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Lung cancer, predominantly by non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths over the world. Late diagnosis is one of important reasons for high mortality rate in lung cancer. Current diagnostic approaches have disadvantages such as low accuracy, high cost, invasive procedure, etc. MicroRNAs were previously proposed as promising novel biomarkers in cancer screening. In this study, we evaluated the predictive power of four candidate miRNAs in NSCLC detection. Our study involved 152 NSCLC patients and 300 healthy controls. Blood samples were obtained from the total 452 subjects. After miRNA extraction from serum, the expression of miRNAs in cases and controls were quantified by qRT-PCR and normalized to the level of U6 small RNA. Statistical analyses were performed to compare miRNA levels between cases and controls. Stratified analyses were employed to compare miRNA levels in NSCLC patients with different clinical characteristics. Serum miR-148a, miR-148b, and miR-152 were significantly downregulated in NSCLC patients. However, overexpression of serum miR-21 was observed in NSCLC patients. The combination of four candidate miRNAs exhibited the highest predictive accuracy in NSCLC screening compared with individual miRNAs (AUC = 0.97). Low level of miRNA-148/152 members may associate with advanced stage, large tumor size, malignant cell differentiation, and metastasis. High expression of miR-21 was possibly correlated with large size tumor and advanced cancer stage. Our results showed the dysregulation of miR-148/152 family and miR-21 in NSCLC patients. Hence, the four candidate miRNAs have great potential to serve as promising novel biomarkers in NSCLC screening. Further large-scale studies are needed to validate our results.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/sangre , MicroARNs/sangre , Anciano , Biomarcadores de Tumor/sangre , Detección Precoz del Cáncer , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares , Masculino , Persona de Mediana Edad , Estadificación de NeoplasiasRESUMEN
BACKGROUND: There is controversy over the drainage threshold for removal of chest tubes in the absence of significant air leakage after selective pulmonary resection. METHODS: A comprehensive search of online databases (PubMed, Web of Science, Embase, Cochrane Library, Scopus, Ovid, Elsevier, Ebsco, and Wiley) and clinical trial registries (WHO-ICTRP and ClinicalTrials.gov) was performed to investigate the efficacy and safety of early chest tube removal with high-output drainage. Primary outcome (postoperative hospital day) and secondary outcomes (30-day complications, rate of thoracentesis, and chest tube placement) were extracted and synthesized. Subgroup analysis, meta-regression, and sensitivity analysis were used to explore the potential heterogeneity. Study quality was assessed with the Newcastle-Ottawa Scale, and evidence was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment by the online GRADEpro Guideline Development Tool. RESULTS: Six cohort studies with a total of 1262 patients were included in the final analysis. The postoperative hospital stay in the high-output group was significantly shorter than in the conventional treatment group (weighted mean difference: -1.34 [-2.34 to -0.34] day, Pâ =â .009). While there was no significant difference between 2 groups in 30-day complications (relative ratio [RR]: 0.92 [0.77-1.11], Pâ =â .38), the rate of thoracentesis (RR: 1.93 [0.63-5.88], Pâ =â .25) and the rate of chest tube placement (RR: 1.00 [0.37-2.70], Pâ =â .99). According to the sensitivity analysis, the relative impacts of the 2 groups had already stabilized. Subgroup analysis revealed that postoperative hospital stay was modified by Newcastle-Ottawa Scale score. The online GRADEpro Guideline Development Tool presented very low quality of evidence for the available data. CONCLUSIONS: This meta-analysis revealed that it is feasible and safe to remove a chest tube with high-output drainage after pulmonary resection for selected patients.
Asunto(s)
Tubos Torácicos , Complicaciones Posoperatorias , Humanos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Drenaje/efectos adversos , Neumonectomía/efectos adversos , Toracocentesis , Tiempo de InternaciónRESUMEN
BACKGROUND: CircLARP4 is reported to act as a tumor suppressor in some cancers. However, the detailed roles and molecular basis of circLARP4 in non-small cell lung cancer (NSCLC) tumorigenesis are still unclear. The aim of the study is to explore the potential roles and molecular basis of circLARP4 in NSCLC tumorigenesis. MATERIALS AND METHODS: qRT-PCR was taken to detect circLARP4 and miR-135b expressions. MTT assay, transwell invasion assay and flow cytometry analysis were applied to evaluate cell proliferation, invasion and apoptosis, respectively. Glycolysis was assessed by measuring hexokinase2 (HK2) expression, glucose consumption and lactate production. Association between circLARP4 and miR-135a was examined by luciferase reporter and RIP assays. The changes of the phosphatase and tension homolog (PTEN)/protein kinase B (AKT)/hypoxia-inducible factor-1α (HIF-1α) pathway were evaluated by Western blot. The nude mouse xenograft models were applied to verify the regulation of circLARP4 in vivo. RESULTS: CircLARP4 was decreased in NSCLC tissues and cells. CircLARP4 overexpression blocked cell proliferation and invasion, and facilitated apoptosis in NSCLC cells. Meanwhile, circLARP4 overexpression suppressed glycolysis in NSCLC cells, as evidenced by the reduced HK2, glucose consumption and lactate production levels. Further analyses proved a downregulation of miR-135b by circLARP4 in a ceRNA-dependent manner in NSCLC cells. CircLARP4-mediated tumor suppression on NSCLC progression was partially overturned by overexpressing miR-135b. Moreover, we confirmed that circLARP4 had antitumor effect on xenograft tumors and downregulated miR-135b. Furthermore, circLARP4 overexpression inhibited the PTEN/AKT/HIF-1α pathway in NSCLC cells and xenograft tumors by downregulating miR-135b. CONCLUSION: Our findings suggested that circLARP4 suppressed NSCLC progression by sponging miR-135b through inactivation of the PTEN/AKT/HIF-1α pathway, which broadens our understanding concerning the roles of circLARP4 in NSCLC tumorigenesis.
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A capillary electrophoresis method was developed for the simultaneous determination of five flavonoids such as luteolin-7-O-glucoside, isorhamnetin, apigenin, luteolin and quercetin in Lamiophlomis rotata (Benth.) Kudo. Optimal conditions were obtained at pH 9.0 with 30 mM borate as buffer containing 8% (v/v) acetonitrile, 20 kV as driving voltage and 210 nm as detection wavelength. The association constant K and the change in Gibbs free energy (DeltaG) of the interaction of flavonoids with borate anion ion (a typical ion-dipole or ion-induced dipole interaction) were calculated for the quantitative evaluation and characterization of the interaction. The described method was successfully applied for the rapid and efficient quality control by quantifying flavonoids in L. rotata. Repeatability tests showed that the R.S.D.s of both intra- and inter-day migration times and peak areas were less than 5%. The LOD of the five flavonoids was less than 3.75 mg/l. Recovery results ranged from 94.2% to 105.1%.