Regulatory effects of smoking cessation on the cellular microenvironment and differentially expressed genes in precancerous lesions of pulmonary nodules in mice based on single-cell RNA sequencing and immune repertoire-sequencing

by Xintong Wang, Fang Tang, Jiayu Qin, Tiquan Xiao, Liwei Shi, Shujun Zhang, Chunli Che

Background

Smoking cessation decreases lung cancer progression; however, its effects on precancerous lesions and the underlying mechanisms remain unclear. This study established a mouse model of precancerous pulmonary nodules and employed single-cell RNA sequencing (scRNA-seq) and immune repertoire sequencing (IR-seq) to elucidate the regulatory mechanisms by which smoking cessation influences the development of lung precancerous lesions.

Methods

A B[a]P-induced mouse model of pulmonary precancerous lesions was established after 6 weeks of B[a]P treatment. Lung nodules were identified via micro-MRI, and histopathological features were assessed by H&E staining. After confirming the establishment of precancerous lesions in smoking-exposed mice, graded B[a]P withdrawal for 4 and 8 weeks was implemented. Nodule size was measured using Generic Medical Imaging software. scRNA-seq and IR-seq analyzed immune cell composition, proportions, signaling, and gene expression.

Results

B[a]P withdrawal reduced new lung nodule formation and decreased the diameter, area, and volume of existing nodules. It alleviated cellular atypia, reduced inflammation, and altered the tumor microenvironment by increasing T-, B-, and NK cells while reducing monocytes and neutrophils. Concurrently, B[a]P withdrawal downregulated Vim, GPX1, Atf3, CD44, and Arpc5 and upregulated Hsph1, Hsp90aa, and Hspa1b. B[a]P withdrawal upregulated CD80 and ICOS, suppressed intercellular communication via Icam1-(Itgal+Itgb2), Ppia-Bsg, and Thbs1-Cd47 pathways. The APP-CD74 pathway emerged as a novel regulator in precancerous lesions. IR-seq revealed restored T- and B-cell receptor diversity, CDR3 sequence alterations, and V(D)J gene regulation.

Conclusions

B[a]P withdrawal reduces lung nodules, inhibits progression, potentially by enhancing immune surveillance by modulating immune cells, signaling pathways, and gene expression, while promoting ferroptosis, suppressing inflammation, and preventing tumor stem cell-like traits. These findings may provide mechanistic insights into the beneficial effects associated with smoking cessation.

Clinical characteristics and management strategies in adult foreign-body airway obstruction: A retrospective cohort study

by Hongzhen Yin, Tong Wang, Changshun Zhong, Yingya Cao, Xiaogan Jiang, Qiancheng Xu, Weihua Lu

Airway foreign-body aspiration in adults is uncommon but can be life-threatening.Flexible bronchoscopy is the standard first-line therapy,but critically ill patients may need extracorporeal life support.This study aims to characterize the diagnosis,management,and outcomes of adult airway foreign-body cases treated at a single center over nearly 12 years to inform a standardized clinical pathway.A single-center retrospective observational study of consecutive patients aged ≥14 years with confirmed airway foreign body who were treated at a tertiary hospital in China were conducted.Medical records of consecutive adolescent and adult patients diagnosed with airway foreign-body aspiration and admitted to the hospital from 01/01/ 2014–30/11/2025 were reviewed.Data included demographics,imaging,extraction method, respiratory support and so on.Descriptive statistics were reported as medians with interquartile ranges or counts and percentages.A total of 41 patients were included,with a median age of 59.5 years(interquartile ranges 51–72) and 65.85% male.Flexible bronchoscopy was attempted as the primary intervention in 38 patients(92.68%) and succeeded in 81.58%(31/38) to remove airway foreign body.Most patients(78.05%) required only nasal cannula oxygen,while nine patients(21.95%) needed advanced support including mechanical ventilation (14.63%),high-flow oxygen(4.88%),and extracorporeal life support (2.44%).At discharge,most survivors had a good neurological outcome,with 36 patients(87.80%) having a Cerebral Performance Categories score of 1.The 28-day survival rate was 92.68%.These findings show that flexible bronchoscopy is an effective first-line therapy,and rigid bronchoscopy or surgery is useful when flexible bronchoscopy fails.In unstable cases,timely extracorporeal life support can bridge to definitive removal.These results support a tiered,multidisciplinary approach incorporating early chest computed tomography,flexible bronchoscopy,and escalation to advanced airway or extracorporeal support.