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Rationale and objectives: Bleeding is a major complication of transbronchial lung cryobiopsy (TBLC), and pre-placing a bronchial balloon is one of the clinical practices used to prevent it, but with very weak evidence, which should be confirmed. This study aimed to conduct whether pre-placing a bronchial balloon in TBLC for diagnosing interstitial lung disease (ILD) is more safety. Materials and methods: In this prospective, single-center, randomized controlled trial, patients with suspected ILD were enrolled and randomly assigned to pre-placed balloon and none-pre-placed balloon groups. The primary outcome was incidence of moderate bleeding in each group. The secondary endpoints were the incidence of severe bleeding, pneumothorax, and other procedural complications. Results: Exactly 250 patients were enrolled between August 2019 and March 2022, with 125 in each group. There were no significant differences in severe bleeding between the none-pre-placed balloon group and pre-placed balloon group (1.6% vs. 0.8%; adjusted p = 0.520), while more moderate bleeding occurred in the none-pre-placed balloon group (26.4% vs. 6.4%, adjusted p = 0.001), as well as more use of hemostatic drug (28.0% vs. 6.4%, adjusted p = 0.001). Three patients in the none-pre-placed balloon group used the bronchial balloon. More samples could be acquired in the pre-placed balloon group than in the none-pre-placed balloon group (3.8 ± 0.9 vs. 3.1 ± 0.9, p < 0.001). There were no significant differences in multidisciplinary discussion (MDD) between the two groups (89.6% vs. 91.2%, adjusted p = 0.182). Conclusion: A pre-placed bronchial balloon can reduce the incidence of moderate bleeding and increase the confidence of the bronchoscopists. However, it had no effect on increasing the diagnostic rate of MDD and reducing severe bleeding. Registration number: NCT04047667 (www.clinicaltrials.gov identifier). [ABSTRACT FROM AUTHOR]

There are many similarities between embryonic development and tumorigenesis, and gene expression profiles show that certain correlations exist between the gene signature during development and the clinical phenotypes of different cancers. Our group previously reported the gene expression profiles of human lung development, and the expression of one group of proliferation‐related genes (PTN1 genes) steadily decreased during lung development. Here, we examined the prognostic value of PTN1 genes in 5 independent lung adenocarcinoma (ADC) and 5 lung independent squamous cell carcinoma (SCC) microarray datasets and found that the expression levels of PTN1 genes were associated with survival in lung ADC but not lung SCC. All of the lung ADC datasets contained a set of highly correlated genes from PTN1 genes, but the lung SCC datasets had no similar set of genes. We identified 63 unique core genes from the PTN1 genes in the 5 lung ADC datasets: 17 of these core genes appeared in at least 4 of the lung ADC datasets, and the 17 corresponding proteins clearly interacted more strongly with each other in lung ADC than in lung SCC. Moreover, 16 of the 17 core genes play major roles in the G2/M phase of the cell cycle. These data indicate that proliferation‐related genes in lung development have a significant prognostic value for lung ADC; the synergistic effects of the 17 core genes play an important role in lung ADC prognosis. These genes may have significant clinical implications for the treatment and prognosis of lung ADC. [ABSTRACT FROM AUTHOR]

Oxidative stress and chronic inflammation play key roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). Astaxanthin (AXT) is a keto-carotenoid with a variety of biological functions, including antioxidant and anti-inflammatory effects This study aimed to explore the protective role and underlying mechanism of AXT in the pathogenesis of COPD. In this study, we found AXT alleviated pulmonary emphysema in a CS-exposed mouse model and regulated the expression of MMP-9/TIMP-1. And, AXT attenuates CSE-induced small airway fibrosis. Meanwhile, AXT inhibited Nrf2-modulated oxidative stress and the p65 NF-κB-regulated inflammatory pathway in both the mouse model and CSE-treated HBE cells. Mechanistically, AXT could directly bind to SIRT1 (the binding energy of the complex was −8.8 kcal/mol) and regulate the deacetylation activity of SIRT1. Finally, by activating SIRT1 deacetylation, AXT deacetylated Nrf2 and contributed to its action of reducing oxidative stress by generating antioxidant enzymes, and inhibiting p65 NF-κB transcriptional activity to suppress the inflammatory response. Our results show that treatment with AXT significantly reverses the oxidative stress and inflammation induced by cigarette smoke both in vivo and in vitro in a sirtuin 1-dependent manner. [Display omitted] • Astaxanthin alleviated cigarette smoke extract-induced pulmonary emphysema and small airway fibrosis. • Astaxanthin inhibited Nrf2-modulated oxidative stress and the NF-κB-regulated inflammatory pathway. • Astaxanthin directly binds and activates SIRT1. • AXT upregulates the deacetylation levels of Nrf2 and NF-κB p65 exert antioxidant and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Recent studies have emphasized the close relationship between macrophages and tumor immunity, and the prognosis of lung adenocarcinoma (LUAD) patients is intimately linked to this. Nonetheless, the prognostic signature and classification of different immune patterns in LUAD patients based on the macrophages is largely unexplored. Two sc-RNAseq datasets of LUAD patients were collected and reprocessed. The differentially expressed genes (DEGs) related to macrophages between LUAD tissues and normal lung tissues were then identified. Based upon the above genes, three distinct immune patterns in the TCGA-LUAD cohort were identified. The ssGSEA and CIBERSORT were applied for immune profiling and characterization of different subtypes. A four-gene prognostic signature for LUAD patients was established based on the DEGs between the subtypes using stepwise multi-Cox regression. TCGA-LUAD cohort was used as training set. Five GEO-LUAD datasets and an independent cohort containing 112 LUAD samples were used for validation. TIDE (tumor immune dysfunction and exclusion) and drug sensitivity analyses were also performed. Macrophage-related differentially expressed genes were found out using the publicly available scRNA-seq data of LUAD. Three different immune patterns which were proved to have distinct immune infiltration characteristics in the TCGA-LUAD cohort were recognized based on the above macrophage-related genes. Thereafter, 174 DEGs among the above three different immune patterns were figured out; on the basis of this, a four-gene prognostic signature was constructed. This signature distinguished the prognosis of LUAD patients well in various GSE datasets as well as our independent cohort. Further analyses revealed that patients which had a higher risk score also accompanied with a lower immune infiltration level and a worse response to several immunotherapy biomarkers. This study highlighted that macrophage were significantly associated with TME diversity and complexity. The four-gene prognostic signature could be used for predicting outcomes and immune landscapes for patients with LUAD. [Display omitted] • Depicting the LUAD landscape and acquiring macrophage-related differentially expressed genes from scRNAseq data of LUAD. • Identifying and depicting 3 distinct LUAD subtypes with distinct immune landscapes which were termed as "immune-infiltrated phenotype", "immune-excluded phenotype" and "immune-desert phenotype". • Establishment of a four-gene prognostic model for LUAD patients and validation of the signature using publicly attainable LUAD cohorts and an independent cohort containing 112 LUAD samples. [ABSTRACT FROM AUTHOR]

Background Conventional bronchoscopy with brushing alone for diagnosing peripheral pulmonary lesions ( PPLs) is of low sensitivity. A manual mapping method was introduced and evaluated in this study, which could be routinely applied with bronchoscopic brushing to improve the sensitivity for malignant PPLs. Methods This mapping method involves the bronchoscopist drawing the route with a series of bronchial opening sketches and marking the leading bronchus at every bifurcation point based on thin-section computed tomography. This map is then used to guide bronchoscope insertion for brushing. A cross-sectional study on the evaluation of this method for the diagnosis of malignant PPLs was conducted on patients from July 2010 to June 2013. Results The sensitivity for malignant PPLs of conventional brushing, conventional brushing with mapping on a portion of patients, and conventional brushing with mapping method increased from 17.0% to 25.8% to 31.5% ( P < 0.001), respectively. For lesion sizes over 3 cm, the rate of these three groups increased from 25.1% to 38.6% to 50.9% ( P < 0.001), respectively. The sensitivity of this mapping method for malignant PPLs was statistically associated with lesion size, lesion character, relationship between the lesion and the leading bronchus, linear distance between the targeted bronchus and the opening of the lobe bronchus, and accessibility ( P < 0.001, P = 0.039, P < 0.001, P = 0.031, and P = 0.020, respectively). Conclusions The manual mapping method greatly increased the bronchoscopic brushing sensitivity for malignant PPLs compared to the conventional brushing method. During routine clinical work, it is economical and convenient for guiding bronchoscope insertion. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that interferon (IFN) alpha/beta are involved in antitumor immunity and cancer immunoediting, but information on the antitumor effects of IFN alpha/beta in lung cancer is limited. In our study, we elucidated the IFN alpha/beta signature during both human fetal lung development and lung tumorigenesis. Our findings indicated gradual upregulation in the IFN alpha/beta signature during human fetal lung development. In addition, this signature was progressively downregulated in normal human airway epithelial cells from lung cancer patients, in immortalized human bronchial epithelial cell lines from later passages, in late-stage lung squamous cell carcinoma (LSCC) tissues, and in LSCC tissues exhibiting lymph node metastasis. Therefore, from its earliest stages, lung tumorigenesis may be associated with a decreased IFN alpha/beta signature. This association may provide insight to guide the detection of high-risk lung cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: Subglottic stenosis, manifested by granulation tissue hyperplasia, is challenging and requires multiple repeated treatments and stent maintenance at times. Corticosteroids prevent severe subglottic stenosis development owing to their antifibrotic and antiinflammatory properties. Submucosal injection of glucocorticoids or mitomycin, a useful adjuvant therapeutic method, improves the mean interval between endoscopic procedures and reduces airway restenosis risks., Case Presentation: We report a rare case of a man with complex subglottic stenosis who underwent balloon dilatation combined with cryotherapy, stent placement, and adjuvant submucosal triamcinolone injection. The drug was injected efficiently and safely into the submucosal layer under percutaneous ultrasound guidance, and subglottic stenosis was well-controlled at a low cost., Conclusion: POCUS-guided medication injections may be a useful adjuvant medical therapy for subglottic stenosis., (S. Karger AG, Basel.)

Rationale: The diagnostic yield of traditional ultrasound-guided pleural biopsy remains unsatisfactory, particularly when the pleural thickness is ⩽5 mm and/or no pleural nodules are detected. Pleural ultrasound elastography (UE) has a better diagnostic yield than traditional ultrasound for malignant pleural effusion (MPE). However, studies on UE-guided pleural biopsies are lacking. Objectives: To evaluate the feasibility and safety of UE-guided pleural biopsy. Methods: In this multicenter prospective single-arm trial, patients with pleural effusion whose pleural thickness was ⩽5 mm with no pleural nodules were enrolled between July 2019 and August 2021. The diagnostic yield of UE-guided pleural biopsy for pleural effusion and its sensitivity for detecting MPE were evaluated. Results: Ninety-eight patients (mean age, 62.4 ± 13.2 yr; 65 men) were prospectively enrolled. The diagnostic yield of UE-guided pleural biopsy for making any diagnosis was 92.9% (91/98), and its sensitivity for MPE was 88.7% (55/62). In addition, its sensitivity for pleural tuberculosis was 69.6% (16/23). The rate of postoperative chest pain was acceptable, and there was no pneumothorax. Conclusions: UE-guided pleural biopsy is a novel technique for diagnosing MPE with good diagnostic yield and sensitivity. Clinical trial registered with https://www.chictr.org.cn (ChiCTR2000033572).

Similarities in gene expression between both developing embryonic and precancerous tissues and cancer tissues may help identify much-needed biomarkers and therapeutic targets in lung squamous carcinoma. In this study, human lung samples representing ten successive time points, from embryonic development to carcinogenesis, were used to construct global gene expression profiles. Differentially expressed genes with similar expression in precancerous and cancer samples were identified. Using a network-based greedy searching algorithm to analyze the training cohort (n = 69) and three independent testing cohorts, we successfully identified a significant 22-gene module in which expression levels were correlated with overall survival in lung squamous carcinoma patients.