Development and validation of a predictive model for pulmonary infection risk in patients with traumatic brain injury in the ICU: a retrospective cohort study based on MIMIC-IV.

OBJECTIVE: To develop a nomogram for predicting occurrence of secondary pulmonary infection in patients with critically traumatic brain injury (TBI) during their stay in the intensive care unit, to further optimise personalised treatment for patients and support the development of effective, evidence-based prevention and intervention strategies. DATA SOURCE: This study used patient data from the publicly available MIMIC-IV (Medical Information Mart for Intensive Care IV) database. DESIGN: A population-based retrospective cohort study. METHODS: In this retrospective cohort study, 1780 patients with TBI were included and randomly divided into a training set (n=1246) and a development set (n=534). The impact of pulmonary infection on survival was analysed using Kaplan-Meier curves. A univariate logistic regression model was built in training set to identify potential factors for pulmonary infection, and independent risk factors were determined in a multivariate logistic regression model to build nomogram model. Nomogram performance was assessed with receiver operating characteristic (ROC) curves, calibration curves and Hosmer-Lemeshow test, and predictive value was assessed by decision curve analysis (DCA). RESULT: This study included a total of 1780 patients with TBI, of which 186 patients (approximately 10%) developed secondary lung infections, and 21 patients died during hospitalisation. Among the 1594 patients who did not develop lung infections, only 85 patients died (accounting for 5.3%). The survival curves indicated a significant survival disadvantage for patients with TBI with pulmonary infection at 7 and 14 days after intensive care unit admission (p<0.001). Both univariate and multivariate logistic regression analyses showed that factors such as race other than white or black, respiratory rate, temperature, mechanical ventilation, antibiotics and congestive heart failure were independent risk factors for pulmonary infection in patients with TBI (OR>1, p<0.05). Based on these factors, along with Glasgow Coma Scale and international normalised ratio variables, a training set model was constructed to predict the risk of pulmonary infection in patients with TBI, with an area under the ROC curve of 0.800 in the training set and 0.768 in the validation set. The calibration curve demonstrated the model's good calibration and consistency with actual observations, while DCA indicated the practical utility of the predictive model in clinical practice. CONCLUSION: This study established a predictive model for pulmonary infections in patients with TBI, which may help clinical doctors identify high-risk patients early and prevent occurrence of pulmonary infections.

Circular RNA hsa_circ_0008003 promotes the progression of non-small-cell lung cancer by sponging miR-548I and regulating KPNA4 expression.

OBJECTIVE: The study aimed to explore the effect of circ_0008003 on the progression of non-small-cell lung cancer (NSCLC) and its underlying regulation mechanism. METHODS: Expression of hsa_circ_0008003, miRNA (miR)-548I and karyopherin subunit α 4 (KPNA4) was examined by quantitative real-time polymerase chain reaction. Cell viability and proliferation ability were detected by cell counting kit-8 assay and 5-ethynyl-2'-deoxyuridine assay, respectively. Flow cytometry was performed to monitor cell apoptosis. Western blot assay was used to evaluate the protein levels of KPNA4, Bax, and Bcl-2. Cell migration and invasion were assessed by transwell assays. The targeted relationship between miR-548I and hsa_circ_0008003 or KPNA4 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. Furthermore, the role of hsa_circ_0008003 in vivo was investigated by xenograft assay. RESULTS: Circ_0008003 expression was increased in NSCLC tissues and cell lines. Circ_0008003 knockdown reduced cell viability, migration, invasion, angiogenesis, and caused apoptosis in NSCLC cells. Moreover, miR-548I was targeted by circ_0008003, and miR-548I knockdown reversed the influence of circ_0008003 silence on NSCLC progression. KPNA4 was targeted by miR-548I, and miR-548I overexpression suppressed cell viability, migration, invasion, angiogenesis, and promoted cell apoptosis via decreasing KPNA4. In addition, circ_0008003 regulated KPNA4 expression via miR-548I. Circ_0008003 knockdown decreased NSCLC cell growth in the xenograft model. CONCLUSION: Circular RNA hsa_circ_0008003 promoted progression in NSCLC by sponging miR-548I and regulating KPNA4 expression, hinting that circ_0008003 participates in NSCLC pathogenesis.

A Prognostic Model for the Respiratory Function of Patients with Nonsevere Pulmonary Infection Based on Breathing Exercises and Acupuncture Therapy: Development and Validation.

Objective: In this study, a prognostic model for the respiratory function was constructed based on the treatment methods of patients with nonsevere pulmonary infection, aiming to provide a reference for clinical decision-making. Method: A total of 500 patients with nonsevere pulmonary infection were included in this study. The patients were randomized into training set (n = 350) and validation set (n = 150), and the baseline characteristics were collected. All patients received breathing exercises or breathing exercises combined with acupuncture therapy for 3 months, and then the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) was assessed. Next, an ordinal multinomial logistic regression model was used to analyze prognostic factors affecting respiratory function of patients with nonsevere pulmonary infection. The Test of Parallel Lines was used to determine the accuracy (ACC) of the model and screen the influencing factors. The confusion matrix was drawn, and the ACC and harmonic mean (F1 score) were calculated to evaluate the feasibility of the model results. Results: Results of the ordinal multinomial logistic regression model showed that age (P = 0.000), treatment method (P = 0.000), underlying diseases (P < 0.001), and sex (P = 0.389) were independent factors affecting the respiratory function of patients in the training set. The ACC value of the training set was 88.86%, and that of the validation set was 91.33%, indicating a high accuracy and favorable predictive ability of the model. Besides, the F1 score was 62.38%, indicating a high reliability of the model. Conclusion: The prognostic model for respiratory function of patients with nonsevere pulmonary infection constructed in this study had favorable predictive performance, which is of great significance in the clinical nursing and treatment of patients with pulmonary infection.

MicroRNA-302a-3p induces ferroptosis of non-small cell lung cancer cells via targeting ferroportin.

Ferroptosis is a newly described regulated form of cell death that contributes to the progression of non-small cell lung cancers (NSCLCs). MicroRNA-302a-3p (miR-302a-3p) plays critical roles in the tumorigenicity of different cancers; however, its function and underlying mechanism in ferroptosis and NSCLCs remain unclear. Human NSCLCs cells were incubated with miR-302a-3pmimic or inhibitor in the presence or absence of erastin or RSL3. Cell viability, colony numbers, lactate dehydrogenase (LDH) releases, lipid peroxidation and intracellular iron level were measured. Besides, the synergistic effects of cisplatin and paclitaxel with miR-302a-3p were determined. miR-302a-3p level was reduced in human NSCLCs cells and tissues. ThemiR-302a-3p mimic induced lipid peroxidation, iron overload and ferroptosis, thereby inhibiting cell growth and colony formation of NSCLCs cells. Conversely, the miR-302a-3p inhibitor block ederastin- or RSL3-related ferroptosis and tumor suppression. Additionally, we found that miR-302a-3p directly bound to the 3'-untranslational region of ferroportin to decrease its protein expression, and that ferroportin overexpression significantly prevented miR-302a-3p mimic-induced ferroptosis and tumor inhibition. Moreover, the miR-302a-3p mimic sensitized NSCLCs cells to cisplatin and paclitaxel chemotherapy. miR-302a-3p functions as a tumor inhibitor, at least partly, via targeting ferroportin to induce ferroptosis of NSCLCs.

Long non-coding RNA HAGLROS facilitates the malignant phenotypes of NSCLC cells via repressing miR-100 and up-regulating SMARCA5.

BACKGROUND: Long non-coding RNA (lncRNA) is implicated in the progression of multiple cancers. This study aimed to explore the expression characteristics, biological function and molecular mechanism of lncRNA HAGLROS expression in NSCLC. METHODS: Quantitative real-time polymerase chain reaction (RT-PCR) was adopted to detect HAGLROS expression in NSCLC tissues and normal lung tissues. Survival curve was plotted by Kaplan-Meier method. Gain-of-function and loss-of-function models were respectively established to investigate the biological functions of HAGLROS, miR-100 and SMARCA5. MTT and Transwell assays were carried out to monitor the changes in proliferation, migration and invasion of NSCLC cells. Bioinformatics analysis and dual-luciferase reporter assay were used to verify the binding sites between HAGLROS and miR-100. Western blot was performed to determine the regulatory effects of HAGLROS and miR-100 on SMARCA5 protein expression. RESULTS: Up-regulated HAGLROS expression was observed in NSCLC tissues and cell lines. Over-expressed HAGLROS promoted the malignant phenotypes of NSCLC cells; conversely, HAGLROS knockdown repressed the malignant phenotypes of NSCLC cells. HAGLROS repressed miR-100 expression to promote SMARCA5 expression in NSCLC cells, and miR-100 overexpression or SMARCA5 knockdown counteracted the oncogenic functions of HAGLROS. CONCLUSIONS: These results conclude that HAGLROS is a tumor promoter in NSCLC, and it regulates the malignant phenotypes of NSCLC cells via miR-100/SMARCA5 axis.