Bidirectional correlation between gastroesophageal reflux disease and sleep problems: a systematic review and meta-analysis.

Objectives: Gastroesophageal reflux disease (GERD) and sleep problems are highly prevalent among the general population. Both them are associated with a variety of psychiatric disorders such as depression and anxiety, which is highlighting an underexplored connection between them. This meta-analysis aims to explore the association between sleep problems and GERD. Methods: We conducted a comprehensive search on PubMed, Cochrane Library, Embase, and Web of Science, using Medical Subject Headings (MeSH) and keywords, covering articles from the inception of the databases until August 2023. Stata statistical software, version 14.0, was utilized for all statistical analyses. A fixed-effects model was applied when p > 0.1 and I2 ≤ 50%, while a random-effects model was employed for high heterogeneity (p < 0.1 and I2 > 50%). Funnel plots and Egger's test were used to assess publication bias. Results: Involving 22 studies, our meta-analysis revealed that insomnia, sleep disturbance, or short sleep duration significantly increased the risk of GERD (OR = 2.02, 95% CI [1.64-2.49], p < 0.001; I2 = 66.4%; OR = 1.98, 95% CI [1.58-2.50], p < 0.001, I2 = 50.1%; OR = 2.66, 95% CI [2.02-3.15], p < 0.001; I2 = 62.5%, respectively). GERD was associated with an elevated risk of poor sleep quality (OR = 1.47, 95% CI [1.47-1.79], p < 0.001, I2 = 72.4%), sleep disturbance (OR = 1.47, 95% CI [1.24-1.74], p < 0.001, I2 = 71.6%), or short sleep duration (OR = 1.17, 95% CI [1.12-1.21], p < 0.001, I2 = 0). Conclusion: This meta-analysis establishes a bidirectional relationship between four distinct types of sleep problems and GERD. The findings offer insights for the development of innovative approaches in the treatment of both GERD and sleep problems.

The key role of glutamine for protein expression and isotopic labeling in insect cells.

Nuclear magnetic resonance studies of many physiologically important proteins have long been impeded by the necessity to express such proteins in isotope-labeled form in higher eukaryotic cells and the concomitant high costs of providing isotope-labeled amino acids in the growth medium. Economical routes use isotope-labeled yeast or algae extracts but still require expensive isotope-labeled glutamine. Here, we have systematically quantified the effect of 15N2-glutamine on the expression and isotope labeling of different proteins in insect cells. Sufficient levels of glutamine in the medium increase the protein expression by four to five times relative to deprived conditions. 1H-15N nuclear magnetic resonance spectroscopy shows that the 15N atoms from 15N2-glutamine are scrambled with surprisingly high (60-70%) efficiency into the three amino acids alanine, aspartate, and glutamate. This phenomenon gives direct evidence that the high energy demand of insect cells during baculovirus infection and concomitant heterologous protein expression is predominantly satisfied by glutamine feeding the tricarboxylic acid cycle. To overcome the high costs of supplementing isotope-labeled glutamine, we have developed a robust method for the large-scale synthesis of 15N2-glutamine and partially deuterated 15N2-glutamine-α,ß,ß-d3 from inexpensive precursors. An application is shown for the effective large-scale expression of the isotope-labeled ß1-adrenergic receptor using the synthesized 15N2-glutamine-α,ß,ß-d3.

Role of potassium ferrate in anaerobic digestion of waste activated sludge: Phenotypes and genotypes.

The specific effects of potassium ferrate (PF) on acid and methane production in anaerobic digestion need further exploration. This study comprehensively investigated the role of PF in organic matter conversion in waste activated sludge (WAS) digestion. Due to the high pH produced by PF self-decomposition, the hydrolysis of organic matter was promoted, whereas the methanogenesis was inhibited. PF could further directly oxidize protein and polysaccharides released by hydrolysis to produce volatile fatty acids (VFAs) and involve in the transformation of ammonia nitrogen. PF could induce the enrichment of functional genes related to fermentation pathways and lessen those related to methanogenesis, and the phylum resistant to PF oxidation and the strains capable of producing VFAs were enriched, resulting in VFAs accumulation. This study analyzed the participation way of PF in anaerobic digestion and provided a theoretical basis for the application of PF in promoting VFAs recovery from sludge digestion.

Nanobody GPS by PCS: An Efficient New NMR Analysis Method for G Protein Coupled Receptors and Other Large Proteins.

NMR chemical shift changes can report on the functional dynamics of biomacromolecules in solution with sizes >1 MDa. However, their interpretation requires chemical shift assignments to individual nuclei, which for large molecules often can only be obtained by tedious point mutations that may interfere with function. We present here an efficient pseudocontact shift NMR method to assign biomacromolecules using bound antibodies tagged with lanthanoid DOTA chelators. The stability of the antibody allows positioning the DOTA tag at many surface sites, providing triangulation of the macromolecule nuclei at distances >60 Å. The method provides complete assignments of valine and tyrosine 1H-15N resonances of the ß1-adrenergic receptor in various functional forms. The detected chemical shift changes reveal strong forces exerted onto the backbone of transmembrane helix 3 during signal transmission, which are absorbed by its electronic structure. The assignment method is applicable to any soluble biomacromolecule for which suitable complementary binders exist.

Learning Spatial-Spectral-Temporal EEG Representations with Deep Attentive-Recurrent-Convolutional Neural Networks for Pain Intensity Assessment.

Electroencephalogram (EEG)-based quantitative pain measurement is valuable in the field of clinical pain treatment, providing objective pain intensity assessment especially for nonverbal patients who are unable to self-report. At present, a key challenge in modeling pain events from EEG is to find invariant representations for intra- and inter-subject variations, where current methods based on hand-crafted features cannot provide satisfactory results. Hence, we propose a novel method based on deep learning to learn such invariant representations from multi-channel EEG signals and demonstrate its great advantages in EEG-based pain classification tasks. To begin, instead of using typical EEG analysis techniques that ignore spatial information of EEG, we convert raw EEG signals into a sequence of multi-spectral topography maps (topology-preserving EEG images). Next, inspired by various deep learning techniques applied in neuroimaging domain, a deep Attentive-Recurrent-Convolutional Neural Network (ARCNN) is proposed here to learn spatial-spectral-temporal representations from EEG images. The proposed method aims to jointly preserve the spatial-spectral-temporal structures of EEG, for learning representations with high robustness against intra-subject and inter-subject variations, making it more conducive to multi-class and subject-independent scenarios. Empirical evaluation on 4-level pain intensity assessment within the subject-independent scenario demonstrated significant improvement over baseline and state-of-the-art methods in this field. Our approach applies deep neural networks (DNNs) to pain intensity assessment for the first time and demonstrates its potential advantages in modeling pain events from EEG.

Enhanced biogas production in anaerobic digestion of sludge medicated by biochar prepared from excess sludge: Role of persistent free radicals and electron mediators.

The addition of biochars to promote the efficiency of anaerobic digestion (AD) has widely received concerns. However, the role of persistent free radicals (PFRs) and the electron transfer ability of biochar in AD has not yet been noticed. In this study, biochars were prepared from excess sludge under 400 °C (B400) or 600 °C (B600) and different ratios of sludge to biochar (5:1, 10:1, 20:1) were applied in the AD of sludge. The results verified that PFRs in biochar participated in the sterilization of microorganisms in sludge, resulting in the release of organic matters. Similar to electron mediators, biochars possessed electron exchangeability and the addition of biochars boosted the biogas production by maximum of 54.5%. The enhancing effect of B400 surpassed that of B600 as high temperature destroyed functional groups and reduced the defect degree of biochar. This study achieved in-situ resource utilization and provided references for the improvement of anaerobic digestion.

Expression of β-1,6 glucosaminyl (N-acetyl) transferase 2 in gastric cancer and its clinical significance / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨β-1,6 N-乙酰氨基葡萄糖转移酶2（GCNT2）基因在胃癌（GC）组织中的表达及其在GC发生、发展和诊断及预后中的作用。方法：利用TIMER、GEPIA2、Oncomine和UALCAN等数据库数据，以及2018年1月至2019年12月滨州医学院附属医院手术切除的25例GC患者的癌和配对癌旁组织标本，分析GCNT2基因在GC组织中的表达及其在GC诊断和预后中的价值，利用LinkedOmics、GSEA和ssGSEA分析GCNT2所涉及的主要信号通路及其与免疫浸润之间的相关性。将pc-GCNT2及其阴性对照质粒转染进胃癌SGC-7901和BGC-823细胞，用克隆形成实验和Transwell实验检测GCNT2对GC细胞增殖和侵袭的影响，WB法检测细胞中GCNT2、STAT3和PD-L1蛋白的表达水平。结果：GCNT2 mRNA在GC组织中的表达水平显著低于癌旁组织（P<0.05或P<0.01），其表达水平与患者预后显著相关（P<0.05），其对GC诊断有较高的价值。GCNT2在GC组织中的甲基化状态显著高于癌旁组织，GCNT2基因参与的生物过程主要是参与细胞形态发生的成分、细胞间黏附、多细胞生物信号和突触传递等。单基因GSEA分析发现，GCNT2在GC中主要抑制IL-6/JAK/STAT3、IL-2/STAT5信号通路和炎症反应、α/γ干扰素响应与NF-κB表达等。GCNT2的表达与GC组织的免疫浸润具有显著相关性。过表达GCNT2可显著抑制GC细胞的增殖和侵袭能力（均P<0.01），降低细胞中STAT3和PD-L1的表达水平（均P<0.01）。结论：GCNT2基因在GC组织中低表达，与GC的诊断及预后显著相关，其主要通过抑制IL-6/JAK/STAT3和免疫相关致癌信号通路而在GC的发生、发展中发挥重要的作用。

Application of Montgomery T-Tube Placement in Treating Cotton-Myer IV Subglottic Airway Atresia after Bi-Level Airway Recanalization.

OBJECTIVE: The purpose of this study is to explore the effectiveness and safety of Montgomery T-tube placement in treating Cotton-Myer IV subglottic airway atresia after bi-level airway recanalization. METHODS: This study is a retrospective study. 11 patients who were treated for IV subglottic airway atresia between January 2017 and January 2019 in the Second Affiliated Hospital of Jiaxing University were involved in this study. The 11 patients all had undergone tracheotomies at our hospital, and they were transferred to the Department of Pulmonary and Critical Care Medicine for Montgomery T-tube placement after bi-level airway recanalization when their subglottic airway was atretic. Patients were observed for their clinical manifestations after placement. The effectiveness of T-tube placement after bi-level airway recanalization was assessed. The incidence of short-term and long-term complications after surgery was assessed. Patients were followed up for 3 to 24 months for evaluating their airway recovery. RESULTS: T-tubes were successfully placed in 11 patients. The atretic airways of all patients were recanalized after treatment. Eight patients got restoration of vocal ability, and 3 patients could only say simple words. None of the patients needed assisted oxygen inhalation. The SpO2 average level was increased from 95 ± 2% before treatment to 97 ± 3% after treatment. Patients had significant relief of cough or sputum, and they had less difficulty in dyspnea. All short- or long-term complications were self-relieved or controlled without further malignant progression after treatment by doctors. The average postoperative extubating time was (14.86 ± 3.62) months. CONCLUSION: The application of Montgomery T-tube placement in treating Cotton-Myer IV subglottic airway atresia after bi-level airway recanalization is well effective and safe for patients, and it can be promoted in clinical treatment.

Innovative method for Amplatzer device implantation in patients with bronchopleural fistulas.

BACKGROUND: Bronchopleural fistula (BPF) is a relatively rare complication after various types of pulmonary resection. The double-sided mushroom-shaped occluder (Amplatzer device, AD) has been gradually used for BPF blocking due to its reliable blocking effect. We have improved the existing AD implantation methods to facilitate clinical use and named the new approach Sheath-free method (SFM). The aim of the present report was to explore the reliability and advantages of the SFM in AD implantation. METHODS: We improved the existing implantation methods by abandoning the sheath of the AD and using the working channel of the bronchoscope to directly store or release the AD without general anesthesia, rigid bronchoscopy, fluoroscopy, or bronchography. A total of 6 patients (5 men and 1 woman, aged 66.67 ± 6.19 years [mean ± SD]) had BPF blocking and underwent the SFM in AD implantation. RESULTS: AD implantation was successfully performed in all 6 patients with the SFM, 4 persons had a successful closure of the fistula, one person died after few days and one person did not have a successful closure of the fistula. The average duration of operation was 16.17 min (16.17 ± 4.67 min [mean ± SD]). No patients died due to operation complications or BPF recurrence. The average follow-up time was 13.2 months (range 10-17 months). CONCLUSION: We observed that the SFM for AD implantation-with accurate device positioning and a clear field of vision-is efficient and convenient. The AD is effective in BPF blocking, and could contribute to significantly improved symptoms of patients.

Acid treatment enhances phosphorus release and recovery from waste activated sludge: Performances and related mechanisms.

Waste activated sludge (WAS) has attracted considerable attention as an excellent material for P recovery from sewage. This study took concentrated phosphorus removal sludge as objective, and aimed at providing an effective route to promote the transformation of polyphosphate in sludge pellets to dissolved phosphate. After acid pH adjustment, total dissolved phosphate at pH 3.0 was 37.3-fold higher than that at natural pH. The P distribution results illustrated that acid pH accelerated the degradation of short chain polyphosphate into orthophosphate. Furthermore, cell staining results confirmed that the polyphosphate was sourced from the leakage of intracellular matters. Low field NMR and rheology properties analysis were adopted to illustrate that acid pH treatment further improved WAS dewatering performances. Accompanied with the reduction of heavy metals in WAS pellets, the acid pH treatment was also beneficial for WAS subsequent treatment or final disposal. Lastly, Fe3+ addition was proposed as favorable P recovery method, and spherical nanometric materials of FePO4 crystal was obtained accordingly.

Efficacy and Safety Profile of Montgomery T-Tube Implantation in Patients with Tracheal Stenosis.

Background: Tracheal stenosis is able to lead to airway obstruction. Objective: To evaluate the efficacy and safety profile of Montgomery T-tube implantation in patients with tracheal stenosis. Methods: Fifty-two patients with tracheal stenosis diagnosed between 2016 and 2019 were included in this retrospective cohort study. The patients were divided into observation group (n = 25 cases) and control group (n = 27). The therapeutic effect, arterial blood gas analysis, arterial oxygen partial pressure (PaO2), arterial carbon dioxide partial pressure (PaCO2), shortness of breath score, airway diameter change, dyspnea score, quality of life, and safety were compared between the two groups before and after treatment. Results: The therapeutic effect of the observation group gained better results than that of the control group (84.00% vs. 62.96%). One week after operation, the pH value, SaO2, PaCO2, shortness of breath score, airway diameter change, dyspnea score, life quality, and incidence of postoperative complications in the observation group exerted better results as compared to the control group. Conclusion: The implantation of Montgomery T-tube has effective function in terms of improving the symptoms of dyspnea and the life quality of patients with safety profile in patients harboring tracheal stenosis.

Probing the correlation between ligand efficacy and conformational diversity at the α1A-adrenoreceptor reveals allosteric coupling of its microswitches.

G protein-coupled receptors (GPCRs) use a series of conserved microswitches to transmit signals across the cell membrane via an allosteric network encompassing the ligand-binding site and the G protein-binding site. Crystal structures of GPCRs provide snapshots of their inactive and active states, but poorly describe the conformational dynamics of the allosteric network that underlies GPCR activation. Here, we analyzed the correlation between ligand binding and receptor conformation of the α1A-adrenoreceptor, a GPCR that stimulates smooth muscle contraction in response to binding noradrenaline. NMR of [13CϵH3]methionine-labeled α1A-adrenoreceptor variants, each exhibiting differing signaling capacities, revealed how different classes of ligands modulate the conformational equilibria of this receptor. [13CϵH3]Methionine residues near the microswitches exhibited distinct states that correlated with ligand efficacies, supporting a conformational selection mechanism. We propose that allosteric coupling among the microswitches controls the conformation of the α1A-adrenoreceptor and underlies the mechanism of ligand modulation of GPCR signaling in cells.

The Gene Expression Biomarkers for Chronic Obstructive Pulmonary Disease and Interstitial Lung Disease.

COPD (chronic obstructive pulmonary disease) and ILD (interstitial lung disease) are two common respiratory diseases. They share similar clinical traits but require different therapeutic treatments. Identifying the biomarkers that are differentially expressed between them will not only help the diagnosis of COPD and ILD, but also provide candidate drug targets that may facilitate the development of new treatment for COPD and ILD. Due to the irreversible complex pathological changes of COPD, there are very limited therapeutic options for COPD patients. In this study, we analyzed the gene expression profiles of two datasets: one training dataset that includes 144 COPD patients and 194 ILD patients, and one test dataset that includes 75 COPD patients and 61 ILD patients. Advanced feature selection methods, mRMR (minimal Redundancy Maximal Relevance) and incremental feature selection (IFS), were applied to identify the 38-gene biomarker. An SVM (support vector machine) classifier was built based on the 38-gene biomarker. Its accuracy, sensitivity, and specificity on training dataset evaluated by leave one out cross-validation were 0.905, 0.896, and 0.912, respectively. And on independent test dataset, the accuracy, sensitivity, and specificity on were as great as and were 0.904, 0.933, and 0.869, respectively. The biological function analysis of the 38 genes indicated that many of them can be potential treatment targets that may benefit COPD and ILD patients.

Long noncoding RNA UPAT promoted cell proliferation via increasing UHRF1 expression in non-small cell lung cancer.

Evidence indicates that long non-coding RNAs (lncRNAs) serve a critical role in the regulation of non-small cell lung cancer (NSCLC) progression. LncRNA Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) protein associated transcript (UPAT) has been identified to be overexpressed in a variety of types of cancer. The present study demonstrated that lncRNA UPAT expression was upregulated in NSCLC tissues and significantly associated with tumor size and Tumor-Node-Metastasis stage. Additionally, UPAT promoted NSCLC cell proliferation and G1-S phase transition in vitro. Furthermore, UPAT promoted NSCLC cell proliferation, partly via increasing UHRF1 expression and consequently epigenetically silencing RASSF1 and CDH13 transcription. In addition, the knockdown of UHRF1 partially decreased the promotion of cell growth and G1-S phase transition caused by UPAT overexpression. In conclusion, these data suggest that the lncRNA UPAT promotes the NSCLC cell proliferation and may be a potential therapeutic target of NSCLC.

Determinants of Ligand Subtype-Selectivity at α1A-Adrenoceptor Revealed Using Saturation Transfer Difference (STD) NMR.

α1A- and α1B-adrenoceptors (α1A-AR and α1B-AR) are closely related G protein-coupled receptors (GPCRs) that modulate the cardiovascular and nervous systems in response to binding epinephrine and norepinephrine. The GPCR gene superfamily is made up of numerous subfamilies that, like α1A-AR and α1B-AR, are activated by the same endogenous agonists but may modulate different physiological processes. A major challenge in GPCR research and drug discovery is determining how compounds interact with receptors at the molecular level, especially to assist in the optimization of drug leads. Nuclear magnetic resonance spectroscopy (NMR) can provide great insight into ligand-binding epitopes, modes, and kinetics. Ideally, ligand-based NMR methods require purified, well-behaved protein samples. The instability of GPCRs upon purification in detergents, however, makes the application of NMR to study ligand binding challenging. Here, stabilized α1A-AR and α1B-AR variants were engineered using Cellular High-throughput Encapsulation, Solubilization, and Screening (CHESS), allowing the analysis of ligand binding with Saturation Transfer Difference NMR (STD NMR). STD NMR was used to map the binding epitopes of epinephrine and A-61603 to both receptors, revealing the molecular determinants for the selectivity of A-61603 for α1A-AR over α1B-AR. The use of stabilized GPCRs for ligand-observed NMR experiments will lead to a deeper understanding of binding processes and assist structure-based drug design.

Gastric Schwannoma: A Tumor Must Be Included in Differential Diagnoses of Gastric Submucosal Tumors.

Gastric schwannoma (GS) is a rare neoplasm of the stomach. It accounts for 0.2% of all gastric tumors and is mostly benign, slow-growing, and asymptomatic. Due to its rarity, GS is not widely recognized by clinicians, and the precise differential diagnosis between GS and other gastric submucosal tumors remains difficult preoperatively. The present study reports a case of GS misdiagnosed as gastrointestinal stromal tumor and reviews the clinical, imaging, and pathological features, treatment, and follow-up of 221 patients with GS previously reported in the English literature. Although GS is rare, the case reported in the current study highlights the importance of including GS in differential diagnoses of gastric submucosal tumors. Furthermore, the findings of the review suggest that although many cases are asymptomatic, the most common symptoms are abdominal pain or discomfort, not gastrointestinal bleeding, and malignant GSs present with clinical symptoms more commonly. Although large-sample multicenter studies on the efficacy, safety, and oncological outcomes of minimally invasive techniques are required, the findings presented herein may be helpful for clinicians when diagnosing or treating GS.

Comparison between CT and MRI in the assessment of pulmonary embolism: A meta-analysis.

OBJECTIVE: Besides pulmonary arteriography, a number of imaging techniques, such as magnetic resonance imaging (MRI) and computed tomography (CT), were adopted in the detection of identifying pulmonary embolism (PE). However, the contrast of sensitivity and specificity in these methods was studied little in a statistical way. To compare the effects of MRI and CT, this study used a series of methods to analyze data in included researches. METHODS: A comprehensive computer search was conducted through internet up to July 2016. The quality assessment was performed by the Quality Assessment Tool for Diagnostic Accuracy Studies, version 2 tool. The diagnostic value of comparison between MRI and CT was evaluated by using the pooled estimate of sensitivity, specificity, and summary receiver operating characteristic (SROC) curve. In addition, sensitivity analysis and bias analysis were applied to ensure the accuracy of the results. RESULTS: Ten studies with 590 cases were involved in the study. Only 2 trials had high risk regarding bias while other trials were supposed to be at low risk of applicability. Heterogeneity existed in analysis of both CT and MRI. The pooled sensitivity of CT was 0.90 (95% CI: 0.85-0.93), pooled specificity was 0.88 (95% CI: 0.77 to 0.95), the pooled sensitivity of MRI was 0.92 (95% CI: 0.89-0.94), and pooled specificity was 0.91 (95% CI: 0.77-0.97). The Q index of sensitivity and specificity for CT and MRI were 71.38, 19.67, 47.14, and 12.35, respectively. The SROC curve area under the curve of CT and MRI were 0.94 (95% CI: 0.91-0.96) and 0.93 (95% CI: 0.91-0.95), respectively. CONCLUSION: This meta-analysis demonstrates that MRI has better sensitivity and specificity in detecting subsegmental artery PE. MRI is a relatively better detection technique for PE. This conclusion is consistent with many published researches.

Associations between the Epithelial-Mesenchymal Transition Phenotypes of Circulating Tumor Cells and the Clinicopathological Features of Patients with Colorectal Cancer.

In this study, we identified CTCs using the previously reported CanPatrol CTC enrichment technique from peripheral blood samples of 126 patients with colorectal cancer (CRC) and found that CTCs could be classified into three subpopulations based on expression of epithelial cell adhesion molecule (EpCAM) (E-CTCs), the mesenchymal cell marker vimentin (M-CTCs), or both EpCAM and vimentin (biphenotypic E/M-CTCs). Circulating tumor microemboli (CTMs) were also identified in peripheral blood samples. Meanwhile, E-CTCs, M-CTCs, E/M-CTCs, and CTMs were detected in 76.98%, 42.06%, 56.35%, and 36.51% of the 126 patients, respectively. Interestingly, the presence of CTMs and each CTC subpopulation was significantly associated with blood lymphocyte counts and tumor-node-metastasis stage (P < 0.001). Lymphocyte counts and the neutrophil-to-lymphocyte ratio (NLR) in patients lacking CTCs were significantly different from those in patients testing positive for CTMs and each CTC subpopulation (P < 0.001). Our results indicate that tumor metastasis is more significantly associated with the presence of CTMs and M-CTCs than with other CTC subpopulations and suggest that EMT may be involved in CTC evasion of lymphocyte-mediated clearance.

Cold snare resection for the treatment of benign airway lesions.

The objective was to assess the safety and outcome of cold snare technique used by flexible bronchoscopy in the treatment of airway benign neoplasms. The clinical data of 21 patients, who had airway benign neoplasm and were treated through the cold snare method in Sir Run Run Shaw Hospital, affiliated with the Zhejiang University, were retrospectively analyzed. The relief of the symptoms and occurrence of complications were observed and evaluated. All the tumors were benign and removed by cold snare. Postoperatively, we found that the treatment was completely effective in 12 patients, and there was a significant improvement in 7 patients and a moderate improvement in 2 patients, and no recurrence in follow-up visit. In conclusion, the cold snare technique is an economically feasible, safe, and effective method in the treatment of airway neoplasms.