Patent conversion of a novel closed chest drainage device.

Closed chest drainage is typically necessary following Lobar and Sublobar resections to evacuate gases and fluids from the thoracic cavity, eliminate residual pleural space for lung expansion, and maintain negative pressure. Currently, three conventional closed chest drainage systems are commonly employed: single-chamber, double-chamber, and triple-chamber systems; each system has its own advantages and disadvantages. Despite the emergence of digital drainage systems in recent years, their high cost hinders their widespread adoption. Based on this premise, our research team has achieved a patent for a micro air pump-integrated chest closed drainage bottle, which has been further developed into a novel device integrating a three-chamber system with negative pressure control and power supply capabilities. This device enables patients undergoing perioperative lung procedures to ambulate freely while simultaneously receiving chest suction therapy-a concept that theoretically promotes rapid postoperative recovery. Moreover, this device offers economic benefits and holds potential for clinical implementation (particularly in economically underdeveloped regions). In this article, we modified the thoracic closed drainage device based on our patent and presented this novel thoracic closed drainage device after 3D printing and assembly.

Drp1-mediated mitochondrial fission promotes pulmonary fibrosis progression through the regulation of lipid metabolic reprogramming by ROS/HIF-1α.

OBJECTIVE: To confirm the mechanism of dynamic-related protein 1 (Drp1)-mediated mitochondrial fission through ROS/HIF-1α-mediated regulation of lipid metabolic reprogramming in the progression of pulmonary fibrosis (PF). METHODS: A mouse model of PF was established by intratracheal instillation of bleomycin (BLM) (2.5 mg/kg). A PF cell model was constructed by stimulating MRC-5 cells with TGF-ß (10 ng/mL). Pathological changes in the lung tissue and related protein levels were observed via tissue staining. The indicators related to lipid oxidation were detected by a kit, and lipid production was confirmed through oil red O staining. Inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). RT-qPCR, Western blotting and immunofluorescence staining were used to detect the expression of genes and proteins related to the disease. We used CCK-8 and EdU staining to confirm cell proliferation, flow cytometry was used to confirm apoptosis and ROS levels, α-SMA expression was detected by immunofluorescence staining, and mitochondria were observed by MitoTracker staining. RESULTS: The BLM induced lung tissue structure and alveolar wall thickening in mice. Mitochondrial fission was observed in MRC-5 cells induced by TGF-ß, which led to increased cell proliferation; decreased apoptosis; increased expression of collagen, α-SMA and Drp1; and increased lipid oxidation and inflammation. Treatment with the Drp1 inhibitor mdivi-1 or transfection with si-Drp1 attenuated the induction of BLM and TGF-ß. For lipid metabolism, lipid droplets were formed in BLM-induced lung tissue and in TGF-ß-induced cells, fatty acid oxidation genes and lipogenesis-related genes were upregulated, ROS levels in cells were increased, and the expression of HIF-1α was upregulated. Mdivi-1 treatment reversed TGF-ß induction, while H2O2 treatment or OE-HIF-1α transfection reversed the effect of mdivi-1. CONCLUSION: In PF, inhibition of Drp1 can prevent mitochondrial fission in fibroblasts and regulate lipid metabolism reprogramming through ROS/HIF-1α; thus, fibroblast activation was inhibited, alleviating the progression of PF.

Sestrin2 Regulates Endoplasmic Reticulum Stress-Dependent Ferroptosis to Engage Pulmonary Fibrosis by Nuclear Factor Erythroid 2-Related Factor 2/Activating Transcription Factor 4 (NRF2/ATF4).

Pulmonary fibrosis (PF) can lead to chronic inflammation, the destruction of alveoli and irreversible lung damage. Sestrin2 is a highly protective stress-inducible protein that is involved in the cell response to various stress factors and the regulation of homeostasis and has a certain protective effect against PF. In this study, TGF-ß1 was used to establish a PF cell model. Bleomycin was used to induce PF in mice, and the expression levels of related proteins were detected by western blotting. The levels of the inflammatory cytokine, TNF-α, IL-6, and IL-1ß were detected by enzyme-linked immunosorbent assays. Immunoprecipitation was used to verify the interaction between ATF4 and NRF2 and between Sestrin2 and NRF2 to explore the specific mechanism by which Sestrin2 affects PF. The results showed that Sestrin2 inhibited fibroblast-to-myofibroblast transition (FMT), improved inflammation, promoted cell proliferation, and alleviated PF. Activating transcription factor 4/nuclear factor erythroid 2-related factor 2 (NRF2/ATF4) signaling pathway activation could alleviate endoplasmic reticulum stress, inhibit ferroptosis and FMT, and reduce reactive oxygen species levels, thereby alleviating PF. Overexpression of ATF4 and the addition of a ferroptosis inducer reversed Sestrin2-mediated alleviation of PF. In conclusion, Sestrin2 alleviates PF and endoplasmic reticulum stress-dependent ferroptosis through the NRF2/ATF4 pathway.

IL-27 induces autophagy through regulation of the DNMT1/lncRNA MEG3/ERK/p38 axis to reduce pulmonary fibrosis.

PURPOSE: Previous studies have shown that interleukin-27 (IL-27) can reduce bleomycin (BLM)-induced pulmonary fibrosis (PF). However, the underlying mechanism by which IL-27 attenuates PF is not fully clear. METHODS: In this research, we used BLM to construct a PF mouse model, and MRC-5 cells stimulated by transforming growth factor-ß1 (TGF-ß1) were used to construct a PF model in vitro. The lung tissue status was observed by Masson and hematoxylin and eosin (HE) staining. To detect gene expression, RT‒qPCR was used. The protein levels were detected by western blotting and immunofluorescence staining. EdU and ELISA were used to detect cell proliferation viability and hydroxyproline (HYP) content, respectively. RESULTS: Aberrant IL-27 expression was observed in BLM-induced mouse lung tissues, and the use of IL-27 attenuated mouse lung tissue fibrosis. TGF-ß1 induced autophagy inhibition in MRC-5 cells, and IL-27 alleviated MRC-5 cell fibrosis by activating autophagy. The mechanism is inhibition of DNA methyltransferase 1 (DNMT1)-mediated lncRNA MEG3 methylation and ERK/p38 signaling pathway activation. Overexpression of DNMT1, knockdown of lncRNA MEG3, autophagy inhibitor or ERK/p38 signaling pathway inhibitors reversed the positive effect of IL-27 in a lung fibrosis model in vitro. CONCLUSION: In conclusion, our study shows that IL-27 upregulates MEG3 expression through inhibition of DNMT1-mediated lncRNA MEG3 promoter methylation, which in turn inhibits ERK/p38 signaling pathway-induced autophagy and attenuates BLM-induced PF, providing a contribution to the elucidation of the potential mechanisms by which IL-27 attenuates PF.

Comprehensive Analysis of Circular RNA Expression Profiles in Gefitinib-Resistant Lung Adenocarcinoma Patients.

Introduction: Gefitinib is a selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) widely used in lung adenocarcinoma (LUAD) patients harboring sensitive EGFR mutations. Although it has a good initial efficacy, acquired resistance to gefitinib is eventually inevitable. Studies have shown that circular RNA (circRNA) is involved in the development of acquired resistance to different anti-cancer drugs, but the comprehensive analysis of its expression profile and functions on acquired gefitinib resistance remains poor. Methods: To explore the aberrant circRNAs expression profiles, we collected peripheral plasma samples from 4 gefitinib-sensitive and 4 gefitinib-resistant patients for performing microarray analysis. Candidates of differentially expressed circRNAs were used and analyzed by bioinformatics modalities including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and a constructed circRNA-microRNA RNA network. The differential expression of selected circRNAs was verified by quantitative real-time PCR (qRT-PCR). Results: A total of 2571 circRNAs with significantly different expression between the groups were identified by microarray analysis. GO, KEGG, and pathway enrichment analyses reveal that these differentially expressed circRNAs (DECs) were complicated in many biological pathways that may be related to EGFR-TKI resistance such as ABC transporter and PI3K-Akt pathways. A circRNA-microRNA network was constructed by 10 circRNAs potentially involved in EGFR-TKI resistance togethering with their corresponding microRNAs (miRNAs). Consistent with the results of microarray assay, hsa_circ_0030591 and hsa_circ_0040348 were validated to be upregulated in gefitinib-resistant patients by qRT-PCR. Conclusions: Our study provides valuable data on circRNAs expression profiles detected in liquid biopsy for LUAD patients with acquired gefitinib resistance, and we validate that upregulations of hsa_circ_0030591 and hsa_circ_0040348 may play key roles in EGFR-TKI resistance and thus serving as candidates for biomarker.

hsa_circ_0072309 Expression Profiling in Non-small-Cell Lung Carcinoma and Its Implications for Diagnosis and Prognosis.

Circular RNAs (circRNAs), which fall into the category of endogenous ncRNAs, are linked to disease progression of neoplastic diseases. Whereas, it remains uncharacterized regarding hsa_circ_0072309's function and implications in lung carcinoma (LC). Gene Expression Omnibus (GEO) database was utilized for identifying circRNAs with aberrantly expression in LC. qRT-PCR was responsible for determining hsa_circ_0072309 levels in lung adenocarcinoma (LAC). Also, its involvement in LC cell progression was investigated. Experimentally, hsa_circ_0072309 was identified as one of the most aberrantly down-regulated circRNAs in the GEO database (GSE101684 and GSE112214). qRT-PCR revealed notably down-regulated hsa_circ_0072309 in LAC tissue, which had a close association with adverse 3-year survival, as well as LNM and advanced TNM stage. Based on ROC, the AUC of hsa_circ_0072309 was determined to be 0.887, and its specificity and susceptibility can be improved by combined detection of either CYFRA21-1 or CEA. In a word, hsa_circ_0072309 is lowly expressed in lung cancer patients and the survival rate of lowly expressed patients is significantly lower, a candidate marker with prognostic utility for the disease.

Ageing as key factor for distant metastasis patterns and prognosis in patients with extensive-stage Small Cell Lung Cancer.

Background: Small cell lung cancer (SCLC) represents about 13% of lung cancer cases, which is highly invasive and has a high mortality rate, with the 5-year overall survival (OS) rate being only 6.3%. Age at diagnosis of advanced SCLC is much older, but studies describing the ageing factor for distant metastasis patterns and prognosis of extensive-stage SCLC (ES-SCLC) are limited. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) registry, we identified 18,682 patients with ES-SCLC (9,089 women and 9,053 men) who had complete clinical information between 2008 and 2015. Patients were classified into three groups (older group: ≥80 yrs, middle-aged group: 60-79 yrs, and younger group: ≤59 yrs). The role of different age at diagnosis of ES-SCLC (especially older group) in metastasis patterns was investigated, and OS and cancer-specific survival (CSS) of different age groups of metastatic ES-SCLC was assessed. Results: The most metastasis of ES-SCLC patients in the three groups was multiorgan metastases (MOM) metastasis (71.2%, 70.3% and 66.3%, respectively), the most single organ metastasis in the younger group was the lung (3.3%), the middle-aged group and the older group were the brain (3.5%, 3.1%, respectively). The analysis revealed that older patients were less likely to have MOM, but more likely to have all organs metastases than other two groups (p<0.001). Older group had the worst OS (p<0.001) and CSS (p<0.001). Furthermore, Radiotherapy and chemotherapy can improve survival (p<0.001), but the rate of radiotherapy and chemotherapy in older patients is lower than that in middle-aged and younger patients (50.4% vs 38.6% vs 20.7%, p<0.05). Compared with other two group, older group (odds ratios, ORs) for lung, all organ metastases, and MOM were 0.43 (95% CI 0.27-0.67), 1.77 (95% CI 1.55-2.03), 0.68 (95% CI 0.6-0.77), respectively. Conclusion: The mortality risk is highest with MOM and all organs metastasis followed by brain, lung, bone and liver metastases in elderly ES-SCLC patients. These results will be helpful for pre-treatment evaluation regarding the prognosis of ES-SCLC patients.

Deguelin Attenuates Allergic Airway Inflammation via Inhibition of NF-κb Pathway in Mice.

Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling, resulting in a substantial economic burden on both patients and society. Deguelin, a constituent of the Leguminosae family, exhibits anti-proliferative and anti-inflammatory activities in cancer mice models via inhibiting phosphatidylinositol 3-kinases and the NF-κB pathway. We demonstrated that deguelin effectively reduced OVA-induced inflammatory cell recruitment, decreased lung tissue inflammation and mucus production, suppressed airway hyperresponsiveness, and inhibited serum immunoglobulin and Th2 cytokine levels in a dose-dependent manner in asthmatic mice. In addition, we found that deguelin reduced inflammatory gene expressions both in vivo and in vitro, which were closely associated with activation of the NF-κB signaling pathway. Thus, we further explored the underlying mechanisms of deguelin in normal human bronchial epithelial cells (BEAS-2B). Our results suggested that deguelin inhibited NF-κB binding activity by enhancing the ability of IκBα to maintain NF-κB in an inactive form in the cytoplasm and preventing the TNF-α induced translocation of p65 to the nucleus. In conclusion, our research indicates that deguelin attenuates allergic airway inflammation via inhibition of NF-κB pathway in mice model and may act as a potential therapeutic agent for patients with allergic airway inflammation.

MicroRNA-206 inhibits the viability and migration of human lung adenocarcinoma cells partly by targeting MET.

MicroRNA (miRNA)-based targeting in cancer has emerged as a potential therapeutic strategy. miR-206 has recently been implicated in cancer. However, the role and molecular mechanism of miR-206 in lung adenocarcinoma are still unclear. The present study revealed that miR-206 was downregulated in human lung adenocarcinoma tissues. Overexpression of miR-206 in human lung adenocarcinoma-derived cells significantly inhibited cell viability and migration. Further experiments indicated that the overexpression of miR-206 decreased the expression of MET at the messenger RNA and protein levels via direct targeting of MET in a 3'-untranslated region-dependent manner. The knockdown of MET by small interfering RNA partly led to a phenocopy effect of miR-206. In conclusion, the present study identified miR-206 as a potential tumor suppressor of lung adenocarcinoma that exerts its functions, in part, by negative regulation of MET.

Interleukin-10 promoter gene polymorphisms and susceptibility to tuberculosis: a meta-analysis.

OBJECTIVE: As an update to other recent meta-analyses, the purpose of this study was to explore whether interleukin-10 (IL-10) polymorphisms and their haplotypes contribute to tuberculosis (TB) susceptibility. METHODS: We searched for published case-control studies examining IL-10 polymorphisms and TB in PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Wanfang databases and the Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strengths of the associations. RESULTS: A total of 28 studies comprising 8,242 TB patients and 9,666 controls were included in the present study. There were no significant associations between the -1082G/A, -819C/T, and -592A/C polymorphisms and TB in the pooled samples. Subgroup analyses revealed that the -819T allele was associated with an increased TB risk in Asians in all genetic models (T vs. C: OR=1.17, 95% CI=1.05-1.29, P=0.003; TT vs. CC: OR=1.37, 95% CI=1.09-1.72, P=0.006; CT+TT vs. CC: OR=1.33, 95% CI=1.09-1.63, P=0.006; TT vs. CT+CC: OR=1.17, 95% CI=1.02-1.35, P=0.03) and that the -592A/C polymorphism was significantly associated with TB in Europeans under two genetic models (A vs. C: OR=0.77, 95% CI=0.60-0.98, P=0.03; AA vs. CC: OR=0.53, 95% CI=0.30-0.95, P=0.03). Furthermore, the GCC IL-10 promoter haplotype was associated with an increased risk of TB (GCC vs. others: P=1.42, 95% CI=1.02-1.97, P=0.04). Subgroup analyses based on ethnicity revealed that the GCC haplotype was associated with a higher risk of TB in Europeans, whereas the ACC haplotype was associated with a lower TB risk in both Asians and Europeans. CONCLUSIONS: This meta-analysis suggests that the IL-10-819T/C polymorphism is associated with the risk of TB in Asians and that the IL-10-592A/C polymorphism may be a risk factor for TB in Europeans. Furthermore, these data indicate that IL-10 promoter haplotypes play a vital role in the susceptibility to or protection against the development of TB.