Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis.

BACKGROUND: Mechanism underlying the malignant progression of precancer to early-stage lung adenocarcinoma (LUAD) as well as their indolence nature remains elusive. METHODS: Single-cell RNA sequencing (scRNA) with simultaneous T cell receptor (TCR) sequencing on 5 normal lung tissues, 3 precancerous and 4 early-stage LUAD manifested as pulmonary ground-glass nodules (GGNs) were performed. RESULTS: Through this integrated analysis, we have delineated five key modules that drive the malignant progression of early-stage LUAD in a disease stage-dependent manner. These modules are related to cell proliferation and metabolism, immune response, mitochondria, cilia, and cell adhesion. We also find that the tumor micro-environment (TME) of early-stage LUAD manifested as GGN are featured with regulatory T (Tregs) cells accumulation with three possible origins, and loss-functional state (decreased clonal expansion and cytotoxicity) of CD8 + T cells. Instead of exhaustion, the CD8 + T cells are featured with a shift to memory phenotype, which is significantly different from the late stage LUAD. Furthermore, we have identified monocyte-derived macrophages that undergo a lipid-phenotype transition and may contribute to the suppressive TME. Intense interaction between stromal cells, myeloid cells including lipid associated macrophages and LAMP3 + DCs, and lymphocytes were also characterized. CONCLUSIONS: Our work provides new insight into the molecular and cellular mechanism underlying malignant progression of LUAD manifested as GGN, and pave way for novel immunotherapies for GGN. Video Abstract.

Ultrasound versus manipulation to determine an intercostal space for single-port thoracoscopy surgery: a diagnostic accuracy study.

BACKGROUND: Malposition of the intercostal space used for single-port thoracoscopy surgery can lead to problems. This study was to assess the accuracy of point-of-care ultrasound in verifying the position of intercostal space. METHODS: A total of 200 patients, ASA (American Society of Anesthesiologists) physical status I or II, who underwent single-port thoracoscopic lobectomy, were enrolled. After the induction of anesthesia, a thoracic team confirmed the incision position. Firstly, the intercostal space was located by a young resident thoracic surgeon by ultrasound. Secondly, the intercostal space was located by an experienced thoracic surgeon by manipulation. Finally, the investigator verified the location of the intercostal space under direct vision through thoracoscopy, which was recognized as standard method. The time required by ultrasound and manipulation were recorded. RESULTS: The inter-relationships between ultrasound and the standard method and between manipulation and the standard method were consistent. Manipulation positioning showed a sensitivity of 90.6% and specificity of 30% while ultrasound positioning showed a sensitivity of 87.1% and specificity of 60%. The specificity of ultrasound positioning was higher than that of manipulation position. The time required by ultrasound was shorter than that required by manipulation. CONCLUSIONS: Compared with the manipulation method, the ultrasound-guided method could accurately locate the intercostal space. Ultrasound requires less time than manipulation. TRIAL REGISTRATION: ISRCTN10722758. Registered 04 June 2019.

Clinical characteristics and prognosis of SARS-CoV-2 infection in lung transplant recipients.

Objective: This study aimed to investigate the clinical manifestations and prognosis of lung transplant (LTx) recipients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease (COVID-19) pandemic. Methods: The research participants were LTx recipients who underwent surgery and were regularly followed up at our center. From 1 December 2022 to 28 February 2023, during the COVID-19 pandemic in China, research participants were interviewed either online or in person. SARS-CoV-2 nucleic acid or self-tested antigens were detected according to accessibility. Diagnosis and treatment were performed according to the Diagnosis and Treatment Plan for COVID-19 (10th edition) issued by the National Health Commission of the People's Republic of China. Hospitalized patients underwent chest imaging examinations, routine blood tests, biomarkers for infection and inflammation, and biochemical tests, all of which were taken and recorded. Data were analyzed to describe the features of COVID-19 in LTx recipients. Results: In total, 52 patients were enrolled in this study, comprising 48 men and 4 women, with a mean age of 51.71 ± 11.67 years. By 1 December 2022, the mean survival period was 33.87 ± 25.97 months, of which 84.61% of the patients (44/52) had a survival period longer than 12 months. The SARS-CoV-2 infection rate in these LTx recipients was 82.69% (43/52), with 3.85% (2/52) of the infected recipients being asymptomatic, 50.00% (26/52) of the infected recipients experiencing mild COVID-19, 11.54% (6/52) having moderate COVID-19, and 17.31% (9/52) having severe or critical COVID-19. The mortality rate among severe and critical patients was 66.67% (6/9). Conclusion: LTx recipients in this cohort exhibited a notable susceptibility to SARS-CoV-2, with 82.69% of individuals diagnosed with COVID-19. Moreover, the mortality rate among critically ill patients was high.

KDM5C Expedites Lung Cancer Growth and Metastasis Through Epigenetic Regulation of MicroRNA-133a.

BACKGROUND: KDM5C, a histone H3K4-specific demethylase, possess various biological functions in development of cancers. However, its relation to the microRNA (miRNA) regulation in lung cancer remains unknown. This study aims to study the regulatory role of KDM5C on modification of miR-133a in the progression of lung cancer. METHODS: Differentially expressed miRNAs were filtered from 34 paired lung cancer and paracancerous tissues. The correlation between miR-133a expression and the prognosis of lung cancer patients was determined by a bioinformatics website. Furthermore, malignant aggressiveness of lung cancer cells was detected after miR-133a upregulation by CCK-8, flow cytometry, and Transwell assays and in vivo tumorigenesis and metastasis experiments. Subsequently, we analyzed mRNA downregulated in cells overexpressing miR-133a using m microarray analysis and expounded the upstream regulatory mechanism of miR-133a using bioinformatics website prediction and functional validation. RESULTS: miR-133a was reduced in lung cancer tissues, and patients with low expression of miR-133a have worse survival rates. miR-133a restoration curtailed growth and metastasis of lung cancer cells in vitro and in vivo. Moreover, miR-133a downregulated PTBP1 expression, whereas overexpression of PTBP1 attenuated the suppressive effect of miR-133a on lung cancer cell aggressiveness. The level of methylation modification of miR-133a was reduced in lung cancer cells. KDM5C inhibited the expression of miR-133a by promoting the demethylation modification of its promoter histone. CONCLUSION: Histone demethylase KDM5C inhibits the expression of miR-133a by elevating the demethylation modification of the promoter histone of miR-133a, thereby promoting the expression of PTBP1, which finally accelerates lung cancer cell growth and metastasis.

SLCO4A1-AS1 promotes cell growth and induces resistance in lung adenocarcinoma by modulating miR-4701-5p/NFE2L1 axis to activate WNT pathway.

Long noncoding RNAs (lncRNAs) possessed essential functions in the biological behaviors of various human cancers. SLCO4A1 antisense RNA 1 (SLCO4A1-AS1) is a lncRNA that has been reported as a oncogenic regulator in colorectal cancer and bladder cancer. However, whether it exerted functions in the gene expression and cellular processes in lung adenocarcinoma (LUAD) remains still obscure. In the present research, we unveiled the high level of SLCO4A1-AS1 in LUAD tissues and cells. Moreover, functional assays indicated that SLCO4A-AS1 facilitated LUAD cell proliferation, motility, and cisplatin-resistance. Besides, mechanism investigation revealed that miR-4701-5p could interact with SLCO4A1-AS1 and directly target to NFE2L1. The expression correlation between miR-4701-5p and SLCO4A1-AS1 or NFE2L1 was found to be negative. Moreover, NFE2L1 was expressed at a same tendency with SLCO4A1-AS1 in LUAD tissues and cells. In addition, it was confirmed that NFE2L1 was involved in SLCO4A1-AS1-mediated activation of WNT pathway. According to rescue assays, NFE2L1 could involve in SLCO4A1-AS1-mediated LUAD cell growth. Conclusively, our study demonstrated that SLCO4A1-AS1 facilitated cell growth and enhanced the resistance of LUAD cells to chemotherapy via activating WNT pathway through miR-4701-5p/NFE2L1 axis.