Mesenchymal Stem Cells on Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The Coronavirus disease-2019 (COVID-19) pandemic continues, and the death toll continues to surge. This meta-analysis aimed to determine the efficacy of mesenchymal stem cells (MSCs) on mortality in patients with COVID-19. METHODS: A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of COVID-19 with MSCs, compared with placebo or blank, were reviewed. Studies were pooled to risk ratios (RRs), with 95% confidence intervals (CIs). RESULTS: Seventeen RCTs (enrolling 1019 participants) met the inclusion criteria. MSCs showed significant effect on 28-day mortality (RR 0.76, 95% CI 0.62 to 0.93; P = 0.008). There was no statistically significant difference in 60-day mortality (RR 0.87, 95% CI 0.70 to 1.09; P = 0.22), and 90-day mortality (RR 0.91, 95% CI 0.72 to 1.15; P = 0.44) between the two groups. CONCLUSIONS: MSCs significantly reduced 28-day mortality in patients with COVID-19. The long-term effect of MSCs on mortality require further study.

Benefits of Macitentan in Patients with Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: This systematic review and meta-analysis aimed to determine the efficacy of macitentan in patients with pulmonary hypertension (PH). Methods: A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of PH with macitentan, compared with placebo or blank, were reviewed. Studies were pooled to weighted mean differences (WMDs) and risk ratios (RRs), with 95% confidence intervals (CIs). Results: Six RCTs (enrolling 1,003 participants) met the inclusion criteria. Macitentan showed significant effects on 6-min walk distance (6MWD) (WMD 12.06 m, 95% CI 2.12 to 21.99 m), pulmonary vascular resistance (PVR) (WMD -186.51 dyn·s/cm-5, 95% CI -232.72 to -140.29 dyn·s/cm-5), mean pulmonary artery pressure (mPAP) (WMD -3.20 mmHg, 95% CI -5.93 to -0.47 mmHg), N-terminal pro-brain natriuretic peptide (NT-proBNP) (WMD -232.47 ng/L, 95% wCI -318.22 to -146.72 ng/L), and cardiac index (WMD 0.39 L/min/m2, 95% CI 0.20 to 0.58 L/min/m2). Conclusion: Macitentan significantly improved 6MWD, PVR, mPAP, NT-proBNP, and cardiac index in patients with PH. Macitentan should be further validated in patients with PH.

Long-term safety of macitentan in patients with pulmonary hypertension: A meta-analysis of randomised controlled trials.

BACKGROUND: Macitentan has demonstrated its effectiveness in patients with pulmonary hypertension (PH), but its safety, especially for long-term use, needs to be further explored. This systematic review and meta-analysis aimed to determine the safety of long-term use of macitentan in patients with PH. METHODS: A systematic search was made of PubMed, Embase, Cochrane Library and clinicaltrials.gov, without language restrictions. Randomised controlled trials (RCTs) on treatment of PH with macitentan, compared with placebo, were reviewed. Estimated effects of included studies were pooled as risk ratios (RRs), with 95% confidence intervals (CIs). RESULTS: Six RCTs (enrolling 1003 participants) met the inclusion criteria. Anaemia (RR 3.86, 95% CI 2.05-7.30), headache (RR 1.52, 95% CI 1.02-2.26) and bronchitis (RR 2.24, 95% CI 1.30-3.87) were more frequent in the macitentan groups. There was no statistically significant difference in the proportion of patients with at least one adverse event (AE) or serious adverse event (SAE), AEs leading to discontinuation of study treatment, all-cause death, right ventricular failure (RVF) and peripheral oedema between the two groups. CONCLUSIONS: The long-term use of macitentan is safe for patients with PH, although with a higher risk of anaemia, headache and bronchitis.

Statins in hospitalized COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis aimed to determine the efficacy of statins in hospitalized patients with coronavirus disease-2019 (COVID-19). A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of COVID-19 with statins, compared with placebo or standard of care, were reviewed. Seven RCTs (enrolling 1830 participants) met the inclusion criteria. There was no statistically significant difference in all-cause mortality (risk ratio [RR]: 0.92, 95% confidence interval [CI]: 0.75-1.13), length of hospital stay (weighted mean difference: -0.21 days, 95% CI: -1.01 to 0.59 days), intensive care unit (ICU) admission (RR: 1.84, 95% CI: 0.45-7.55), and mechanical ventilation (RR: 1.09, 95% CI: 0.70-1.70) between the two groups. Statins failed to reduce mortality, ICU admission, mechanical ventilation, and length of stay in hospitalized patients with COVID-19. Statins probably should not be used routinely in COVID-19 patients.

LXA4 inhibits TGF-ß1-induced airway smooth muscle cells proliferation and migration by suppressing the Smad/YAP pathway.

The aims of the present study were to examine the signaling mechanisms for transforming growth factor-ß1 (TGF-ß1)-induced rat airway smooth muscle cells (ASMCs) proliferation and migration and to determine the effect of lipoxin A4 (LXA4) on TGF-ß1-induced rat ASMCs proliferation and migration and its underlying mechanisms. TGF-ß1 upregulated transcriptional coactivator Yes-associated protein (YAP) expression by activating Smad2/3 and then upregulated cyclin D1, leading to rat ASMCs proliferation and migration. This effect was reversed after treatment with the TGF-ß1 receptor inhibitor SB431542. YAP is a critical mediator of TGF-ß1-induced ASMCs proliferation and migration. Knockdown of YAP disrupted the pro-airway remodeling function of TGF-ß1. Preincubation of rat ASMCs with LXA4 blocked TGF-ß1-induced activation of Smad2/3 and changed its downstream targets, YAP and cyclin D1, resulting in the inhibition of rat ASMCs proliferation and migration. Our study suggests that LXA4 suppresses Smad/YAP signaling to inhibit rat ASMCs proliferation and migration and therefore has potential value in the prevention and treatment of asthma by negatively modulating airway remodeling.

Anakinra was not associated with lower mortality in hospitalised COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

The Coronavirus disease-2019 (COVID-19) pandemic continues, and the death toll continues to surge. This meta-analysis aimed to determine the efficacy of anakinra on mortality in patients with COVID-19. A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials on treatment of COVID-19 with anakinra, compared with placebo or blank, were reviewed. Studies were pooled to risk ratios (RRs), with 95% confidence intervals (CIs). Five Randomized controlled trials (enrolling 1859 participants) met the inclusion criteria. There was no statistically significant difference in 14-day mortality (RR 0.78, 95% CI 0.43-1.39; P = 0.40), 28-day mortality (RR 1.06, 95% CI 0.89-1.26; P = 0.51), and 90-day mortality (RR 1.01, 95% CI 0.73-1.39; P = 0.97) between the two groups. Sensitivity analyses further confirmed these results. Anakinra was not associated with reduced mortality in hospitalised patients with COVID-19. Anakinra probably should not be used routinely in COVID-19 patients.

Resveratrol Ameliorates LPS-induced Acute Lung Injury Mouse Model via Induction of Tristetraprolin.

AIM: In this study, we aimed to investigate whether resveratrol has anti-inflammatory effects on LPS-induced ALI via TTP enhancement. BACKGROUND: Acute lung injury (ALI) is a syndrome of diffuse infammatory lung injury with increased pulmonary edema and the rapid onset of hypoxemic respiratory failure. Resveratrol is a stilbenoid, a form of natural phenol, and a phytoalexin produced by a variety of plants in reaction to injury or when they are attacked by pathogens like bacteria or fungi. Resveratrol exhibits a potent antiinflammatory effect in LPS-induced ALI, while the underlying mechanisms remain elusive. OBJECTIVE: Tristetraprolin (TTP) is a RNA binding protein that is an important endogenous inhibitor of inflammation. The objective of the present study is to investigate whether resveratrol has anti- inflammatory effects on LPS-induced ALI via TTP enhancement. METHODS: Forty male C57BL/6 mice were randomly assigned to four groups and intratracheally instilled with 5 mg/kg lipopolysaccharide (LPS) to induce ALI. RESULTS: LPS-induced lung pathological damage, lung edema, and neutrophil infiltration were reduced by resveratrol pretreatment. Furthermore, resveratrol inhibited the LPS-induced rise in TNF- α, IL-1ß and IL-6 levels in BAL fluids. In the LPS-challenged mouse's lung tissue, resveratrol clearly boosted sirtuin1 (SIRT1) and TTP protein expression, while also increasing TTP expression while reducing proinflammatory cytokines. EX527, on the other hand, reversed resveratrol's effects. CONCLUSION: According to our findings, resveratrol attenuated pulmonary inflammation and lung injury in mice with LPS­induced ALI， at least partly correlated with promoting the activation of SIRT1/TTP signaling pathway, highlighting these pathways as potential targets for intervention in LPS -induced lung injury.

Benefits of ozone on mortality in patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: The Coronavirus disease-2019 (COVID-19) pandemic continues, and the death toll continues to surge. Ozone therapy has long been used in the treatment of a variety of infectious diseases, probably through its antioxidant properties and the supply of oxygen to hypoxic tissues. This systematic review and meta-analysis aimed to determine the efficacy of ozone on mortality in patients with COVID-19. METHODS: A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Prospective controlled trials on treatment of COVID-19 with ozone, compared with placebo or blank, were reviewed. Studies were pooled to risk ratios (RRs) and weighted mean differences (WMDs), with 95% confidence intervals (CIs). RESULTS: Eight trials (enrolling 371 participants) met the inclusion criteria. Ozone therapy showed significant effects on mortality (RR 0.38, 95% CI 0.17-0.85; P = 0.02), length of hospital stay (WMD -1.63 days, 95% CI -3.05 to -0.22 days; P = 0.02), and polymerase chain reaction (PCR) positivity (RR 0.07, 95% CI 0.01-0.34; P = 0.001). CONCLUSIONS: Ozone therapy significantly reduced mortality, PCR positivity, and length of stay in hospitalized patients with COVID-19. Ozone therapy should be considered for COVID-19 patients.

Selexipag in Patients With Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Despite the availability of treatments for all subgroups of pulmonary hypertension (PH), the prognosis for PH remains poor. This systematic review and meta-analysis aimed to determine the efficacy and safety of selexipag in patients with PH. A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of PH with selexipag, compared with placebo or blank, were reviewed. Studies were pooled to weighted mean differences (WMDs) and risk ratios (RRs), with 95% confidence intervals (CIs). Selexipag was safe and significantly improved hospitalization for worsening of PH, WHO FC, mPAP, NT-proBNP, and cardiac index in patients with PH. Selexipag should be considered in patients with pulmonary arterial hypertension or chronic thromboembolic PH.

Association between constipation and the development of asthma: a meta-analysis.

BACKGROUND: Constipation has been hypothesized to be associated with the increased risk of wheezing or asthma. However, the relation remains a subject of debate. We conducted this meta-analysis to assess whether constipation influences the risk of wheezing/asthma. METHODS: PubMed, Embase, and Web of Science were systematically searched for studies published between 1955 and January 2022. Two reviewers independently extracted data and assessed the quality of each study. Results were pooled using fixed-effects models or random-effects models as appropriate. RESULTS: In total, 3 original articles with 178,661 participants, which met the criteria, were included in this meta-analysis. Constipation was associated with an increased risk of wheezing/asthma in later life (RR = 2.02, 95% CI = 1.24-3.29, P < 0.01). CONCLUSIONS: The meta-analysis suggests an association between constipation and the subsequent development of wheezing/asthma. Well-designed and highly standardized prospective studies that adequately address concerns for potential confounding factors are required to validate the risk identified in our current meta-analysis.

Benefits of continuous positive airway pressure on blood pressure in patients with hypertension and obstructive sleep apnea: a meta-analysis.

This meta-analysis was performed to determine the effects of continuous positive airway pressure (CPAP) on blood pressure (BP) in patients with systemic hypertension and obstructive sleep apnea (OSA). A systematic search was conducted using PubMed, Embase, Web of Science, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials on the treatment of hypertension and OSA with CPAP, compared with sham CPAP or no CPAP, were reviewed. Studies were pooled to obtain weighted mean differences (WMDs) with 95% confidence intervals (CIs). Nineteen trials (enrolling 1904 participants) met the inclusion criteria. CPAP had significant effects on 24-h systolic blood pressure (SBP) (WMD -5.01 mmHg, 95% CI -6.94 to -3.08; P < 0.00001), 24-h diastolic blood pressure (DBP) (WMD -3.30 mmHg, 95% CI -4.32 to -2.28; P < 0.00001), daytime SBP (WMD -4.34 mmHg, 95% CI -6.27 to -2.40; P < 0.0001), daytime DBP (WMD -2.97 mmHg, 95% CI -3.99 to -1.95; P < 0.00001), nighttime SBP (WMD -3.55 mmHg, 95% CI -5.08 to -2.03; P < 0.00001), nighttime DBP (WMD -2.33 mmHg, 95% CI -3.27 to -1.40; P < 0.00001), office SBP (WMD -3.67 mmHg, 95% CI -5.76 to -1.58; P = 0.0006), office DBP (WMD -2.61 mmHg, 95% CI -4.25 to -0.97; P = 0.002), and heart rate (WMD -2.79 beats/min, 95% CI -4.88 to -0.71; P = 0.009). CPAP treatment was associated with BP reduction in patients with systemic hypertension and OSA, except when the follow-up period was shorter than 3 months.

Benefits of plasma exchange on mortality in patients with COVID-19: a systematic review and meta-analysis.

OBJECTIVE: The COVID-19 pandemic continues, and the death toll continues to surge. This systematic review and meta-analysis aimed to determine the efficacy of therapeutic plasma exchange (TPE) on mortality in patients with COVID-19. METHODS: A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Controlled clinical trials on treatment of COVID-19 with TPE, compared with standard of care, were reviewed. Studies were pooled according to risk ratios (RRs) and weighted mean differences, with 95% confidence intervals (CIs). RESULTS: A total of six trials (enrolling 343 participants) met the inclusion criteria. Therapeutic plasma exchange showed significant effect on mortality (RR 0.41, 95% CI 0.24 to 0.69; P = 0.0008). CONCLUSION: TPE significantly reduced mortality in hospitalized patients with moderate-to-critical COVID-19. Plasma exchange therapy should be considered for patients with COVID-19.

Benefits of LAMA in patients with asthma-COPD overlap: A systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis to determine the efficacy of long-acting muscarinic antagonist (LAMA) in patients with asthma-COPD overlap (ACO) was conducted. METHODS: A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of ACO with LAMA, compared with placebo or blank, were reviewed. RESULTS: Six RCTs (enrolling 1151 participants) met the inclusion criteria. LAMA showed significant effects on forced expiratory volume in 1 s (FEV1) (WMD 98.31 mL, 95% CI 94.32 to 102.30 mL), forced vital capacity (FVC) (WMD 128.00 mL, 95% CI 121.89 to 134.12 mL), peak expiratory flow (PEF) (WMD 20.60 L/min, 95% CI 19.90 to 21.29 L/min), and rescue medicine use (WMD -0.67 puffs/day, 95% CI -1.11 to -0.23 puffs/day). CONCLUSIONS: The addition of LAMA significantly improved lung function and rescue medicine use in patients with asthma-COPD overlap.

The safety of long-term use of inhaled corticosteroids in patients with asthma: A systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis was performed to determine the safety of long-term use of ICS in patients with asthma. METHODS: A systematic search was made of PubMed, Embase, Web of Science, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of asthma with ICS, compared with non-ICS treatment (placebo or other active drugs), were reviewed. RESULTS: Eighty-six RCTs (enrolling 51,538 participants) met the inclusion criteria. Oral or oropharyngeal candidiasis (RR 2.58, 95% CI 2.00 to 3.33), and dysphonia/hoarseness (RR 1.56, 95% CI 1.31 to 1.85) were less frequent in the control group. There was no statistically significant difference in the risk of upper respiratory tract infection, lower respiratory tract infection, influenza, decline in bone mineral density, and fractures between the two groups. CONCLUSION: In addition to the mild local adverse events, the long-term use of ICS was safe in patients with asthma.

The Association Between the Baseline and the Change in Neutrophil-to-Lymphocyte Ratio and Short-Term Mortality in Patients With Acute Respiratory Distress Syndrome.

Background: Two previous studies have shown that increased neutrophil to lymphocyte ratio (NLR) is associated with short-term prognosis in patients with acute respiratory distress syndrome (ARDS), but it is usually assessed as a single threshold value at baseline. We investigated the relationship between the baseline and the early change in NLR and 30-day mortality in patients with ARDS to evaluate the prognostic value of NLR baseline and NLR changes during the first 7 days after ICU admission. Methods: This is a retrospective cohort study, with all ARDS patients diagnosed according to the Berlin definition from the Medical Information Mart for Intensive Care III (MIMIC-III) database. We calculated the NLR by dividing the neutrophil count by the lymphocyte count. The multivariable logistic regression analysis was used to investigate the relationship between the baseline NLR and short-term mortality. Then the generalized additive mixed model was used to compare trends in NLR over time among survivors and non-survivors after adjusting for potential confounders. Results: A total of 1164 patients were enrolled in our study. Multivariable logistic regression analysis showed that after adjusting for confounders, elevated baseline NLR was a significant risk factor predicting 30-day mortality (OR 1.02, 95%CI 1.01, 1.03, P = 0.0046) and hospital mortality (OR 1.02, 95%CI 1.01, 1.03, P = 0.0003). The result of the generalized additive mixed model showed that the NLR decreased in the survival group and increased in the non-survival group gradually within 7 days after ICU admission. The difference between the two groups showed a trend of increase gradually and the difference increased by an average of 0.67 daily after adjusting for confounders. Conclusions: We confirmed that there was a positive correlation between baseline NLR and short-term mortality, and we found significant differences in NLR changes over time between the non-survival group and the survival group. The early increase in NLR was associated with short-term mortality in ARDS patients.

Association between early bronchiolitis and the development of childhood asthma: a meta-analysis.

OBJECTIVE: Early life bronchiolitis has been hypothesised to be associated with the subsequent risk of persistent wheezing or asthma. However, the link remains controversial. The objective of our study was to evaluate the association between bronchiolitis before 2 years of age and the late-onset wheezing/asthma. DESIGN: Systematic review and meta-analysis. METHODS: PubMed, Embase and Web of Science databases were systematically searched for studies published between 1955 and January 2020. Meanwhile, we also checked through the reference lists of relevant articles to see whether these references included reports of other studies that might be eligible for the review. Cohort and case-control studies assessing the association between early-life bronchiolitis and late-onset wheezing/asthma were included in this meta-analysis. Data were extracted by two independent reviewers. Results were pooled using a random-effects model or fixed-effects model according to the heterogeneity among studies. RESULTS: 32 original articles with 292 844 participants, which met the criteria, were included in this meta-analysis. Bronchiolitis before 2 years of age was associated with an increased risk of subsequent wheezing/asthma (relative risk=2.46, 95% CI 2.14 to 2.82, p<0.001). After categorising studies into different groups based on age at the end of follow-up, geographical region and study quality, the association still remained significant. CONCLUSIONS: The meta-analysis indicates an association between bronchiolitis before 2 years of age and the wheezing/asthma in later life. Well-designed and highly standardised prospective studies that better address bias due to potential confounding factors are needed to validate the risk identified in our meta-analysis.PROSPERO registration numberCRD42018089453.

Benefits of continuous positive airway pressure on glycaemic control and insulin resistance in patients with type 2 diabetes and obstructive sleep apnoea: A meta-analysis.

AIM: To conduct a meta-analysis to determine the effects of continuous positive airway pressure (CPAP) treatment on glycaemic control and insulin resistance in patients with type 2 diabetes and obstructive sleep apnoea (OSA). METHODS: A systematic search was made of the MEDLINE, SCOPUS, ISI Web of Science, Cochrane databases, and clinicaltrials.gov, without language restrictions. Randomized controlled trials on treatment of type 2 diabetes and OSA with CPAP, compared with sham CPAP or no CPAP, were reviewed. Studies were pooled to obtain standardized mean differences (SMDs), with 95% confidence intervals (CIs). RESULTS: Seven trials (enrolling 691 participants) met the inclusion criteria. CPAP showed significant effects on glycated haemoglobin (HbA1c; SMD -0.32, 95% CI -0.60 to -0.03; P = 0.029), fasting glucose (SMD -0.39, 95% CI -0.76 to -0.02; P = 0.040), homeostatic model assessment of insulin resistance (HOMA-IR; SMD -1.05, 95% CI -1.91 to -0.19; P = 0.016), systolic blood pressure (SMD -1.18, 95% CI -2.29 to -0.07 mm Hg; P = 0.037), and diastolic blood pressure (SMD -1.29, 95% CI -2.48 to -0.09; P = 0.035). CONCLUSIONS: Continuous positive airway pressure treatment significantly improved glycaemic control and insulin resistance, as shown by the decreased HbA1c levels, fasting glucose levels and HOMA-IR values in patients with type 2 diabetes and OSA.

Benefits of statins in chronic obstructive pulmonary disease patients with pulmonary hypertension: A meta-analysis.

PURPOSE: This meta-analysis was performed to evaluate the efficacy of statins in chronic obstructive pulmonary disease (COPD) patients with pulmonary hypertension (PH). METHODS: A systematic search was made of MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases. Randomized clinical trials on treatment of COPD-PH with the statins, compared with placebo, were reviewed. Studies were pooled to weighted mean differences (WMD), with 95% confidence interval (CI). RESULTS: Five trials (enrolling 270 participants) met the inclusion criteria. Compared with placebo, the statins presented significant effects on systolic pulmonary artery pressure (WMD -4.52 mmHg; 95% CI -6.32 to -2.72 mmHg) and 6-min walk distance (6MWD) (WMD 32.46 m; 95% CI 13.63-51.29 m). CONCLUSIONS: Statins therapy significantly improves PH and 6MWD in COPD patients with PH.

PPARγ Agonist PGZ Attenuates OVA-Induced Airway Inflammation and Airway Remodeling via RGS4 Signaling in Mouse Model.

Peroxisome proliferator-activated receptor-γ (PPARγ) agonist pioglitazone (PGZ) exhibits potential protective effects in asthma. Recently, regulator of G protein 4 (RGS4) has been reported to be associated with immunological and inflammatory responses. However, no evidence has shown the influence of PPARγ on RGS4 expression in airway disorders. In this study, BALB/c mice received ovalbumin (OVA) sensitization followed by OVA intranasal challenge for 90 days to establish a chronic asthma mouse model. Accompanied with OVA challenge, the mice received administration of PPARγ agonist PGZ (10 mg/kg) intragastrically or RGS4 inhibitor CCG 63802 (0.5 mg/kg) intratracheally. Invasive pulmonary function tests were performed 24 h after last challenge. Serum, bronchoalveolar lavage fluid (BALF), and lung tissues were collected for further analyses after the mice were sacrificed. We found that PPARγ agonist PGZ administration significantly attenuated the pathophysiological features of OVA-induced asthma and increased the expression of RGS4. In addition, the attenuating effect of PGZ on airway inflammation, hyperresponsiveness (AHR), and remodeling was partially abrogated by administration of RGS4 inhibitor CCG 63802. We also found that the downregulation of RGS4 by CCG 63802 also significantly increased inflammatory cell accumulation and AHR, and increased levels of IL-4, IL-13, eotaxin, IFN-γ, and IL-17A in BALF, and total and OV-specific IgE in serum. Furthermore, the inhibitory effects of PGZ on the activations of ERK and Akt/mTOR signaling, and MMPs were apparently reversed by CCG 63802 administration. In conclusion, the protective effect of PGZ on OVA-induced airway inflammation and remodeling might be partly regulated by RGS4 expression through ERK and Akt/mTOR signaling.

A new method for wind speed forecasting based on copula theory.

How to determine representative wind speed is crucial in wind resource assessment. Accurate wind resource assessments are important to wind farms development. Linear regressions are usually used to obtain the representative wind speed. However, terrain flexibility of wind farm and long distance between wind speed sites often lead to low correlation. In this study, copula method is used to determine the representative year's wind speed in wind farm by interpreting the interaction of the local wind farm and the meteorological station. The result shows that the method proposed here can not only determine the relationship between the local anemometric tower and nearby meteorological station through Kendall's tau, but also determine the joint distribution without assuming the variables to be independent. Moreover, the representative wind data can be obtained by the conditional distribution much more reasonably. We hope this study could provide scientific reference for accurate wind resource assessments.