Background:The mortality rate for elderly patients with community-acquired pneumonia (CAP) admitted to intensive care units (ICU) is high. The combination assessment of Systemic Immune-inflammation Index (SII) and Prognostic Nutritional Index (PNI) can provide a more comprehensive evaluation of the patient's immune response, systemic inflammatory burden, and nutritional metabolic status. Methods:From the Medical Information Mart for Intensive Care IV database (MIMIC-IV, version 3.1), we selected 12457 patients with CAP admitted to the ICU. After exclusions, 634 patients were included and randomly split into training (n = 444, 70%) and internal validation (n = 190, 30%). Meanwhile, an independent external validation cohort comprised 149 patients admitted to The Affiliated People's Hospital of Ningbo University (January 2024-March 2025) was collected. Optimal thresholds for SII and PNI were derived from receiver operating characteristic (ROC) analysis in the training cohort, which were subsequently used to calculate the SII-PNI score. Model performance was evaluated through net reclassification improvement, decision-curve analysis, logistic regression analysis, and Kaplan-Meier curves. Validation was performed in internal and external cohorts to assess the model's predictive value in geriatric CAP patients. Results:Receiver operating characteristic analysis determined the optimal cutoff values for SII (2030.28; AUC = 0.573, 95% CI 0.517-0.628, p < 0.05) and PNI (29.07; AUC = 0.638, 95% CI 0.584-0.692, p < 0.001) in the training cohort. The SII-PNI scoring model was subsequently developed using these thresholds and demonstrated predictive value for 30-day in-hospital mortality [OR: 2.19 (95% CI: 1.62-2.95), p < 0.001]. Kaplan-Meier survival analysis confirmed consistent prognostic performance across all cohorts, that patients with a score of 2 on the SII-PNI scale had significantly higher 30-day mortality compared to those with scores of 0 or 1 (p < 0.05). Conclusion:The SII-PNI may serve as a adjunct for evaluating the 30-day mortality rate among elderly ICU patients admitted with CAP.

Leukemia inhibitory factor (LIF) is an established oncogenic driver in multiple cancers. However, its functional contribution and mechanistic underpinnings in lung squamous cell carcinoma (LSCC) remain incompletely defined. To delineate the role of LIF in LSCC progression, and elucidate the underlying molecular mechanisms. LIF protein expression in clinical LSCC tissues was assessed by immunohistochemistry (IHC) and Western blotting. LIF gain-of-function (using recombinant LIF protein) and loss-of-function (via LIF knockdown) assays were performed in vitro to assess its impact on the malignant phenotypes of LSCC cells. The changes in signaling pathways were analyzed by Western blotting and immunofluorescence. The functional role of LIF was further validated in patient-derived organoid models and a nude mouse xenograft model. LIF protein was significantly upregulated in LSCC tissues, and its high expression was correlated with unfavorable clinical outcomes. Recombinant LIF (rLIF) significantly enhanced the proliferation, migration, and invasion of LSCC cells in vitro in a dose-dependent manner, and the dosage of 200 ng/mL exerted the most pronounced effects. Conversely, LIF knockdown suppressed these malignant phenotypes. LIF activated the PI3K/AKT pathway, leading to inhibitory phosphorylation of GSK-3β at Ser 9, which consequently stabilized β-catenin and facilitated its nuclear accumulation. Furthermore, rLIF also promoted the growth of patient-derived organoids, and upregulated the expression of Ki-67 and α-SMA. In contrast, LIF knockdown significantly attenuated the growth of LSCC xenografts in vivo, and this effect was partially reversed by exogeneous rLIF. The oncogenic effects of LIF were associated with increased expression levels of p-AKT, p-GSK-3β, and β-catenin. LIF mediates LSCC progression by activating the PI3K/AKT/GSK-3β/β-catenin pathway. Therefore, LIF and its effectors warrant further study as potential diagnostic biomarkers and therapeutic targets in LSCC.

Background:Chronic obstructive pulmonary disease (COPD) remains a major public health burden. Understanding the distribution of demographic, clinical, and socioeconomic characteristics across severity stages may support improved disease management. This study examined characteristics associated with COPD severity among adults aged 60-80 years in a hospital-based screening cohort in Ningbo, China. Methods:A cross-sectional analysis was conducted from January 2022 to December 2025 among 18,832 spirometry-confirmed COPD patients identified through a hospital-based screening program. COPD severity was classified according to the 2023 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Group differences were evaluated using χ2 tests for categorical variables and Welch's analysis of variance (ANOVA) for continuous variables. Factors associated with severity stage were examined using ordinal logistic regression. Results:Most patients were classified as GOLD stage I or II. In univariate analyses using χ2 tests and Welch's ANOVA, several demographic, symptom-related, and socioeconomic characteristics differed significantly across severity stages. In multivariable ordinal logistic regression, older age [adjusted odds ratio (aOR) =1.015, 95% confidence interval (CI): 1.008-1.023], higher COPD Screening Questionnaire (SQ) score (aOR =1.03, 95% CI: 1.02-1.04), higher COPD Population Screener (PS) score (aOR =1.20, 95% CI: 1.17-1.23), and a history of frequent long-lasting lower respiratory infections (aOR =1.39, 95% CI: 1.27-1.51) were positively associated with higher severity stages. Female sex (aOR =0.87, 95% CI: 0.81-0.94), higher educational attainment (aOR =0.75, 95% CI: 0.65-0.86), and higher socioeconomic status (aOR =0.80, 95% CI: 0.74-0.86) were inversely associated with severity classification. Conclusions:In this hospital-based screening cohort, COPD severity varied systematically across demographic, symptom-related, and socioeconomic characteristics. These findings describe stage-related gradients within the screened population and may inform targeted management strategies.

BackgroundAccurately predicting the risk of weaning failure is crucial for optimizing clinical decision-making and improving patient prognosis. Despite widespread use, the predictive value of diaphragm ultrasound remains controversial, and the compensatory role of auxiliary respiratory muscles has been overlooked. This study aims to evaluate whether the diaphragm-intercostal index (DII), a novel ultrasound index for joint assessment of diaphragm and intercostal muscle function, can predict weaning failure more accurately than traditional parameters.MethodsThis prospective single-center cohort study enrolled invasive mechanical ventilation patients (≥48 h) ready for weaning. Ultrasound was performed 30 min into the spontaneous breathing trial (SBT) (pre-extubation, for primary predictive analysis) and 24 h post-extubation (for exploratory descriptive analysis only). Measurements included diaphragmatic excursion (DE), diaphragm thickening fraction (TFdi), and intercostal muscle thickening fraction (TFic). DII was calculated as TFic/TFdi. The primary outcome was weaning failure, defined as SBT failure or need for therapeutic non-invasive ventilation (NIV), reintubation, or death within 48 h post-extubation. Sensitivity analysis was performed after excluding SBT failure patients to assess DII’s performance in predicting true post-extubation failure. Lasso-logistic regression and ROC curves assessed predictive performance.ResultsOf 107 patients, 81 weaned successfully and 26 failed. Among failures, 5 (19.23%) had SBT failure, 8 (30.77%) required reintubation, 11 (42.31%) required therapeutic NIV, and 2 (7.69%) died. DII’s AUC was 0.952 (95% CI: 0.907–0.998), significantly outperforming RSBI (AUC = 0.789) and TFdi (AUC = 0.830). The optimal DII cutoff was >0.485 (sensitivity 80.8%, specificity 97.5%). In the sensitivity analysis excluding SBT failures, DII’s AUC for predicting true post-extubation failure remained high at 0.942 (95% CI: 0.887–0.996), and DeLong test showed no significant difference from the primary analysis (p = 0.779).ConclusionDII can effectively quantify the compensation of the auxiliary respiratory muscles relative to the diaphragm, showing favorable predictive performance for predicting weaning failure, strikingly superior to traditional parameters. However, validation in large-scale, multi-center studies is needed, particularly after standardizing SBT protocols with positive end-expiratory pressure (PEEP) as per guidelines, and in populations including obese and heart failure patients.

OBJECTIVES:The 9th edition of the tumor-node-metastasis (TNM) staging system for lung cancer was proposed at the 2023 World Conference on Lung Cancer in Singapore. This study aimed to externally validate and compare the latest staging of small-cell lung cancer (SCLC). METHODS:Four hundred and eight patients with limited-stage SCLC were collected after lung resection from four centers. Survival curves by TNM stages were drawn using the Kaplan-Meier method and further compared by the Log-rank test. The Cox regression, receiver operating characteristics curves, area under the curve (AUC), Akaike information criterion (AIC), Bayesian information criterion (BIC), and Concordance index (C-index) were used in this study. RESULTS:In comparing IA vs. IIB, IIA vs. IIB, IIA vs. IIIA, IIA vs. IIIB, and IIIA vs. IIIB, the 9th edition had a better distinguishing ability than the eighth staging system (all p < 0.05). Besides, the 9th edition TNM staging had better predictive power and accuracy for the overall survival (OS) of SCLC patients over the 8th edition (AUC of 3-year OS: 0.680 vs. o.668; AIC: 4425.25 vs. 4444.52; BIC: 4493.44 vs. 4512.71; C-index: 0.637 [0.04] vs. 0.629 [0.039], p < 0.001). CONCLUSIONS:Our external validation demonstrates that the ninth edition of pathological TNM staging for limited-stage SCLC is reasonable and valid based on a multicenter study. The ninth edition has better prognostic accuracy than the eighth edition.

Inhibitors of the programmed death receptor 1 (PD-1) or its ligand PD-L1 are widely used in cancer treatment. Despite their efficacy, these immunotherapies can induce adverse effects, particularly dermatitis and pneumonitis. However, the prognosis of these conditions is infrequently reported. The present study discusses a case of a patient with non-small-cell lung cancer (NSCLC) who developed severe dermatitis and grade 4 pneumonitis following treatment with pembrolizumab. Initially, the patient was administered methylprednisolone at a dosage of 4 mg/kg/day. Reducing the dosage to 1 mg/kg/day exacerbated the pneumonitis, following which the patient was administered mycophenolate mofetil (MMF), which notably ameliorated both conditions. The methylprednisolone dosage was then gradually reduced to 4 mg daily. The present case represents a rare instance of simultaneous severe dermatitis and grade 4 pneumonitis in a patient with NSCLC following immunotherapy. The conditions were successfully managed with a combination of MMF with methylprednisolone, resolving the steroid-dependent dermatitis and pneumonitis. The patient maintained a partial remission, with a tumor size of >30% smaller compared with the initial tumor size, for >3 years following the cessation of immunotherapy.

Background Airway mucus hypersecretion is a key pathophysiological feature in many respiratory diseases and could lead to airway obstruction and repeated infections, consequently accelerating disease progression, which impacts on pulmonary function and quality of life (QoL), highlighting the importance of mucolytic therapy targeting airway mucus hypersecretion.Objectives To investigate the safety and efficacy of inhalable ambroxol hydrochloride aerosol for adult patients with respiratory diseases.Design An open-label, single-arm, multicentre postmarketing surveillance study.Methods Adult patients with acute or chronic respiratory diseases were eligible to receive aerosol inhalation of ambroxol hydrochloride (3 mL and 7.5 mg/mL) using a nebuliser two times per day given at least 6 hours apart between doses. The treatment lasted for a maximum of 7 days. The primary safety outcome was the frequency and severity of adverse events (AEs), and the primary efficacy outcome was changes in sputum scale scores.Results Among 1201 eligible patients, 1192 received study medication and were included in the full analysis set and the safety set. Any grade AEs occurred in 16.3% of the patients, including serious AEs in four (0.3%) patients. The three most frequent AEs were respiratory symptoms and signs (1.5%), nausea and vomiting (0.8%) and digestive tract symptoms and signs (0.7%). In the full analysis set, the patients showed a mean reduction of 77.6% (95% CI, 75.9% to 79.3%) in the sputum scale score at the end of treatment, with a mean difference of −1.7±0.7 from baseline (p<0.001).Conclusion Inhalable ambroxol hydrochloride aerosol is well tolerated and effective in easing expectoration and alleviating cough, reducing sputum and improving the QoL of adult patients with acute and chronic respiratory diseases.Trial registration number ChiCTR2100043736.

Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) implicated in the onset and advancement of various human cancers. Among these, circFOXK2 has been linked to non-small cell lung cancer (NSCLC); however, its precise functions and underlying molecular mechanisms are not fully understood. This study shows the first experimental findings that circFOXK2 promotes NSCLC tumor progression by modulating the miR-328-5p/PKP3 signaling pathway. Levels of circFOXK2, miR-328-5p, and PKP3 were evaluated by qRT-PCR. Cellular (NSCLSC) proliferation was examined via CCK-8 assays, migratory capacity via wound healing, and invasive potential via Transwell assays. Potential binding interactions between miR-328-5p and circFOXK2 were first assessed using bioinformatic analysis and verified using a dual-luciferase reporter assay (DLRGAs). Regulatory relationships among circFOXK2, miR-328-5p, and PKP3 were further investigated through qRT-PCR analysis. Elevated expression of circFOXK2 and reduced levels of miR-328-5p were observed in NSCLC cell lines and tissues. Functionally, circFOXK2 enhanced cellular propagation, dissemination, and invasion in vitro. Mechanistic evaluation revealed that circFOXK2 upregulates PKP3 by acting as an miR-328-5p sponge. The findings demonstrate that circFOXK2 contributes to NSCLC tumorigenesis via modulation of the miR-328-5p/PKP3 pathway, identifying this signaling axis as a potential therapeutic target in NSCLC.

Background Conditional reprogramming (CR) technology enables rapid and long-term expansion of primary cells while preserving their tumor-specific traits, differentiation potential, and viability. Using this approach, we established primary lung adenocarcinoma cells to explore the antitumor mechanisms of kaempferol, a natural flavonoid known to inhibit proliferation, metastasis, and epithelial–mesenchymal transition (EMT) in various cancers. Methods Short tandem repeat (STR) analysis and immunofluorescence were performed to authenticate primary lung adenocarcinoma cells derived from a patient. The effects of kaempferol on proliferation and invasion were evaluated in this cellular model. Mechanistic insights were further obtained by Western blot analysis of key proteins in the IGF-1R/PI3K/AKT pathway and epithelial-mesenchymal transition (EMT)-related markers. Results STR analysis and immunofluorescence confirmed that the primary human lung adenocarcinoma cells maintained genetic stability during in vitro culture. Kaempferol treatment significantly suppressed the viability, proliferation, and invasive capacity of these cells. At the molecular level, kaempferol reduced phosphorylation of IGF-1R, PI3K, and AKT, while upregulating E-cadherin and downregulating vimentin and α-SMA expression, collectively indicating partial reversal of epithelial-mesenchymal transition. Conclusions The CR technique enables the successful culture of primary lung cancer cells while preserving their fundamental genetic characteristics. Moreover, kaempferol suppresses the proliferation and metastasis of primary human lung adenocarcinoma cells, likely through inhibiting the IGF-1R/PI3K/AKT pathway and partially reversing EMT. These findings suggest that kaempferol may represent a potential therapeutic agent for the treatment of lung adenocarcinoma.

Background:While both the systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) have demonstrated prognostic value in various diseases, the clinical utility of their combined score (SII-PNI) for predicting outcomes in patients with severe community-acquired pneumonia (SCAP) remains incompletely understood. The aim of this study is to explore the predictive value of SII-PNI score in patients with SCAP. Methods:We conducted a retrospective analysis of the clinical data of 138 patients diagnosed with SCAP. The SII, PNI, and the SNII-PNI score were calculated. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal threshold of SII-PNI. Multivariable logistic regression models were used to assess the association between the SII-PNI score and 28-day mortality. Results:The cutoff values for predicting 28-day mortality were >4689.82 for SII and <32.18 for PNI, respectively, with sensitivities of 59.1% and 60.3% and specificities of 85.3% and 68.2%. Multivariate analysis reveals that a SII-PNI score of 2 (OR, 14.11; 95% CI, 3.18-62.66; p = 0.001) was independently associated with a high risk of 28-day mortality. Conclusion:Our results indicate that a higher SII-PNI score at admission was linked to poor prognosis in SCAP patients. The combined SII-PNI score can effectively help clinicians assess disease progression and optimize risk assessment and clinical management for SCAP patients.

Objective The aim of this study was to analyze the detection and epidemiological characteristics of common influenza viruses (IVA/IVB) and respiratory syncytial virus (RSV) in a teaching hospital in Shanghai from 2017 to 2023, and to investigate the impact of the COVID-19 epidemic on the transmission and detection rates of these viruses. Methods Retrospective analysis of IVA/IVB and RSV cases detected in hospitals from 2017 to 2023. Data was categorized into pre, during and post outbreaks based on the timing of the COVID-19 outbreak and further subdivided by season and age group. PCR and colloidal gold methods were used for virus detection and statistical analyses were performed accordingly. Results Positive detection rates of pathogens were statistically different by age, period, season and detection method employed. Before the epidemic, the pathogen infections showed obvious seasonality but disappeared after 2019. Positive detection rates of influenza were higher in adolescents and young and middle-aged people while RSV detection was highest in adolescents. Detection by Gene Xpert real-time fluorescent PCR was superior in terms of timeliness and efficiency. Conclusion The COVID-19 pandemic and the massive public health intervention campaign have led to widespread changes in human behavior, significantly affecting the spread and activity of other seasonal respiratory viruses. Further, advances in detection methods have contributed to increased pathogen detection rates.

Background: The interactions between fibroblasts and bronchial epithelial cells play important roles in the development of chronic obstructive pulmonary disease (COPD). Interleukin (IL)-17A triggers the activation of fibroblasts and the secretion of inflammatory mediators, which promotes epithelial-mesenchymal transition (EMT) in bronchial epithelial cells. Fibroblasts secrete C-X-C motif chemokine ligand 12 (CXCL12), which specifically binds to its receptor, C-X-C motif chemokine receptor 4 (CXCR4) to mediate inflammatory responses. This study aims to investigate IL-17A- and CXCL12-induced airway remodeling. Methods: Primary lung fibroblasts were isolated from human and murine lung tissue for the in vitro experiments, and a mouse model of cigarette smoke (CS)-induced COPD was established for the in vivo experiments. The results were analyzed using a one-way analysis of variance and Tukey's test or Bonferroni's test for the post-hoc test. A p-value < 0.05 was considered statistically significant. Results: Through in vitro experiments, we found that IL-17A-activated primary lung fibroblasts secreted CXCL12 and stimulated EMT in bronchial epithelial cells. However, these effects could be blocked by neutralizing IL-17A or CXCL12. In vivo, an anti-IL-17A antibody or a CXCR4 antagonist could reverse the degree of EMT in the lungs of the COPD mouse model. The IL-17A-induced EMT and increased CXCL12 expression occurred via extracellular signal-regulated kinase (ERK)/phosphorylated-ERK pathways. Conclusion: This study showed that exposure of mice to CS and IL-17A stimulation upregulated CXCL12 expression and induced EMT by activating the ERK signaling pathway. These data offer a novel perspective regarding the molecular mechanism of CXCL12/CXCR4 signaling in IL-17A-induced EMT related to airway remodeling.

Background: To evaluate the efficacy and safety of allogenic CD8 + natural killer T (CD8+ NKT) immunotherapy combined with gefitinib in the treatment of advanced or metastatic EGFR mutant non-small cell lung cancer (NSCLC). Methods: This study is prospective. The NSCLC patients with exon 19 (Ex19del) or exon 21 L858R point mutations, and response to gefitinib treatment were enrolled into the trial to be randomly assigned into the gefitinib arm and the gefitinib/NKT arm. Allogenic CD8+ NKT cells were cultured in vitro and adaptive transferred into the patients via vein in the gefitinib/NKT arm. The primary endpoint was progression-free survival (PFS). Secondary endpoint analysis included time to disease progression (TTP), overall survival (OS), levels of serum tumour markers for carcinoembryonic antigen (CEA) and alanine aminotransferase (ALT) in the blood, the response rate and safety. From July 2017 to June 2021, 19 patients were randomly assigned to the gefitinib arm (n = 8) and the gefitinib/NKT arm (n = 11). Results: The estimated median survival PFS in the gefitinib/NKT arm was significantly longer than that of the gefitinib arm (12 months vs 7 months). Similar results were also observed for the median TTP. Moreover, the gefitinib/NKT arm had better CEA control than the gefitinib arm. Clinical grade 3 adverse reactions occurred in 64% and 39% of patients in the gefitinib/NKT arm and the gefitinib arm, respectively. The most common grade 3 adverse events in the gefitinib/NKT arm included abnormal liver function in 8 cases (73%) and diarrhoea in 1 case (9%), both of which resolved after drug intervention. Conclusion: The PFS of EGFR-mutated advanced NSCLC treated with allogenic CD8+ NKT cells combined with gefitinib was longer than that of gefitinib alone. No obvious serious adverse reactions occurred, and the patients compliance and survival status were good.

BackgroundLung adenocarcinoma (LUAD) is the most common lung cancer subtype, and the prognosis of affected patients is generally poor. The traditional Chinese medicine Uncaria rhychophaylla has been reported to exhibit anti-lung cancer properties. Accordingly, the main bioactive ingredient in Uncaria rhychophaylla, Corynoxine, may hold great value as a treatment for lung cancer.MethodsThe impact of Corynoxine on the viability of LUAD cells was assessed using the Cell Counting Kit-8 (CCK-8) assay. Apoptosis in A549 cells was evaluated via flow cytometry. Migration and invasion capabilities were determined through wound healing and Transwell assays, respectively. The key pathways targeted by Corynoxine in LUAD were identified using a network pharmacology approach. Additionally, Western immunoblotting, quantitative real-time PCR (qRT-PCR), and ELISA assays were conducted to validate the underlying mechanisms. The in vivo anti-tumor efficacy of Corynoxine was assessed in xenograft nude mice.ResultsIn this study, Corynoxine treatment was found to markedly suppress in vitro LUAD cell proliferative, migratory, and invasive activity. It additionally downregulated Vimentin and promoted E-cadherin upregulation consistent with the disruption of epithelial-mesenchymal transition (EMT) induction while also accelerating apoptotic death. Furthermore, network pharmacology analysis revealed that the PI3K/AKT pathway is a potential target of Corynoxine in LUAD. In vitro assays demonstrated that treatment with Corynoxine resulted in the suppression of PI3K/AKT signaling and a consequent drop in cyclooxygenase-2 (COX-2) expression. These findings were further confirmed in vivo in mice harboring A549 tumor xenografts in which Corynoxine was able to interfere with the PI3K/AKT/COX-2 signaling axis.ConclusionThis study elucidated the potential effects of Corynoxine in suppressing proliferation and metastasis in LUAD, along with investigating the underlying mechanisms. These data highlight the promise of Corynoxine as a novel therapeutic tool for the treatment of individuals diagnosed with LUAD.

BackgroundCancer-associated fibroblasts (CAFs) and their secretion, C-X-C motif chemokine ligand 12 (CXCL12), play an important role in the development of lung adenocarcinoma (LUAD). Interleukin 17A (IL-17A) is also crucial in regulating tumor progression. Herein, we explored the specific relationships between these two factors and their mechanisms in the progression of LUAD.MethodsImmunohistochemistry was utilized to assess the differential expression levels of IL-17A and CXCL12 in tumor versus normal tissues of LUAD patients, followed by gene correlation analysis. Cell counting kit-8 (CCK8), wound-healing and transwell assays were performed to investigate the effect of IL-17A on the function of LUAD cells. qPCR, immunofluorescence, immunohistochemistry and western blot analyses were conducted to elucidate the potential mechanism by which IL-17A facilitates the development of LUAD via CXCL12. Male BALB-C nude mice were used to explore the role of IL-17A in subcutaneous LUAD mouse models.ResultsElevated expression levels of IL-17A and CXCL12 were observed in LUAD tissues, exhibiting a positive correlation. Further studies revealed that IL-17A could stimulate CAFs to enhance the release of CXCL12, thereby facilitating the growth, proliferation, and metastasis of LUAD. The binding of CXCL12 to its specific receptor influences the activation of the Wnt/β-Catenin pathway, which in turn affects the progression of LUAD. In vivo experiments have demonstrated that IL-17A enhances the growth of LUAD tumors by facilitating the secretion of CXCL12. Conversely, inhibiting CXCL12 has been demonstrated to impede tumor growth.ConclusionsWe discovered that IL-17A promotes the release of CAFs-derived CXCL12, which in turn facilitates the development of LUAD via the Wnt/β-Catenin signaling pathway.

Background Lung cancer is a malignant tumor with the highest mortality worldwide. Abnormalities in the ubiquitin proteasome system are considered to be contributed to lung cancer progression with deleterious effects. DDB1 and CUL4 associated factor 13 (DCAF13) is a substrate receptor of the E3 ubiquitin ligase CRL4, but its role in lung cancer remains unknown. In this study, we aimed to investigate the regulatory mechanisms of DCAF13 in lung adenocarcinoma (LUAD). Methods So as to investigate the effect of DCAF13 on lung adenocarcinoma cell function using in vivo and in vitro. Mechanistically, we have identified the downstream targets of DCAF13 by using RNA-sequencing, as well as ubiquitination assays, co-immunoprecipitation, immunofluorescence, immunohistochemistry and chromatin immunoprecipitation - qPCR experiments. Results Our findings reveal that DCAF13 is a carcinogenic factor in LUAD, as it is highly expressed and negatively correlated with clinical outcomes in LUAD patients. Through RNA-sequencing, it has been shown that DCAF13 negatively regulates the p53 signaling pathway and inhibits p53 downstream targets including p21, BAX, FAS, and PIDD1. We also demonstrate that DCAF13 can bind to p53 protein, leading to K48-linked ubiquitination and degradation of p53. Functionally, we have shown that DCAF13 knockdown inhibits cell proliferation and migration. Our results highlight the significant role of DCAF13 in promoting LUAD progression by inhibiting p53 protein stabilization and the p53 signaling pathway. Furthermore, our findings suggest that high DCAF13 expression is a poor prognostic indicator in LUAD, and DCAF13 may be a potential therapeutic target for treating with this aggressive cancer. Conclusions The DCAF13 as a novel negative regulator of p53 to promote LUAD progression via facilitating p53 ubiquitination and degradation, suggesting that DCAF13 might be a novel biomarker and therapeutical target for LUAD.

Background: It has been increasingly recognized that circular RNAs (circRNAs) act as a pivotal factor in the onset and progression of human malignancies. Yet, the specific activities and mechanistic roles of these RNAs in the context of lung adenocarcinoma (LUAD) are not fully understood. Methods: Microarray analysis identified a novel LUAD-associated circular RNA, termed hsa_circ_0006357 (also referred to as circEZH2). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized for the analysis of circEZH2 expression in tissues and cell lines. The characteristics of circEZH2 were verified by RNase R treatment and fluorescence in situ hybridization (FISH) assays. The functions of circEZH2 were detected by Cell Counting Kit-8 (CCK-8), colony formation, wound healing, and Transwell assays. The molecular mechanism of circEZH2 was clarified through bioinformatics analysis as well as RNA pulldown, dual-luciferase reporter, RT-qPCR, and immunoblotting assays. The role of circEZH2 in vivo was investigated using a xenograft model. Results: This investigation revealed that circEZH2 expression was elevated in LUAD cell lines and tumor samples. This elevation was associated with enhanced cell proliferation, migratory capacity, epithelial-mesenchymal transition (EMT), and invasion in vitro. Conversely, silencing of circEZH2 in vivo resulted in a notable decrease in LUAD tumorigenesis, whereas its overexpression led to the opposite effects. Mechanistically, circEZH2 appeared to act as a sponge for miR-495-3p, facilitating the upregulation of tumor protein D52 (TPD52) and triggering the nuclear factor kappa B (NF-kappa B) signaling pathway, thus contributing to the progression of LUAD. Conclusion: These findings indicate that circEZH2 may function as a competitive endogenous RNA (ceRNA), driving the progression of LUAD by manipulating the miR-495-3p/TPD52 axis and activating the NF-kappa B pathway.

Adult congenital localized diaphragmatic eventration (DE) is an uncommon condition that, due to the absence of notable symptoms, is often ignored and is consequently not frequently treated following diagnosis. Furthermore, the progression of localized DE into complete DE is rare. The recent coronavirus disease 2019 pandemic has placed a strain on global health care systems, including those in China, and exacerbated several underlying medical complications and diseases. This has resulted in a rapid progression of underlying diseases and even death in cases of diabetes or pre-existing respiratory diseases and other chronic conditions. The present study describes the case of a patient with congenital localized DE that progressed to complete DE following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The patient had a medical history of localized DE with persistent cough, chest tightness and abdominal distension following infection with SARS-CoV-2. Chest X-ray and computed tomography examinations confirmed the diagnosis of complete DE on the left side. Therefore, the patient underwent thoracic surgery for left-sided diaphragmatic plication. At the 6-month follow-up visit, the patient had recovered well and did not show any complications. Overall, the present study demonstrated that SARS-CoV-2 infection exacerbated the progression of left-sided congenital localized DE, which had no obvious symptoms, to complete DE accompanied by severe symptoms.

Background:The interactions between fibroblasts and bronchial epithelial cells play important roles in the development of chronic obstructive pulmonary disease (COPD). Interleukin (IL)-17A triggers the activation of fibroblasts and the secretion of inflammatory mediators, which promotes epithelial-mesenchymal transition (EMT) in bronchial epithelial cells. Fibroblasts secrete C-X-C motif chemokine ligand 12 (CXCL12), which specifically binds to its receptor, C-X-C motif chemokine receptor 4 (CXCR4) to mediate inflammatory responses. This study aims to investigate IL-17A- and CXCL12-induced airway remodeling. Methods:Primary lung fibroblasts were isolated from human and murine lung tissue for the in vitro experiments, and a mouse model of cigarette smoke (CS)-induced COPD was established for the in vivo experiments. The results were analyzed using a one-way analysis of variance and Tukey's test or Bonferroni's test for the post-hoc test. A p-value < 0.05 was considered statistically significant. Results:Through in vitro experiments, we found that IL-17A-activated primary lung fibroblasts secreted CXCL12 and stimulated EMT in bronchial epithelial cells. However, these effects could be blocked by neutralizing IL-17A or CXCL12. In vivo, an anti-IL-17A antibody or a CXCR4 antagonist could reverse the degree of EMT in the lungs of the COPD mouse model. The IL-17A-induced EMT and increased CXCL12 expression occurred via extracellular signal-regulated kinase (ERK)/phosphorylated-ERK pathways. Conclusion:This study showed that exposure of mice to CS and IL-17A stimulation upregulated CXCL12 expression and induced EMT by activating the ERK signaling pathway. These data offer a novel perspective regarding the molecular mechanism of CXCL12/CXCR4 signaling in IL-17A-induced EMT related to airway remodeling.

目的 探讨棕榈酸(C16:0)通过调控环状含有DENN结构域蛋白4C(circ_DENND4C)抑制非小细胞肺癌(NSCLC)发生、发展的作用机制.方法 将NSCLC A549细胞构建成C16:0组(使用C16:0刺激A549细胞)和对照组实验模型,采用高通量环状RNA(circRNAs)转录组测序技术,对C16:0组及对照组的A549细胞进行检测,筛选出C16:0调控的circRNAs,并在A549细胞中通过qRT-PCR技术进行验证.随后,通过质粒转染技术在A549细胞中对筛选的circ_DENND4C进行过表达,将细胞分为空白对照组(NC组)、C16:0组、circ_DENND4C质粒过表达组(pex-0086466组)、circ_DENND4C质粒过表达联合C16:0组(pex-0086466+C16:0组)进行细胞功能实验.采用细胞计数试剂盒(CCK-8)法、细胞克隆形成试验检测细胞增殖能力;细胞划痕试验检测细胞迁移能力;Transwell侵袭实验检测细胞侵袭能力;探究circ_DENND4C过表达对A549细胞功能的影响及其是否可以逆转C16:0对A549细胞增殖、迁移和侵袭能力的影响.结果 通过高通量测序发现C16:0可以引起广泛circRNAs表达的改变,其中肿瘤相关circ_DENND4C的表达水平在C16:0刺激后显著下调.通过细胞功能实验进一步发现过表达circ_DENND4C对A549细胞的增殖、迁移与侵袭起促进作用.通过上调circ_DENND4C表达水平可以逆转C16:0对A549细胞的增殖、迁移与侵袭抑制作用.结论 C16:0通过抑制circ_DENND4C表达来抑制A549细胞的增殖、迁移与侵袭,从而为治疗NSCLC提供了重要的实验依据.