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To compare the average number of culprit arteries per patient, clinical success rate, and hemoptysis-free survival rate between hemoptysis patients with multidetector computed tomography (MDCT) angiography prior to bronchial artery embolization (BAE) and those without preprocedural MDCT angiography This retrospective study was approved by the institutional review board with waiver of patient informed consent. From September 2012 to March 2017, 157 consecutive hemoptysis patients had been undergoing BAE. Among them, 106 patients received preprocedural MDCT angiography (MDCT group), while 51 patients did not receive preprocedural MDCT angiography (control group). The average number of culprit arteries per patient, clinical success rate, and hemoptysis-free survival rate were compared between the two groups. The average number of culprit ectopic bronchial arteries and that of non-bronchial systemic arteries originating from the subclavian and internal mammary arteries per patient in the MDCT group were both significantly higher than those in the control group (0.15 ± 0.51 vs 0.04 ± 0.20, p = 0.022, and 0.17 ± 0.56 vs 0.08 ± 0.39, p = 0.040, respectively). The clinical success rate of BAE with preprocedural MDCT angiography tended to be higher than that without MDCT angiography (97.2 vs 88.2%, p = 0.057). Importantly, patients in the MDCT group had a significantly higher hemoptysis-free early survival rate compared to those in the control group (96.1 vs 86.7%, p = 0.031). Preprocedural MDCT angiography helps detect culprit ectopic bronchial arteries and non-bronchial systemic arteries originating from subclavian and internal mammary arteries during BAE, and can improve the hemoptysis-free early survival rate, which could be recommended as a regular examination prior to BAE in patients with hemoptysis. • Preprocedural MDCT angiography helps detect culprit ectopic bronchial arteries and NBSAs originating from subclavian and internal mammary arteries during BAE. • Conducting MDCT angiography prior to BAE can improve hemoptysis-free early survival rate in hemoptysis patients.

Communication is vital for all organisms including microorganisms, which is clearly demonstrated by the bacterial quorum-sensing system. However, the molecular mechanisms underlying communication among viruses (phages) via the quorum-sensing-like 'arbitrium' system remain unclear. Viral or host densities are known to be related to an increased prevalence of lysogeny; however, how the switch from the lytic to the lysogenic pathway occurs is unknown. Thus, we sought to reveal mechanisms of communication among viruses and determine the lysogenic dynamics involved. Structural and functional analyses of the phage-derived SAIRGA and GMPRGA peptides and their corresponding receptors, phAimR and spAimR, indicated that SAIRGA directs the lysis-lysogeny decision of phi3T by modulating conformational changes in phAimR, whereas GMPRGA regulates the lysis-lysogeny pathway by stabilizing spAimR in the dimeric state. Although temperate viruses are thought to share a similar lytic-lysogenic cycle switch model, our study suggests the existence of alternative strain-specific mechanisms that regulate the lysis-lysogeny decision. Collectively, these findings provide insights into the molecular mechanisms underlying communication among viruses, offering theoretical applications for the treatment of infectious viral diseases.

The aim of this network meta-analysis was to evaluate the comparative efficacy and safety of dabigatran, rivaroxaban, apixaban, interrupted vitamin K antagonist (I-VKA), and continuous VKA (C-VKA) in patients undergoing radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify clinical trials comparing dabigatran, rivaroxaban, or apixaban with I-VKA or C-VKA, or against each other, in AF patients undergoing RFCA. A network meta-analysis was conducted to directly and indirectly compare the efficacy and safety of competitive anticoagulation regimens with a Bayesian random-effects model. A total of 39 studies enrolling 27,766 patients were included. C-VKA demonstrated significant superiority over I-VKA in reducing thromboembolic events (risk difference [RD] −0.0068, 95 % confidence interval [CI] −0.0106 to −0.0032) and major bleeding complications (RD −0.0044, 95 % CI −0.0098 to −0.0006). Rivaroxaban compared with I-VKA was associated with a lower risk of thromboembolism (RD −0.0073, 95 % CI −0.0134 to −0.0012), being at the best ranking position among all of the compared anticoagulation regimens in terms of both the efficacy and safety. None of the remaining comparisons reached statistically significant difference in the rate of thromboembolism or major bleeding. The present study suggests that C-VKA is superior to I-VKA for AF patients undergoing RFCA. Rivaroxaban is the highest probability to be the optimal alternative to C-VKA among the three non-VKA oral anticoagulants in AF ablation.

The purpose of our indirect comparison was to explore the optimal switching time to noninvasive ventilation for further weaning in patients with chronic obstructive pulmonary disease (COPD) undergoing invasive mechanical ventilation. A comprehensive literature search was performed to identify randomized controlled trials comparing noninvasive weaning at spontaneous breathing trial (SBT) failure after meeting simple weaning criteria or at the pulmonary infection control window (PIC window) with conventional invasive weaning in COPD patients. Using conventional invasive weaning as a bridge, we indirectly compared the two noninvasive weaning strategies using the Bucher approach. Noninvasive weaning at SBT failure after meeting simple weaning criteria was associated with an extended duration of endotracheal mechanical ventilation (standardized mean difference 1.90, 95% CI 1.27-2.53, P < 0.001) compared with noninvasive weaning at the PIC window. No significant differences in mortality or the rate of ventilator-associated pneumonia were observed. Our study suggests that the PIC window may be a promising switching time for noninvasive weaning in COPD patients.

Background Cumulative studies have shown that asthma is associated with depression but the underlying mechanisms are poorly understood. This study aimed to determine whether asthma with depression is characterized by unique pathophysiological pathways by analyzing the global gene expression patterns of CD4+ T-cells from asthmatics with or without depression. Materials and methods Four groups of subjects (non-depressive asthmatics, depressive asthmatics, depression patients, and healthy controls) consisting of 6 participants in each group were studied. Peripheral CD4+ T-cells were isolated and the global transcriptomic profiles were defined by using the Agilent SurePrint G3 Human GE 8x60K microarray. The differences in transcriptomic profiles between asthma with or without depression, depression patients and healthy controls were examined. Pathway enrichment analyses of differentially expressed genes were performed using the Ingenuity Pathway Analysis. Selected genes were verified and correlated to the clinical characteristics. Results A total of 1448 differentially expressed transcripts were identified in any of the non-depressive asthma vs. healthy control, depressive asthma vs. healthy control, or depression vs. healthy control comparisons after correction for multiple comparisons. Among these, 156 were demonstrated as differentially expressed genes only in depressive asthma vs. healthy control. Twenty significant biological pathways were identified and were involved in inflammation, metabolism, immunity, tumor and cell cycle. Increased expression of phosphoinositide-3-kinase, regulatory subunit 1 (alpha) was confirmed in depressive asthmatics and it was inversely correlated with lung function (FEV1/FVC%). Conclusions Asthmatics with depression exhibit unique pathophysiological pathways and this result may provide clues for specific molecular mechanisms underlying asthma with depression.

PURPOSE Systemic inflammation relates to the initiation and progression of acute respiratory distress syndrome (ARDS). As neutrophil-to-lymphocyte ratio (NLR) has been shown to be a prognostic inflammatory biomarker in various diseases, in this study, we sought to explore whether NLR is a prognostic factor in patients with ARDS. METHODS A retrospective study was performed on patients diagnosed as ARDS admitted to the intensive care unit (ICU). We calculated the NLR by dividing the neutrophil count by the lymphocyte count and categorized patients into four groups based on quartile of NLR values. The association of NLR quartiles and 28-day mortality was assessed using multivariable Cox regression. Secondary outcomes included ICU mortality and hospital mortality. RESULTS A total of 224 patients were included in the final analysis. The median (interquartile range) NLRs from first quartile to fourth quartile were as follows: 6.88 (4.61-7.94), 13.06 (11.35-14.89), 20.99 (19.09-23.19), and 39.39 (32.63-50.15), respectively. The 28-day mortalities for the same groups were as follows: 10.7%, 19.6%, 41.4%, and 53.6% (P

Background The effects of aspirin in preventing the occurrence of acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) among adult patients are controversial. We aimed to further determine the effectiveness of aspirin in reducing the rate of ARDS/ALI. Methods The Pubmed, Embase, Medline, ClinicalTrials.gov , Cochrane Central Register of Controlled Trials (CENTRAL) as well as the Information Sciences Institute (ISI) Web of Science were searched for all controlled studies that research the role of aspirin in adult patients who have the risk of ARDS/ALI. The outcomes were the ARDS/ALI rate and the mortality. Cochrane systematic review software, Review Manager (RevMan), the R software for statistical computing version 3.2.0, and the metafor package were used to test the hypothesis by Mann-Whitney U test. The heterogeneity test and sensitivity analyses were conducted, and random-effects or fixed-effects model was applied to calculate odds ratio (OR) and mean difference (MD) for dichotomous and continuous data, respectively. Results Six trials involving 6562 patients were pooled in our final study. No significant heterogeneity was found in outcome measures. Aspirin could reduce the rate of ARDS/ALI (OR 0.71, 95% confidence interval (CI) 0.58–0.86) but not the mortality (OR 0.87, 95% CI 0.71–1.07). Conclusions In patients with risk of ARDS/ALI, aspirin could provide protective effect on the rate of ARDS/ALI, but it could not reduce the mortality.

Background: Severe pneumonia is the predominant cause for acute respiratory distress syndrome (ARDS). Identification of ARDS from patients with severe pneumonia remains a significant clinical problem due to the overlap of clinical presentations and symptoms. Early recognition of risks for ARDS from severe pneumonia is of great clinical value. Methods: From April 2014 to December 2015, patients with severe pneumonia at admission were retrieved from the hospital database, of which ARDS developed within 7 days were further identified. We compared the demographic and clinical characteristics at admission between severe pneumonia patients with and without ARDS development, followed by analysis of potential predictors for ARDS development and mortality. Multivariate logistic regression and receiver operating characteristic (ROC) curves were performed to screen independent risk factors and identify their sensitivity in predicting ARDS development and prognosis. Results: Compared with severe pneumonia without ARDS development, patients with ARDS development had shorter disease duration before admission, higher lung injury score (LIS), serum fibrinogen (FiB), and positive end-expiratory pressure (PEEP), lower Marshall score, sequential organ failure assessment score and proportion of cardiovascular and gastrointestinal diseases, but similar mortality. Serum FiB >5.15 g/L [adjusted odds ratio (OR) 1.893, 95% confidence interval (CI): 1.141–3.142, P=0.014] and PEEP >6.5 cmH2O (adjusted OR 1.651, 95% CI: 1.218–2.237, P=0.001) were independent predictors for ARDS development with a sensitivity of 58.3% and 87.5%, respectively, and pH Conclusions: ARDS development risk could be early recognized by PEEP >6.5 cmH2O and serum FiB >5.15 g/L in severe pneumonia patients, and pH

Background The effects of high flow nasal cannula (HFNC) on adult patients after extubation remain controversial. We aimed to further determine the effectiveness of HFNC in comparison to noninvasive positive pressure ventilation (NIPPV) and conventional oxygen therapy (COT). Methods The Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trails (CENTRAL) as well as the Information Sciences Institute (ISI) Web of Science were searched for all the controlled study comparing HFNC with NIPPV and COT in adult patients after extubation. The primary outcome was rate of reintubation and the secondary outcomes were intensive care unit (ICU) mortality and length of ICU stay (ICU LOS). Results Eight trials with a total of 2936 patients were pooled in our final studies. No significant heterogeneity was found in outcome measures. Compared with COT, HFNC was associated with lower rate of reintubation (Z = 2.97, P = 0.003), and the same result was found in the comparison between HFNC and NIPPV (Z = 0.87, P = 0.38). As for the ICU mortality and ICU LOS, we did not find any advantage of HFNC over COT or NIPPV. Conclusions In patients after extubation, HFNC is a reliable alternative of NIPPV to reduce rate of reintubation compared with COT.

Background and Objectives: Gastroesophageal reflux disease may be an important factor for poorly controlled asthmatics. We thus aimed to systematically assess whether proton pump inhibitors (PPIs) could facilitate the control of refractory asthma in adults. Methods: A comprehensive literature search was performed to identify randomized controlled trials (RCTs) evaluating the effect of PPIs on refractory asthma in adults. The primary outcome was morning peak expiratory flow (mPEF). Secondary outcomes included evening PEF (ePEF) and asthma symptoms score. Meta-analysis was conducted to pool homogeneous data, while descriptive analysis was performed for heterogeneous data. Results: We identified 6 RCTs enrolling 2580 adults with refractory asthma. Meta analysis showed that PPIs compared with placebo were associated with a small magnitude of increased mPEF (mean difference 4.82 L/min, 95% CI 0.61- 9.03，P = 0.02), whereas no significant difference was observed on ePEF. A total of 5 RCTs reported asthma symptoms score according to different criteria, of which only 1 RCT indicated that PPIs could improve asthma symptoms compared to placebo. Conclusions: Current evidence suggests that PPIs may not be recommended as a routine treatment for refractory asthma in adults.

Long non-coding RNAs (lncRNAs) are critical gene regulators with important roles in a wide variety of biological processes, including tumorigenesis. ZEB1-AS1 was significantly increased in NSCLC tissues and cell lines, and its expression levels were highly associated with aggressive tumor progression and poor prognosis. Down-regulation of ZEB1-AS1 suppresses NSCLC cell proliferation and invasion in vitro, as well as inhibits xenograft tumor growth in vivo. Mechanistically, we found that ZEB1-AS1 down-regulation effectively suppressed EMT process through reducing ZEB1 expression, and the ectopic expression of ZEB1 restored the migratory and invasive abilities of NSCLC cells inhibited by ZEB1-AS1 down-regulation. In conclusion, these findings revealed that ZEB1-AS1 plays regulatory roles in NSCLC and it might become a novel molecular indicator of prognosis and therapeutic target in NSCLC.

Background The effects of high flow nasal cannula (HFNC) on adult patients when used before mechanical ventilation (MV) are unclear. We aimed to determine the effectiveness of HFNC when used before MV by comparison to conventional oxygen therapy (COT) and noninvasive positive pressure ventilation (NIPPV). Methods The Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL) as well as the Information Sciences Institute (ISI) Web of Science were searched for all the controlled studies that compared HFNC with NIPPV and COT when used before MV in adult patients. The primary outcome was the rate of endotracheal intubation and the secondary outcomes were intensive care unit (ICU) mortality and length of ICU stay (ICU LOS). Results Eight trials with a total of 1084 patients were pooled in our final studies. No significant heterogeneity was found in outcome measures. Compared both with COT and NIPPV, HFNC could reduce both of the rate of endotracheal intubation (OR 0.62, 95% CI 0.38–0.99, P = 0.05; OR 0.48, 95% CI 0.31–0.73, P = 0.0006) and ICU mortality (OR 0.47, 95% CI 0.24–0.93, P = 0.03; OR 0.36, 95% CI 0.20–0.63, P = 0.0004). As for the ICU LOS, we did not find any advantage of HFNC over COT or NIPPV. Conclusions When used before MV, HFNC can improve the prognosis of patients compared both with the COT and NIPPV.

Population-based studies have demonstrated that asthma patients with depression symptoms are more likely to have poor asthma control and worse asthma outcomes. However, the underlying mechanism of the relationship between asthma and depression is still unclear. The present study aimed to examine the cerebral anatomical changes in female asthma patients with and without depression.Using structural magnetic resonance imaging (MRI) and a voxel-based morphometry technique, the primary effects of and the interaction between asthma and depression were analyzed. The cerebral gray matter volume (GMV) was compared between the groups. Correlation analyses between the GMV value of the brain regions and the clinical parameters were completed.The interaction effect of asthma and depression was found on the right superior temporal gyrus (STG) and the left middle temporal gyrus. Patients with both asthma and depression showed less GMV in the right STG, the bilateral precuneus, and the right superior frontal gyrus compared to patients with asthma only. The GMV of the right STG showed a decrement form among the asthma only group, healthy controls and asthma plus depression group. In patients with asthma and depression, the volume of the right STG was positively correlated with PD20 (r = 0.714, p = 0.047) and negatively correlated with the nocturnal awakening score in the Asthma Control Test (r = -0.061, p = 0.038).Current findings provided convergent evidence to support the critical role of the right STG in the brain mechanism that mediates asthma and depression.

Introduction: MET mutations have been linked with highly progressive clinical behaviors and poor prognosis in several tumor types. Savolitinib (also known as AZD6094, HMPL-504 and volitinib) is a novel, potent, highly selective MET inhibitor and investigated in solid tumors. Methods: This is an open-label, single arm, multi-center phase II study to evaluate the efficacy and safety of savolitinib in MET exon 14 skipping mutant PSC or other types of NSCLC (NCT02897479). Eligible patients (pts) were diagnosed with unresectable or metastatic PSC or other types of NSCLC harboring MET exon 14 skipping mutations identified in tumor, plasma and/or pleural effusion. Mutations identified by local lab required to be confirmed by central lab test. Savolitinib 600mg was taken orally, once daily, until disease progression. The primary endpoint was objective response rate (ORR) per RECIST version 1.1. Here we report interim results after the first 34 enrolled pts. Results: As of 17 December 2018, 315 pts were prescreened or confirmed by central lab, 49 identified/confirmed with MET exon 14 skipping mutations, and 34 treated (14 PSC; 20 other types of NSCLC). Median age was 69 years (range 54-85) and 68% pts were male. Prior antitumor drugs for advanced disease: 17 pts were treatment naïve, 13 pts received 1 regimen, and 4 pts ≥2 regimens. According to investigators’ assessment of 31 patients, 12 pts had confirmed partial responses (PR); 4 pts with newly reported, yet to be confirmed PRs; 10 had stable disease; 2 had disease progression; and 3 pts were efficacy non-evaluable due to early discontinuation. The remaining 3 pts had not been evaluated yet. Tumor histology for the confirmed PR pts was as follows: 6 with PSC, 5 adenocarcinoma, 1 adenosquamous carcinoma. Median treatment duration for the confirmed PR pts was 34+ weeks (range: 16-96+ weeks). Among all 34 pts, the most common (≥20%) drug-related treatment emergent adverse events (TEAEs) were nausea (41%), edema peripheral (38%), alanine aminotransferase increased (32%), aspartate aminotransferase increased (29%) and vomiting (21%). Overall, 12 (35%) pts had ≥ grade 3 related TEAEs, and 5 (15%) pts discontinued treatment due to related TEAEs. The most common related TEAE leading to treatment discontinuation was drug-induced liver toxicity (6%). Five pts have died on-treatment: 3 unrelated/unlikely related AEs, 1 probably related to treatment (tumor lysis syndrome), and 1 primary cause unknown. Conclusion: Preliminary data suggested encouraging antitumor activity and an acceptable safety profile of savolitinib in pts with MET exon 14 mutated PSC or other types of NSCLC. Accrual of subjects in this study is ongoing. Citation Format: Shun Lu, Jian Fang, Lejie Cao, Xingya Li, Qisen Guo, Jianying Zhou, Ying Cheng, Liyan Jiang, Yuan Chen, Helong Zhang, Zongan Liang, Xin Zhang, Biao Wu, Jianhua Shi, Hua Xu, Jianjin Huang, Zhixiong Yang, Shan Zeng, Yanping Hu, Xiaodong Zhang, Jingxun Wu, Gongyan Chen, Nong Yang, Longzhen Zhang, Yinjia Fu, Jing Li, Linfang Wang, Yongxin Ren, Weiguo Su. Preliminary efficacy and safety results of savolitinib treating patients with pulmonary sarcomatoid carcinoma (PSC) and other types of non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT031.

Background The effects of body mass index (BMI) on the prognosis of acute respiratory distress syndrome (ARDS) are controversial. We aimed to further determine the relationship between BMI and the acute outcomes of patients with ARDS. Methods We searched the Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and ISI Web of Science for trials published between 1946 and July 2016, using “BMI” or “body mass index” or “overweight” or “obese” and “ARDS” or “ALI” or “acute respiratory distress syndrome” or “acute lung injury”, without limitations on publication type or language. Heterogeneity and sensitivity analyses were conducted, and a random-effects model was applied to calculate the odds ratio (OR) or mean difference (MD). Review Manager (RevMan) was used to test the hypothesis using the Mann-Whitney U test. The primary outcome was unadjusted mortality, and secondary outcomes included mechanical ventilation (MV)-free days and length of stay (LOS) in the intensive care unit (ICU) and in hospital. Results Five trials with a total of 6268 patients were pooled in our final analysis. There was statistical heterogeneity between normal-weight and overweight patients in LOS in the ICU (I 2 = 71%, χ 2 = 10.27, P = 0.02) and in MV-free days (I 2 = 89%, χ 2 = 18.45, P

Venous thromboembolism (VTE), including pulmonary thromboembolism (PTE) and deep venous thrombosis (DVT), is a common disease with a considerably high morbidity and mortality. Mirtazapine, a novel antidepressant with a unique mode of action, is currently widely used in psychiatric practice. Preliminary clinical studies show that it is an effective and fast-acting antidepressant with few side effects, and the reports about mirtazapine inducing VTE are rare. We present a case of VTE in a woman with depression without any major risk factors for thrombosis, and Mirtazapine was suspected to be the major associated factor in the development of VTE. In addition, we reviewed the literatures to further explore the association between antidepressant drug use and the risk of VTE. As a result, certain association was indeed found between the two, but no consistent conclusion has been reached.

Background:Blomia tropicalis is an important domestic dust mite in the tropics and subtropics. This study describes cDNA cloning of the group 4 allergen of B. tropicalis, and the evaluation of the sensitization of this allergen in atopic populations from 2 geographic regions. Methods: cDNA cloning was carried out using the Smart RACE cDNA amplification kit. The full-length Blo t 4 cDNA was isolated by cDNA library screening, 5′ and 3′ rapid amplification of cDNA ends and long-distance PCR. Sequence analysis was performed with a combination of the Clustal W, CGC and Blast program packages. The cDNA was expressed in Pichia pastoris yeast. The skin prick test was used to evaluate the sensitization profile of recombinant Blo t 4, crude dust mite allergen extracts and major B. tropicalis recombinant allergen Blo t 5. Results: The cloned Blo t 4 had a molecular weight of 56 kDa and had 68% amino acid homology with group 4 allergens of Dermatophagoides pteronyssinus and 65% with those of Euroglyphus maynei. A sensitization profile to the expressed recombinant Blo t 4 allergen (28%) showed an unusually higher frequency than to the major allergen Blo t 5 (22%) in allergic subjects from Chengdu, PR China. In comparison, the subjects from Singapore showed very low sensitization to Blo t 4 (4%) compared with Blo t 5 (84%). Conclusions: Group 4 allergens of B. tropicalis may be an important dust mite allergen in certain distinct populations.

Background Smear-negative pulmonary tuberculosis (PTB) is common and difficult to diagnose. In this study, we investigated the diagnostic value of nucleic acid amplification testing and sequencing combined with acid-fast bacteria (AFB) staining of needle biopsy lung tissues for patients with suspected smear-negative PTB. Methods Patients with suspected smear-negative PTB who underwent percutaneous transthoracic needle biopsy between May 1, 2012, and June 30, 2015, were enrolled in this retrospective study. Patients with AFB in sputum smears were excluded. All lung biopsy specimens were fixed in formalin, embedded in paraffin, and subjected to acid-fast staining and tuberculous polymerase chain reaction (TB-PCR). For patients with positive AFB and negative TB-PCR results in lung tissues, probe assays and 16S rRNA sequencing were used for identification of nontuberculous mycobacteria (NTM). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of PCR and AFB staining were calculated separately and in combination. Results Among the 220 eligible patients, 133 were diagnosed with TB (men/women: 76/57; age range: 17–80 years, confirmed TB: 9, probable TB: 124). Forty-eight patients who were diagnosed with other specific diseases were assigned as negative controls, and 39 patients with indeterminate final diagnosis were excluded from statistical analysis. The sensitivity, specificity, PPV, NPV, and accuracy of histological AFB (HAFB) for the diagnosis of smear-negative were 61.7% (82/133), 100% (48/48), 100% (82/82), 48.5% (48/181), and 71.8% (130/181), respectively. The sensitivity, specificity, PPV, and NPV of histological PCR were 89.5% (119/133), 95.8% (46/48), 98.3% (119/121), and 76.7% (46/60), respectively, demonstrating that histological PCR had significantly higher accuracy (91.2% [165/181]) than histological acid-fast staining (71.8% [130/181]), P < 0.001. Parallel testing of histological AFB staining and PCR showed the sensitivity, specificity, PPV, NPV, and accuracy to be 94.0% (125/133), 95.8% (46/48), 98.4% (125/127), 85.2% (46/54), and 94.5% (171/181), respectively. Among patients with positive AFB and negative PCR results in lung tissue specimens, two were diagnosed with NTM infections (Mycobacterium avium-intracellulare complex and Mycobacterium kansasii). Conclusion Nucleic acid amplification testing combined with acid-fast staining in lung biopsy tissues can lead to early and accurate diagnosis in patients with smear-negative pulmonary tuberculosis. For patients with positive histological AFB and negative tuberculous PCR results in lung tissue, NTM infection should be suspected and could be identified by specific probe assays or 16S rRNA sequencing.

Background: Non-invasive weaning may be ideally suitable for intubated patients with COPD. Either spontaneous breathing trial (SBT) failure after meeting simple weaning criteria or pulmonary infection control window (PIC window) is adopted as switching timing for non-invasive weaning. This study aimed to explore the optimal timing of sequential non-invasive ventilation to reduce mortality and intubation-associated complications. Methods: A comprehensive literature search was performed to identify randomized controlled trials (RCTs) comparing non-invasive weaning at the two switching points with conventional invasive weaning in intubated patients with COPD. The primary outcome was mortality. Secondary outcomes included ventilator associated pneumonia (VAP) and duration of endotracheal mechanical ventilation (ETMV). Using conventional invasive weaning as a bridge, we indirectly compared the two non-invasive weaning strategies by Bucher approach. Results: We identified 7 RCTs enrolling 357 intubated patients with COPD. Indirect comparison showed that no significant difference was observed on mortality (RR 1.11, 95%CI 0.40 to 3.07, P=0.8479) and VAP (RR 0.58, 95%CI 0.16 to 2.06, P=0.3952). Compared with non-invasive weaning at PIC window, non-invasive weaning at SBT failure after meeting simple weaning criteria was associated with increased duration of ETMV (SMD 1.51, 95%CI 0.48 to 2.54, P=0.0039). Conclusions: Current evidence indicated that non-invasive weaning using PIC window as switching timing might decrease duration of ETMV though had no effect on mortality and VAP. The optimal timing for non-invasive weaning in intubated patients with COPD remains to be further elucidated.

Studies examining the role of interleukin (IL)-1β -511C/T promoter polymorphism in the pathogenesis of chronic obstructive pulmonary disease (COPD) have shown inconsistent results. This meta-analysis was performed to assess the association between the IL-1β-511C/T promoter polymorphism and COPD susceptibility. Published case-control, cross-sectional, and cohort studies from Pubmed, Embase, and China National Knowledge Infrastructure databases were retrieved. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Twelve studies with 1692 cases and 2009 controls were included in this meta-analysis. Pooled effect size showed an overall but not significantly decreased risk of IL-1β-511 C/T with COPD susceptibility (OR = 0.89, 95%CI = 0.78-1.01) in a complete overdominant genetic model (TT+CC vs CT), indicating that homozygous individuals (CC and TT) have a decreased risk for COPD compared with heterozygotes (CT). In subgroup analysis by ethnicity, IL-1β-511C/T was significantly correlated with a decreased risk of COPD in Asians (OR = 0.73, 95%CI = 0.60-0.88, P = 0.001), but not in Caucasians (OR = 1.02, 95%CI = 0.83- 1.24, P = 0.46), confirming a protective role of IL-1β-511C/T in COPD in Asians. Moreover, after excluding studies that included populations not in Hardy-Weinberg equilibrium, the pooled results were robust and no publication bias was observed. This meta-analysis suggests that the IL-1β-511C/T promoter polymorphism deceases the risk of COPD in Asians.

Pulmonary fibrosis is one of the most common complications of paraquat (PQ) poisoning, which demands for more effective therapies. Accumulating evidence suggests adiponectin (APN) may be a promising therapy against fibrotic diseases. In the current study, we determine whether the exogenous globular APN isoform protects against pulmonary fibrosis in PQ-treated mice and human lung fibroblasts, and dissect the responsible underlying mechanisms. BALB/C mice were divided into control group, PQ group, PQ + low-dose APN group, and PQ + high-dose APN group. Mice were sacrificed 3, 7, 14, and 21 days after PQ treatment. We compared pulmonary histopathological changes among different groups on the basis of fibrosis scores, TGF-β1, CTGF and α-SMA pulmonary content via Western blot and real-time quantitative fluorescence-PCR (RT-PCR). Blood levels of MMP-9 and TIMP-1 were determined by ELISA. Human lung fibroblasts WI-38 were divided into control group, PQ group, APN group, and APN receptor (AdipoR) 1 small-interfering RNA (siRNA) group. Fibroblasts were collected 24, 48, and 72 hours after PQ exposure for assay. Cell viability and apoptosis were determined via Kit-8 (CCK-8) and fluorescein Annexin V-FITC/PI double labeling. The protein and mRNA expression level of collagen type III, AdipoR1, and AdipoR2 were measured by Western blot and RT-PCR. APN treatment significantly decreased the lung fibrosis scores, protein and mRNA expression of pulmonary TGF-β1, CTGF and α-SMA content, and blood MMP-9 and TIMP-1 in a dose-dependent manner (p

Objective No optimal housekeeping genes (HKGs) have been identified for CD4+ T cells from non-depressive asthmatic and depressive asthmatic adults for normalizing quantitative real-time PCR (qPCR) assays. The aim of present study was to select appropriate HKGs for gene expression analysis in purified CD4+ T cells from these asthmatics. Methods Three groups of subjects (Non-depressive asthmatic, NDA, n = 10, Depressive asthmatic, DA, n = 11, and Healthy control, HC, n = 10 respectively) were studied. qPCR for 9 potential HKGs, namely RNA, 28S ribosomal 1 (RN28S1), ribosomal protein, large, P0 (RPLP0), actin, beta (ACTB), cyclophilin A (PPIA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase 1 (PGK1), beta-2-microglobulin (B2M), glucuronidase, beta (GUSB) and ribosomal protein L13a (RPL13A), was performed. Then the data were analyzed with three different applications namely BestKeeper, geNorm, and NormFinder. Results The analysis of gene expression data identified B2M and RPLP0 as the most stable reference genes and showed that the level of PPIA was significantly different among subjects of three groups when the two best HKGs identified were applied. Post-hoc analysis by Student-Newman-Keuls correction shows that depressive asthmatics and non-depressive asthmatics exhibited lower expression level of PPIA than healthy controls (p

BACKGROUND Observational studies from Asia suggest that maxingshigan-yinqiaosan may be effective in the treatment of acute H1N1 influenza. OBJECTIVE To compare the efficacy and safety of oseltamivir and maxingshigan-yinqiaosan in treating uncomplicated H1N1 influenza. DESIGN Prospective, nonblinded, randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00935194) SETTING Eleven hospitals from 4 provinces in China. PATIENTS 410 persons [corrected] aged 15 to 69 [corrected] years with laboratory-confirmed H1N1 influenza. INTERVENTION Oseltamivir, 75 mg twice daily; maxingshigan-yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan-yinqiaosan; or no intervention (control). Interventions and control were given for 5 days. MEASUREMENTS Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction. RESULTS Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20% to 46%]; P < 0.001), maxingshigan-yinqiaosan (37% [CI, 23% to 49%]; P < 0.001), and oseltamivir plus maxingshigan-yinqiaosan (47% [CI, 35% to 56%]; P < 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with oseltamivir plus maxingshigan-yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores (P = 0.38). Two patients who received maxingshigan-yinqiaosan reported nausea and vomiting. LIMITATIONS Participants were young and had mild H1N1 influenza virus infection. Missing viral data precluded definitive conclusions about viral shedding. CONCLUSION Oseltamivir and maxingshigan-yinqiaosan, alone and in combination, reduced time to fever resolution in patients with H1N1 influenza virus infection. These data suggest that maxingshigan-yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection. PRIMARY FUNDING SOURCE Beijing Science and Technology Project and Beijing Nova Program.

Blomia tropicalis is an important domestic dust mite in the tropics and subtropics. This study describes cDNA cloning of the group 4 allergen of B. tropicalis, and the evaluation of the sensitization of this allergen in atopic populations from 2 geographic regions.cDNA cloning was carried out using the Smart RACE cDNA amplification kit. The full-length Blo t 4 cDNA was isolated by cDNA library screening, 5' and 3' rapid amplification of cDNA ends and long-distance PCR. Sequence analysis was performed with a combination of the Clustal W, CGC and Blast program packages. The cDNA was expressed in Pichia pastoris yeast. The skin prick test was used to evaluate the sensitization profile of recombinant Blo t 4, crude dust mite allergen extracts and major B. tropicalis recombinant allergen Blo t 5.The cloned Blo t 4 had a molecular weight of 56 kDa and had 68% amino acid homology with group 4 allergens of Dermatophagoides pteronyssinus and 65% with those of Euroglyphus maynei. A sensitization profile to the expressed recombinant Blo t 4 allergen (28%) showed an unusually higher frequency than to the major allergen Blo t 5 (22%) in allergic subjects from Chengdu, PR China. In comparison, the subjects from Singapore showed very low sensitization to Blo t 4 (4%) compared with Blo t 5 (84%).Group 4 allergens of B. tropicalis may be an important dust mite allergen in certain distinct populations.

Background Paraoxonase 1 (PON1) is a plasma enzyme that is capable of inhibiting the progression of atherosclerosis, and is significantly associated with the susceptibility of coronary artery disease (CAD). Recently, PON total protein expression was found in human aortic tissue and it played an important role in progression of atherosclerosis. For studying its crucial role in preventing CAD, we performed the PON1 immunohistochemical analysis in human coronary arteries, explored its polymorphisms and plasma status, and analysed its association with the risk of CAD. Methods The expression of PON1 in human coronary arterial tissues was detected by immunohistochemical staining analysis. PON1 gene polymorphisms were determined by polymerase chain reaction (PCR) direct sequencing in 2456 unrelated Chinese Han individuals. Serum PON1 level was reflected indirectly by PON1 activity towards paraoxon and phenylacetate by spectrophotometry separately and directly by its concentration using human enzyme linked immunosorbent kit (ELISA). Results Immunohistochemical analysis showed that PON1 expression in human coronary arteries was lower in atherosclerotic arteries than in normal arteries. Among all of the studied polymorphisms, only PON1 Q192R (rs662) had a significant effect on the risk of CAD (p = 0.001). In a logistic regression model, after adjusting the conventional risk factors of CAD, R allele carriers had a significantly higher risk of CAD than other allele carriers. Both serum PON1 activity and concentration were significantly reduced in CAD patients compared with the controls (p Conclusion Decreased PON1 expression in human atherosclerotic coronary arteries was associated with CAD. Moreover, our finding indicated that PON1 Q192R polymorphism might be a genetic risk factor for the susceptibility of CAD in Chinese Han population, and the R allele might be an independent predictor for CAD.