This study aimed to explore the molecular mechanism by which mesenchymal stem cells (MSCs) mediate lung cancer progression. Extracellular vesicles (EVs) were isolated from transfected or untransfected MSCs, and were co-cultured with lung cancer cells with/without microRNA-130b-3p (miR-130b-3p) inhibitor, mimic, overexpression plasmids of FOXO3/NFE2L2, or shRNAs. CCK-8 assay, colony formation, transwell assay, and flow cytometry were carried out to determine the biological functioning of lung cancer cells. Furthermore, FOXO3, Keap1, NFE2L2, and TXNRD1 expression was determined by qRT-PCR and western blot analysis. A tumor xenograft mouse model was used to determine role of EVs-miR-130b-3p and its target FOXO3 in lung cancer progression
in vivo
. miR-130b-3p was highly expressed in lung cancer tissues and MSC-derived EVs. Moreover, the MSC-derived EVs transferred miR-130b-3p to lung cancer cells to promote cell proliferation, migration, and invasion while repress cell apoptosis. miR-130b-3p directly targeted FOXO3, and FOXO3 elevated Keap1 expression to downregulate NFE2L2, thus inhibiting TXNRD1. FOXO3 overexpression or silencing of NFE2L2 or TXNRD1 diminished lung cancer cell proliferation, invasion, and migration but enhanced apoptosis. EV-delivered miR-130b-3p or FOXO3 silencing promoted lung cancer progression
in vivo
. In summary, MSC-derived EVs with upregulated miR-130b-3p suppressed FOXO3 to block the NFE2L2/TXNRD1 pathway, thus playing an oncogenic role in lung cancer progression.
BackgroundThe diagnostic value of clinical and laboratory features to differentiate between malignant pleural effusion (MPE) and benign pleural effusion (BPE) has not yet been established.ObjectivesThe present study aimed to develop and validate the diagnostic accuracy of a scoring system based on a nomogram to distinguish MPE from BPE.MethodsA total of 1,239 eligible patients with PE were recruited in this study and randomly divided into a training set and an internal validation set at a ratio of 7:3. Logistic regression analysis was performed in the training set, and a nomogram was developed using selected predictors. The diagnostic accuracy of an innovative scoring system based on the nomogram was established and validated in the training, internal validation, and external validation sets (n = 217). The discriminatory power and the calibration and clinical values of the prediction model were evaluated.ResultsSeven variables [effusion carcinoembryonic antigen (CEA), effusion adenosine deaminase (ADA), erythrocyte sedimentation rate (ESR), PE/serum CEA ratio (CEA ratio), effusion carbohydrate antigen 19-9 (CA19-9), effusion cytokeratin 19 fragment (CYFRA 21-1), and serum lactate dehydrogenase (LDH)/effusion ADA ratio (cancer ratio, CR)] were validated and used to develop a nomogram. The prediction model showed both good discrimination and calibration capabilities for all sets. A scoring system was established based on the nomogram scores to distinguish MPE from BPE. The scoring system showed favorable diagnostic performance in the training set [area under the curve (AUC) = 0.955, 95% confidence interval (CI) = 0.942–0.968], the internal validation set (AUC = 0.952, 95% CI = 0.932–0.973), and the external validation set (AUC = 0.973, 95% CI = 0.956–0.990). In addition, the scoring system achieved satisfactory discriminative abilities at separating lung cancer-associated MPE from tuberculous pleurisy effusion (TPE) in the combined training and validation sets.ConclusionsThe present study developed and validated a scoring system based on seven parameters. The scoring system exhibited a reliable diagnostic performance in distinguishing MPE from BPE and might guide clinical decision-making.
Background
Vascular air embolism (VAE) is a rare but important complication that has not been paid enough attention to in the medical process such as surgery and anesthesia.
Case presentation
We report for the first time that a 54-year-old male patient with central lung cancer developed severe complications of CAE after right pneumonectomy. After targeted first-aid measures such as assisted breathing, mannitol dehydration and antibiotic treatment, the patient gradually improved. The patient became conscious at discharge after 25 days of treatment but left limb was left with nerve injury symptoms.
Conclusion
We analyzed the possible causes of CAE in this case, and the findings from this report would be highly useful as a reference to clinicians.
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