The effects of cigarette smoking (CS) cessation on the diaphragm are unknown, as are the CS-induced diaphragmatic mitochondrial changes. We examined the changes in diaphragm contractility, as well as alterations in mitochondrial morphology, function and homoeostasis during CS exposure and after cessation. Rats were randomly divided into CS exposure and CS cessation groups: 3-month CS (S3), 6-month CS (S6), 6-month CS followed by 3-month cessation (S6N3). The changes in the diaphragm were investigated, including contractile properties, the ultrastructure, mitochondrial function and the expression of markers of mitochondrial homoeostasis. CS caused irreversible histological disruption and functional depression in the lungs, along with significantly declines in diaphragmatic contractility and more severely in extensor digitorum longus muscular contractility. Such declines were recovered after 3-month CS cessation. CS exposure disrupted the diaphragmatic mitochondrial morphology and function (S6), which was significantly alleviated in the S6N3 group. The mitochondrial homoeostasis was depressed (S6), as indicated by the downregulation of Pink1 and Mfn1. Interestingly, the Mfn1 level was recovered after smoking cessation (S6N3). In conclusion, smoking cessation eased CS-induced diaphragmatic dysfunction and mitochondrial deregulation, which are likely associated with deregulated mitochondrial homoeostasis.

Abstract Background: Cigarette smoking (CS) is one of the greatest risk factors for the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). Although CS cessation is beneficial in preventing COPD progression, the effects of cessation on the diaphragm are unknown, as are the CS-induced mitochondrial changes in the diaphragm during COPD and CS-cessation. In this study, we examined the alterations in mitochondrial morphology and homeostasis, as well as changes in diaphragm contractility during CS exposure and after cessation.Methods: Rats were randomly divided into control, CS-exposure, and CS-cessation groups, including 3-month CS (S3), 6-month CS (S6), 6-month CS followed by 3 months cessation (S6N3), and age-matched control groups. The histological and functional changes in the lungs were examined to evaluate the CS-induced COPD model. The alterations in the diaphragm were further investigated, including contractile properties, the ultrastructure, and the expression of markers of mitochondrial homeostasis.Results: CS exposure caused histological disruption and functional depression in the lungs, and CS cessation failed to result in a significant recovery. CS induced a significant decline in diaphragmatic muscle contractility, accompanied with sever contractile dysfunction in extensor digitorum longus muscles, which was recovered after 3-month CS cessation. CS exposure in parallel disrupted the mitochondrial morphology in diaphragmatic muscle, including decreases in volume density and number density in the S6 group, which was significantly alleviated in the S6N3 group. The mitochondrial quality control was likely depressed in the S6 group, as indicated by the downregulation of Pink1 and Mfn1, markers for mitophagy and mitochondrial fusion/fission. Interestingly, the Mfn1 protein level was recovered after smoking cessation in the S6N3 group.Conclusions: Smoking cessation eased CS-induced diaphragmatic dysfunction and mitochondrial deregulation, but not the adverse changes in pulmonary structure. These diaphragmatic muscle changes are likely associated with deregulated mitochondrial homeostasis, including mitophagy and mitochondrial fusion/fission.

Purpose To examine the levels of 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero phosphatidylcholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-phosphatidylcholine (PGPC) (the oxidized phosphatidylcholines) in HDL during the course of sepsis and to evaluate their prognostic value. Materials and Methods This prospective cohort pilot study enrolled 25 septic patients and 10 healthy subjects from 2020 to 2021. The HDLs were extracted from patient plasmas at day 1, 3 and 7 after sepsis onset and from healthy plasmas (total 81 plasma samples). These HDLs were then subjected to examining POVPC and PGPC by using an ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) system. We further measured the levels of 38 plasma cytokines by Luminex and evaluated the correlation of HDL-POVPC level with these cytokines. Patients were further stratified into survivors and non-survivors to analyze the association of HDL-POVPC level with 28-day mortality. Results Septic patients exhibited significant increase of HDL-POVPC at day 1, 3 and 7 after sepsis onset (POVPC-D1, p=0.0004; POVPC-D3, p=0.033; POVPC-D7, p=0.004, versus controls). HDL-PGPC was detected only in some septic patients (10 of 25) but not in healthy controls. Septic patients showed a significant change of the plasma cytokines profile. The correlation assay showed that IL-15 and IL-18 levels were positively correlated with HDL-POVPC level, while the macrophage-derived chemokine (MDC) level was negatively correlated with HDL-POVPC level. Furthermore, HDL-POVPC level in non-survivors was significantly increased versus survivors at day 1 and 3 (POVPC-D1, p=0.002; POVPC-D3, p=0.003). Area under ROC curves of POVPC-D1 and POVPC-D3 in predicting 28-day mortality were 0.828 and 0.851. POVPC-D1and POVPC-D3 were the independent risk factors for the death of septic patients (p=0.046 and 0.035). Conclusions HDL-POVPC was persistently increased in the course of sepsis. POVPC-D1 and POVPC-D3 were significantly correlated with 28-mortality and might be valuable to predict poor prognosis.

Acute respiratory distress syndrome (ARDS) is characterized by acute lung injury (ALI) secondary to an excessive alveolar inflammatory response. Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum (ER) lumen protein in the secretory pathway. We previously reported the indispensable role of Rcn3 in type II alveolar epithelial cells (AECIIs) during lung development and the lung injury repair process. In the present study, we further observed a marked induction of Rcn3 in the alveolar epithelium during LPS-induced ALI. In vitro alveolar epithelial (MLE-12) cells consistently exhibited a significant induction of Rcn3 accompanied with NF-κB activation in response to LPS exposure. We examined the role of Rcn3 in the alveolar inflammatory response by using mice with a selective deletion of Rcn3 in alveolar epithelial cells upon doxycycline administration. The Rcn3 deficiency significantly blunted the ALI and alveolar inflammation induced by intratracheal LPS instillation but not that induced by an intraperitoneal LPS injection (secondary insult); the alleviated ALI was accompanied by decreases in NF-κB activation and NLRP3 levels but not in GRP78 and cleaved caspase-3 levels. The studies conducted in MLE-12 cells consistently showed that Rcn3 knockdown blunted the activations of NF-κB signaling and NLRP3-dependent inflammasome upon LPS exposure. Collectively, these findings suggest a novel role for Rcn3 in regulating the alveolar inflammatory response to pulmonary infection via the NF-κB/NLRP3/inflammasome axis and shed additional light on the mechanism of ARDS/ALI.

Background:: High density lipoprotein-cholesterol (HDL-C) concentration decreases in septic patients and the low level of HDL-C is associated with poor prognosis. However, no study has yet analyzed its prognostic implication specifically in pneumonia-ARDS cohort. Objectives:: To evaluate the prognostic value of HDL-C levels in ARDS patients secondary to bacterial and viral pneumonia. Methods:: This was a retrospective observational study on 108 pneumonia-ARDS patients in RICU from 2017 to 2019. These patients were stratified into bacterial ARDS group (56) and viral ARDS group (52). The primary outcome was the association between HDL-C levels and 28-day mortality. Results:: HDL-C levels were statistically lower in bacterial ARDS patients than those in viral ARDS patients (p<0.001). There were statistic negative correlations between HDL-C and APACHE II/SOFA score in bacterial ARDS patients (r=-0.284, p = 0.034 and r=-0.369, p = 0.005), but not in viral ARDS patients (r=-0.103, p = 0.469 and r=-0.225, p = 0.108). ROC analysis demonstrated that HDL-C had superior prediction value for 28-day mortality and identified HDL-C < 0.42 mmol/L was significantly associated with adverse outcomes in bacterial ARDS patients. The low HDL-C was an independent risk factor for death of bacterial ARDS patients (OR 0.027, 95% CI [0.001-0.9051,P= 0.044). Conclusions:: HDL-C might be a valuable marker to assess the 28-d mortality for bacterial ARDS patients rather than viral ARDS patients. (C) 2020 Elsevier Inc. All rights reserved.

Background Septic acute respiratory distress syndrome (ARDS), characterized by the acute lung injury (ALI) secondary to aberrant systemic inflammatory response, has high morbidity and mortality. Despite increased understanding of ALI pathogenesis, the therapies to prevent lung dysfunction underlying systemic inflammatory disorder remain elusive. The high density lipoprotein (HDL) has critical protective effects in sepsis and its dysfunction has a manifested contribution to septic organ failure. However, the adverse changes in HDL composition and function in septic ARDS patients are large unknown. Method To investigate HDL remodeling in septic ARDS, we analyzed composition changes of plasma HDL from 40 patients with septic ARDS (A-HDL) and 40 matched normal controls (N-HDL). To determine the deleterious functional remodeling of HDL, A-HDL or N-HDL was administrated to C57BL/6 and apoA-I knock-out (KO) mice after cecal ligation and puncture (CLP) procedure. Mouse lung microvascular endothelial cells (MLECs) were further treated by these HDLs to investigate whether the adverse effects of A-HDL were associated with endothelial dysfunction. Results ARDS patients showed significant changes of HDL composition, accompanied with the dramatic decrease in plasma HDL-C. We further indicated that A-HDL treatment aggravated CLP induced ALI. Intriguingly, this deleterious effects of A-HDL were associated with pulmonary endothelial dysfunction, rather than the deregulation of plasma lipopolysaccharide (LPS). Further in vitro results demonstrated the direct effects of A-HDL on MLECs, including increased expressions of adhesion proteins and pro-inflammatory cytokines via activating NF-κB signaling and decreased junction protein expression. Conclusions Our results depicted a sepsis induced remodeling in HDL quality, which predisposes lung to ARDS via inducing ECs dysfunction. These results also demonstrated the importance of circulating HDL in regulating alveolar homeostasis.

1Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Emergency Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4The Clinical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China Aims: The aim of the study was to explore the functional and structural changes of the diaphragm and underlying mechanisms in response to 12 or 24 weeks of cigarette smoke (CS) exposure in rats. Materials and Methods: Rats were exposed to CS to develop a COPD model and the rats exposed to room air served as a control group. Rats were randomly divided into four groups: CS12W, CON12W, CS24W, and CON24W. Pulmonary function, lung histopathology, and the contractile properties and ultrastructure of diaphragm muscle were examined in these rats. The changes of transcriptomic profiling of diaphragm muscle were further compared between CS and control rats by the RNA Seq. Results: Both CS groups showed lower FEV0.3/FVC, elevated mean linear intercept (MLI), and reduced mean alveolar numbers (MAN) vs the control groups. The fatigue index (FI) of the diaphragm muscle from the CS12W group, but not CS24W, was significantly increased. Conversely, the force–frequency curves of the diaphragm muscle from the CS24W group, but not CS12W group, were significantly decreased. Consistently, mitochondrial number density (NA) and volume density (Vv) were increased in the CS12W diaphragm muscle, while being decreased in the CS24W group. Furthermore, the diaphragm transcriptomic profiling results showed that genes regulating cell proliferation and energy metabolic activity were un-regulated and genes regulating protein degradation were down-regulated in the CS12W diaphragm, while CS24W diaphragm showed opposite changes. Conclusion: These observations suggested a transition of diaphragm muscle from initial compensatory to decompensatory changes in function, structure, and gene expression during the development of COPD.

Controlled mechanical ventilation (CMV) can cause diaphragmatic motionlessness to induce diaphragmatic dysfunction. Partial maintenance of spontaneous breathing (SB) can reduce ventilation-induced diaphragmatic dysfunction (VIDD). However, to what extent SB is maintained in CMV can attenuate or even prevent VIDD has been rarely reported. The current study aimed to investigate the relationship between SB intensity and VIDD and to identify what intensity of SB maintained in CMV can effectively avoid VIDD. Adult rats were randomly divided according to different SB intensities: SB (0% pressure controlled ventilation (PCV)), high-intensity SB (20% PCV), medium-intensity SB (40% PCV), medium-low intensity SB (60% PCV), low-intensity SB (80% PCV), and PCV (100% PCV). The animals underwent 24-h controlled mechanical ventilation (CMV). The transdiaphragmatic pressure (Pdi), the maximal Pdi (Pdi max) when phrenic nerves were stimulated, Pdi/Pdi max, and the diaphragmatic tonus under different frequencies of electric stimulations were determined. Calpain and caspase-3 were detected using ELISA and the cross-section areas (CSAs) of different types of muscle fibers were measured. The Pdi showed a significant decrease from 20% PCV and the Pdi max showed a significant decrease from 40% PCV (P<0.05). In vivo and vitro diaphragmatic tonus exhibited a significant decrease from 40% PCV and 20% PCV, respectively (P<0.05). From 20% PCV, the CSAs of types I, IIa, and IIb/x muscle fibers showed significant differences, which reached the lowest levels at 100% PCV. SB intensity is negatively associated with the development of VIDD. Maintenance of SB at an intensity of 60%-80% may effectively prevent the occurrence of VIDD.

Aims: The aim of the study was to explore the functional and structural changes of the diaphragm and underlying mechanisms in response to 12 or 24 weeks of cigarette smoke (CS) exposure in rats. Materials and Methods: Rats were exposed to CS to develop a COPD model and the rats exposed to room air served as a control group. Rats were randomly divided into four groups: CS12W, CON12W, CS24W, and CON24W. Pulmonary function, lung histopathology, and the contractile properties and ultrastructure of diaphragm muscle were examined in these rats. The changes of transcriptomic profiling of diaphragm muscle were further compared between CS and control rats by the RNA Seq. Results: Both CS groups showed lower FEV0.3/FVC, elevated mean linear intercept (MLI), and reduced mean alveolar numbers (MAN) vs the control groups. The fatigue index (FI) of the diaphragm muscle from the CS12W group, but not CS24W, was significantly increased. Conversely, the force-frequency curves of the diaphragm muscle from the CS24W group, but not CS12W group, were significantly decreased. Consistently, mitochondrial number density (N A ) and volume density (Vv) were increased in the CS12W diaphragm muscle, while being decreased in the CS24W group. Furthermore, the diaphragm transcriptomic profiling results showed that genes regulating cell proliferation and energy metabolic activity were un-regulated and genes regulating protein degradation were down-regulated in the CS12W diaphragm, while CS24W diaphragm showed opposite changes. Conclusion: These observations suggested a transition of diaphragm muscle from initial compensatory to decompensatory changes in function, structure, and gene expression during the development of COPD.

Purpose: To determine whether there is a certain relationship between spontaneous breathing intensity and the severity of ventilator-induced diaphragmatic dysfunction (VIDD) and which spontaneous breathing intensity could effectively prevent VIDD. Materials and Methods: Sixty Sprague-Dawley rats were randomly assigned to one of the following: 1) absolute spontaneous breathing (100%SB); 2) 80% of spontaneous breathing intensity (80%SB); 3) 60% of spontaneous breathing intensity (60%SB); 4) 40% of spontaneous breathing intensity (40%SB); 5) 20% of spontaneous breathing intensity (20%SB); or 6) absolute CMV (0%SB). After 24 hours of respective mechanical ventilation, we carried out the following measurements on diaphragm specimens: transdiaphragmatic pressure (Pdi), Pdi max, diaphragmatic tetanic force (in vivo and in vitro), active calpain and casepase-3 levels, myofiber cross-sectional area (CSA). Results: With the decrease of the spontaneous breathing intensity, Pdi, Pdi max, in vivo and in vitro diaphragmatic tetanic force decreased, active calpain and casepase-3 levels increased, and myofiber CSA reduced. Compared to the intensity with 100% SB, those with less than 60%-80% SB resulted in a significant decrease in Pdi, Pdi max, in vivo and in vitro diaphragmatic tetanic force, those with less than 20% SB resulted in a significant increase in active calpain and casepase-3 levels, and those with less than 80% SB resulted in a significant decrease in myofiber CSA. Conclusions: There is a significant negative correlation between spontaneous breathing intensity and VIDD; preserving spontaneous breathing with the intensity of more than 60%-80% may be helpful to prevent VIDD.

BACKGROUND:To assess the usefulness of the neutrophil/lymphocyte ratio (NLR), a marker of inflammation and/or stress, for predicting weaning failure in patients receiving invasive mechanical ventilation (IMV), compared to levels of leukocytes and C-reactive protein (CRP). METHODS:This observational prospective cohort study was conducted from July 2013 to December 2016 in an intensive care unit in China, enrolling 269 consecutive patients receiving IMV. Patients underwent a spontaneous breathing trial (SBT) if they were ready to wean, and underwent extubation if they passed the SBT. The evaluated markers were measured immediately prior to SBT, and compared between weaning-failure and weaning-success patients. Receiver-operating characteristic (ROC) curve and logistic regression analyses were used to evaluate the ability of these markers to predict weaning failure. RESULTS:In all, 94 (34.9%) patients failed the weaning process (66 failed SBT and 28 presented with post-extubation respiratory distress). NLR was a better predictor of failure (area under the ROC curve, 0.69; 95% CI, 0.62-0.76) than leukocyte levels (0.60, 0.53-0.67) and CRP values (0.58, 0.51-0.65). NLR >11, leukocyte counts >10.5×109/L, and CRP >58 mg/L prior to weaning had the best combination of sensitivity (73%, 64%, and 63%, respectively), specificity (59%, 55%, and 63%), positive predictive value (49%, 43%, and 48%), negative predictive value (81%, 74%, and 76%), and diagnostic accuracy (64%, 58%, and 63%) for predicting weaning failure. However, only NLR >11 (odds ratio, 5.91; 95% CI, 3.08-11.33; P<0.001) was an independent predictor of weaning failure in the adjusted logistic regression model. CONCLUSIONS:NLR may be a useful marker for predicting weaning failure, and weaning at NLR >11 might be considered with caution. Further study with a larger sample size and with weaning outcome as a variable of concern is warranted. Trial registration: ClinicalTrials.gov identifier: NCT02981589.

We evaluated the impact of renal impairment on lung function, frequency of acute exacerbations, and quality of life of patients with chronic obstructive pulmonary disease (COPD). This retrospective observational study was conducted at the Beijing Chaoyang Hospital, China, from Jan. 2012 to Dec. 2015. A total of 182 COPD patients were stratified into four groups based on disease severity and followed for up to one year. Indicators of renal injury (proteinuria and estimated glomerular filtration rate [eGFR]) were measured. Questionnaire surveys (COPD assessment test [CAT], quality of life assessment [British Medical Research Council, mMRC]), lung function, and 6-min walking distance (6WMD) were conducted every three months. The prevalence of renal impairment increased with COPD severity class (X-2 = 10.823, P = 0.013). COPD patients with renal impairment had significantly worse lung functions, CAT and mMRC scores, 6WMD, and increased frequency of exacerbations compared with patients without renal injury. In summary, impaired renal function is a common aggravating factor in patients with COPD which negatively affects lung function, increases frequency of exacerbations, and impairs the quality of life of patients with COPD.

Background/Aims Pigeon breeder’s lung (PBL) results from Th1/Th2 cell imbalance. B cells inhibit the immune activity of Th1, and EBF3 is a key B cell factor. This study explored the relationship between EBF3 and Th1/Th2 imbalance in chronic PBL cases complicated with pulmonary fibrosis (PF). Methods Twenty Uygur PBL+PF patients, 20 pigeon breeders without PBL or PF, and 20 healthy individuals without pigeon breeding history constituted the patient I, negative control, and normal control groups, respectively. Peripheral blood specimens and case backgrounds were collected between June 2016 and March 2017. EBF3 gene methylation was analyzed by matrix assisted laser desorption ionization-time of flight mass spectrometry. To compare different mechanisms of PF progression in PBL, samples from 20 Uygur PBL patients without PF (at acute and sub-acute stages) were collected between October 2017 and February 2018, constituting the patient II group. EBF3 mRNA expression was evaluated by real-time polymerase chain reaction. IFN-γ, IL-4 and IL-10 expression and Th1/Th2 imbalance in PBL were evaluated by enzyme-linked immunosorbent assay and flow cytometry. Results CpG-2 and general methylation rates in the patient I group were lower than those in the control groups (P˂0.017). The level of EBF3 mRNA expression in the patient I group was significantly higher than that in any other group. Compared with the control groups, the patient I group showed a significantly higher level of IL-4, whereas the patient II group showed a significantly lower level. IL-10 was also expressed more highly in the patient I group than in any other group (P< 0.01). Flow cytometry showed INF-γ dominance (Th1 cytokine) in PBL at the acute/sub-acute stage and IL-4 dominance (Th2 cytokine) at the chronic stage after PF occurred. The general methylation rate was negatively correlated with the mRNA level, with the latter being positively correlated with the IL-10 level and number of pigeons bred in the past 3 months. IL-4 expression was negatively correlated with INF-γ but positively correlated with PF area and duration of pigeon breeding history. Conclusions After PF occurs in chronic PBL, the inflammation type changes from Th1 dominance to Th2 dominance. During PBL development, IL-10 increases before IL-4 does, which may be associated with EBF3 hypomethylation and the involvement of B lymphocytes.

Background Despite the positive outcomes of the use of noninvasive positive pressure ventilation (NPPV) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), NPPV fails in approximately 15% of patients with AECOPD, possibly because the inspiratory pressure delivered by conventional low-intensity NPPV is insufficient to improve ventilatory status for these patients. High-intensity NPPV, a novel form that delivers high inspiratory pressure, is believed to more efficiently augment alveolar ventilation than low-intensity NPPV, and it has been shown to improve ventilatory status more than low-intensity NPPV in stable AECOPD patients. Whether the application of high-intensity NPPV has therapeutic advantages over low-intensity NPPV in patients with AECOPD remains to be determined. The high-intensity versus low-intensity NPPV in patients with AECOPD (HAPPEN) study will examine whether high-intensity NPPV is more effective for correcting hypercapnia than low-intensity NPPV, hence reducing the need for intubation and improving survival. Methods/design The HAPPEN study is a multicenter, two-arm, single-blind, prospective, randomized controlled trial. In total, 600 AECOPD patients with low to moderate hypercapnic respiratory failure will be included and randomized to receive high-intensity or low-intensity NPPV, with randomization stratified by study center. The primary endpoint is NPPV failure rate, defined as the need for endotracheal intubation and invasive ventilation. Secondary endpoints include the decrement of arterial carbon dioxide tension from baseline to 2 h after randomization, in-hospital and 28-day mortality, and 90-day survival. Patients will be followed up for 90 days after randomization. Discussion The HAPPEN study will be the first randomized controlled study to investigate whether high-intensity NPPV better corrects hypercapnia and reduces the need for intubation and mortality in AECOPD patients than low-intensity NPPV. The results will help critical care physicians decide the intensity of NPPV delivery to patients with AECOPD. Trial registration ClinicalTrials.gov, NCT02985918 . Registered on 7 December 2016.

Purpose: We evaluated and compared the value of neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), and C-reactive protein (CRP) prior to weaning in predicting weaning outcome in invasively ventilated patients. Materials and Methods: We conducted an observational cohort study over a 3.5-year period in a 12-bed ICU. Patients underwent an spontaneous breathing trial (SBT) when they were ready to wean, and were extubated when they passed the trial. Immediately before the SBT, we measured the evaluated diagnosis tools. Results: Among the 269 patients in the study, 94 (34.9%) failed the weaning process. NLR values were positively correlated with PCT levels and CRP levels in both weaning success and weaning failure group. The adjusted logistic regression model demonstrated that NLR value >11 (odds ratio [OR], 4.66; 95% confidence interval [CI], 2.63–8.26; p = 0.000), PCT level >4 ng/mL (OR, 5.96; 95% CI, 3.11–11.41; p = 0.000) and CRP level >58 mg/L (OR, 3.16; 95% CI, 1.84–5.41; p = 0.000) were the independent predictors for weaning failure. The area under the ROC curves for NLR value, PCT level, and CRP level were 0.77, 0.70, 0.58, respectively. A NLR value of >11, PCT level of >4ng/mL, and CRP level of >58 mg/L prior to weaning had the best combination of sensitivity, specificity, positive predictive value, and negative predictive value, and diagnostic accuracy for predicting weaning failure. Conclusions: Measuring NLR valve, PCT level, and CRP level prior to weaning may help to predict weaning outcome.

Objective To explore the curative effect of home mechanical ventilation plus oxygen therapy on severe stable chronic obstructive pulmonary disease.Methods Those patients met the following conditions were selected in this study: ① they were diagnosed chronic obstructive pulmonary disease according to diagnostic criteria of the 2011 GOLD;② they were diagnosed as severe COPD according to their lung function, that was 30%≤ FEV1<50%;③ they received non-invasive positive pressure ventilation therapy in our hospital from January 2013 to January 2015, and then they left the hospital with a improved symptom.According to the purchase of noninvasive ventilator, the enrolled patients were divided into the treatment group and the control group.16 patients had their own noninvasive ventilator and worn it more than 4 hours plus oxygen therapy every day were enrolled into the treatment group, while the others 23 patients received normal medical therapy such as inhaled corticosteroid were enrolled into the control group.They were followed up 1 year from the day leaving hospital.Their arterial blood gas (PaO2, PaCO2), hospital stay and cost, and life quality score were compared by St.George's respiratory questionnaire.Results The level of PaCO2 decreased and PaO2 increased significantly 1 year after treatment (P<0.05), while the control group didn't improved significantly (P>0.05).The hospital stay and cost was significantly lower in the treatment group than in the control group (P<0.05).However, there was no significant difference in hospitalization times and life quality score between the two groups (P>0.05).Conclusion Home mechanical ventilation, as a bridge connection from hospital therapy to home therapy, is a kind of optional therapy for severe stable COPD patients.

Smad3 is a key protein in the transforming growth factor-beta (TGF-β)/Smad signaling pathway, which is involved in fibrosis in many organs. We investigated the relationship between Smad3 gene methylation and pulmonary fibrosis in pigeon breeder's lung (PBL). Twenty Uygur PBL patients with pulmonary fibrosis in Kashi between October 2015 and March 2016 were enrolled. Twenty PBL-free pigeon breeders and 20 healthy non-pigeon breeders enrolled during the same period constituted the negative and normal control groups, respectively. Participants' data and peripheral blood samples were collected, and three Smad3 CpG loci were examined. Distributions of CpG_2 and CpG_4 methylation rates did not differ across groups, whereas distributions of CpG_3 methylation rates were significantly different among the three groups. The CpG_3 methylation rate was significantly lower in the patient group than in the negative control group. Smad3 mRNA expression was significantly higher in the patient group than in the negative control group but did not differ between the two control groups. TGF-βlevels were significantly higher in the patient group than in either control group (both P<0.01). Smad3 gene methylation and Smad3 mRNA expression were negatively correlated, with a correlation coefficient of -0.84. The number of pigeons bred during the preceding three months was positively correlated with Smad3 mRNA expression, with a correlation coefficient of 0.77. Smad3 gene hypomethylation might promote pulmonary fibrosis in Uygur PBL patients via increased Smad3 mRNA expression. Smad3 methylation, Smad3 mRNA expression and TGF-β level were correlated with the number of pigeons bred by patients.

Objective To investigate the influence of chronic renal disease (CKD) on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and hospitalization.Methods Fifty patients clinically diagnosed as COPD complicating CKD in our hospital from January 2011 to June 2013 were selected as the observation group and 50 patients with CKD-free COPD were taken as a control group.The comparative analysis was performed by retrospecting the data of lung function,exercise tolerance and hospitalization situation in 1 year follow up.Results The mortality rate,total occurrence rate of AECOPD,occurrence rate of severe AECOPD,hospitalization rate,hospitalization time,self-rating test (CAT) score,mMRC dyspnea index,CRP and blood creatinine level in the observation group were higher than those in the control group,the difference was statistically significant (P<0.05);FEV1%pred,6MWD and creatinine clearance rate in the observation group were lower than those in the control group,the difference was statistically significant (P<0.05);FEV1/FVC had no statistical difference between the two groups (P>0.05).Conclusion The condition in COPD patients complicating CKD at 1 year after clinical diagnosis is significantly aggravated compared with COPD patients without complicating CKD,and the prognosis for patients complicated with CKD is poorer.

BACKGROUND To examine the bone mineral density (BMD) and the role of bone biomarkers, including bone formation marker procollagen type I aminoterminal propeptide (PINP) and N-terminal midmolecule fragment osteocalcin (N-MID), bone resorption marker b-C-telopeptides of type I collagen (b-CTX) and tartrate-resistant acid phosphatase 5b (TRACP5b) in the pathogenesis of PSP. METHODS Eighty-three consecutive primary spontaneous pneumothorax (PSP) patients (PSP group) and 87 healthy individuals (control group) were enrolled in this study. General data, including gender, age, height, weight, and body mass index (BMI), were recorded. Dual-energy X-ray absorptiometry, electrochemiluminescence immunoassay (ECLIA), and ELISA were used to evaluate bone mineral density and expression levels of bone metabolism markers, including PINP, b-CTX, TRACP5b, N-MID, and 25-hydroxyvitamin D (25-OH VD). RESULTS Mean height was significantly greater in the PSP group compared with the control group, whereas weight and BMI were lower. Patients in the PSP group had significantly lower average bone mineral density, which mainly manifested as osteopenia (11/12, 91.7%); however, only one patient (8.3%) developed osteoporosis. Serum overexpression of PINP, b-CTX, TRACP5b, and N-MID were found in PSP patients. Expression of 25-OH VD was low in PSP patients. Bone resorption markers showed positive linear relationships with bone formation markers in all participants; whereas only TRACP5b expression negatively correlated with 25-OH VD. Expression levels of all bone turnover markers negatively correlated with BMI. Regression analysis identified risk factors of PSP as age, height, weight, and TRACP5b and 25-OH VD expression levels; whereas gender and PINP, b-CTX, and N-MID expression levels were not significantly associated with the onset of PSP. CONCLUSIONS It had lower bone mineral density in PSP patients. Bone formation marker PINP, N-MID and bone resorption marker b-CTX, TRACP5b were upregulated in PSP patients. 25-OH VD expression was relatively low in this population of PSP patients. Age, height, weight, and expression levels of TRACP5b and 25-OH VD may be risk factors for PSP.

Objective To explore the clinical characteristics and imaging manifestations of actinomycosis and discuss the misdiagnosis reasons for actinomycosis.Methods Herein,this article described the case of 57-year-old patient that was misdiagnosed as pneumonia,and summarized the clinical characteristics and imaging manifestations of the actinomycosis,and then the reasons for misdiagnosis were analysised systematically.Results With a low incidence,actinomycosis was extremely easy to be misdiagnosed.As for the main causes of misdiagnosis,the common clinical symptoms,the varied imaging findings,it was difficult to get actinomyces specimen and needed long time to judge curative effect are all on the list.Therefore,clinician should make great efforts to get more knowledge about actinomycosis and communicate with medical laboratory for furthermore detecting techniques such as anaerobic bacteria culture and special dyeing,so that diagnostic accuracy could be improved and the misdiagnosis could be reduced.Conclusions As a rare disease,actinomycosis is easily to be misdiagnosed clinically.However,making a right diagnosis at early stage and implementing comprehensive therapy are benefit for the patients.