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*

Objective:To evaluate the effect of intravenous infusion of dexmedetomidine before induction of anesthesia on concentrations of blood potassium and blood glucose in the patients with gastrointestinal tumors.Methods:One hundred and twenty patients, irrespective of gender, aged 18-75 yr, with body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, scheduled for elective radical gastrointestinal tumor surgery, were divided into 3 groups ( n=40 each) using a random number table method: control group (group C), dexmedetomidine 0.5 μg/kg group (group D 1), and dexmedetomidine 1.0 μg/kg group (group D 2). Dexmedetomidine 0.5 and 1.0 μg/kg were intravenously infused prior to anesthesia induction over 10 min in D 1 and D 2 groups, while the equal volume of normal saline 20 ml was intravenously infused instead in group C. Before intravenous infusion (T 0), at 15 min after intravenous infusion (T 1), and at 30 min after intravenous infusion (T 2), blood samples from the radial artery were collected for blood gas analysis, and concentrations of blood potassium and blood glucose were recorded. The occurrence of complications such as hyperglycemia, hypoglycemia, hyperkalemia, hypokalemia, hypotension, hypertension, tachycardia and bradycardia was also recorded. Results:Compared with C group, the blood glucose concentrations were significantly increased at T 1 in D 1 and D 2 groups and at T 2 in D 2 group ( P<0.05). The blood glucose concentrations were significantly higher at T 1, 2 in D 2 group than in D 1 group ( P<0.05). There was no significant difference in blood potassium concentrations at T 0-T 2 among the three groups ( P>0.05). No patients presented with complications such as hyperglycemia, hypoglycemia, hyperkalemia, hypokalemia, hypotension, hypertension, tachycardia and bradycardia. Conclusions:Intravenous infusion of dexmedetomidine before induction of anesthesia exerts no marked effect on blood potassium concentrations and can increase glucose concentrations to a certain extent, but the elevation has no clinical significance in the patients with gastrointestinal tumors.

Humans ; Botany/history* ; History, 20th Century ; China

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.

Unrestrained inflammation is harmful to tissue repair and regeneration. Immune cell membrane-camouflaged nanoparticles have been proven to show promise as inflammation targets and multitargeted inflammation controls in the treatment of severe inflammation. Prevention and early intervention of inflammation can reduce the risk of irreversible tissue damage and loss of function, but no cell membrane-camouflaged nanotechnology has been reported to achieve stage-specific treatment in these conditions. In this study, we investigated the prophylactic and therapeutic efficacy of fibroblast membrane-camouflaged nanoparticles for topical treatment of early inflammation (early pulpitis as the model) with the help of in-depth bioinformatics and molecular biology investigations in vitro and in vivo. Nanoparticles have been proven to act as sentinels to detect and competitively neutralize invasive Escherichia coli lipopolysaccharide (E. coli LPS) with resident fibroblasts to effectively inhibit the activation of intricate signaling pathways. Moreover, nanoparticles can alleviate the secretion of multiple inflammatory cytokines to achieve multitargeted anti-inflammatory effects, attenuating inflammatory conditions in the early stage. Our work verified the feasibility of fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage, which widens the potential cell types for inflammation regulation.
Escherichia coli ; Fibroblasts ; Humans ; Inflammation/drug therapy* ; Nanoparticles

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 explore the difference of methylation status of CpG island in promoter re?gion of DAT1 and DRD4 genes between children with attention deficit hyperactivity disorder ( ADHD) and normal controls,and further understand the pathogenesis of ADHD from a epigenetics point of view. Methods 111 ADHD patients and 118 normal controls were enrolled in the present study. The demographic data and peripheral venous blood were collected from both groups. Bisulfite genomic sequencing ( BGS) was used to confirm the methylation status of every CpG site in promoter region of DAT1 and DRD4 genes. Results No significant differences were found between ADHD patients and normal controls on percentage of methylated CpG sites in total CpG islands for both DAT1 and DRD4 (P>0.05) . However,the percentage of methylation in No. 17 CpG site for DAT1 and No. 8 CpG site for DRD4 was higher in ADHD patients ( 23. 42% and 64.86% respectively)compared with that in normal controls(11.86% and 47.46% respectively)(P<0.05).In all samples,the percentage of methylated CpG site in total CpG island for DAT1 was higher in males com?pared with that in females(P<0.05),whereas that for DRD4 was higher in females compared with that in males (P<0.05);the same gender difference on methylation level for DAT1 was also found in ADHD patients and for DRD4 in normal controls(P<0.05) . In all samples and in ADHD patients,percentage of methylated CpG site in total CpG island for DAT1 was higher in individuals over 7 years old compared with that in indi?viduals younger than or equal to 7 years old(P<0.05). Conclusions Methylation status of CpG island in DAT1 and DRD4 genes promoter region might correlate with ADHD susceptibility.Methylation status of CpG island in DAT1 and DRD4 genes show differences in different age span and sex.

Objective To investigate the correlation of methylation status in DA T1 and DRD4 genes and severity of clinical manifestations in ADHD patients.Methods One hundrd eleven DSM-Ⅳ defined ADHD patients were enrolled in this study and the demographic data were collected.Clinical symptoms were also assessed by Attention Deficit Hyperactivity Disorder Rating Scale-Ⅳ Home Version (ADHD-RS-Ⅳ) and self-developed Oppositional Defiant Disorder (ODD) rating scale.Bisulfite genomic sequencing (BGS) was used to detect the methylation status of every CpG site in DA T1 and DRD4 promoter CpG island in peripheral venous blood.Results The DNA methylation level in total CpG island for DA T1 was higher in individuals without depression,anxiety or ADHD family history compared to individuals with above family histories (P＜0.05).The differences on methylation levels for DA T1 and DRD4 were not significant between high and low ADHD-RS-Ⅳ total score (≤30 vs.＞30),ADHD-RS-Ⅳ inattention score (≤ 17 vs.＞17),and ADHD-RS-Ⅳ hyperactivity/impulsivity score (≤13 vs.＞13) subgroups (all P＜0.05).The methylation levels in total CpG island in DA T1 was higher in individuals whose ODD score were ＜9 compared to those whose ODD score were ≥9 (P＜0.05).Conclusions Methylation status of CpG island in DAT1 may influence the severity of oppositional defiant symptom in ADHD patients,which is correlated with depression,anxiety and ADHD family histories.

Through the literature collection on Chinese marine materia medica,this study analyzed medication rules of Chinese marine materia medica prescription,understood general conditions of Chinese marine materia medica prescription,in order to conduct data mining on medication rules of Chinese marine materia medica prescription.The name of Chinese marine materia medica was used as the search term.Chinese marine materia medica prescriptions were searched in related literatures of Chinese Medicine Code,Chinese Marine Materia Medica,Chinese Materia Medica,Chinese Pharmacopoeia and Great Dictionary of Chinese Medicine.The information was extracted and standardized to construct database for the initial data mining of related information and medication rules of Chinese marine materia medica prescriptions.The results showed that 16715 Chinese marine materia medica prescriptions were screened,which contained 144014 items of data,involving 218 kinds of Chinese marine materia medica.Decoction was the most common dosage form.The amount of Chinese marine materia medica prescription in the Ming and Qing dynasties was the largest.The highest frequency of Chinese marine materia medica in one prescription was 1 to 3 types.The prescription composed all by Chinese marine materia medica occupied 8.065％.Other prescriptions contained the compatibility of Chinese terrestrial materia medica.The prescription containing materia medica half from the sea and half from the land,occupied 7.754％.The Chinese marine materia medica used with the highest frequency in all prescriptions was oyster.The frequently used Chinese terrestrial materia medica was licorice and angelica in Chinese marine materia medica prescriptions.It was concluded that the number of Chinese marine materia medica prescription was large.Its compatibility and clinical application had a certain characteristic,which provided data foundation for the further research and development of Chinese marine materia medica.