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Kongbo Zhu,1 Shaolei Ma,2 Hui Chen,3 Jianfeng Xie,3 Dan Huang,1 Cuiping Fu,4 Genshan Ma,1 Yingzi Huang3 1Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Department of Emergency and Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 4Department of Respiratory Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of ChinaCorrespondence: Yingzi Huang, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, 210009, People’s Republic of China, Email yz_huang@126.comBackground: The pathogenicity of Omicron is different from that of the previous strains. The value of hematological indicators in patients at high risk of Omicron infection remains unclear. We need rapid, inexpensive and widely available biomarkers to guide the early detection of people at risk of pneumonia and to provide early intervention. We aimed to assess the value of hematological indicators as risk factors for pneumonia in symptomatic COVID-19 patients infected with the SARS-CoV-2 Omicron variant.Patients and Methods: The study enrolled 144 symptomatic COVID-19 patients with Omicron infection. We collected available clinical details, including laboratory tests and CT examinations. Univariate and multivariate logistic analyses and receiver operating characteristic (ROC) curve analyses were used to assess the value of laboratory markers in predicting the development of pneumonia.Results: Among the 144 patients, 50 (34.7%) had pneumonia. The ROC analysis revealed that the areas under the ROC curve (AUC) for leukocytes, lymphocytes, neutrophils, and fibrinogen were 0.603 (95% confidence interval (CI): 0.501– 0.704, P=0.043), 0.615 (95% CI: 0.517– 0.712, P=0.024), 0.632 (95% CI: 0.534– 0.730, P=0.009) and 0.635 (95% CI: 0.539– 0.730, P=0.008), respectively. The AUC for neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), fibrinogen to lymphocyte ratio (FLR), and fibrinogen to D-dimer ratio (FDR) were 0.670 (95% CI: 0.580– 0.760, P=0.001), 0.632 (95% CI: 0.535– 0.728, P=0.009), 0.669 (95% CI: 0.575– 0.763, P=0.001) and 0.615 (95% CI: 0.510– 0.721, P=0.023), respectively. Univariate analysis showed that elevated levels of NLR (odds ratio (OR): 1.219, 95% CI: 1.046– 1.421, P=0.011), FLR (OR: 1.170, 95% CI: 1.014– 1.349, P=0.031) and FDR (OR: 1.131, 95% CI: 1.039– 1.231, P=0.005) were significantly correlated with the presence of pneumonia. Multivariate analysis indicated elevated NLR (OR: 1.248, 95% CI: 1.068– 1.459, P=0.005) and FDR (OR: 1.160, 95% CI: 1.054– 1.276, P=0.002) levels were associated with the existence of pneumonia. The AUC for the combination of NLR and FDR was 0.701 (95% CI: 0.606– 0.796, P< 0.001, sensitivity 56.0%, specificity 83.0%).Conclusion: NLR and FDR can predict the presence of pneumonia in symptomatic COVID-19 patients infected with the SARS-CoV-2 Omicron variant.Keywords: COVID-19, Omicron, pneumonia, neutrophil to lymphocyte ratio, fibrinogen, D-dimer

To investigate mental health symptoms (anxiety, depression, and sleep status) and their associated factors among people infected with the SARS-CoV-2 omicron variant during the quarantine period in Shanghai.To investigate the mental health symptoms among participants with SARS-CoV-2 omicron infection, an anonymous online survey questionnaire was used. The survey panel included the 9-item Patient Health Questionnaire-9 (PHQ-9), 7-item Generalized Anxiety Disorder Scale (GAD-7), Pittsburgh Sleep Quality Index (PSQI), and 22-item Ruminative Responses Scale (RRS). Group comparisons and correlation analyses were employed to explore the epidemiological characteristics of patients and factors related to depression and anxiety symptoms.A total of 960 participants completed the survey. Of the total respondents, 583 participants (60.7%) were male, and the mean (SD) age was 34.33 (9.21) years (95% CI: 33.74-34.91). The prevalence of depressive and anxiety symptoms among the participants was 13.7% (n = 151, 95% CI: 11.6%-15.7%) and 8.6% (n = 90, 95% CI: 6.9%-10.3%), respectively. Age-stratified analysis showed that the prevalence of anxiety among the 36- to 45-year-old group (12.9%; n = 35, 8.9%-16.9%) was significantly higher than that of the 18- to 15-year-old group (7.4%; n = 42, 5.3%-9.6%, p = .011). Spearman's correlation analyses showed that rumination (assessed by the RRS) was significantly and positively correlated with depression (rho = .706, p .001) and anxiety symptoms (rho = .758, p .001).The results suggest that female and middle-aged populations manifest higher susceptibility to mental health distress during the current Omicron wave of the COVID-19 pandemic. Population-specific psychological crisis intervention is warranted to improve the quality of epidemic prevention methods and to promote the mental well-being of the public.

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.

Oxidative stress caused by chronic intermittent hypoxia (CIH) is the hallmark of obstructive sleep apnea (OSA). Among the first line of defense against oxidative stress is the dismutation of superoxide radicals, which in the mitochondria is carried out by manganese superoxide dismutase (SOD2). In this study, wild-type (WT) and SOD2-heterozygous knockout (SOD2+/−) mice were exposed to CIH or normoxic (Nor) conditions. After 4 weeks, pulmonary artery pressure was measured, and the mice were processed to harvest either serum for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that heterozygous deletion of SOD2 markedly deteriorated pulmonary remodeling and increased the oxidative stress, especially promoted the infiltration of macrophages in the lungs of CIH mouse. Moreover, in the intermittent hypoxia (IH)-treated RAW264.7 cells, SOD2 knockdown increased the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation accompanied with the IL-1β elevation and caspase-1 activity. Additionally, mitochondrial ROS (mtROS) scavenger mito-TEMPO abolished NLRP3 inflammasome activation in IH-treated RAW264.7 cells. Collectively, our results supported that SOD2 contributed to the pathogenesis of CIH-induced lung remodeling. Meanwhile, SOD2 knockdown exacerbates oxidative damage through assembly and activation of NLRP3 inflammasome in macrophages. SOD2 may be a novel therapeutic target for CIH-induced pulmonary inflammation and arteriole remodeling.

Objective To investigate the clinical manifestations and imaging characteristics of pulmonary cryptococcosis, and discuss its guidance in diagnosing. Methods The clinical data of patients diagnosed with cryptococcosis in our hospital from January 2014 to May 2020 were collected and retrospectively analyzed. Patients were divided into the immunocompromised group and the immunocompetent group. The symptomatic features, laboratory examination, imaging manifestations, and curative effect were analyzed. Results The most common symptoms of patients were cough and sputum production, followed by fever. The immunocompetent group has a significantly higher accident rate of cough and fever than the immunocompromised group, while the immunocompromised group has a significantly higher accident rate of headache and dizziness (P P P Conclusions Cryptococcosis has an insidious onset, which can infect healthy people as well. Conducting a CrAg test is good for screening and diagnosing cryptococcosis. We should be alert for the high risk of cryptococcal meningoencephalitis in patients with compromised immune function.

Objective: Balanced fluid with no critical increase of chloride in serum was recommended in clinic. Whether hyperchloremia could make a difference for intensive care unit (ICU) patients with a higher acute kidney injury (AKI) occurrence remains controversial.Methods: The Medical Information Mart for Intensive Care III (MIMIC-III) database was searched to identify patients hyperchloremia or non-hyperchloremia, and relationship between level of chloride and AKI incidence was analyzed using the univariate and multivariate logistic regression. Patients were divided into four disease subgroups based on the diagnosis at admission: cardiac, cerebral, gastrointestinal, respiratory. The association between maximum chloride (chloride_max) and incidence of AKI in each subgroup was evaluated using the Lowess Smoothing technique. Receiver operating characteristic curves were applied to analyze the diagnostic value of hyperchloremia (chloride_max>110mmol/L) in these four subgroup patients.Results: A total of 34,617 patients were included in our study, of which 12667 patients (36.6%) was diagnosed with hyperchloremia. The risk of incidence of AKI was increased in the hyperchloremia group. As the higher level of hyperchlorimia, the bigger adjusted odds ratio (OR) presented in terms of AKI, with the OR increasing from 1.13 (95%CI 1.06-1.21; P110mmol/L) in any subgroup of cerebral, cardiac, respiratory and gastrointestinal disease. The diagnostic performance was good for cerebral disease (AUC=0.617), cardiac disease (AUC=0.636), respiratory disease (AUC=0.623) and gastrointestinal disease (AUC=0.633). The optimal cut-off value in terms of chloride_max for diagnosing AKI was 116mmol/L for the subgroup of cerebral, respiratory and gastrointestinal diseases, and 115 mmol/L for cardiac patients.Conclusion: Hyperchloremia was associated with increased risk adjusted AKI incidence among critical ill patients. For ICU patients with cerebral, gastrointestinal and respiratory admission diagnose, the predictive threshold was at 116mmoL/L, and cardiac diagnose was at 115 mmol/L.

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 

Background The effectiveness of Tai Chi for chronic obstructive pulmonary disease (COPD) so far is unclear. The present systematic review aimed to determine the influence of Tai Chi among people with COPD. Methods We searched six electronic databases for relevant studies in September, 2019. The methods of standard meta-analysis were used for identifying relevant studies, quality appraisal, and synthesis. The primary outcomes were six-minute walking distance (6MWD), percentage predicted forced expiratory flow volume in the first second (%PredFEV1), and St. George's Respiratory Questionnaire (SGRQ) score. Results A total of 23 studies including 1663 participants were included in the meta-analysis. The pooled data showed that the Tai Chi group was associated with a significant improvement in 6MWD [mean difference (MD) 40.83 m, 95% CI: 32.47 to 49.19], %PredFEV1 (MD 1.67%, 95% CI: 0.41 to 2.93), SGRQ score (MD -6.57, 95% CI: -10.17 to -2.98), and Chronic Respiratory Disease Questionnaire (CRQ) (MD 1.60, 95% CI: 0.89 to 2.30) relative to the blank control population. When compared with breathing exercises, the 6MWD was significantly enhanced with Tai Chi (MD 14.15 m, 95% CI: 3.76 to 24.53). Finally, when compared with breathing and walking exercises, Tai Chi was associated with a significant improvement in 6MWD (MD 7.68 m, 95% CI: 2.28 to 13.09 m) and SGRQ score (MD -6.31, 95% CI: -9.13 to -1.48). Conclusions Tai Chi may have the potential to reduce dyspnoea, enhance exercise capacity, and improve the quality of life in COPD patients. People with COPD may obtain benefit from practicing Tai Chi.

Background To explore the differences in short and middle term adverse factors of pulmonary embolism (PE) outcome. Methods This was a single-center retrospective study of inpatients admitted from Zhongshan Hospital, Fudan University, with first-time PE. Clinical data were collected from patients with objectively confirmed PE, and a 2-year follow up was conducted. Results The sample contained 310 patients with PE, ranging in age from 18 to 86 years old (mean 63.28 ± 15.30) and including 165 men (53.2%) and 145 women (46.8%). Successful treatment was achieved in 285 cases (91.9%) and unsuccessful treatment turned out in 25 cases (8.1%). Logistical regression analysis showed that massive PE [odds ratio (OR) = 23.625, 95% confidence interval (CI) 6.248-89.333], hypoxemia (OR = 11.915, 95% CI 1.900-74.727), leukocytosis (OR = 9.120, 95% CI 2.227-37.349) and active cancer (OR = 6.142, 95% CI 1.233-30.587) were associated with a poor prognosis for acute PE in the short term (in hospital). Seventy-seven PE cases with complete electronic records were finally included in the follow up. Cox regression analysis showed that elevated pulmonary artery systolic pressure (PASP, ⩾50 mmHg) (HR = 9.240, 95% CI, 2.307-37.013) and active cancer with PE (HR = 3.700, 95% CI, 1.010-13.562) were associated with an increased risk of mid-term mortality after a follow-up period of 2 years. Conclusions Massive PE, hypoxemia, leukocytosis and active cancer may contribute to a poor prognosis for patients with acute PE in hospital. Elevated PASP and active cancer may negatively impact survival time and increase the risk of death for patients with acute PE after 2-year follow up. Short-term adverse factors of acute PE are not exactly the same as the mid-term risk factors of acute PE.

Introduction. The clinical benefit of high-flow nasal cannula (HFNC) on factors related to pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) patients remains unclear. This meta-analysis aimed at synthesizing the available evidence on the efficacy of HFNC on exercise capacity, lung function, and other factors related to pulmonary rehabilitation in COPD patients. Methods. Electronic databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science) were searched for randomized trials comparing with conventional oxygen therapy (COT) or noninvasive ventilation (NIV). Primary outcomes were respiratory rate, FEV1, tidal volume, oxygen partial pressure, total score of St. George’s respiratory questionnaire, 6-minute walk test, and exercise endurance time. Results. Ten trials met the criteria for inclusion. Combined data from six studies showed that HFNC showed a lower respiratory rate in COPD patients [mean difference -1.27 (95% CI: -1.65–(-0.89)]. Combined data from three studies showed a lower forced expiratory volume in one second (FEV1) in the group of HFNC. No difference in tidal volume was showed between the HFNC and control groups in COPD patients. No significant oxygen improvement between the HFNC groups and control groups. The total score of St. George’s respiratory questionnaire was improved by the subgroup analysis of HFNC versus COT but no NIV. Two multicenter RCTs showed the six-minute walk test, and statistical results showed that the length of the six-minute walk capacity was increased after usage of HFNC compared to the control group [mean difference -8.65 (95% CI: -9.12–(-8.19)]. No increase of exercise capacity after usage of HFNC (mean difference -12.65). Conclusion. In the first meta-analysis of the area, the current evidence did not show so much positive effect on tidal volume or oxygen improvement in COPD patients. Length of the six-minute walk capacity was increased after using HFNC, while other pulmonary rehabilitation parameters, namely, the score of St. George’s respiratory questionnaire and exercise capacity show no increase in the group of HFNC. The variance in the quality of the evidence included in this meta-analysis highlights the need for this evidence to be followed up with further high-quality and more randomized trials.

Background High prevalence of obstructive sleep apnea (OSA) in the pulmonary hypertension (PH) population suggests that chronic intermittent hypoxia (CIH) is an important pathogenic factor of PH. However, the exact mechanism of CIH induced PH is not clear. One of the molecules that plays a key role in regulating pulmonary artery function under hypoxic conditions is superoxide dismutase 2 (SOD2). Methods Our study utilized heterozygous SOD2−/+ mice firstly in CIH model to explore the exact role of SOD2 in CIH causing PH. Expression of SOD2 was analyzed in CIH model. Echocardiography and pulmonary hypertension were measured in wild type (WT) and SOD2−/+ mice under normal air or CIH condition. Hematoxylin–Eosin (H&E) staining and masson staining were carried out to evaluate pulmonary vascular muscularization and remodeling. Micro-PET scanning of in vivo 99mTc-labelled- MAG3-anti-CD11b was applied to assess CD11b in quantification and localization. Level of nod-like receptor pyrin domain containing 3 (NLRP3) was analyzed by real time PCR and immunohistochemistry (IHC). Results Results showed that SOD2 was down-regulated in OSA/CIH model. Deficiency of SOD2 aggravated CIH induced pulmonary hypertension and pulmonary vascular hypertrophy. CD11b+ cells, especially monocytic myeloid cell line-Ly6C+Ly6G− cells, were increased in the lung, bone marrow and the blood under CIH condition, and down-regulated SOD2 activated NLRP3 in CD11b+ cells. SOD2-deficient-CD11b+ myeloid cells promoted the apoptosis resistance and over-proliferation of human pulmonary artery smooth muscle cells (PASMCs) via up-regulating NLRP3. Conclusion CIH induced down-regulating of SOD2 increased pulmonary hypertension and vascular muscularization. It could be one of the mechanism of CIH leading to PH.

Additional file 1: Figure S1. Representative RVSP wave in SOD2-/+ and WT mice by exposure to CIH for 6 weeks. Figure S2. Medial vascular wall thickness showed by elastica van gieson staining in the group of WT mice and SOD2-/+ mice under CIH condition. a. Representative image of elastica van gieson staining of mice in the four groups. b. Statistical results of vascular thickness of the four groups. N = 5. *p

Emerging evidence shows that signal transducer and activator of transcription 6 (STAT6) plays critical roles in tumor development. We previously found high-level expression of STAT6 in human lung adenocarcinoma and squamous cell carcinoma, specifically in infiltrated immune cells located in the lung interstitium. Nevertheless, the role of STAT6 signaling in lung carcinogenesis and lung cancer proliferation and its underlying mechanisms remain unclear. This study aimed to investigate the role of STAT6 and the interaction between STAT6 and the tumor microenvironment in pulmonary tumorigenesis. We established a murine model of primary lung carcinogenesis in STAT6-deficient (STAT6−/−) and STAT6 wild-type (WT) BALB/c mice using the carcinogen urethane. Two-month-old male mice were intraperitoneally injected with urethane (1 g/kg) dissolved in phosphate buffered saline (PBS). Primary tumors were monitored in vivo by positron emission tomography scanning. At 4, 6, and 9 months after urethane injection, lung tumors were harvested from the STAT6−/− and WT mice for analysis. Small interfering RNA was used to downregulate the expression of STAT6 in tumor cells. Fluorescence activated cell sorting analysis was used to analyze fluorescence-conjugated cell markers. Transwell assays were used in coculturing experiments. STAT6 protein expression was detected by Western blotting, immunohistochemistry, and immunofluorescence. STAT6 mRNA expression was detected by quantitative real time-polymerase chain reaction. Cell Counting Kit-8 and colony formation assays were performed to evaluate cell proliferation. We detected high expression of STAT6 in CD11b+ cells of lung carcinoma. Our results indicate that STAT6 deficiency inhibits carcinogen-induced tumor growth and improves prognosis. STAT6 deficiency also decreased the mobilization and differentiation of CD11b+ cells. STAT6 deficiency in CD11b+ cells but not tumor cells decreased interleukin (IL)-4 secretion and the differentiation of CD11b+ cells into M2 macrophage cells. In conclusion, our findings indicate that IL-4/STAT6 signaling in CD11b+ cells promotes lung cancer progression by triggering an IL-4 positive feedback loop and increasing M2 myeloid cells. STAT6 may be a new therapeutic target for the prevention and treatment of lung cancer.

This paper introduces a paper-based closed Au-bipolar electrode (BPE) biosensing system for the rapid and sensitive electrochemiluminescence (ECL) detection of miRNA-155. This microfluidic paper-based sensing platform is formed by wax-printing technology, screen printing method and in-situ Au nanoparticles (NPs) growth to form hydrophilic cells, hydrophobic boundaries, water proof electronic bridge, driving electrode regions and bipolar electrode regions. For rapid and sensitive detection, the cathode of bipolar electrode was modified with the prepared DNA (S1)–AuPd NPs by hybridization chain reaction, in which the target could initiate multiple cycles reaction to load more AuPd NPs which catalyzed H2O2 reduction. In addition, a classical ECL system tris (2,2′-bipyridine) ruthenium (II)- tripropylamine (Ru(bpy)32+/TPrA) exists at the anode of the bipolar electrode. Due to the charge balance between the anode and the cathode of BPE, the ECL signal response of Ru(bpy)32+/TPrA system was enhanced in the reporting cell. The intensity of ECL was quantitatively correlated with the concentration of miRNA-155 in the range of 1 pM–10 μM with the detection limit 0.67 pM. Moreover, this method paves a novel way for highly sensitive detection of miRNA-155 in clinical application.

A photoelectrochemical (PEC) biosensor was constructed based on cascade enzyme-assisted cycling process and Co3O4-Au polyhedron for miRNA-141 detection. The biotin-modified DNA was immobilized on ITO/TiO2/Bi2S3 to link streptomycin-modified Co3O4-Au through the specific interaction between streptavidin and biotin. The Co3O4-Au with the competitive consumption effect of electron donor and excitation light energy could effectively reduce the photocurrent signal. Additionally, Co3O4-Au as peroxidase mimetics enzyme could catalyze the formation of benzo-4-chlorohexanedione (4-CD) precipitate on the electrode surface, which could efficiently prevent electron transfer and decrease the photocurrent signal of PEC biosensor. In the cascade enzyme-assisted cycling process, a small amount of miRNA-141 triggered the double-strand specific endonucleases-assisted cycling process, which could generate DNA fragment for next step experiment. Then the biotin-modified DNA was decomposed by Exonuclease III (Exo III) in the Exo III-assisted cycling process, resulting in the separation of biotin from the electrode surface and the reduction in the loading of streptomycin-modified Co3O4-Au. The fabricated PEC biosensor with a wide linear range and a low detection limit has potential applications in highly accurate and ultrasensitive monitoring of bioanalysis and disease diagnostics.

Gastric aspiration lung injury is one of the most common clinical events. This study investigated the effects of bone‐marrow‐derived mesenchymal stem cells (BMSCs) on combined acid plus small non‐acidified particle (CASP)‐induced aspiration lung injury. Enhanced green fluorescent protein (EGFP +) or EGFP − BMSCs or 15d‐PGJ 2 were injected via the tail vein into rats immediately after CASP‐induced aspiration lung injury. Pathological changes in lung tissues, blood gas analysis, the wet/dry weight ratio (W/D) of the lung, levels of total proteins and number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) were determined. The cytokine levels were measured using ELISA. Protein expression was determined by Western blot. Bone‐marrow‐derived mesenchymal stem cells treatment significantly reduced alveolar oedema, exudation and lung inflammation; increased the arterial partial pressure of oxygen; and decreased the W/D of the lung, the levels of total proteins and the number of total cells and neutrophils in BALF in the rats with CASP‐induced lung injury. Bone‐marrow‐derived mesenchymal stem cells treatment decreased the levels of tumour necrosis factor‐α and Cytokine‐induced neutrophil chemoattractant (CINC)‐1 and the expression of p‐p65 and increased the levels of interleukin‐10 and 15d‐PGJ 2 and the expression of peroxisome proliferator‐activated receptor (PPAR)‐γ in the lung tissue in CASP‐induced rats. Tumour necrosis factor‐α stimulated BMSCs to secrete 15d‐PGJ 2. A tracking experiment showed that EGFP + BMSCs were able to migrate to local lung tissues. Treatment with 15d‐PGJ 2 also significantly inhibited CASP‐induced lung inflammation and the production of pro‐inflammatory cytokines. Our results show that BMSCs can protect lung tissues from gastric aspiration injury and inhibit lung inflammation in rats. A beneficial effect might be achieved through BMSC‐derived 15d‐PGJ 2 activation of the PPAR‐γ receptor, reducing the production of proinflammatory cytokines.

Background Adaptive servoventilation (ASV) is a new therapeutic modality to treat sleep-disordered breathing (SDB) especially for central sleep apnoea associated with Cheyne–Stokes respiration, whereas the role of ASV in SDB patients with heart failure (HF) is controversial. The purpose of this study was to evaluate the effects of ASV on these patients through a meta-analysis of published data. Methods A comprehensive literature search was performed to identify studies focused on ASV through databases, including PubMed, Medline, Embase, Cochrane Library and Web of science from 1950 to 2014. Parallel randomised controlled trials which compared ASV to other controls in HF and SDB patients with extractable data were meet our inclusion criteria. Random effects meta-analysis models were applied using RevMan 5.2. Results Seven studies involving 301 patients were recruited in the meta-analysis. The weighted mean difference in apnoea hyponea index (−17.73 events/h, 95% CI, −21.85 to −2.94) and left ventricular ejection fraction (MD: 4.68, 95% CI, 2.74–6.63) both favored ASV compared to control conditions. The urinary noradrenaline level (MD: −32.18, 95%CI: −44.07 to −20.09) was decreased, while the exercise capacity measured by 6-min walk distance (MD: 41.26, 95% CI, 17.06–65.45) was improved after ASV treatment. Whereas neither left ventricular end-diastolic diameter (LVEDD) nor Epworth sleepiness-scale score (ESS) significantly changed after ASV therapy. Conclusions ASV is superior to other therapy, as it can result in good consequences for patients with SDB and improve their prognosis in cardiac function. Further studies will still be needed to assess the benefit of it.

Background: The bidirectional relationship of asthma and obstructive sleep apnea (OSA) has been confirmed in recent years. However, in the clinical practice, majority of asthma patients did not pay adequate attention to their sleep apnea condition. Berlin questionnaire (BQ) and STOP-Bang questionnaire (SBQ) are two most common OSA screening questionnaires to screen high-risk patients for OSA. This study aimed at evaluating the predictive performance of BQ and SBQ for OSA in asthma patients. Methods: Asthma outpatients of Zhongshan Hospital were enrolled into the study. All patients were asked to fill in the BQ and SBQ and clinical characteristics and asthma characteristics were recorded. Univariate and multivariate logistic regression analyses were applied to identify risk factors of OSA in asthma patients. With the gold standard of laboratory-based overnight polysomnography (PSG), the predictive performance of SBQ and BQ was evaluated and compared. The probability of OSA severity was predicted by various SBQ scores in asthma patients. Results: A total of 123 asthma patients (average age 47.56±12.12 years; 57.72% males) were enrolled and underwent PSG diagnosis overnight at Sleep Center. Logistic regression analyses showed that rhinitis (adjusted OR =4.30; 95% CI: 1.50–12.37, P=0.007) and dyslipidemia (adjusted OR =2.75; 95% CI: 1.16–6.51, P=0.021) were associated with OSA in asthma patients after adjusting for known OSA risk factors. No asthma functional characteristic differences were found to be associated with OSA severity in the study. The prevalence of moderate-to-severe OSA (AHI ≥15) in the asthmatic population sample was 36.59% (45/123). Questionnaires predictive results showed that compared with BQ, SBQ has higher diagnostic sensitivity (84.4% vs . 60%), lower specificity (79.5% vs . 91%) lower positive predictive value (PPV): (70.4% vs . 79.4%) and higher negative predictive value (NPV) (90% vs . 80%) to detect moderate-to-severe OSA at the cut-off as AHI of 15/h. OSA probability results showed that with the increasing of the questionnaire scores, the moderate and severe OSA probability of SBQ rose significantly. Conclusions: SBQ is a preferable sleep questionnaire better than BQ for detecting moderate and severe OSA in asthma patients which should be validated in larger population sample.

Background and Aims Low-dose computed tomography (LDCT) has been proposed to be a new screening method to discover lung cancers in an early stage, especially those patients who are in a high risk of lung cancer. The primary objective of this meta-analysis is to systematically review the effect of LDCT on screening for lung cancers among the risky population who are older than 49 years old and with smoking exposure. Methods We searched randomized controlled clinical trials (RCTs) about comparing LDCT and chest X-ray or usual caring from MEDLINE, EMBASE, and the Cochrane Library, Web of Knowledge and Springerlink databases (January 1994 to September 2013). Results Nine RCTs met criteria for inclusion. Screening for lung cancer using LDCT resulted in a significantly higher number of stage I lung cancers [odds ratio (OR) 2.15, 95% confidence interval (CI) 1.88–2.47], higher number of total lung cancers (OR 1.31, 95% CI 1.20–1.43) than the control. Four of the nine studies indicated that the screening method did not decrease all-cause mortality (OR 0.96, 95% CI 0.90–1.02), but decreased lung cancer-specific mortality (OR 0.84, 95% CI 0.74–0.96). Five studies showed that LDCT had higher false-positive rates (OR 8.7, 95% CI 7.43–10.19) than the group of control. Conclusion Among the risky population, LDCT screening find out more stage I lung cancers and total lung cancers compared with chest X-ray or no screening, and also shows advantages in decreasing lung cancer-specific mortality, but the screening method does not decrease all-cause mortality and have a higher false-positive rates in diagnosis.

Background: Obstructive sleep apnea-hypopnea syndrome (OSAHS) could cause systematic inflammation including pulmonary inflammatory response, whereas the influence of OSAHS in pulmonary clearance ability remains unknown. The main pathophysiological feature of OSAHS is chronic intermittent hypoxia (CIH). The goal of this study is to clarify the airway clearance of particulate matter (PM) in CIH mice, and to explore the potential mechanism. Methods: Balb/c mice were divided into a CIH group and a control group, exposed to intermittent hypoxia and air chamber, respectively. A radioactive probe, 99mTc labeled PM, was endotracheally inserted into the mice at 10 mg/kg, with a starting dose of 800 μCi. The change of radioactive dose reserved in the lung was observed using single-photon emission computed tomography/computed tomography (SPECT/CT) and reconstructed data were analyzed. Special airway resistance (sRaw) of mice was measured by non-invasive airway mechanics sites. Lung resistive load (RL), elastic resistance, and compliance were measured by a multichannel physiological signal system. Lung injury was judged by hematoxylin-eosin staining and histologic score. Change in mucus secretion was determined using periodic acid-Schiff staining and enzyme-linked immunosorbent assay. Fresh lung tissue was used for real-time polymerase chain reaction and western blot analysis to explore related change of inflammation and signaling molecules and potential mechanical pathway. Results: Mice in the CIH group had higher PM radioactive deposit than the control group (93.37±3.44 μCi vs. 65.98±2.61 μCi). The average radiation dose in the lung was elevated (0.0005 μCi/mm3 vs. 0.0001383 μCi/mm3). Mice in the CIH group have higher value of sRaw, RL, and elastic resistance, whereas pulmonary compliance decreased compared to the control group (2.13±0.29 mL/cmH2O vs. 5.37±1.02 mL/cmH2O). The CIH group showed a higher histopathological score. Several genes associated with mucin secretion such as chemokine (C-X-C motif) ligand 1 (CXCL1), Clara Cell Secretory Protein 16 (CC16), macrophage inflammatory protein 2 (MIP-2), chloride channel regulator 1 (Gob5), and mucin 5AC (MUC5AC) showed elevated expression. Phosphatidylinostol-3-kinase/serine/threonine-specific protein kinase (PI3K/AKT) pathway was activated in the CIH group. Conclusions: CIH decreased pulmonary clearance of PM and increased lung airway resistance, which may be related to inflammatory response and mucus hypersecretion in the lung.

Evidence has shown that hypoxic episodes elicit hypoglossal neuroplasticity which depends on elevated serotonin (5-HT), in contrast to the rationale of obstructive sleep apnea (OSA) that deficient serotonergic input to HMs fails to keep airway patency. Therefore, understanding of the 5-HT dynamic changes at hypoglossal nucleus (HN) during chronic intermittent hypoxia (CIH) will be essential to central pathogenic mechanism and pharmacological therapy of OSA. Moreover, the effect of CIH on BDNF-TrkB signaling proteins was quantified in an attempt to elucidate cellular cascades/synaptic mechanisms following 5-HT alteration. Male rats were randomly exposed to normal air (control), intermittent hypoxia of 3 weeks (IH3) and 5 weeks (IH5) groups. Through electrical stimulation of dorsal raphe nuclei (DRN), we conducted amperometric technique with carbon fiber electrode in vivo to measure the real time release of 5-HT at XII nucleus. 5-HT2A receptors immunostaining measured by intensity and c-Fos quantified visually were both determined by immunohistochemistry. CIH significantly reduced endogenous serotonergic inputs from DRN to XII nucleus, shown as decreased peak value of 5-HT signals both in IH3 and IH5groups, whereas time to peak and half-life period of 5-HT were unaffected. Neither 5-HT2A receptors nor c-Fos expression in HN were significantly altered by CIH. Except for marked increase in phosphorylation of ERK in IH5 rats, BDNF-TrkB signaling and synaptophys consistently demonstrated downregulated levels. These results suggest that the deficiency of 5-HT and BDNF-dependent synaptic proteins in our CIH protocol contribute to the decompensated mechanism of OSA.

The specific DNA is typically impermeable to the plasma membrane due to its natural characters, but DNA tetra structures (DTNs) can be readily uptake by cells in the absence of transfection agents, providing a new strategy to deliver DNA drugs. In this research, the delivery efficiency of tetrahedral DNA nanostructures was measured on adenocarcinomic human alveolar basal epithelial (A549) cells via delivering AS1411 (G4). The DNA tetra-AS1411 complex was rapidly and abundantly uptake by A549 cells, and the induced apoptosis was enhanced. Furthermore, biodistribution in mouse proved the rapid clearance from non-targeted organs in vivo. This study improved the understanding of potential function in DNA-based drug delivery and proved that DTNs-AS1411 could be potentially useful for the treatment of lung cancer.

BACKGROUND Xeroderma pigmentosum complementation group A (XPA) gene is a key member of nucleotide excision repair pathway. It was reported that XPA rs1800975 polymorphism was associated with susceptibility to lung cancer. However, the conclusions were controversial. METHODS We conducted a computer retrieval of PubMed, EMbase, CNKI, CBM, and WanFang infrastructure platform from 1980 to 2014. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength. Publication bias was detected by means of a funnel plot. RESULTS A total of 11 articles (12 studies) involving 4257 cases and 5294 controls were included. Significant associations could be found between rs1800975 and lung cancer risk in these three models (codominant model AG vs. AA, overdominant genetic model AG vs. AA + GG, dominant model AG + GG vs. AA) in overall. In the stratified analysis by ethnicity, we found similar results as above in the Asian population. In the smoking population, the G allele carriers were associated with a significantly reduced risk of lung cancer (AG + GG vs. AA) compared with the AA carriers．Stratified analysis showed the AG genotype and G allele carriers (AG + GG) might be a protective factor compared with the AA gene for squamous carcinoma (AG vs. AA, AG + GG vs. AA). CONCLUSIONS This meta-analysis suggested that the XPA gene rs1800975 Polymorphism was associated with lung cancer susceptibility. By performing multiple separate pairwise comparisons, carriers with AG genotype under the codominant genetic model (AG vs. AA) might play actually the leading role in associating with lung cancer susceptibility in overall and in Asians.

Background Nocturnal heart block often occurs in patients with obstructive sleep apnoea (OSA). It is more likely to be undiagnosed in heart block patients who are ignorant of the symptoms of sleep disorder. Berlin Questionnaire (BQ) is a highly reliable way to discover the risk factors of OSA, whereas the validity in sleep-related heart block patients is uncertain. We performed an observational study to address these issues and confirmed the potential protective effect of continuous positive airway pressure (CPAP). Methods Patients who were previously diagnosed with nocturnal heart block with R-R pauses exceeding 2 seconds were retrospective screened from the ECG centre of Zhongshan hospital. These recruited participants completed Berlin Questionnaire and underwent polysomnography synchronously with 24-hour Holter monitoring. A cross-sectional analysis was performed to confirm the association between nocturnal arrhythmia and OSA, as well as to assess the diagnostic accuracy of the BQ. Subsequently, subjects diagnosed with OSA (apnoea-hypopnoea index > 5) underwent 3 consecutive days of CPAP therapy. On the third day, patients repeated 24-hour Holter monitoring within the institution of CPAP. Results The symptoms of disruptive snoring and hypersomnolence in 72 enrolled patients were more related to the occurrence of nocturnal heart block (r = 0.306, 0.226, respectively, p = 0.015, 0.019) than syncope (r = 0.134, p = 0.282) and palpitations (r = 0.106, p = 0.119), which were prominent trait of our study population. The sensitivity, specificity, positive and negative predictive value of the BQ at a cut-off point of 5 of AHI for detecting OSA in heart block patients was 81.0 %, 44.4 %, 91.07 % and 25 %. Nocturnal heart block does not appear to occur exclusively in severe sleep apnoea. The frequent occurrence of arrhythmias in prominent oxygen desaturation supports the correlation between them. CPAP therapy resulted in significant decrease in the average number of episodes of heart block, from 148.58 ± 379.44 to 16.07 ± 58.52 (p

Adaptive servoventilation (ASV) is a new therapeutic modality to treat sleep-disordered breathing (SDB) especially for central sleep apnoea associated with Cheyne-Stokes respiration, whereas the role of ASV in SDB patients with heart failure (HF) is controversial. The purpose of this study was to evaluate the effects of ASV on these patients through a meta-analysis of published data.A comprehensive literature search was performed to identify studies focused on ASV through databases, including PubMed, Medline, Embase, Cochrane Library and Web of science from 1950 to 2014. Parallel randomised controlled trials which compared ASV to other controls in HF and SDB patients with extractable data were meet our inclusion criteria. Random effects meta-analysis models were applied using RevMan 5.2.Seven studies involving 301 patients were recruited in the meta-analysis. The weighted mean difference in apnoea hyponea index (-17.73 events/h, 95% CI, -21.85 to -2.94) and left ventricular ejection fraction (MD: 4.68, 95% CI, 2.74-6.63) both favored ASV compared to control conditions. The urinary noradrenaline level (MD: -32.18, 95%CI: -44.07 to -20.09) was decreased, while the exercise capacity measured by 6-min walk distance (MD: 41.26, 95% CI, 17.06-65.45) was improved after ASV treatment. Whereas neither left ventricular end-diastolic diameter (LVEDD) nor Epworth sleepiness-scale score (ESS) significantly changed after ASV therapy.ASV is superior to other therapy, as it can result in good consequences for patients with SDB and improve their prognosis in cardiac function. Further studies will still be needed to assess the benefit of it.

Raf1 kinase inhibitor protein (RKIP) negatively regulates the Raf1/MEK/ERK pathway which is vital for cell growth and differentiation. It is also a biomarker in clinical cancer diagnosis. RKIP binds to the N-terminus of Raf1 kinase but little is known about the structural basis of RKIP binding with Raf1. Here, we demonstrate that the N-terminus of human Raf1 kinase (hRaf11-147aa) binds with human RKIP (hRKIP) at its ligand-binding pocket, loop "127-149", and the C-terminal helix by NMR experiments. D70, D72, E83, Y120, and Y181 were further verified as the key residues participating in the interaction of hRKIP and hRaf11-147aa. G143-R146 fragment was also critical for hRKIP binding with hRaf11-147aa, for its deletion decreased the binding affinity around 300 times, from 154 to 0.46 mM(-1). Our results provide important structural clues for designing the lead compound that disrupts RKIP-Raf1 interaction.

Chronic intermittent hypoxia is the primary pathophsiological feature of obstructive sleep apnea/hypopnea syndrome. The characteristics of CIH can be imitated by animal experiment models thus to study CIH related systemic organ injuries, including respiratory systems. Sixteen male SD rats were randomly divided into two groups: CIH group (n = 8) and control group (n = 8). The CIH group was exposed to intermittent hypoxia circumstance for 5 weeks (8 h/day) and control group was placed in the same animal chamber exposed to normal air circumstance. Between the two groups, the inflammatory factors of IL-6 and TNF-α within serum and BALF were measured by ELISA; the structure and ultrastructure of lungs were evaluated by HE staining and electronmicroscopy. The nuclear factor-κB (NF-κB) in lung tissue was detected by Western blot. The concentration of IL-6 and TNF-α in serum in CIH group increased significantly (138.63 ± 43.82 vs. 41.82 ± 5.24 pg/ml and 126.62 ± 34.81 vs. 73.43 ± 5.72 pg/ml, both P