RESUMO
Background: 7-Methylguanosine (m7G) is an important posttranscriptional modification that regulates gene expression and is involved in tumorigenesis and development. Tumor microenvironment has been proven to be highly involved in tumor progression and prognosis. However, how m7G-associated genes affect the tumor microenvironment of patients with lung adenocarcinoma (LUAD) remains to be further clarified. Methods: The genetic alterations of m7G-associated genes and their associations with the prognosis and tumor microenvironment in LUAD patients were systemically analyzed. An m7G-Riskscore was established and analyzed for its performance in disease prognosis and association with patient response to immunotherapy. Expression of the model genes at the protein level was investigated through ex vivo experiments. A nomogram was finally obtained based on the m7G-Riskscore and several significant clinical pathological features. Results: m7G-Associated genes were obtained from five LUAD datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases, and their expression pattern was determined. Based on the m7G-associated genes, three LUAD clusters were defined. The differentially expressed genes from the three clusters were screened and used to further divide the LUAD patients into two gene clusters. It was demonstrated that the alterations of m7G-associated genes were associated with the clinical pathological features, prognosis, and tumor immune infiltration in LUAD patients. An m7G-Riskscore including CAND1, RRM2, and SLC2A1 was obtained with robust and accurate prognostic performance. WB and cell immunofluorescence also showed significant dysregulation of CAND1, RRM2, and SLC2A1 in LUAD. In addition, a nomogram was established to improve the clinical feasibility of the m7G-Riskscore. Correlation analysis revealed that patients with a lower m7G-Riskscore had higher immune and stromal scores, responded well to chemotherapeutics and multiple targeted drugs, and survived longer. Patients with a higher m7G-Riskscore tended to suffer from a higher tumor mutation burden. Furthermore, the m7G-Riskscore exhibited significant associations with immune cell infiltration and cancer stemness. Conclusion: This study systemically analyzed m7G-associated genes and identified their potential role in tumor microenvironment and prognosis in patients with LUAD. The findings of the present study may help better understand LUAD from the m7G perspective and also provide a new thought toward the prognosis and treatment of LUAD.
RESUMO
OBJECTIVE: To explore the effect of high positive end-expiratory pressure (PEEP) for the treatment of neurological pulmonary edema (NPE) in patients undergoing mechanical ventilation, and to look for the best mechanical ventilation strategy to improve the prognosis. METHODS: A prospective study was conducted, and 120 patients with NEP admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Guangxi Traditional Chinese Medical University from January 2010 to August 2013 were enrolled and divided into two groups according to random number table (n=60 in each group). The patients in two groups were given empiric treatment for the disease, and they underwent mechanical ventilation. In the normal PEEP group PEEP was 3-10 cmH2O (1 cmH2O=0.098 kPa), and in the high PEEP group PEEP was 11-30 cmH2O, and all the rest parameters were the same. Clinical indices before and 7 days after treatment, and 28-day morality rate were compared between two groups. RESULTS: The 28-day morality rate in high PEEP group was obviously lower than that in the normal PEEP group [25.0% (15/60) vs. 65.0% (39/60), χ(2)=6.465, P=0.011]. The clinical signs in both groups were improved after treatment. Compared with the normal PEEP group, the clinical indices in high PEEP group were more significantly improved. There were significant differences in body temperature (37.4±0.5 centigrade vs. 38.5±0.6 centigrade), respiratory rate (18.3±3.1 times/min vs. 23.3±3.5 times/min), heart rate (94.7±8.5 beats/min vs. 113.5±8.0 beats/min), white blood cell count (WBC: 12.5±2.1 ×10(9)/L vs. 17.1±1.7 ×10(9)/L), acute physiology and chronic health evaluation II (APACHEII) score (15.6±3.2 vs. 19.8±3.7), Glasgow coma score (GCS: 12.5±2.1 vs. 8.5±2.9), gastrointestinal dysfunction score (3.9±3.0 vs. 3.6±2.4), oxygenation index (PaO2/FiO2: 196.5±45.1 mmHg vs. 134.1±22.3 mmHg), serum creatinine (SCr: 86.5±35.6 µmol/L vs. 98.5±37.7 µmol/L), total bilirubin (TBil: 39.7±23.5 µmol/L vs. 41.5±16.2 µmol/L), C-reacting protein (CRP: 53.7±21.4 mmol/L vs. 108.4±26.3 mmol/L), prothrombin time (PT: 15.0±2.1 s vs. 20.4±2.2 s), activated partial thromboplastin time (APTT: 37.3±4.9 s vs. 56.7±13.6 s), international normalized ratio (INR: 2.52±0.64 vs. 4.01±0.77), extra vascular lung water index (EVLWI: 7.53±1.21 mL/kg vs. 15.85±3.41 mL/kg), pulmonary vascular permeability index (PVPI: 6.07±0.89 vs. 9.47±1.26), mean arterial pressure (MAP: 87.3±10.9 mmHg vs. 98.7±13.6 mmHg), cardiac output (CO: 7.15±1.42 L/min vs. 5.65±1.82 L/min), systemic vascular resistance index (SVRI: 112.4±9.5 KP vs. 136.5±11.9 KP), and blood lactate (2.53±1.23 mmol/L vs. 5.81±2.17 mmol/L) between high PEEP group and normal PEEP group (P<0.05 or P<0.01). CONCLUSIONS: Prognosis can be improved in NPE patients with the use of high PEEP in mechanical ventilation.
