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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.

Luminescent metal-organic frameworks (MOFs), which incorporate some guest luminescent molecules/ions into MOFs, have attracted extensive attention because of their exceptional optical properties. However, traditional luminescent MOFs are mainly responsive to ultraviolet (UV) or visible light, which has limited their bioapplications due to the restrained tissue penetration depths. In this study, we have constructed a diagnostic nanoplatform UCNP@MOF consisting of upconverting metal-organic frameworks, which combine the photo-upconverting characteristics of the upconversion nanoparticles (UCNPs) with the unique physicochemical properties of Al-MOFs. Specifically, the core-shell structured UCNP@MOF nanocomposites were prepared by poly(vinylpyrrolidone) (PVP)-regulated nucleation of Al-MOF layer on the UCNP surface. When excited by a 980 nm laser light, the green signal released from UCNPs can trigger the photosensitive Al-MOFs to produce a large amount of singlet oxygen (

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.

Pulmonary hypertension (PH) is prevalent in patients with obstructive sleep apnea (OSA) syndrome, and coexistence of PH and OSA indicates a worse prognosis and higher mortality. Chronic intermittent hypoxia (CIH) is the key pathogenesis of OSA. Also, microRNA-223 (miR-223) plays a role in the regulation of CIH-induced PH process. However, the detailed mechanism of CIH inducing PH is still unclear. This study aimed to investigate the pathological process of CIH associated PH and explore the potential therapeutic methods. In this study, adult Sprague-Dawley rats were exposed to CIH or normoxic (N) conditions with 2-methoxyestradiol (2-Me) or vehicle treatment for 6 weeks. The results showed that 2-Me treatment reduced the progression of pulmonary angiogenesis in CIH rats, and alleviated proliferation, cellular migration, and reactive oxygen species formation was induced by CIH in pulmonary artery smooth muscle cells (PASMCs). CIH decreased the expression of miR-223, whereas 2-Me reversed the downregulation of miR-223 both in vivo and in vitro. Furthermore, the antiangiogenic effect of 2-Me observed in PASMCs was abrogated by miR-223 inhibitor, while enhanced by miR-223 mimic. These findings suggested that miR-223 played an important role in the process of CIH inducing PH, and 2-Me might reverse CIH-induced PH via upregulating miR-223.

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.

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.

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.

The disruption of signal transducer and activator of transcription 4 (STAT4) signal can inhibit the inflammation and protect organs from injury during severe bacterial infection. However, the mechanism of STAT4 signal in lung injury remains poor understood. Here we report that STAT4 deficiency decreased the lethality and protein leakage in STAT4(-/-) mice and protected lipopolysaccharid (LPS)-induced lung injury with ameliorated edema, inflammatory infiltration and hemorrhage. The expression of CD11b(+)Gr-1(+) myeloid derived suppressor cells (MDSCs) markedly increased in the circulation of STAT4(-/-) mice after LPS stimuli, accompanying with increased macrophages infiltration in inflamed lung tissue. In addition, the levels of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 decreased while anti-inflammatory cytokine (IL-10) increased in the bronchoalveolar lavage fluid of STAT4(-/-) mice. Thus, these results indicate that the accumulation of MDSCs and macrophages play a critical role in LPS-induced lung injury. Targeting MDSCs and macrophages polarization through a STAT4 dependent signaling pathway might help to reduce the inflammation and damage of lung tissue.

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.

Chronic intermittent hypoxia (CIH) is the main pathophysiological feature of obstructive sleep apnea (OSA). It destroys the normal sleep rhythm and affects many basic physiological processes, leading to repeated arousal from sleep. Orexin, a very potent arousal neuromodulator found in the brain, has been shown to play a significant role in the promotion and maintenance of arousal. These findings may indicate that orexin participates in the arousal-promoted processes induced by CIH. However, so far, little is known about alterations in orexin and its receptors during CIH. In the present study, the influence of CIH and re-oxygenation on the expression of prepro-orexin (PPO) in the hypothalamus and orexin receptors in the hypothalamus and the medulla of rats were evaluated. The expression of PPO, OX1R, and OX2R mRNA was evaluated by RT-PCR after the rats had been exposed to intermittent hypoxia (IH) for either 1 week or 5 weeks. The control group was exposed to intermittent air (IA). The results showed the levels of expression of PPO, OX1R, and OX2R mRNA to be significantly higher in the brains of rats exposed to IH for 5 weeks than in the brains of control rats. This effect was reversed by 5 weeks of re-oxygenation. These findings indicated that CIH could increase the expression of orexin and its receptors in the brain. This may contribute to the sleep fragmentation experienced by patients with OSA, which is induced by repeated arousal.

Protein–nanoparticle interactions are important in biomedical applications of nanoparticles and for growing biosafety concerns about nanomaterials. In this study, the interactions of four plasma proteins, human serum albumin (HSA), myoglobin (MB), hemoglobin (HB), and trypsin (TRP), with Au and Ag nanoparticles were investigated by FT-IR spectroscopy. The secondary structure of thio-proteins changed with time during incubation with Au and Ag nanoparticles, but the secondary structures of non-thio-proteins remained unchanged. The incubation time for structural changes depended on the sulfur–metal bond energy; the stronger the sulfur–metal energy, the less the time needed. H/D exchange experiments revealed that protein–NP complexes with thio-proteins were less dynamic than free proteins. No measurable dynamic differences were found between free non-thio-proteins and the protein–Au (or Ag) nanoparticle complex. Therefore, the impact of covalent bonds on the protein structure is greater than that of the electrostatic force.

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

The aim of this study was to determine whether chronic intermittent hypoxia (CIH) could affect the secretion of adipokines, such as resistin, leptin, and adiponectin, in non-obese rats and to investigate the potential mechanisms. An established rodent model of CIH was utilized, in which rats were exposed to varying oxygen levels (7–21 %) respectively over a period of 5 weeks. The area under the curve (AUCG) and the insulin resistance index (homeostasis model of assessment for insulin resistance index, HOMA-IR) were calculated. The levels of several secretory factors in the blood were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA levels and protein expression in adipose tissues was measured by reverse transcription-polymerase chain reaction (RT-PCR). Glucose tolerance and the levels of adiponectin in non-obese rats were decreased in the CIH group both in the serum and adipose tissue compared with the controls, while the insulin resistance index and the levels of resistin and leptin were increased. Moreover, the expressions of hypoxia inducible factor-1α and lactate dehydrogenase A were significantly higher in chronic intermittent hypoxia rats than in control rats, suggesting the presence of adipose tissue hypoxia. These results show that CIH leads to insulin resistance (IR) and impaired glucose tolerance (IGT) in a non-obese rodent model of obstructive sleep apnea-hypopnea syndrome, and these effects may be due to the dysregulation of adiponectin, resistin, and leptin.

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