ABSTRACT
Cigarette smoke has been considered a major contributor to the pathogenesis of chronic obstructive pulmonary disease (COPD). In COPD patients, the airway smooth muscle layer has been observed to be markedly thickened and the proliferation of airway smooth muscle cells (ASMCs) was therefore used by the present study as a model to assess the impact of cigarette smoke extract (CSE). ASMCs were exposed to various concentrations of CSE and the proliferation of the cells was analyzed by an MTT assay. Furthermore, the expression levels of calreticulin and CCAAT/enhancer-binding protein alpha (C/EBP-α) in CSE-stimulated ASMCs were determined by polymerase chain reaction and western blot analyses. In addition, the effects of RNA interference (RNAi) to knockdown calreticulin and/or C/EBP-α on ASMC proliferation were studied. CSE was found to promote the proliferation of ASMCs, which was associated with increased expression of calreticulin and decreased expression of C/EBP-α. Knockdown of calreticulin resulted in the upregulation of C/EBP-α and inhibition of cell proliferation, while simultaneous knockdown of C/EBP-α promoted cell proliferation. The present study revealed that CSE promoted the proliferation of ASMCs, which was mediated by inhibition of C/EBP-α. These findings shed new light on airway remodeling in COPD and may provide novel approaches for therapies.
ABSTRACT
As a new anti-anginal agent, ranolazinehas been shown to play a cardioprotective role in regulating myocardial ischemic injury. Given that plasma norepinephrine (NE) and brain natriuretic peptide (BNP, also termed B-type natriuretic peptide-45 in rats) are considered neuron-hormones to indicate heart failure progression. This study aims to examine effects of ranolazine on plasma NE and BNP-45 of rats with chronic ischemic heart failure (CHF). CHF was induced by myocardial infarction following ligation of a left anterior descending artery in adult Sprague-Dawley rats. We hypothesized that ranolazine attenuates the elevated levels of NE and BNP-45 observed in CHF rats thereby leading to improvement of the left ventricular function. Results showed that levels of plasma NE and BNP-45 were increased in CHF rats 6-8 weeks after ligation of the coronary artery. Our data demonstrate for the first time that ranolazine significantly attenuated the augmented NE and BNP-45 induced by CHF (P<0.05 vs. saline control). In addition, a liner relation was observed between NE/BNP-45levels and left ventricular fractional shortening as indication of left ventricular function (r=0.91 and P<0.01 for NE; and r=0.93 and P<0.01 for BNP-45) after administration of ranolazine. In conclusion, CHF increases the expression of NE and BNP-45 in peripheral circulation and these changes are related to the left ventricular function. Ranolazine improves the left ventricular function likely by decreasing heightened NE and BNP-45 induced by CHF. Therefore, our data indicate the role played by ranolazine in improving cardiac function in rats with CHF.
ABSTRACT
PURPOSE: This study examined the efficacy and safety of using nintedanib as single-regimen in 2(nd)-line chemotherapy for Chinese patients with advanced (beyond stage IIIB) non-small-cell lung cancer (NSCLC). METHODS: Chinese patients were those with stage IIIB or IV NSCLC and had unsuccessful 1(st)-line platinum based chemotherapy. Patients received two oral intakes of 200 mg nintedanib everyday from day 1 to day 21, on every 4-week cycle. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and disease control rate. RESULTS: There were 62 eligible patients enrolled in the study. Half of the patients were male (n = 31, 50.0%). The median age was 64.2 years with youngest age of 33 years and oldest age of 83 years. Median PFS was 3.9 months (95% CI, 2.7-6.4 months). Median OS was 6.7 months (95% CI, 4.8-10.1 months). No patients (0.0%) had complete response. Thirty-one patients (50.0%) had stable disease and 23 patients (37.1%) had partial response. The most common severe adverse events (AEs), graded as 3 or 4, were heart failure (n = 12, 19.4%), hypertension (n = 7, 11.8%) and diarrhea (n = 6, 9.8%). CONCLUSION: NSCLC Patients in 2(nd)-line chemotherapy reached similar PFS, as compared with other FDA-approved second-line regimens. Also, the toxicity of nintedanib was well tolerated. Thus, nintedanib may be used as a standard regimen for 2(nd)-line chemotherapy for patients with advanced NSCLC.
ABSTRACT
OBJECTIVE: To investigate the incidence of ischemic stroke and associated risk factors in patients with nonvalvular atrial fibrillation (NVAF) in Haikou. METHODS: Area through follow-up approach and evaluate the effect of antithrombotic therapy as well as the current status of treatment in patients with NVAF. Clinical data of 329 NVAF patients admitted to Hainan hospital from January 1999 to December 2001 were collected. The patients were followed up to identify the incidence of ischemic stroke and associated risk factors. RESULTS: The main cause of NVAF was coronary heart diseases, which happened in 207 cases (62.9%). The logistic regression analysis revealed that age, type of atrial fibrillation, and hypertension were significantly associated with the occurrence of ischemic stroke in patients with NVAF (P=0.0001, 0.006, and 0.04 respectively). Antithrombotic treatments significantly decreased the incidence of stroke (P<0.05). But Warfarin was not applied consistently in Haikou. CONCLUSIONS: Age, type of atrial fibrillation and hypertension are independent risk factors for ischemic stroke in patients with NVAF. Uninterrupted use of aspirin can be beneficial to patients with NVAF.
