AS could adversely affect the HRQoL of patients. Measuring HRQoL should be considered as an essential part of the overall assessment of health status of AS patients, which would provide valuable clues for improving the management of disease and making decisions regarding treatment.

Neurite extension and branching are affected by activity-dependent modulation of intracellular Ca 2+ , such that an optimal window of [Ca 2+ ] i is required for outgrowth. Our understanding of the molecular mechanisms regulating this optimal [Ca 2+ ] i remains unclear. Taking advantage of the large growth cone size of cultured primary neurons from pond snail Lymnaea stagnalis combined with dsRNA knockdown, we show that neuronal calcium sensor-1 (NCS-1) regulates neurite extension and branching, and activitydependent Ca 2+ signals in growth cones. An NCS-1 C-terminal peptide enhances only neurite branching and moderately reduces the Ca 2+ signal in growth cones compared with dsRNA knockdown. Our findings suggest that at least two separate structural domains in NCS-1 independently regulate Ca 2+ influx and neurite outgrowth, with the C-terminus specifically affecting branching. We describe a model in which NCS-1 regulates cytosolic Ca 2+ around the optimal window level to differentially control neurite extension and branching.

BackgroundCognitive impairment has been found in chronic obstructive pulmonary disease (COPD) patients. However, the structural alteration of the brain and underlying mechanisms are poorly understood.MethodsThirty-seven mild-to-moderate COPD patients, forty-eight severe COPD patients, and thirty-one control subjects were recruited for cognitive test and neuroimaging studies. Serum levels of S100B,pulmonary function and arterial blood gas levels were also evaluated in each subject.ResultsThe hippocampal volume was significantly smaller in COPD patients compared to the control group. It is positively correlated with a mini mental state examination (MMSE) score, SaO2 in mild-to-moderate COPD patients, the levels of PaO2 in both mild-to-moderate and severe COPD patients. Higher S100B concentrations were observed in mild-to-moderate COPD patients, while the highest S100B level was found in severe COPD patients when compared to the control subjects. S100B levels are negatively associated with MMSE in both mild-to-moderate and severe COPD patients and also negatively associated with the hippocampal volume in the total COPD patients.ConclusionsHippocampal atrophy based on quantitative assessment by magnetic resonance imaging does occur in COPD patients, which may be associated with cognitive dysfunction and the most prevalent mechanism accountable for hippocampal atrophy is chronic hypoxemia in COPD. Higher serum S100B levels may be peripheral biochemical marker for cognitive impairment in COPD.

Background: Chronic obstructive pulmonary disease (COPD) is understood to be a complex multicomponent disorder. The impairment of cognition is lasting and profound. However, the pattern of the cognitive decline and potentially adverse factors are poorly understood. Objectives: To evaluate the cognitive performances and the relevant factors in COPD patients and to investigate the relationship between cognition deficits and the classification of severity of the disease. Methods: Twenty-seven mild-to-moderate COPD patients, 35 severe COPD patients and 27 control subjects were recruited. Cognitive states were investigated by the Mini-Mental State Examination (MMSE). Pulmonary function, arterial blood gas and serum clusterin level were evaluated in each subject. Results: Lower MMSE score and higher serum clusterin concentration were observed in mild-to-moderate COPD patients, while the lowest MMSE score and the highest serum clusterin level were found in severe COPD patients when compared with control subjects. MMSE score is positively correlated with arterial oxygen tension and is inversely associated with serum clusterin level in both mild-to-moderate and severe COPD patients. Furthermore, MMSE scores and serum clusterin concentrations were correlated with forced expiratory volume in 1 s in severe COPD patients. Conclusion: Cognitive impairment was found in COPD patients. It is associated with the classification of disease severity, hypoxemia and serum clusterin level. An increased serum clusterin level may be a relevant peripheral biomarker of cognitive dysfunction in COPD patients.

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The use of TCZ could significantly reduce the need of corticosteroids for AOSD patients. Impressive improvements were attained in both clinical and laboratory parameters. Compared with conventional therapy, TCZ treatment was safety. In conclusion, TCZ was effective and well tolerated for the treatment of AOSD.

Toll-like receptor 2 (TLR2) is suggested to initiate the activation of NLRP3 inflammasome, and considered to be involved in asthma. The findings that melatonin modulates TLRs-mediated immune responses, together with the suppressing effect of TLRs on endogenous melatonin synthesis, support the possibility that a feedback loop exists between TLRs system and endogenous melatonin synthesis. To determine whether TLR2-melatonin feedback loop exists in allergic airway disease and regulates NLRP3 inflammasome activity, wild-type (WT) and TLR2 −/− mice were challenged with OVA to establish allergic airway disease model. Following OVA challenge, WT mice exhibited increased-expression of TLR2, activation of NLRP3 inflammasome and marked airway inflammation, which were all effectively inhibited in the TLR2 −/− mice, indicating that TLR2-NLRP3 mediated airway inflammation. Meanwhile, melatonin biosynthesis was reduced in OVA-challenged WT mice, while such reduction was notably rescued by TLR2 deficiency, suggesting that TLR2-NLRP3-mediated allergic airway inflammation was associated with decreased endogenous melatonin biosynthesis. Furthermore, addition of melatonin to OVA-challenged WT mice pronouncedly ameliorated airway inflammation, decreased TLR2 expression and NLRP3 inflammasome activation, further implying that melatonin in turn inhibited airway inflammation via suppressing TLR2-NLRP3 signal. Most interestingly, although melatonin receptor antagonist luzindole significantly reduced the protein expressions of ASMT, AANAT and subsequent level of melatonin in OVA-challenged TLR2 −/− mice, it exhibited null effect on leukocytes infiltration, Th2-cytokines production and NLRP3 activity. These results indicate that a TLR2-melatonin feedback loop regulates NLRP3 inflammasome activity in allergic airway inflammation, and melatonin may be a promising therapeutic medicine for airway inflammatory diseases such as asthma.

Background: Chronic obstructive pulmonary disease (COPD) exacerbations are accompanied with increased systemic inflammation, which accelerate the pulmonary function injury and impair the quality of life. Prompt and effective treatments for COPD exacerbations slow down the disease progression, but an objective instrument to assess the efficacy of the treatments following COPD exacerbations is lacking nowadays. The COPD Assessment Test (CAT) is an 8-item questionnaire designed to assess and quantify health status and symptom burden in COPD patients. We hypothesize that the change in CAT score is related to the treatment response following COPD exacerbations. Methods: 78 inpatients with clinician-diagnosed acute exacerbation of COPD (AECOPD) completed the CAT, St George's Respiratory Questionnaire (SGRQ) and modified Medical Research Council (mMRC) Dyspnea Scale both at exacerbation and the 7th day of therapy, and a subgroup of 39 patients performed the pulmonary function test. Concentrations of serum C-reactive protein (CRP) and plasma fibrinogen were assayed at the same time. Correlations between the CAT and other measurements were examined. Results: After 7 days' therapy, the CAT and SGRQ scores, mMRC grades, as well as the concentrations of CRP and fibrinogen all decreased significantly (P < 0.001). Meanwhile, the FEV1% predicted had a significant improvement (P < 0.001). The CAT scores were significantly correlated with concurrent concentrations of CRP and fibrinogen, SGRQ scores, FEV1% predicted and mMRC grades (P < 0.05). The change in CAT score was positively correlated with the change of CRP (r = 0.286, P < 0.05), SGRQ score (r = 0.725, P < 0.001) and mMRC grades (r = 0.593, P < 0.001), but not with fibrinogen (r = 0.137, P > 0.05) or FEV1% predicted (r = −0.101, P > 0.05). No relationship was found between the changes of SGRQ score and CRP and fibrinogen (P>0.05).