Abstract.A 53-year-old male was admitted to Xinhua Hospital (Shanghai, China) due to coughing and dyspnea that had persisted for half a year, with aggravation of chest tightness and dyspnea for 1 week. Chest computed tomography (CT) revealed a mass within the distal third of the trachea. Flexible bronchoscopy confirmed an ~2.0 cm, smooth, tan-colored mass in the trachea, 2 cm above the carina. Endoscopic resection by argon plasma coagulation combined with electronic snaring was applied, however, recurrence was found 2 weeks later. Finally, the tumor was completely removed by surgery and the post-operative course was uneventful. Since schwannoma is rare in the intrapulmonary region and extremely rare in the trachea, a review of 51 cases of primary tracheal schwannoma previously reported in the English literature was performed. The majority of cases occurred in adults and were usually located in the distal third of the trachea. The predominant tumor size was 1-3 cm and airway obstruction symptoms were common. Half of the patients were misdiagnosed with asthma, and CT scan and bronchoscopy were contributory to the correct diagnosis. The treatment of choice depended on the patient's condition, however, surgery should be chosen in the event of local recurrence following endoscopic treatment.

BackgroundStudies have reported inconsistent findings regarding the association between obstructive sleep apnea (OSA) and future risks of cardiovascular and all-cause mortality. We conducted a meta-analysis to investigate whether OSA is an independent predictor for future cardiovascular and all-cause mortality using prospective observational studies.MethodsElectronic literature databases (Medline and Embase) were searched for prospective observational studies published prior to December 2012. Only observational studies that assessed baseline OSA and future risk of cardiovascular and all-cause mortality were selected. Pooled hazard risk (HR) and corresponding 95% confidence intervals (CI) were calculated for categorical risk estimates. Subgroup analyses were based on the severity of OSA.ResultsSix studies with 11932 patients were identified and analyzed, with 239 reporting cardiovascular mortality, and 1397 all-cause mortality. Pooled HR of all-cause mortality was 1.19 (95% CI, 1.00 to 1.41) for moderate OSA and 1.90 (95% CI, 1.29 to 2.81) for severe OSA. Pooled HR of cardiovascular mortality was 1.40 (95% CI, 0.77 to 2.53) for moderate OSA and 2.65 (95% CI, 1.82 to 3.85) for severe OSA. There were no differences in cardiovascular mortality in continuous positive airway pressure (CPAP) treatment compared with healthy subjects (HR 0.82; 95% CI, 0.50 to 1.33).ConclusionsSevere OSA is a strong independent predictor for future cardiovascular and all-cause mortality. CPAP treatment was associated with decrease cardiovascular mortality.

Video-assisted mediastinoscopy (VAM) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are the two most commonly used invasive methods for mediastinal staging of lung cancer. The objective of this review is to assess and compare the overall diagnostic values of VAM and EBUS-TBNA. PubMed, Embase, Web of Science and the Cochrane Library were searched for studies that evaluated EBUS-TBNA or VAM accuracy. Quantitative meta-analysis was used to pool sensitivity and specificity, and study quality was evaluated. Meta-regression was applied to indirectly compare EBUS-TBNA and VAM after adjusting quality score, study design, and station number. A total of ten studies with 999 EBUS-TBNA patients and seven studies with 915 VAM patients were included. Since the pooled specificity was 100% for both modalities, sensitivity was mainly analyzed. The pooled sensitivities for EBUS-TBNA and VAM were 0.84 (95% CI 0.79-0.88) and 0.86 (95% CI 0.82-0.90), respectively. Subgroup analyses of quality score, study design, station number and rapid on-site cytologic evaluation showed no significant influence on the overall sensitivity of the two modalities. After adjusting quality score, study design, and station number, the pooled sensitivities of VAM and EBUS-TBNA were not significantly different. However, more procedural complications and fewer false negatives (FN) were found with VAM than EBUS-TBNA. VAM and EBUS exhibited equally high diagnostic accuracy for mediastinal staging of lung cancer. Due to lower morbidity with EBUS-TBNA and fewer FN with VAM, EBUS-TBNA should be performed first, followed by VAM in the case of a negative needle result.

Previous studies proved that bone marrow-derived mesenchymal stem cells (BMSCs) could improve a variety of immune-mediated disease by its immunomodulatory properties. In this study, we investigated the effect on airway remodeling and airway inflammation by administrating BMSCs in chronic asthmatic mice. Forty-eight female BALB/c mice were randomly distributed into PBS group, BMSCs treatment group, BMSCs control group, and asthmatic group. The levels of cytokine and immunoglobulin in serum and bronchoalveolar lavage fluid were detected by enzyme-linked immunosorbent assay. The number of CD4(+) CD25(+) regulatory T cells and morphometric analysis was determined by flow cytometry, hematoxylin-eosin, immunofluorescence staining, periodic-acid Schiff, and masson staining, respectively. We found that airway remodeling and airway inflammation were evident in asthmatic mice. Moreover, low level of IL-12 and high levels of IL-13, IL-4, OVA-specific IgG1, IgE, and IgG2a and the fewer number of CD4(+) CD25(+) regulatory T cells were present in asthmatic group. However, transplantation of BMSCs significantly decreased airway inflammation and airway remodeling and level of IL-4, OVA-specific IgE, and OVA-specific IgG1, but elevated level of IL-12 and the number of CD4 + CD25 + regulatory T cells in asthma (P < 0.05). However, BMSCs did not contribute to lung regeneration and had no significant effect on levels of IL-10, IFN-Y, and IL-13. In our study, BMSCs engraftment prohibited airway inflammation and airway remodeling in chronic asthmatic group. The beneficial effect of BMSCs might involved the modulation imbalance cytokine toward a new balance Th1-Th2 profiles and up-regulation of protective CD4 + CD25 + regulatory T cells in asthma, but not contribution to lung regeneration.

Asthma is the most common chronic disease and is characterized by airway remodeling and chronic inflammation. Increasingly, studies have found that the activation and M1 phenotypic transformation of macrophages play important roles in asthma progress, including airway remodeling. However, the reversal of M1 macrophages to the M2 phenotype has been shown to attenuate airway remodeling. Exosomes are nano-sized extracellular vesicles derived from endosomes; they play direct roles in governing physiological and pathological conditions by the intracellular transfer of bioactive cargo, such as proteins, enzymes, nucleic acids (microRNA [miRNA], mRNA, DNA), and metabolites. However, transfer mechanisms are unclear. To uncover potential therapeutic mechanisms, we constructed an ovalbumin-induced asthma mouse model and lipopolysaccharide-induced RAW264.7 macrophages cells. Highthroughput sequencing showed that mmu_circ_0001359 was downregulated in asthmatic mice when compared with normal mice. Adipose-derived stem cell (ADSC)-exosome treatment suppressed inflammatory cytokine expression by the conversion of M1 macrophages to the M2 phenotype, under lipopolysaccharide-induced conditions. Exosomes from mmu_circ_0001359 overexpression in ADSCs increased therapeutic effects, in terms of cytokine expression, when compared with wild-type exosomes. Luciferase reporter assays confirmed that exosomes from mmu_circ_0001359-modified ADSCs attenuated airway remodeling by enhancing FoxO1 signalingmediated M2-like macrophage activation, via sponging miR-183-5p. In conclusion, mmu_circ_0001359-enriched exosomes attenuated airway remodeling by promoting M2-like macrophages.

Mesenchymal stem cells attenuate the severity of lung injury due to their immunomodulatory properties. The effect of bone marrow-derived mesenchymal stem cells on asthma is seldom reported. We have examined the effect of BMSCs on airway inflammation in asthma. Forty female BALB/c mice were equally randomised into PBS group, BMSCs treatment group, BMSCs control group and asthmatic group. Reactivity of the airway to acetylcholine was measured by barometric plethysmography. Cytokine profiles of bronchoalveolar lavage fluid and serum were determined by enzyme-linked immunosorbent assay. Morphometric analysis was done with haematoxylin and periodic-acid Schiff staining. Engraftment of BMSCs in asthmatic mice significantly decreased the number of eosinophils and mononuclear cells in bronchoalveolar lavage fluid and the airway (P < 0.05). Both goblet cell hyperplasia and responsiveness to acetylcholine were significantly reduced in BMSCs treatment groups. Moreover, BMSCs engraftment caused significant increases the ratio of Treg in pulmonary lymph node and interleukin-10 (IL-10) and interleukin-12 levels in BALF and serum. We conclude that BMSCs engraftment ameliorated airway inflammation and improved lung function in asthmatic mouse and the protective effect might be mediated by upregulating Treg and partly involved with increasing IL-10.

This study aimed to investigate whether bone marrow-derived mesenchymal stem cells (BM-MSCs) can inhibit function of dendritic cells (DCs) by secreting Galectin-1 (Gal-1). BM-MSCs have been shown to inhibit the maturation and function of DCs, further inhibiting the activation and proliferation of T cells. However, the detailed mechanism remains unknown. In this current study, MSCs and DCs derived from mouse bone marrow were cocultured using Transwell culture plates under different in vitro conditions. The results showed that as the ratio of MSC to DC of the coculture system increased and the coculture time of the two cells prolonged, the concentrations of Gal-1, interleukin- (IL-) 10, and IL-12 in the supernatants were increased and the protein expression of Gal-1 on and within DCs was also enhanced. The phosphorylation of extracellular signal-regulated kinase (ERK) pathway in DCs was boosted, whereas p38 mitogen-activated protein kinase (MAPK) pathway phosphorylation was weakened. Meanwhile, the expression of costimulatory molecules on the surface of DCs was decreased, and the proliferative effect of DCs on allogeneic T cells was also decreased. Therefore, this present study indicated that Gal-1 secreted from MSCs upregulated expression of Gal-1 and stimulated formation of tolerance immunophenotype on DCs, where the underlying mechanism was the regulation of the MAPK signaling pathway in DCs, thereby inhibiting the function of DCs.

Four distinct clinical phenotypes of asthma were identified by cluster analysis. The results of the MSCT and pathological examinations may suggest specific pathogeneses among the phenotypes.