Background: Obstructive sleep apnea is associated with increased lung cancer incidence and mortality. Cancer stem cells (CSCs) are characterized by their self-renewing ability, which contributes to metastasis, recurrence, and drug resistance. ATPase family AAA domain-containing protein 2 (ATAD2) induces malignancy in different types of tumors. However, a correlation between ATAD2 expression and CSCs in lung cancer has not yet been reported. Methods: The relative messenger RNA (mRNA) levels of ATAD2, CD44, CD133, and hypoxia-inducible factor (HIF)-1α were determined using reverse-transcription quantitative polymerase chain reaction. ATAD2 protein levels were determined using Western blotting. Cell counting kit-8, 5-ethynyl-2′-deoxyuridine (EdU), and colony formation assays were performed to analyze the proliferation of lung cancer cells. Transwell migration and invasion assays were performed to evaluate cell migration and invasion, respectively. Tumor sphere formation analysis was used to determine tumor spheroid capacity. The link between ATAD2 and HIF-1α was verified using a dual-luciferase reporter assay. Immunofluorescence staining was performed to assess mitochondrial reactive oxygen species (mtROS) production. Flow cytometry analysis was conducted to determine the CD133 and CD44 positive cell ratio. Results: We evaluated the relative expression of ATAD2 in four lung cancer cell lines (A549, SPC-A1, H460, and H1299 cells) and found increased mRNA and protein levels of ATAD2 in lung cancer samples. ATAD2 overexpression was a poor prognostic factor for lung cancer patients. Loss of ATAD2 reduced lung cancer cell viability and proliferation. Additionally, ATAD2 knockdown repressed lung cancer cell migration, invasion, stem-cell-like properties, and mtROS production. Chronic intermittent hypoxia (CIH)-induced HIF-1α expression significantly activated ATAD2 during lung cancer progression. Conclusions: This study found that CIH induced HIF-1α expression, which acts as a transcriptional activator of ATAD2. The present study also suggests a novel mechanism by which the integrity of CIH-triggered HIF-1α/ATAD2 may determine lung cancer aggressiveness via the interplay of mtROS and stemness in lung cancer cells.

BACKGROUND:Head and neck squamous cell carcinoma (HNSC) is an invasive malignancy with a high worldwide mortality, despite considerable recent advancements in diagnosis and treatment. Increasing evidence indicates that the Lamin C (LAMC) gene family is associated with the progression of diverse cancers, nevertheless, this association is not well understood. MATERIAL AND METHODS:A systematic study addressing the expression and prognostic value of LAMC, and the relationship between LAMC and tumor immune response in HNSC was done. Finally, we performed drug screening to identify specific drugs. RESULTS:Compared to normal samples, expressions of LAMC1 and LAMC2 were significantly increased in HNSC, and LAMC2 was obviously correlated with an adverse prognosis for patients. LAMC2 expression level was significantly correlated with the infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, and macrophages. Moreover, LAMC2 exhibited strong correlations with diverse immune markers, immune microenvironment, and immune checkpoint molecules. Finally, candidate drugs that targeted LAMC2 were identified. CONCLUSIONS:This study suggests that LAMC2 could serve as a new prognostic biomarker, and it could be used for efficacy of target for immune response and for drug sensitivity prediction in HNSC.

Ventilator-associated pneumonia (VAP) is a major cause of morbidity in critically ill patients, and the SARS-CoV-2 infection has influenced the lung microbiome. This study aimed to examine the lower respiratory tract microbiome in VAP patients during different phases of the Shanghai COVID-19 epidemic. A total of 175 patients were included and divided into pre-epidemic (Pre), during-epidemic (Dur), and post-epidemic (Post) groups for analysis. Bronchoalveolar lavage fluid and serum were analyzed using next-generation sequencing. The intensive care unit (ICU) mortality rates were 48.3% (Pre group), 60.3% (Dur group), and 28.8% (Post group). Cytokine levels were lower in the Post group compared to the Pre group. Acinetobacter , Candida , and Herpes Simplex Virus 1 ( HSV-1 ) were the most frequently detected organisms. The prevalence of Klebsiella pneumoniae , Enterococcus faecium , Aspergillus fumigatus , and HSV-1 was higher in the Dur group. α-Diversity of bacteria was significantly lower in the Dur group ( P < 0.05), indicating reduced microbiome diversity. Multivariable Cox regression analysis identified APACHE II score (hazard ratio [HR] = 1.04, P = 0.029) and maximum bacterial load (HR = 1.67, P = 0.046) as independent risk factors for ICU mortality. This study highlights changes in microbiome composition across epidemic phases, which may inform treatment strategies. IMPORTANCE: With the development of next-generation sequencing technology, it is increasingly being applied in clinical practice, especially in evaluating the prognosis of severe infections and co-infections. This study characterized the composition of microorganisms in the lower respiratory tract of ventilator-associated pneumonia (VAP) patients across three phases of the COVID-19 epidemic. Our study emphasizes that the relative abundance of bacteria, fungi, and viruses in bronchoalveolar lavage fluid of VAP patients may vary with the progression of the local epidemic and host immune status. These findings provide a mechanistic basis for optimizing targeted therapies in VAP management during infectious disease outbreaks.

Low-flow extracorporeal carbon dioxide removal (ECCO ₂ R) may be useful when severe hypercapnia limits ultra-protective ventilation but full venovenous extracorporeal membrane oxygenation (VV-ECMO) is not pursued. We describe a 68 year old man with metastatic lung adenocarcinoma who developed amivantamab-associated immune-related interstitial lung disease complicated by acute respiratory distress syndrome (ARDS) and active airway hemorrhage. After endotracheal intubation, the dominant physiologic problem was hypercapnic acidosis (pH 7.12; PaCO ₂ 83.4 mm Hg) with very poor respiratory system compliance, whereas oxygenation impairment was moderate (PaO ₂ /FiO ₂ 160 mm Hg). Because of terminal malignancy and the burden of large-bore cannulation, VV-ECMO was not pursued. Electrical impedance tomography showed no benefit from prone positioning. A hybrid strategy was then initiated: inhaled nitric oxide to improve ventilation-perfusion (V/Q) matching and ECCO ₂ R to control carbon dioxide clearance. Within 2 hours, PaCO ₂ fell to 60.7 mm Hg and pH rose to 7.32; oxygenation also improved. The circuit remained functional for 13 days without recurrent airway bleeding or documented circuit thrombosis. This case illustrates the feasibility of concurrently applying inhaled nitric oxide and low-flow ECCO ₂ R as a physiology-guided, low-intensity rescue approach in a highly selected patient when VV-ECMO was not pursued.