BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality worldwide, with above 80% of cases be non-small cell lung cancer (NSCLC), among which lung squamous cell carcinoma (LUSC) occupies a significant proportion. Although comprehensive cancer therapies have considerably improved the overall survival of patients, patients with advanced LUSC have a poorer prognosis. Therefore, there is a need for a biomarker to predict the progress of advanced LUSC in order to improve prognosis through early diagnosis. Previous studies have shown that miRNAs are differentially expressed in lung cancer tissues and play roles as potential oncogenes or tumor suppressors. The aim of this study is to identify differentially expressed miRNAs between early-stage and advanced-stage LUSC, and to establish a set of miRNAs that can predict the progress of advanced LUSC. METHODS: Clinical data and miRNA-related data of LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatic methods were applied to analyze the data. Receiver operating characteristic (ROC) curves were plotted, and various online tools were used to predict target genes, with subsequent analysis of the potential biological mechanisms of these genes. RESULTS: A total of 58 differentially expressed miRNAs were identified between the experiment group and the control group. Seven miRNAs were selected for potential construction of a miRNA biomarker through LASSO regression, and based on the area under the curve (AUC) values of each miRNA, four of these miRNAs (miR-377-3p, miR-4779, miR-6803-5p, miR-3960) were ultimately chosen as biomarkers for predicting advanced LUSC. The AUC under the ROC curve for the combined four miRNAs was 0.865. Enrichment analysis showed that these target genes were involved in several pathways, including cancer-related pathways, mitogen-activated protein kinase (MAPK) signaling pathway, serine/threonine kinase, and tyrosine kinase signaling pathways. CONCLUSIONS The combined use of miR-377-3p, miR-4779, miR-6803-5p and miR-3960 provides a good predictive ability for the progress of advanced LUSC patients, with an AUC of 0.865.
Humans ; MicroRNAs/metabolism* ; Lung Neoplasms/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Prognosis ; ROC Curve ; Middle Aged

BACKGROUND: Lung cancer represents the main cause of cancer-related deaths worldwide, and non-small cell lung cancer (NSCLC) is the most main subtype. More than half of NSCLC patients have already developed distant metastasis (DM) at the time of diagnosis and have a poor prognosis. Therefore, it is necessary to find new biomarkers for predicting NSCLC DM in order to guide subsequent treatment and thus improve the prognosis of NSCLC patients. Numerous studies have shown that microRNAs (miRNAs) are abnormally expressed in lung cancer tissues and play an important role in tumorigenesis and progression. The aim of this study is to identify differentially expressed miRNAs in lung adenocarcinoma tissues with DM group compared to those with non-distant metastasis (NDM) group, and to construct a miRNA signature for predicting DM of lung adenocarcinoma. METHODS: We first obtained miRNA and clinical data for patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database. Subsequently, bioinformatics analysis, which included different R packages, Kaplan-Meier analysis, receiver operating characteristic (ROC) curve, and a range of online analysis tools, was performed to analyze the data. RESULTS A total of 12 differentially expressed miRNAs were identified between the DM and NDM groups, and 8 miRNAs (miR-377-5p, miR-381-5p, miR-490-5p, miR-519d-5p, miR-3136-5p, miR-320e, miR-2355-5p, miR-6784-5p) were screened for constructing a miRNA signature. The efficacy of this miRNA signature in predicting DM was good with an area under the curve (AUC) of 0.831. Logistic regression analysis showed that this miRNA signature was an independent risk factor for DM of lung adenocarcinoma. Next, target genes of the eight miRNAs were predicted, and enrichment analysis showed that these target genes were enriched in a variety of pathways, including pathways in cancer, herpes simplex virus I infection, PI3K-Akt pathway, MAPK pathway, Ras pathway, etc. CONCLUSIONS: This miRNA signature has good efficacy in predicting DM of lung adenocarcinoma and has the potential to be a predictor of DM of lung adenocarcinoma.
Humans ; MicroRNAs/metabolism* ; Lung Neoplasms/diagnosis* ; Male ; Neoplasm Metastasis ; Female ; Gene Expression Regulation, Neoplastic ; Middle Aged ; Prognosis ; Gene Expression Profiling ; Aged ; Biomarkers, Tumor/genetics*

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Objective To explore the factors affecting methylphenidate (MHP)efficacy in children with attention deficit hyperactivity disorder (ADHD). Methods One hunadard eleven DSM-Ⅳ defined ADHD patients were enrolled for 6 weeks systemic MHP titration treatmnet. ADHD Rating Scale-Ⅳ Home Version (ADHD-RS-Ⅳ) were applied as index of clinical efficacy, and Continuous Performance Task (CPT) as index of cognition efficacy. Determining potential influential factors was analyzed on MPH efficacy including demographic,baseline clinical symptoms and cognitive factors. Results Sixty-five (59.1%) were defined as responders and 45 (40.9%) as non-reponders to MHP, respectively. CPT which were conducted in 87 patient showed that 35 (40.2%) were defined as responders on commission errors, 31 (35.6%) on omission errors and 10 (11.5%) on reaction time. Logistic analysis revealed two potential influential factors that predicted better clinical efficacy (P<0.05): better parental relationship (OR=3.516, 95% CI: 1.087~11.375) and baseline ADHD-RS-Ⅳ score above 35 points (OR=3.075, 95%CI: 1.131~8.359). Higher IQ score was the potential influential factor that predicted better commission errors efficacy (OR=1.085, 95%CI: 1.013~1.162) and omission errors efficacy (OR=1.078, 95%CI: 1.008~1.153). Conclusion MHP efficacy may result in better outcomes in children with ADHD who have higher baseline ADHD-RS-Ⅳ score, poorer baseline CPT result, younger onset age, higher IQ and better parental relationship.

Objective To investigate mRNA expression level changes of dopamine transporter gene (DAT1) and dopamine receptor gene(DRD4) in attention deficit hyperactivity disorder(ADHD) children's peripheral blood before and after methylphenidate treatment,and to explore associations between the mRNA expression level and symptom severity,as well as methylphenidate response.Methods Forty five ADHD children by DSM-Ⅳ diagnostic criteria,aged six to fifteen years old participated in a six-week drug titration treatment of metbylphenidate.ADHD-RS-Ⅳ Home Version, WCST and VCPT were used to evaluate the ADHD clinical symptoms and cognitive functions.RNA Simple Total RNA Kit was used to extract the total RNA.After reverse transcription, the obtained c-DNA was used in the following qRT-PCR to evaluate relative mRNA expression of the candidate genges before and after medication.Results The DRD4 mRNA relative expression level after taking methylphenidate was significantly higher than that before methylphenidate treatment (0.23 ± 0.23 vs 0.16± 0.18, P =0.041).There was no significant difference between DAT1 mRNA relative expression level before (0.43 ± 0.40) and after (0.43±0.40) methylphenidate treatment.No significant difference was found on eitber basal DAT1/DRD4 mRNA expression or fold change of DAT1/DRD4 mRNA expression before and after medication between methylphenidate treatment responders and non-responders groups.There was a positively significant correlation between baseline DRD4 mRNA relative expression level and erroneous T score of CPT(r=0.424, P=0.025) , however, no other statistically significant correlation was found between basal DRD4 mRNA relative expression level and ADHD-RS-Ⅳ total score,WCST conceptual level, CPT missing T score, and CPT reaction T sco~ (all P＞0.05).There was also no statistical significant correlation between basal DAT1 mRNA relative expression level and ADHD-RS-Ⅳ total score,WCST conceptual level,and CPT T scores(all P＞0.05).Conclusion DRD4 gene function may be increased after methylphenidate treatment and play an important role in impulsivity behavior of ADHD.Therefore, DRD4 mRNA expression level might be a biomarker for ADHD diagnosis and a predicting indicator of drug efficacy.