Autocrine TGF-alpha is associated with Benzo(a)pyrene-induced mucus production and MUC5AC expression during allergic asthma.

OBJECTS: Benzo(a)pyrene (BaP), an environmental pollutant, is present in high concentrations in urban smog and cigarette smoke and has been reported to promote high mucin 5AC (MUC5AC) expression. Epithelium-derived inflammatory cytokines are considered an important modulator of mucus oversecretion and MUC5AC overexpression. Here, we investigated whether the effect of BaP on MUC5AC overexpression was associated with cytokine autocrine activity in vivo and in vitro. METHODS: In vivo, BALB/c mice were treated with ovalbumin (OVA) in the presence or absence of BaP. Allergy-induced mucus production was assessed by Alcian Blue Periodic acid Schiff (AB-PAS) staining. The human airway epithelial cell line NCI-H292 was used in vitro. MUC5AC and transforming growth factor (TGF)-α mRNA levels were assessed with real-time quantitative PCR. The concentration of cytokines was measured by ELISA. The MUC5AC, p-ERK, ERK, p-EGFR and EGFR proteins were detected by Western blotting in cells or by immunohistochemistry in mouse lungs. Small-interfering RNAs were used for gene silencing. RESULTS: TGF-α was overproduced in the supernatant of NCI-H292 cells treated with BaP. Knockdown of TGF-α expression inhibited the BaP-induced increase in MUC5AC expression and subsequent activation of the EGFR-ERK signalling pathway. Knocking down aryl hydrocarbon receptor (AhR) expression or treatment with an ROS inhibitor (N-acetyl-L-cysteine) could relieve the TGF-α secretion induced by BaP in epithelial cells. In an animal study, coexposure to BaP with OVA increased mucus production, MUC5AC expression and ROS-EGFR-ERK activation in the lung as well as TGF-α levels in bronchoalveolar lavage fluid (BALF). Furthermore, the concentration of TGF-α in BALF was correlated with MUC5AC mRNA levels. Additionally, TGF-α expression was found to be positively correlated with MUC5AC expression in the airway epithelial cells of smokers. Compared with non-smoker asthma patients, TGF-α serum levels were also elevated in smoker asthma patients. CONCLUSION: Autocrine TGF-α was associated with BaP-induced MUC5AC expression in vitro and in vivo. BaP induced TGF-α secretion by activating AhR and producing ROS, which led to activation of the EGFR-ERK pathway.

High flow nasal cannula versus conventional oxygen therapy in postoperative patients at high risk for pulmonary complications: A systematic review and meta-analysis.

BACKGROUND: The effects of high flow nasal cannula (HFNC) on postoperative patients at high risk for pulmonary complications(PC) are controversial. We aimed to further determine the effectiveness of HFNC in postoperative patients at high risk for PC by comparison to conventional oxygen therapy (COT). METHODS: We performed a comprehensive search that compared HFNC with COT in postoperative patients at high risk for PC. The main outcomes were length of hospital stay (hospital LOS) and respiratory complications. RESULTS: Six trials with a total of 733 patients were pooled in our final studies. Except for Hospital LOS (I2  = 53%, χ2  = 8.51, P = .07) and rate of intubation or non-invasive ventilation (NIV) for respiratory failure (RF) (I2  = 49%, χ2  = 1.97, P = .16) between HFNC and COT, no significant heterogeneity was found in outcome measures. Compared with COT, HFNC was associated with a lower rate of intubation or NIV for RF (RR 0.23, 95% CI 0.08-0.66, P = .006) and rate of hypercapnia (RR 0.37, 95% CI 0.20-0.68, P = .002). As for the Hospital LOS, ICU LOS, rate of requirement of O2 after discontinuous and hypoxemia, HFNC did not show any advantage over COT. Trial Sequential Analysis (TSA) for Hospital LOS showed that monitoring boundaries were finally not surpassed and required information size (RIS) was not met. CONCLUSIONS: The available randomised controlled trials (RCTs) suggest that, among the postoperative patients at high risk for PC, HFNC therapy compared with the COT significantly reduces rate of incubation or NIV for RF and rate of hypercapnia, meanwhile is safely administered. Further large-scale, multicenter, randomised and controlled studies are needed to confirm our results.

Performance of brief ICF-sleep disorders and obesity core set in obstructive sleep apnea patients.

BACKGROUND: Clinical questionnaires are mainly applied as screening tools for identification of the Obstructive sleep apnea (OSA) patients. Little attention has been paid to assess the body functions and health status of the patients. International Classification of Functioning, Disability and Health (ICF) was designed for better understanding and describing functioning and disability of patients. This study adopted the Brief ICF-Sleep Disorders and Obesity Core Set to evaluate the impairment of functioning and health status of OSA patients. METHODS: Five hundred ninety-two participants were enrolled in this cross-sectional study. Data were collected using Brief ICF-Sleep Disorders and Obesity Core Set Polysomnography was performed and basic characteristics of the patients were recorded. RESULTS: The scores for the component Body Functions and Code b130, b134, b140, b440, b530, s330, d160, d240, d450 of the two core sets were significantly different among the patients divided by apnea-hypopnea index (AHI) or oxygen saturation (SaO2) nadir, but the frequency of code s330, d160, d240, d450 was low. The Body Functions component of the both sets were closely related to neck circumference (NC), body mass index (BMI), apnea-hypopnea index (AHI) of the OSA patients. Body Functions of the Brief ICF-Sleep Disorders performed better with a threshold of 4 with sensitivity, specificity and area under the receiver operating characteristic curve (AUC) as 0.62, 0.74, 0.68(AHI ≥ 5), 0.69, 0.63, 0.66 (AHI ≥ 15), 0.75, 0.56, 0.66 (AHI ≥ 30), 0.56, 0.70, 0.63 (SaO2 nadir≤90%), 0.67, 0.66, 0.66 (SaO2 nadir<85%), 0.71, 0.59, 0.65 (SaO2 nadir<80%), separately. CONCLUSION: The Body Functions component of both two sets could be an evaluation tool of impairment of body functions for OSA patients. The Brief ICF-Sleep Disorders Body Functions component performed better with a threshold of 4 and might provide a new insight for physicians to assess OSA patients.

Growth differentiation factor 11 induces skeletal muscle atrophy via a STAT3-dependent mechanism in pulmonary arterial hypertension.

Skeletal muscle wasting is a clinically remarkable phenotypic feature of pulmonary arterial hypertension (PAH) that increases the risk of mortality. Growth differentiation factor 11 (GDF11), centrally involved in PAH pathogenesis, has an inhibitory effect on skeletal muscle growth in other conditions. However, whether GDF11 is involved in the pathogenesis of skeletal muscle wasting in PAH remains unknown. We showed that serum GDF11 levels in patients were increased following PAH. Skeletal muscle wasting in the MCT-treated PAH model is accompanied by an increase in circulating GDF11 levels and local catabolic markers (Fbx32, Trim63, Foxo1, and protease activity). In vitro GDF11 activated phosphorylation of STAT3. Antagonizing STAT3, with Stattic, in vitro and in vivo, could partially reverse proteolytic pathways including STAT3/socs3 and iNOS/NO in GDF11-meditated muscle wasting. Our findings demonstrate that GDF11 contributes to muscle wasting and the inhibition of its downstream molecule STAT3 shows promise as a therapeutic intervention by which muscle atrophy may be directly prevented in PAH.

Protective effects of progesterone on pulmonary artery smooth muscle cells stimulated with Interleukin 6 via blocking the shuttling and transcriptional function of STAT3.

BACKGROUND: Sex hormone paradox is a crucial but unresolved issue in the field of pulmonary artery hypertension (PAH), and is thought to be related to different pathogenic factors. Inflammation is one of pathological mechanisms of PAH development. However, effects of sex hormones on the pulmonary vasculature under the condition of inflammation are still elusive. METHODS: Interleukin-6 (IL-6) was used as a representative inflammatory stimulator. Effects of 17ß-estradiol or progesterone on human pulmonary artery smooth muscle cells (PASMCs) were measured under the condition of IL-6. Cell functions of proliferation and migration were measured by Alarmar Blue, EdU assay, wound-healing assay and transwell chambers. We explored further mechanisms using western blot, immunofluorescence, co-immunoprecipitation, qPCR and chromatin immunoprecipitation. RESULTS: Our results revealed that IL-6 promoted the proliferation of PASMCs, but progesterone could reverse the adverse effect of IL-6. The protective effect was dependent on progesterone receptor (PGR). By interacting with signal transducer and activator of transcription 3 (STAT3), activated PGR could reduce the IL-6-induced nuclear translocation of STAT3 and prevent STAT3-chromatin binding in PASMCs, leading to the decreased transcription of downstream CCND1 and BCL2. Alternatively, progesterone slightly decreased the phosphorylation of pro-proliferative Erk1/2 and Akt kinases and upregulated the anti-proliferative pSmad1-Id1/2 axis in IL-6-incubated PASMCs. CONCLUSIONS: Progesterone played a protective role on PASMCs in the context of IL-6, by blocking the functions of STAT3. Our findings might assist in explaining the clinical phenomenon of better prognosis for women with PAH.

Left atrial dysfunction in patients with obstructive sleep apnea: a combined assessment by speckle tracking and real-time three-dimensional echocardiography.

BACKGROUND: At present, little research concerning the assessment of left atrial (LA) dysfunction in patients with obstructive sleep apnea (OSA) using a combined assessment by speckle tracking (STE) and real-time three-dimensional echocardiography (RT3DE) is available. The objective of this study was to evaluate the LA volume and function by STE and RT3DE in patients with OSA. METHODS: In our cohort study, ninety-two OSA patients and 50 healthy individuals were enrolled. According to the apnea hypopnea index (AHI), patients (AHI >15/h) classified as having moderate and severe OSA were included. The patients were divided into 2 subgroups according to the left ventricular mass index (LVMI): the left ventricular hypertrophy (LVH) group in which patients had LVH (n=30), and the nonLVH group in which patients did not have LVH (n=62). All subjects underwent LA function assessment by conventional techniques and the combination of STE and RT3DE. RESULTS: OSA patients showed impaired LA global longitudinal strain during early diastole (LA S-E) and systole (LA S-S) but increased LA global longitudinal strain during late diastole (LA S-A) compared with controls (all P<0.05). In addition, OSA patients with LVH had lower LA S-S and LA S-E than patients without LVH (all P<0.05). With regard to parameters obtained from RT3DE, indexed LA maximum, minimum, and preatrial contraction volumes (LAVi-max, LAVi-min, LAVi-preA) and the LA active emptying fraction (LAAEF) were significantly higher, whereas the LA passive emptying fraction (LVPEF) was significantly lower in OSA patients in comparison with controls (all P<0.05). The LA total emptying fraction (LVTEF) and the LA expansion index were significantly lower in OSA patients with LVH than in controls (all P<0.05). Additionally, OSA patients with LVH had higher LAVi-min, LAVi-preA and LAAEVi but lower LAPEF than patients without LVH (all P<0.05). CONCLUSIONS: OSA is associated with LA remodeling and dysfunction that occurs in the subclinical stage before the development of LVH and left ventricular diastolic dysfunction, and it will be further aggravated along with the development of LVH and OSA severity. The process can be detected with a detailed evaluation of active and passive functions of the LA using the STE and RT3DE method.

Non-invasive ventilation intervention during exercise training in individuals with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

OBJECTIVE: evidence is inconsistent for the effect of non-invasive ventilation (NIV) for individuals with chronic obstructive pulmonary disease (COPD) during exercise training. This review aimed to determine the effect of NIV in COPD individuals during exercise training on exercise capacity, quality of life, functional performance and symptoms. MATERIAL AND METHODS: we searched for studies evaluating the effect of NIV on COPD individuals during exercise training published until May 2020 in 6 electronic databases (PubMed, Embase, Cochrane Library, Web of Science, clinical trial registers and Wanfang). The included studies were appraised with the Cochrane Risk of Bias tool and Downs and Black criteria. The primary outcomes were improvement in 6-min walking distance and quality of life. Mean difference (MD) or standardized mean difference (SMD) with 95% confidence intervals (CIs) was calculated. RESULTS: among 855 identified articles, reports for 15 studies with heterogeneous populations were eligible, with 520 individuals: 257 in the NIV group and 263 in the control group. Across studies, NIV intervention during exercise training affected exercise performance (6-min walking distance: SMD: 0.33, 95% CI: 0.06; 0.59, P=0.02; quality of life: SMD: -0.77, 95% CI: -1.01; -0.53, P<0.001). In the analysis of dyspnea, pooled estimates demonstrated improvement in the NIV versus control group. NIV intervention was also better than exercise alone in ameliorating oxygen saturation, PaO2, PaCO2, blood lactate level and breath rate. The groups did not differ in duration of exercise, BODE index, minute ventilation, heart rate and systolic blood pressure. CONCLUSIONS: our review suggests that NIV is a relevant adjuvant for exercise training in COPD individuals because the intervention could improve exercise performance and quality of life. The current results also demonstrate the importance of further investigations of higher methodological quality to assess the effect on exercise capacity and quality of life.

Essential Genes and MiRNA-mRNA Network Contributing to the Pathogenesis of Idiopathic Pulmonary Arterial Hypertension.

Background: Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease. Owing to its high fatality rate and narrow therapeutic options, identification of the pathogenic mechanisms of IPAH is becoming increasingly important. Methods: In our research, we utilized the robust rank aggregation (RRA) method to integrate four eligible pulmonary arterial hypertension (PAH) microarray datasets and identified the significant differentially expressed genes (DEGs) between IPAH and normal samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed to analyze their functions. The interaction network of protein-protein interaction (PPI) was constructed to explore the correlation between these DEGs. The functional modules and hub genes were further identified by the weighted gene coexpression network analysis (WGCNA). Moreover, a miRNA microarray dataset was involved and analyzed to filter differentially expressed miRNAs (DE-miRNAs). Potential target genes of screened DE-miRNAs were predicted and merged with DEGs to explore a miRNA-mRNA network in IPAH. Some hub genes were selected and validated by RT-PCR in lung tissues from the PAH animal model. Results: A total of 260 DEGs, consisting of 183 upregulated and 77 downregulated significant DEGs, were identified, and some of those genes were novel. Their molecular roles in the etiology of IPAH remained vague. The most crucial functional module involved in IPAH is mainly enriched in biological processes, including leukocyte migration, cell chemotaxis, and myeloid leukocyte migration. Construction and analysis of the PPI network showed that CXCL10, CXCL9, CCR1, CX3CR1, CX3CL1, CXCR2, CXCR1, PF4, CCL4L1, and ADORA3 were recognized as top 10 hub genes with high connectivity degrees. WGCNA further identified five main functional modules involved in the pathogenesis of IPAH. Twelve upregulated DE-miRNAs and nine downregulated DE-miRNAs were identified. Among them, four downregulated DEGs and eight upregulated DEGs were supposed to be negatively regulated by three upregulated DE-miRNAs and three downregulated DE-miRNAs, respectively. Conclusions: This study identifies some key and functional coexpression modules involved in IPAH, as well as a potential IPAH-related miRNA-mRNA regulated network. It provides deepening insights into the molecular mechanisms and provides vital clues in seeking novel therapeutic targets for IPAH.

LncRNA NEAT1 contributes to the acquisition of a tumor like-phenotype induced by PM 2.5 in lung bronchial epithelial cells via HIF-1α activation.

The hazards of particulate matter (PM2.5) on human respiratory health have been previously reported. However, the molecular mechanisms underlying PM2.5-induced lung carcinogenesis have rarely been studied. In the present study, we explored the effects of PM2.5 on the epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like properties in lung bronchial epithelial cells. We found that exposure of PM2.5 enhanced lung bronchial epithelial cell proliferation and EMT. In addition, the expression level of CSC-like biomarkers, CD133 and CD44, was significantly elevated by PM2.5 in vitro. Nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to participate in lung cancer. Loss of NEAT1 represses the malignant transformation of BEAS-2B and HBE cells induced by PM2.5. NEAT1 interacts with microRNA (miR)-582-5p, and miR-582-5p reverses the pro-tumor effects of NEAT1 overexpression. Hypoxia-inducible factor (HIF)-1α is an important transcription factor in the pathological responses to hypoxia. HIF-1α was a predicted target for miR-582-5p, and a direct correlation between them was identified. Inhibitors of miR-582-5p rescued HIF-1α expression, which was attenuated by a lack of NEAT1. In conclusion, PM2.5 increased NEAT1 expression, which, by binding with miR-582-5p, released HIF-1α and promoted EMT and the acquisition of CSC-like characteristics.

Predictors of mortality for hospitalized young adults aged less than 60 years old with severe COVID-19: a retrospective study.

BACKGROUND: To analyze the clinical characteristics and predictors for mortality of adult younger than 60 years old with severe coronavirus disease 2019 (COVID-19). METHODS: We retrospectively retrieved data for 152 severe inpatients with COVID-19 including 60 young patients in the Eastern Campus of Wuhan University affiliated Renmin Hospital in Wuhan, China, from January 31, 2020 to February 20, 2020. We recorded and analyzed patients' demographic, clinical, laboratory, and chest CT findings, treatment and outcomes data. RESULTS: Of those 60 severe young patients, 15 (25%) were died. Male was more predominant in deceased young patients (12, 80%) than that in recovered young patients (22, 49%). Hypertension was more common among deceased young patients (8, 53%) than that in recovered young patients (7, 16%). Compared with the recovered young patients, more deceased young patients presented with sputum (11, 73%), dyspnea (12, 80%) and fatigue (13, 87%). Only sputum, PSI and neutrophil counts were remained as independent predictors of death in a multivariate logistic regression model. Among ARDS patients, the recovered were administrated with corticosteroid earlier and anticoagulation. The addition of neutrophil counts >6.3×109/L to the SMART-COP score resulted in improved area under the curves. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection in young deceased patients appears to cause exuberant inflammatory responses, leading to compromised oxygen exchange, coagulation and multi-organ dysfunction. In addition, young patients with ARDS could benefit from adjuvant early corticosteroid and anticoagulation therapy. The expanded SMART-COP could predict the fatal outcomes with optimal efficiency.

Respiratory physicians' awareness and referral of pulmonary rehabilitation in China: a cross-sectional study.

BACKGROUND: Pulmonary rehabilitation (PR) has demonstrated physiological, symptom reducing, psychosocial, and health care savings benefits in multiple outcome areas for patients with chronic respiratory diseases. Physicians' PR awareness and PR referral practices are key in PR promotion. However, PR awareness and referral among respiratory physicians in China have rarely been studied. This study aims to explore respiratory physicians' perceptions towards PR and assess the referral of PR in China. METHODS: A self-administered questionnaire was distributed via WeChat and emails to respiratory physicians in hospitals to assess their attitudes toward and knowledge of PR and identify treatment barriers. The study was conducted from June through October 2019. RESULTS: As reported in the 520 questionnaires collected through October 2019 most respondents had heard about PR, and many had knowledge of PR practice, but relatively few had referred patients to PR before having responded to the survey. Education, region of practice, and duration of practice are significant factors that influenced the participating respiratory physicians' awareness of PR. The percentage of referral was influenced by physicians' education, region, and duration of practice. The absence of PR facilities was the main barrier to respiratory physicians' referral of patients to PR. CONCLUSIONS: Chinese respiratory physicians' awareness of PR and referral to PR remain insufficient to support the delivery of PR to patients with chronic respiratory diseases. PR training for respiratory physicians and building PR centers are necessary to remedy these conditions.

Clinical risk factors for mortality of hospitalized patients with COVID-19: systematic review and meta-analysis.

BACKGROUND: New evidence from retrospective cohort studies on risk of death from COVID-19 infection became available. We aimed to systematically review the clinical risk factors for fatal outcome of COVID-19. METHODS: We performed meta-analysis, using PubMed, EMBASE and Cochrane databases from December 1 2019 to June 10 2020. The meta-analysis summarized clinical, laboratory, radiological features, and complications of non-survivors with confirmed COVID-19. In addition, a fixed- or random-effects model was adopted based on the heterogeneity among studies. We also used funnel-plot with Egger's tests to screen potential publication bias. RESULTS: In total, twenty studies with 15,408 COVID-19 cases were included in our meta-analysis. Male, current smoking, and older age were associated with in-hospital death. Patients aged 60 years or over had the highest pooled ORs [OR 4.94 (2.89, 8.44)]. Non-survivors were more likely to have diabetes, hypertension, cardiovascular disease (CVD), respiratory disease, or chronic kidney disease (CKD). Respiratory disease had the highest pooled ORs [OR 2.55 (2.14, 3.05)]. Dyspnea [OR 3.31 (1.78, 6.16); I2 : 83%] and fatigue [OR 1.36 (1.07, 1.73); I2 : 0%] were associated with increased risk of death. Increased white blood cell count, decreased lymphocyte and platelet counts, were also associated with increased risk of death. Biomarkers of coagulation function, inflammation, liver and kidney function, cardiac and muscle injury were also elevated in nonsurvivors. CONCLUSIONS: Male, current smoking patients aged 60 years or over might face a greater risk of in-hospital death and the comorbidities such as diabetes, hypertension, CVD, respiratory disease, and CKD could also influence the prognosis of the COVID-19. Clinical feature such as dyspnea and fatigue could imply the exacerbation and even death. Our findings highlighted early markers of mortality which were beneficial to identify fatal COVID-19.

The effect of coagulation factors in 2019 novel coronavirus patients: A systematic review and meta-analysis.

BACKGROUND: The role of coagulation dysfunction in Severe Coronavirus Disease 2019 (COVID-19) is inconsistent. We aimed to explore the impact of coagulation dysfunction amongst patients with COVID-19. METHODS: We searched PubMed, Cochrane and Embase databases from December 1, 2019 to April 27, 2020 following Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Data about coagulation (Platelets, PT, APTT, fibrin, fibrinogen degradation products, D-dimer), prevalence of coagulation dysfunction and mortality were extracted. Meta regression was used to explore the heterogeneity. RESULTS: Sixteen observational studies were included, comprising 2, 139 patients with confirmed COVID-19. More severe COVID-19 cases tended to have higher mean D-dimer (SMD 0.78, 95% CI 0.53 to 1.03, P < .001). The similar pattern occurred with PT and fibrin, with a contrary trend for PLTs. Coagulation dysfunction was more frequent in severe cases compared to less severe (SMD 0.46, 95% CI 0.25 to 0.67, P < .001). Higher mortality was associated with COVID-19-related coagulopathy (RR 10.86, 2.86 to 41.24, P < .001). Prevalence of ARDS was increased in more severe patients than less severe cases (RR 16.52, 11.27 to 24.22, P < .001). PT, fibrin and D-dimer levels elevated significantly in non-survivors during hospitalization. CONCLUSION: Presence of coagulation dysfunction might be associated with COVID-19 severity, and coagulopathy might be associated with mortality. Coagulation markers including PT, fibrin and D-dimer may imply the progression of COVID-19. This illuminates the necessity of effectively monitoring coagulation function for preventing COVID-19-related coagulopathy, especially in severe patients. For the obvious heterogeneity, the quality of the evidence is compromised. Future rigorous randomized controlled trials that assess the correlation between coagulation and COVID-19 are needed. TRIAL REGISTRATION: PROSPERO (CRD42020183514).

Impact of histaminergic H3 receptor antagonist on hypoglossal nucleus in chronic intermittent hypoxia conditions.

RATIONALE: The hypoglossal nucleus (HN) controls the movement of the genioglossus (GG) muscle whose dysfunction leads to airway occlusion and occurrence of obstructive sleep apnea (OSA). Histamine produced by the tuberomammillary nucleus (TMN) has a potent excitatory action on GG muscle activity. OBJECTIVES: The aim of the study was to investigate the role histaminergic neurons play in the regulation of the genioglossus. METHODS: C57BL/6 mice were exposed to chronic intermittent hypoxia (CIH) for 3 weeks to resemble OSA. The histamine H3 receptor (H3R) antagonist ciproxifan was applied to increase histamine in the brain. Histamine levels and GG activity were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and electromyogram (EMG) separately. Neuronal activity and repair ability of the HN and TMN and key proteins of histamine were analyzed by immunohistochemistry and western blots. RESULTS: Significant decline of histamine level and GG activity of the HN and TMN induced by CIH exposure could be ameliorated by ciproxifan. Application of ciproxifan could also partly reverse the decline of the histidine decarboxylase (HDC) by CIH. CONCLUSIONS: This investigation studied the impacts of ciproxifan on the HN and TMN in CIH conditions and revealed that the negative effects on the HN and TMN caused by CIH could be partly ameliorated by ciproxifan, which might open new perspectives for the development of pharmacological treatment for OSA.

Serum cartilage oligomeric matrix protein is decreased in patients with pulmonary hypertension: a potential protective factor.

Cartilage oligomeric matrix protein (COMP) was a protective factor in the cardiovascular system. Previous studies showed that hypoxia led to decreased COMP in rat models of pulmonary hypertension. However, the expression pattern of COMP in the pulmonary hypertension population was unclear. A total of 35 patients newly diagnosed with pulmonary hypertension and 70 controls were enrolled in the study. Circulating COMP concentrations of serum samples were measured by enzyme-linked immunosorbent assay and were analyzed the association with multiple clinical variables. Serum COMP concentrations in the pulmonary hypertension group were significantly declined in comparison with age- and sex-matched normal controls, especially in the female subgroup. No significant difference of COMP concentrations was observed in the etiological classification, heart function classification, and risk stratification. Major hemodynamic parameters, six-minute walk distance, N-terminal pro brain natriuretic peptide, and short-term prognosis were not statistically associated with COMP. However, some echocardiography parameters, like tricuspid annular plane systolic excursion and mean right atrial pressure, were found the negative relation to COMP concentrations. In conclusion, serum COMP levels were decreased in the patients with pulmonary hypertension, which was in accordance with its known biological effects. Its association with long-term prognosis was worth further exploring.

Clinical predictors of COVID-19 disease progression and death: Analysis of 214 hospitalised patients from Wuhan, China.

INTRODUCTION: COVID-19 has spread rapidly worldwide and has been declared a pandemic. OBJECTIVES: To delineate clinical features of COVID-19 patients with different severities and prognoses and clarify the risk factors for disease progression and death at an early stage. METHODS: Medical history, laboratory findings, treatment and outcome data from 214 hospitalised patients with COVID-19 pneumonia admitted to Eastern Campus of Renmin Hospital, Wuhan University in China were collected from 30 January 2020 to 20 February 2020, and risk factors associated with clinical deterioration and death were analysed. The final date of follow-up was 21 March 2020. RESULTS: Age, comorbidities, higher neutrophil cell counts, lower lymphocyte counts and subsets, impairment of liver, renal, heart, coagulation systems, systematic inflammation and clinical scores at admission were significantly associated with disease severity. Ten (16.1%) moderate and 45 (47.9%) severe patients experienced deterioration after admission, and median time from illness onset to clinical deterioration was 14.7 (IQR 11.3-18.5) and 14.5 days (IQR 11.8-20.0), respectively. Multivariate analysis showed increased Hazards Ratio of disease progression associated with older age, lymphocyte count <1.1 × 109/L, blood urea nitrogen (BUN)> 9.5 mmol/L, lactate dehydrogenase >250 U/L and procalcitonin >0.1 ng/mL at admission. These factors were also associated with the risk of death except for BUN. Prediction models in terms of nomogram for clinical deterioration and death were established to illustrate the probability. CONCLUSIONS: These findings provide insights for early detection and management of patients at risk of disease progression or even death, especially older patients and those with comorbidities.

Effects of neuromuscular electrical stimulation on exercise capacity and quality of life in COPD patients: a systematic review and meta-analysis.

Neuromuscular electrical stimulation (NMES) has been shown to produce benefits in the muscle function of chronic obstructive pulmonary disease (COPD) patients. The definite effectiveness of NMES, applied in isolation or concurrently with conventional pulmonary rehabilitation (PR) or exercise training, remains unclear. This review was to determine the effects of NMES on exercise capacity, functional performance, symptoms, and health-related quality of life (HRQoL) in COPD patients. Electronic databases (PubMed, Embase, Web of Science, the Cochrane Library) were searched for relevant randomized controlled trials (RCTs). Two investigators independently screened the eligible studies up to February 2020 that used NMES as the intervention group. The outcome measures were 6-min walking distance (6MWD), peak rate of oxygen uptake (VO2 peak), St George's Respiratory Questionnaire (SGRQ), and symptoms of dyspnoea and fatigue. Data were extracted using a predefined table and papers were appraised using Downs and Black tool. We analyzed 13 RCTs with 447 COPD patients. In the analysis of 6MWD, pooled estimates showed a significant increase in the NMES group, compared with the control group (mean difference (MD) = 27.05, 95% confidence interval (CI): 8.46-45.63, P<0.001). There were also improvements in symptoms of dyspnea or leg fatigue, and reduction in London Chest Activity of Daily Living (LCADL) scores. No statistically significant difference was observed in VO2 peak, peak power, and SGRQ. NMES could improve exercise capacity and reduce perceived sensation of dyspnea during exercise in patients with COPD, but not to be recommended as an effective alternative training modality in the rehabilitation of stable COPD patients.

The Reliability and Validity of the "Activity and Participation" Component in the Brief ICF Core Set for Chronic Obstructive Pulmonary Diseases Based on Rasch Analysis.

Purpose: To analyze the reliability and validity of the "activity and participation" component of the brief international classification of functioning, disability and health (ICF) core set for chronic obstructive pulmonary disease (COPD) using a Multi-faceted Rasch model. Patients and Methods: A total of 103 patients with COPD were selected by two raters to evaluate their ability levels in the four categories of the "activity and participation" component of brief ICF core set for COPD. The Multi-faceted Rasch model was used for data analysis. The analysis software used FACETS (Minifac) 3.67.0. Results: The "activity and participation" of brief ICF core set for COPD had a high internal consistency (separation index of 5.08, reliability of 0.96, P <0.05) and good inter-rater reliability (mean-square fit statistic range was 0.97-1.04, the separation index was 0.00, the reliability was 0.00, P >0.05), the construct validity was good (mean-square fit statistic range was 0.79-1.36), and the consistency of each category measurement was high (the separation index was 1.70, the reliability was 0.74). Conclusion: The "activity and participation" of brief ICF core set for COPD has good reliability and validity, which can be used to test the daily activities of patients with COPD.

Effects of non-invasive ventilation in subjects undergoing cardiac surgery on length of hospital stay and cardiac-pulmonary complications: a systematic review and meta-analysis.

BACKGROUND: Cardiac surgery often leads to pulmonary complications. Non-invasive ventilation (NIV) is a mechanical ventilation modality that may help to prevent the pulmonary complications, and the role of the prophylactic use of NIV in patients after cardiac surgery remains controversial. METHODS: We searched PubMed, Embase, Web of Science and Cochrane Central for randomized controlled trials comparing the use of NIV (continues positive airway pressure or bi-level positive airway pressure) with standard treatment in post-cardiac surgery subjects without language restriction. Two investigators screened the eligible studies up to July, 2019. Meta-analysis using random effect model or fixed effect model was conducted for pulmonary complications, mortality, rate of reintubation and cardiac complications, and mean difference (MD) or standard mean difference for length of hospital stay and length of ICU stay. RESULTS: We included nine randomized controlled trails with 830 subjects. The use of NIV failed to reduce the risk of pulmonary complications, including atelectasis [risk rate (RR) 0.60; 95% confidence interval (CI): 0.28 to 1.28, P=0.19] and pneumonia (RR 0.27; 95% CI: 0.05 to 1.64, P=0.16). However, it has shortened the length of ICU stay (MD -1.00 h, 95% CI: -1.38 to -0.63, P<0.00001) and the length of hospital stay (MD -1.00 d, 95% CI: -1.12 to -0.87, P<0.00001). NIV also failed to reduce the rate of reintubation (RR 0.68; 95% CI: 0.21 to 2.26, P=0.53) or the risk of cardiac complications (RR 0.81; 95% CI: 0.59 to 1.13, P=0.22). CONCLUSIONS: The prophylactic use of NIV immediately in post-cardiac subjects who underwent cardiac surgery might be able to shorten the length of hospital stay and the length of ICU stay, but it has no significant effect on pulmonary complications, rate of reintubation or cardiac complications.

Effects of Tai Chi training on the physical and mental health status in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Tai Chi is a systematic whole body movement developed in ancient China. It plays an increasingly important role in the field of pulmonary rehabilitation for patients with chronic obstructive pulmonary disease (COPD). Our review aimed to explore the impact of Tai Chi on the physical and mental health of patients with COPD. METHODS: We searched several English and Chinese databases and used the combination of subject words and free words to search for available literature from the establishment of the library until August 28, 2018. Two researchers screened studies and collected the data independently. The study inclusion criteria included: (I) patients diagnosed with COPD; (II) Tai Chi or Tai Chi Qigong as an intervention in addition to routine treatment; (III) routine treatment with or without exercises as control group. The primary outcomes were lung function, exercise capacity and health status; (IV) randomized controlled trials. RESULTS: Sixteen articles were included from 2009 to 2018 (n=1,096). The average time duration of Tai Chi program was 53.4 minutes each session, 4.13 sessions a week for a total of 4.13 months. Comparing with control group, Tai Chi group improved some lung function (forced volume capacity: mean difference =0.12, 95% CI: 0.03-0.21), (forced expiratory volume in 1s: mean difference =0.15, 95% CI: 0.08-0.21), enhanced 6-minute walking distance score (mean difference =30.78, 95% CI: 15.15-46.42), decreased COPD Assessment Test score (mean difference =-5.00, 95% CI: -7.51 to -2.50), decreased St. George's Respiratory Questionnaire score (mean difference =-8.66, 95% CI: -14.60 to -2.72), enhanced Chronic Respiratory Disease Questionnaire score (mean difference =2.16, 95% CI: 1.49-2.83), decreased Hospital Anxiety and Depression Scale score(anxiety: mean difference =-1.04, 95% CI: -1.58 to -0.51; depression: mean difference =-1.25, 95% CI: -1.77 to -0.73). Comparing with exercise group, Tai Chi group statistically enhanced 6-minute walking distance score (mean difference =7.77, 95% CI: 2.63-12.91). CONCLUSIONS: Tai Chi may represent an appropriate alternative or complement to standard rehabilitation programs. However, whether Tai Chi is better than pulmonary rehabilitation exercise has not been determined.