein expressions of PPAR-gamma were 1159 +/- 184, 838 +/- 151, 1272 +/- 189, 1568 +/- 282, 1872 +/- 270 respectively in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 21.53, P < 0.01). The mRNA expressions of MUC5AC (the relative copies) were 35.3 +/- 10.0, 2.2 +/- 0.7, 30.5 +/- 10.2, 18.6 +/- 5.3, 10.8 +/- 2.6 respectively in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 29.67, P < 0.01). The mRNA expressions of PPAR-gamma (the relative copies) were 7.8 +/- 1.9, 2.0 +/- 0.6, 9.8 +/- 2.8, 18.6 +/- 5.3, 31.6 +/- 8.9 in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 39.47, P < 0.01). The expression of MUC5AC mRNA was negatively correlated with the protein expression of PPAR-gamma in the acrolein group (r = -0.880, P < 0.01). CONCLUSIONS: PPAR-gamma was involved in airway mucus hypersecretion induced by acrolein. PPAR-gamma and its ligand rosiglitazone inhibited acrolein-induced airway mucus hypersecretion, possibly through downregulation of MUC5AC.

Inhaled corticosteroids and risk of pneumonia in patients with chronic obstructive pulmonary disease: A meta-analysis of randomized controlled trials.

OBJECTIVE: Inhaled corticosteroids (ICS) are generally used to treat patients with chronic obstructive pulmonary disease (COPD) who suffer from repeated exacerbations. Recently, it was reported that ICS treatment increased the risk of pneumonia in COPD patients. But it is controversial.The objective of this paper is to clarify the associations between ICS treatment and the risk of pneumonia in COPD patients. METHODS: PubMed, Cochrane Library, Clinical Trials.gov, and Embase were searched from February 2019 to June 2019. Randomized clinical trials (RCTs) were incorporatedthat compared ICS with non-ICS treatment on the risk of pneumonia in COPD patients. Meta-analyses were conducted by the Peto and Mantel-Haenszel approaches with corresponding 95% CIs. RESULTS: Twenty-five trials (N = 49,982 subjects) were included. Pooled results demonstrated a significantly increased risk of pneumonia with ICS use in COPD patients (RR, 1.59, 95% CI, 1.33-1.90; I2 = 51%). ICS treatment also increased the risk of severe pneumonia (RR, 2.17, 95% CI, 1.47-3.22; I2 = 29%). The results of subgroup analysis based on doses of ICS were consistent with the above. However, subgroup analyses based on types of ICS revealed that fluticasone therapy was associated with an increased risk of pneumonia but not budesonide. In addition, medium- and low-doses of budesonide treatment also did not increase the risk of pneumonia. CONCLUSIONS: Use of ICS increases the risk of pneumonia in patients with COPD. The above is prominent for fluticasone-containing ICSs but not for budesonide-containing ICSs.

[Interventions of enalapril on airway inflammation in rat models induced by acrolein].

OBJECTIVE: To observe the effect of enalapril on airway inflammation in rat models induced by inhaling acrolein and to explore its mechanism. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into 4 groups (n = 6): 1) control group (inhaled 0.9% normal saline for 3 hours, twice every day); 2) enalapril self-control group [intragastrically administrated enalapril 0.5 mg/(kg x d) only]; 3) model group (stimulated with 4 mg/L acrolein for 3 hours, twice every day); 4) enalapril interventive group [inhaled acrolein and intragastrically administrated enalapril 0.5 mg/(kg x d)]. Lung tissue was acquired after the rats were sacrificed on the 21st day. Histopathology examination of lung tissue section stained with HE. Nuclear factor-kappa B and angiotensin II were assayed by immunohistochemistry. Nuclear factor-kappa B were also detected by Western blot. IL-8 and TNF-alpha in BALF were estimated by ELISA. RESULTS: Compared with the control group and the enalapril interventive group, the expression of Ang II and NF-kappa B in the model group was significantly increased (all P < 0.05). Compared with the control group and the enalapril interventive group, the ratio of NF-kappa B nuclear translocation in the model group was remarkably increased. Neutrophils and the level of IL-8 and TNF-alpha in BALF were higher in model group than those in control group. Enalapril can suppress them significantly. CONCLUSION: Acrolein inhalation could upregulate the expression of Ang II and NF-kappa B and also increase nuclear translocation ratio of NF-kappa B. Enalapril can suppress the airway inflammation induced by acrolein.

[Effect of gefinitib on airway mucus hypersecretion induced by acrolein in rats].

OBJECTIVE: To test the effect of gefinitib, an EGFR-TKI, on airway mucus hypersecretion induced by acrolein in rats. METHODS: Thirty six rats were randomly divided into six groups, each with six rats. Group A did not get any intervention; group B had airway mucus hypersecretion induced by inhaled acrelein; Gefitinib intervention was given to group C, D, and E, with a dose of 10 mg/kg,20 mg/kg, and 30 mg/kg of gefitnib administered by gavage, respectively, 30 min before exposure to acrolein inhalation; group F served as a control group, with gefitinib (30 mg/kg) administered by gavage 30 min before exposure to saline inhalation. After three weeks, the rats were sacrificed. The lung tissue sections were obtained. The immunohistochemistry and RT-PCR were performed to detect the MUC5AC and its mRNA expression. The EGFR was detected by immunohistochemical staining. The goblet cells were identified with Alician Blue-periodic Acid Schiff (AB-PAS). RESULTS: Overexpression of MUC5AC, EGFR and increased goblet cells in the lungs of the rats were found in the rats exposed to acrolein inhalations. Gefitinib intervention inhibited the expression of MUC5AC and the increase of goblet cells induced by acrolein. Gefitinib also reduced the expression of EGFR in the lungs. CONCLUSION: Acrolein increases the expression of MUC5AC through activating EGFR, which indicates that EGFR-TKI such as gefitinib can be useful in the treatment of mucus hypersecretion by regulating the signal transduction pathways of EGFR.

The Role of Vascular Endothelial Growth Factor in Small-airway Remodelling in a Rat Model of Chronic Obstructive Pulmonary Disease.

Small-airway remodelling is one of the most remarkable pathological features of chronic obstructive pulmonary disease (COPD), in which angiogenesis plays a critical role that contributes to disease progression. The endothelial cell-specific mitogen vascular endothelial growth factor (VEGF), as well as its receptors, VEGFR1, VEGFR2, are thought to be the major mediators of pathological angiogenesis, and sunitinib exhibits anti-angiogenesis property through VEGF blockage and has been widely used to treat various cancers. In our study, Sprague-Dawley rats were subjected to lipopolysaccharide (LPS) injection and cigarette smoke (CS) inhalation to induce COPD, following sunitinib administration was conducted. Haematoxylin-eosin, Masson staining and immunostaining analysis were used to evaluate the pathological changes; quantitative real-time PCR and enzyme-linked immunosorbent assay were performed to provide more compelling data on the function of VEGF, VEGFR1, VEGFR2 in angiogenesis. Sunitinib treatment was associated with less angiogenesis in small-airway remodelling with a slightly disordered lung architecture, and lower expression level of VEGF, VEGFR1, VEGFR2. Overall, our results indicate that VEGF is a vital important factor that contributes to the small-airway remodelling in a rat model of COPD through promoting angiogenesis, which mainly depend on the specific binding between VEGF and VEGFR1 and can be effectively attenuated by sunitinib.