Expression of miR-223-3p in patients with hepatitis B virus liver fibrosis and its effect on hepatic stellate cells: An observational study.

To analyze miR-223-3p expression in patients with hepatitis B virus (HBV) live fibrosis and its effects on proliferation, activation, and apoptosis of human hepatic stellate cell line. One hundred patients with HBV-associated liver fibrosis were divided into S0 to 1, S2 to 3, and S4 groups according to Scheuer histological staging; healthy individuals during the same period were enrolled as healthy group. Relative expressions of miR-223-3p in healthy, S0 to 1, S2 to 3, and S4 groups were 0.56 ± 0.11, 1.08 ± 0.27, 2.16 ± 0.42, and 3.59 ± 1.06, respectively. Absorbance values of human hepatic stellate cell line cells at 24, 48, and 72 hours were higher in miR-223-3p-mimic group than in control group (CG) and NC-mimic group and were lower in miR-223-3p-inhibitor group than in CG and NC-inhibitor group (P < .05). mRNA miR-223-3p, α-smooth muscle actin, collagen 1A1, collagen 1A2, collagen 3A1, and transforming growth factor (TGF)-ß1 levels were higher in miR-223-3p-mimic group than in CG and NC-mimic group and lower in miR-223-3p-inhibitor group than in CG and NC-inhibitor group (P < .05). Protein expressions of α-smooth muscle actin, transforming growth factor-ß1, collagen I, collagen III, p-Smad3, p-Smad2, and B-cell lymphoma 2 were higher in miR-223-3p-mimic group than in CG and NC-mimic groups and lower in miR-223-3p-inhibitor group than in CG and NC-inhibitor group, whereas those of B-cell lymphoma 2-associated death promoter, B-cell lymphoma 2 associated X protein, cleaved caspase3, cleaved caspase9, poly ADP-ribose polymerase were lower in miR-223-3p-mimic group than in CG and NC-mimic group and higher in miR-223-3p-inhibitor group than in CG and NC-inhibitor group (P < .05). HBV liver fibrosis patients had elevated expression of miR-223-3p in plasma. Upregulation of miR-223-3p expression may be related to transforming growth factor-ß1/Smad signaling pathway activation.

Hsa_circ_0001073 targets miR-626/LIFR axis to inhibit lung cancer progression.

Circular RNAs (circRNAs) are associated with lung cancer progression. However, it is unclear whether and how circRNA hsa_circ_0001073 (circ_0001073) are involved in lung cancer progression. circ_0001073, microRNA (miR)-626, and leukemia inhibitory factor receptor (LIFR) abundances were determined via quantitative reverse transcription polymerase chain reaction or western blot. Cell viability, invasion, and apoptosis were analyzed by cell counting kit-8, transwell analysis and flow cytometry, respectively. The target correlation was tested by dual-luciferase reporter analysis or RNA immunoprecipitation. Results showed that circ_0001073 abundance was down-regulated in lung cancer cells. circ_0001073 constrained cell viability and invasion and facilitated apoptosis in lung cancer cells. miR-626 was targeted via circ_0001073, and circ_0001073 inhibited lung cancer progression via reducing miR-626 expression. LIFR was targeted via miR-626, and miR-626 knockdown constrained cell viability and invasion and facilitated apoptosis in lung cancer cells via up-regulating LIFR. circ_0001073 increased LIFR expression via miR-626 in lung cancer cells. In conclusion, circ_0001073 represses lung cancer progression via miR-626/LIFR axis, indicating the potential value of circ_0001073 in lung cancer treatment.

A Novel Long Non-coding RNA, MSTRG.51053.2 Regulates Cisplatin Resistance by Sponging the miR-432-5p in Non-small Cell Lung Cancer Cells.

Objective: The aim of this study was to investigate the molecular mechanisms underlying cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC) cells by constructing a competing endogenous RNA (ceRNA) network. Methods: The gene expression profiles of human lung adenocarcinoma DDP-resistant cell line (A549/DDP) and its progenitor (A549) were comparatively evaluated by whole-transcriptome sequencing. The differentially expressed genes (DEGs) were subjected to KEGG pathway analysis. The expression levels of mRNAs involved in several pathways associated with conferring DDP resistance to tumor cells were evaluated. The ceRNA network was constructed based on the mRNA expression levels and the sequencing data of miRNA and lncRNA. Several ceRNA regulatory relationships were validated. Results: We quantified the expression of 17 genes involved in the six pathways by quantitative real-time polymerase chain reaction (qRT-PCR). The differential protein expression levels of eight genes were quantified by western blotting. Western blot analysis revealed six differentially expressed proteins (MGST1, MGST3, ABCG2, FXYD2, ALDH3A1, and GST-ω1). Among the genes encoding these six proteins, ABCG2, ALDH3A1, MGST3, and FXYD2 exhibited interaction with 8 lncRNAs and 4 miRNAs in the ceRNA regulatory network. The expression levels of these lncRNAs and miRNAs were quantified in cells; among these, 6 lncRNAs and 4 miRNAs exhibited differential expression between A549/DDP and A549 groups, which were used to construct a ceRNA network. The ceRNA regulatory network of MSTRG51053.2-miR-432-5p-MGST3 was validated by luciferase reporter assay. Conclusion: The MSTRG51053.2 lncRNA may function as a ceRNA for miR-432-5p to regulate the DDP resistance in NSCLC. The MGST1, MGST3, GST-ω1, and ABCG2 mRNAs, miR-432-5p and miR-665 miRNAs, and MSTRG51053.2 and PPAN lncRNAs can serve as potential DDP drug targets to reverse DDP resistance in NSCLC.

Soluble Myeloid Triggering Receptor Expressed on Myeloid Cell 1 Might Have More Diagnostic Value for Bacterial Ascites than C-reactive Protein.

The timely and accurate diagnosis of ascites is of great significance for early treatment and prognostication. This study explored the value of soluble myeloid triggering receptor expressed on myeloid cell 1 (sTREM-1) and C-reactive protein (CRP) for assessing ascites. A total of 133 patients with ascites who received treatment at the Affiliated Hospital of Taishan Medical University between September 2015 and September 2017 were retrospectively analyzed. The ascites in 22, 45, 33 and 33 patients were tuberculous, bacterial, tumorous, and transudative, respectively. Healthy volunteers (n=30) who received a health examination at the same hospital during the same period constituted the control group. Before treatment, both ascitic sTREM-1 and CRP showed significant differences among the ascites subgroups (P<0.001), with the highest levels in the bacterial subgroup. Serum sTREM-1 and CRP also showed significant differences among the groups. A correlation analysis showed a positive correlation between sTREM-1 and CRP. ROC curves of the bacterial subgroup showed that when the optimal cutoff point was set to 20.2, the sensitivity, specificity, positive predictive value, and negative predictive value of the serum sTREM-1 index were 0.933, 0.955, 0.914, and 0.965, respectively. sTREM-1 may provide more diagnostic value than CRP for the diagnosis of bacterial ascites.

Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1.

Valproic acid (VPA) has been suggested to be a histone deacetylase inhibitor (HDACI). Our present study revealed that VPA at 1 mm, which had no effect on cell proliferation, can significantly increase the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP). VPA treatment markedly decreased the mRNA and protein levels of ABCA1, while had no significant effect on ABCA3, ABCA7 or ABCB10. Luciferase reporter assays showed that VPA can decrease the ABCA1 promoter activity in both A549 and H358 cells. VPA treatment also decreased the phosphorylation of SP1, which can bind to -100 and -166 bp in the promoter of ABCA1. While the phosphorylation of c-Fos and c-Jun were not changed in VPA treated NSCLC cells. Over expression of HDAC2 attenuated VPA induced down regulation of ABCA1 mRNA expression and promoter activities. Over expression of HDAC2 also attenuated VPA induced DDP sensitivity of NSCLC cells. These data revealed that VPA can increase the DDP sensitivity of NSCLC cells via down regulation of ABCA1 through HDAC2/SP1 signals. It suggested that combination of VPA and anticancer drugs such as DDP might be great helpful for treatment of NSCLC patients.

IL-17 protein levels in both induced sputum and plasma are increased in stable but not acute asthma individuals with obesity.

BACKGROUND: Obesity worsens asthma control partly through enhanced airway neutrophilia, altered lung mechanics and comorbidities, including obstructive sleep apnea syndrome, gastroesophageal reflux disease and depression. Although controversial, obesity may also cause poorer outcomes in acute asthma. IL-17 is associated with neutrophilic inflammation, steroid resistance and severe asthma, but its importance in the association between asthma and obesity is unknown. OBJECTIVE: To investigate the role of IL-17 in obese asthma in both acute and stable settings. METHODS: Both stable (n = 177) and acute (n = 78) asthmatics were recruited and categorized into lean (n = 77 and 39 respectively), overweight (n = 41 and 17 respectively) and obese (n = 59 and 22 respectively) groups and compared for clinical characteristics, including sputum and plasma IL-17 protein concentrations, sputum cellularity, spirometry and comorbidities. Correlations of IL-17 expression with other measures were explored. RESULTS: In stable subjects, airway neutrophilia and IL-17 concentrations were most prominent in the obese, and correlated positively with each other. Significant increase in plasma IL-17 levels was also noted and associated with elevated depressive symptoms in obesity. In acute asthma, IL-17 expression, like most other clinical measures, was similar among lean, overweight and obese groups, but was higher in acute versus stable asthma subjects, with sputum IL-17 correlating positively with sputum neutrophils and negatively with FEV1 and plasma IL-17 showing a positive connection to airway eosinophilia during exacerbation. CONCLUSIONS: IL-17 contributes to worse disease control in obese asthma through enhancing airway neutrophilia and depression, and may implicate in asthma exacerbations. Effects of adiposity on acute asthma remain uncertain.

Sertraline hydrochloride treatment for patients with stable chronic obstructive pulmonary disease complicated with depression: a randomized controlled trial.

BACKGROUND: There is a lack of randomized controlled trials to assess the effects of pharmacological treatments in patients with stable chronic obstructive pulmonary disease (COPD) complicated with moderate or severe depression. AIMS: To assess the efficacy of sertraline hydrochloride on improving the quality of life of patients with stable COPD complicated with depression. METHODS: This randomized controlled trial, conducted from May to November 2013 in the Huai'an Second Hospital, Huai'an, China, enrolled 120 patients with stable COPD who had moderate or severe depression. Patients were randomly assigned to control and interventional groups (n = 60 in each group). In addition to the treatment for COPD, interventional group also received sertraline hydrochloride tablets 50 mg/day for 6 weeks, while the control group received placebo. The primary end point included COPD assessment test (CAT) scores and the secondary endpoint included 6-min walk distance and 17-item Hamilton Depression Rating Scale (HAMD-17) scores. Parameters of spirometry and adverse events were also observed. RESULTS: There was no significant difference in improvements in the parameters of spirometry tests before and after the treatment with sertraline hydrochloride tablets between the placebo and interventional groups (P > 0.05). Patients in the sertraline hydrochloride group showed more changes in the HAMD-17 scores and CAT scores after treatment (P < 0.05) and travelled longer distances in the 6-min walk test than in the placebo group (P < 0.05). CONCLUSION: Antidepressant treatment can improve the quality of life and exercise capacity of patients with depression, and it can also improve depression scores, but not lung function.

Utility of uric acid as a risk marker of extubation success in chronic obstructive pulmonary disease.

BACKGROUND: The objective of this observational study was to determine whether there is an association between extubation success and uric acid in chronic obstructive pulmonary disease patients with mechanical ventilation admitted to the intensive care units, and identify the risk markers for extubation success in COPD patients with mechanical ventilation. METHODS: Consecutive COPD patients with intubation were screened at baseline. The study included patients on mechanical ventilation (MV) for over 12 hours and who, in the process of weaning, were subjected to low-level pressure support. Exclusion criteria were age under 18 years, ventilation via tracheotomy, and patients failing to cooperate for different reasons. The final study population consisted of 106 patients. Demographic, clinical, laboratory, and mechanical ventilation parameters were carefully recorded. Logistic regression was used for the multivariate analysis of independent risk factors. RESULTS: Uric acid on admission, duration of mechanical ventilation, pressure support ventilation, and APACHE II score on admission were significantly higher in COPD patients with extubation failure than in those with extubation success (p < 0.05), but lower tidal volume before weaning was observed in COPD patients with extubation failure. Among these patients, multiple logistic analyses indicated the independent risk factors for extubation success in the COPD subjects included serum uric acid level, APACHE II score on admission, and duration of mechanical ventilation. The diagnosis analysis showed that higher uric acid level and APACHE II score on admission and longer duration of mechanical ventilation had a significant ability to reflect extubation success in the COPD patients with respiratory failure. CONCLUSIONS: The novel finding of this study is that the extubation failure in COPD patients with respiratory failure is strongly related to serum uric acid level, APACHE II score on admission, and duration of mechanical ventilation. These results might be helpful for selecting the best time to remove the tracheal intubation and improving extubation success rate in COPD patients with respiratory failure.

Azithromycin attenuates pulmonary inflammation and emphysema in smoking-induced COPD model in rats.

INTRODUCTION: The role of inflammation and immunity in COPD treatment is increasingly being recognized. The relationship between anti-inflammation/immunoregulation and emphysema in COPD lungs remains to be elucidated. The aim of this study was to investigate the effects of azithromycin (Azm) on the development of emphysema in smoking-induced COPD in rats. METHODS: Sprague-Dawley rats (n = 50) were randomly assigned to normal, COPD, saline-treated, Azm-treated, and levofloxacin-treated (Lev) groups. The effects of treatment were assessed by measuring the levels of vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay and measuring the numbers of neutrophil and macrophage in bronchoalveolar lavage fluid, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR2) protein expression by western blotting. Lung function measurements and histopathological evaluations (mean linear intercept and destructive index) were performed. RESULTS: FEV0.3/FVC and peak expiratory flow were lower in the COPD group than in the normal group. Mean linear intercept and destructive index were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. The numbers of neutrophil and macrophage in bronchoalveolar lavage fluid were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. As confirmed by western blotting, the levels of VEGF in lung homogenates were higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. VEGFR2 protein expression was higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. CONCLUSIONS: Azm attenuates pulmonary emphysema by partly reversing the decrease in the numbers of inflammatory cells (neutrophil and macrophage) and VEGF secretion and VEGFR2 protein expression in smoking-induced COPD in rats.

Uric acid levels in obstructive sleep apnea patients with atrial fibrillation.

BACKGROUND AND AIMS: The objective of this observational study was to determine whether there is an association between atrial fibrillation (AF) and uric acid and to identify the risk markers for AF in obstructive sleep apnea (OSA). METHODS: Consecutive patients with newly diagnosed OSA were screened at baseline. The final study population consisted of 516 patients. One hundred and eight patients had AF. Demographic, clinical, laboratory, and echocardiographic characteristics were carefully recorded. Logistic regression was used for the multivariate analysis of independent risk factors. RESULTS: Uric acid, triglyceride, high-density lipoprotein, C-reactive protein (CRP), left atrial diameter, interventricular septum thickness, apnea hypopnea index, and Epworth sleepiness scale were significantly higher in OSA patients with AF than in those without AF (p <0.05). Among these patients, multiple logistic analyses indicated the independent risk factors for AF occurrence in the OSA subjects included serum uric acid level, left atrial diameter, percentage of time with SaO2 <90%, CRP. The diagnosis analysis showed that higher uric acid, CRP, left atrial diameter and percentage of time with SaO2 <90% had a significant ability to reflect the presence of AF occurrence. CONCLUSIONS: The novel finding of this study is that the occurrence of AF in OSA patients is strongly related to serum uric acid level, left atrial diameter, percentage of time with SaO2 <90% and CRP level. These results may be helpful for monitoring AF occurrence in OSA patients.

Risk factors and mortality of patients with nosocomial carbapenem-resistant Acinetobacter baumannii pneumonia.

BACKGROUND: Acinetobacter baumannii is characterized by strictly aerobic, gram-negative, nonmotile, nonlactose-fermenting, oxidase-negative, catalase-positive coccobacilli, and the combination of its environmental resilience and its rapid development of resistance to multiple classes of antimicrobials renders it a successful nosocomial pathogen. OBJECTIVES: The aim of this study was to identify specific risk factors and outcome of nosocomial pneumonia because of carbapenem-resistant Acinetobacter baumannii (CRAB). METHODS: The retrospective study, set in a 1,500-bed referral and tertiary care hospital, was conducted to analyze the clinical and microbiologic data of patients with nosocomial pneumonia because of Acinetobacter baumannii (A baumannii) from January 2006 to December 2011. Comparisons were made between patients with CRAB pneumonia and patients with carbapenem-susceptible A baumannii (CSAB) pneumonia. Only the first isolation of A baumannii was considered. RESULTS: A total of 145 patients with CSAB pneumonia and 97 patients with CRAB pneumonia was included. Among these patients, the independent risk factors for acquiring CRAB pneumonia were Acute Physiology and Chronic Health Evaluation II (APACHE II) score (>20) at admission, systemic illnesses (chronic respiratory disease and cerebrovascular accident), presence of excess noninvasive or invasive devices (mechanical ventilation), and ever used antibiotics within 28 days (carbapenem and cefepime). The patients with CRAB pneumonia had higher mortality rate than CSAB pneumonia. Multivariate analysis showed that, among patients with A baumannii pneumonia, APACHE II score (>20) at pneumonia onset, infections with other microorganisms, and inappropriate therapy were independently associated with 28-day mortality. CONCLUSION: Patients with CRAB pneumonia have a higher mortality rate than those with CSAB pneumonia. The nosocomial occurrence of CRAB pneumonia is strongly related to systemic illnesses, APACHE II score, mechanical ventilation, and ever used antibiotics within 28 days.

Citric acid reduces the decline in P300 amplitude induced by acute alcohol consumption in healthy adults.

Event-related potential (ERP) is a reliable neuroelectric measure of brain activity that helps to confirm the assessment of mental status and cognitive impairment. Many studies have reported that alcoholics show a significantly lower ERP P300 amplitude than the norm. In the present study, ERP P300 waves were measured to evaluate the effect of citric acid on cognitive function during excessive alcohol consumption in healthy adults. Five volunteers were selected through clinical interview, physical examination, and psychiatric assessment for participation in this study. In a double-blind placebo-controlled before-after design, each subject was treated with 5 ml/kg body weight alcohol, 5 ml/kg body weight alcohol and 1 mg citric acid, or a placebo on three separate occasions, one week apart. ERP P300, blood biochemical indicators, blood alcohol concentrations (BACs) and acetaldehyde concentrations were assessed. Repeated measure analysis of variance (ANOVA) with a within-subjects factor was used to evaluate differences in blood biochemical indicators, BACs, blood acetaldehyde concentrations, and ERP P300 in the three sessions of assessments. Several blood biochemical indicators showed significant differences between treatments, including the levels of cholinesterase (CHE), total bile acid (TBA), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and glycylproline dipeptidyl aminopeptidase (GPDA). BACs after consumption of alcohol alone or citric acid with alcohol were significantly higher compared to those after placebo treatment (P<0.05). There were no significant differences in blood acetaldehyde concentrations between the treatments. The P300 amplitudes on the frontal (Fz), central (Cz), and parietal (Pz) regions of the scalp after consumption of alcohol were significantly lower than those after consumption of the placebo or citric acid with alcohol (P<0.05), while there were no significant differences between the latter two treatments. The results of this study suggest that citric acid could reduce the decline in ERP P300 amplitude and cognitive ability induced by acute alcohol consumption. It may also affect some blood biochemical indicators, but the specific mechanisms need further research.