Clinical prognostic value of A FOXM1 related long non-coding RNA expression in gastric cancer.

OBJECTIVE: The aim of this study was to explore FOXM1-related LncRNA 1(FRLnc1) expression level in gastric cancer (GC) and demonstrate its association with the prognosis. PATIENTS AND METHODS: A total of 173 GC patients from Affiliated Hospital of Jining Medical University were enrolled in the study. GC tissue samples were quantified for FRLnc1 expression level using quantitative PCR (qPCR) method. The relevance between FRLnc1 expression and clinicopathological features was determined by x2-test. The association between FRLnc1 expression and overall survival was estimated by the Kaplan-Meier method. Multivariate and univariate analysis were performed to explore whether FRLnc1 was an independent prognostic factor for GC patients. RESULTS: We found that FRLnc1 expression was higher in GC tissues than corresponding adjacent tissues (p < 0.01). Increased FRLnc1 expression was associated with depth of tumor (p = 0.004), differentiation degree (p = 0.032), distant metastasis (p = 0.007), TNM stage (p = 0.006) and lymph node metastasis (p = 0.012). More importantly, Kaplan-Meier survival analysis demonstrated that overall patient survival for those with low FRLnc1 expression was significantly longer than those patients with high FRLnc1 expression (p < 0.001). Multivariate analysis suggested that FRLnc1 expression was an independent prognostic marker for survival in patients with GC. CONCLUSIONS: The data presented in this work firstly suggested that FRLnc1 may be a prognostic predictor in GC.

Enhanced electrical properties at boundaries including twin boundaries of polycrystalline CdTe thin-film solar cells.

The effect of grain boundaries (GBs), in particular twin boundaries (TBs), on CdTe polycrystalline thin films is studied by conductive atomic force microscopy (C-AFM), electron-beam-induced current (EBIC), scanning Kelvin probe microscopy (SKPM), electron backscatter diffraction (EBSD), and scanning transmission electron microscopy (STEM). Four types of CdTe grains with various densities of {111} Σ3 twin boundaries (TBs) are found in Cl-treated CdTe polycrystalline thin films: (1) grains having multiple {111} Σ3 TBs with a low angle to the film surface; (2) grains having multiple {111} Σ3 TBs parallel to the film surfaces; (3) small grains on a scale of not more than 500 nm, composed of Cd, Cl, Te, and O; and (4) CdTe grains with not more than two {111} Σ3 TBs. Grain boundaries (including TBs) exhibit enhanced current transport phenomena. However, the {111} Σ3 TB is much more beneficial to micro-current transport. The enhanced current transport can be explained by the lower electron potential at GBs (including TBs) than the grain interiors (GIs). Our results open new opportunities for enhancing solar cell performances by controlling the grain boundaries, and in particular TBs.

Early diagnostic and prognostic utility of high-sensitive troponin assays in acute myocardial infarction: a meta-analysis.

BACKGROUND/AIM: To determine the diagnostic and prognostic utility of high-sensitive troponin assays in the very early phase of acute myocardial infarction (AMI) (less than 3 h since symptoms onset) by performing a meta-analysis of prospective studies. METHODS: Relevant studies were identified by searches of MEDLINE and Elsevier Sciencedirect until 31 January 2014 and by reviewing the reference lists from retrieved articles. Prospective studies that reported diagnostic utility in AMI using both high-sensitive troponin assays and conventional cardiac troponin, and reported the estimates of hazard ratio (HR) with 95% confidence intervals (CI) for prognostic utility were included. Data were extracted independently by two authors and summary estimates of association were obtained using a random effects model. RESULTS: Of the seven studies included, four studies reported the diagnostic utility of high-sensitive troponin assays (2863 patients) and three reported the prognostic utility in AMI (2329 patients). Within 12 h of symptoms onset, the pooled sensitivity and specificity of high-sensitive troponin assays were 0.89 (95% CI 0.85-0.91) and 0.89 (95% CI 0.85-0.92), respectively, and within 3 h, the pooled sensitivity and specificity of high-sensitive troponin assays were 0.79 (95% CI 0.71-0.85) and 0.92 (95% CI 0.88-0.96) respectively. Compared with conventional cardiac troponin assays, the high-sensitive troponin assays had higher sensitivity (0.89 vs 0.72) but lower specificity (0.89 vs 0.95) in diagnosing AMI within 12 h of symptoms onset. Within 3 h, the sensitivity of high-sensitive troponin assays was still higher (0.79 vs 0.59), but the specificity was almost the same (0.92 vs 0.95) as that of conventional troponin assays. The elevated high-sensitive troponin assays had an overall pooled HR of 2.66 (95% CI 1.31-5.44) and 2.14 (95% CI 1.15-3.98) for the end-points of death and non-fatal AMI respectively. CONCLUSIONS: These findings provide quantitative data supporting high-sensitive troponin assays having early diagnostic and prognostic utility in AMI.

Resveratrol protects against arsenic trioxide-induced cardiotoxicity in vitro and in vivo.

BACKGROUND AND PURPOSE: The clinical use of arsenic trioxide (As(2)O(3)), a potent antineoplastic agent, is limited by its severe cardiotoxic effects. QT interval prolongation and apoptosis have been implicated in the cardiotoxicity of As(2)O(3). The present study was designed to evaluate the effects of resveratrol on As(2)O(3)-induced apoptosis and cardiac injury. EXPERIMENTAL APPROACH: In a mouse model of As(2)O(3)-induced cardiomyopathy in vivo, QT intervals and plasma enzyme activities were measured; cardiac tissues were examined histologically and apoptosis assessed. In H9c2 cardiomyocyte cells, viability, apoptosis, generation of reactive oxygen species (ROS) and cellular calcium levels were measured. KEY RESULTS: In the mouse model, resveratrol reduced As(2)O(3)-induced QT interval prolongation and cardiomyocyte injury (apoptosis, myofibrillar loss and vacuolization). In addition, increased lactate dehydrogenase activity and decreased activities of glutathione peroxidase, catalase and superoxide dismutase were observed in the plasma of As(2)O(3)-treated mice; these changes were prevented by pretreatment with resveratrol. In As(2)O(3)-treated H9c2 cardiomyocytes, resveratrol significantly increased cardiomyocyte viability and attenuated cell apoptosis as measured by acridine orange/ethidium bromide staining, TdT-mediated dUTP nick end labelling assay and caspase-3 activity. As(2)O(3)-induced generation of ROS and intracellular calcium mobilization in H9c2 cells was also suppressed by pretreatment with resveratrol. CONCLUSIONS AND IMPLICATIONS: Our results showed that resveratrol significantly attenuated As(2)O(3)-induced QT prolongation, structural abnormalities and oxidative damage in the heart. In H9c2 cardiomyocytes, resveratrol also decreased apoptosis, production of ROS and intracellular calcium mobilization induced by treatment with As(2)O(3). These observations suggested that resveratrol has the potential to protect against cardiotoxicity in As(2)O(3)-exposed patients.

[Determination of amlodipine in human plasma by liquid chromatography-tandem mass spectrometry].

AIM: To develop a sensitive and specific LC/MS/MS method for determination of amlodipine in human plasma. METHODS: Amlodipine and internal standard 4'-hydroxypropafenone were extracted from plasma using liquid-liquid extraction, then separated on a Zorbax C8 column. The mobile phase consisted of acetonitrile-water-formic acid (75:35:1), at a flow-rate of 0.4 mL.min-1. A Finnigan TSQ tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor-->product ion combinations of m/z 409-->238 and m/z 358-->116 was used to quantify amlodipine and internal standard, respectively. RESULTS: The linear calibration curves were obtained in the concentration range of 0.4-16.0 ng.mL-1. The limit of quantification was 0.4 ng.mL-1. Each plasma sample was chromatographed within 3.7 min. The method was successfully used in several pharmacokinetic studies for amlodipine. More than 1,500 plasma samples were assayed within two weeks. CONCLUSION: The method is proved to be suitable for clinical investigation of amlodipine pharmacokinetics, which offers advantages of specificity, speed, and greater sensitivity over the previously reported methods.

[Enantioselective pharmacokinetics of benproperine in healthy volunteers].

AIM: To investigate the enantioselective pharmacokinetic process of benproperine in healthy volunteers. METHODS: An enantiospecific HPLC method was developed and used to determine the plasma concentrations of each enantiomer. Six healthy Chinese male volunteers received an oral dose of 60 mg (+/-)-benproperine. The ratios of the enantiomers in plasma samples were measured on a chiral AGP column. The plasma concentration of each enantiomer was then calculated using the ratios of enantiomers and total concentration of the two enantiomers previously measured. RESULTS: The plasma levels of (-)-(S)-benproperine were always significantly higher than those of its antipode in six volunteers. The mean AUC0-t and Cmax values for (-)-(S)-benproperine were 2.18 and 2.12 times higher than those of (+)-(R)-benproperine. There was no significant difference between the T1/2 for both enantiomers, tested by paired t test (P > 0.05). Half an hour after administration of benproperine, the S/R ratio in plasma samples was as high as 3.8, and in 2 hours it drastically decreased to about 2.2, then kept on till 24 hours. CONCLUSION: Benproperine showed significant enantioselective pharmacokinetics in the human after an oral dose of the racemate.

[Study on hydroxylated metabolites of benproperine in human urine].

AIM: To investigate the hydroxylation process of benproperine in humans. METHODS: After an oral administration of 60 mg benproperine to ten healthy male volunteers, urine samples collected within 0-24 h were extracted by solid phase extraction and analyzed by liquid chromatography-ion trap mass spectrometry. A microbial transformation of benproperine combined with semi-preparative HPLC was used to get two reference substances of the hydroxylated metabolites, and their structures were then elucidated by NMR. Furthermore, the structures of conjugated metabolites were speculated based on their characteristics in MS fragmentation. RESULTS: Five hydroxylated metabolites of benproperine and some of their conjugates with endogenous glucuronic acid or sulfuric acid were found in urine of volunteers after the dose. The structures of two metabolites were identified as 4"-hydroxybenproperine and 4"'-hydroxybenproperine by comparison of HPLC retention times and mass spectra with those of authentics obtained from the microbial transformation. CONCLUSION: Hydroxylation of benproperine occurs preferentially at para-position of the alkoxyl group in the aromatic ring. The hydroxylated metabolites of benproperine in human urine mainly exist as their glucuronic acid or sulfuric acid conjugates.

Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease.

AIM: To evaluate the efficacy and safety of tablet huperzine-A (Hup) in patients with Alzheimer's disease. METHODS: Using multicenter, prospective, double-blind, parallel, placebo controlled and randomized method, 50 patients were administered orally 0.2 mg (4 tablets) Hup and 53 patients were given po 4 tablets of placebo bid for 8 wk. All patients were evaluated with Wechsler memory scale, Hasegawa dementia scale, mini-mental state examination scale, activity of daily living scale, treatment emergency symptom scale, and measured with BP, HR, ECG, EEG, ALT, AKP, BUN, Cr, Hb, WBC, and urine routine. RESULTS: About 58% (29/50) of patients treated with Hup showed improvements in their memory (P < 0.01), cognitive (P < 0.01), and behavioral (P < 0.01 functions. The efficacy of Hup was better than placebo (36%, 19/53) (P < 0.05). No severe side effect was found. CONCLUSION: Hup is a promising drug for symptomatic treatment of Alzheimer's disease.

Frequency- and voltage-dependent inhibition of delayed outward potassium current by flecainide in isolated atrial cell of guinea pig heart.

Effects of flecainide (Fle) on membrane currents were studied using an isolated single atrial cell from guinea pig hearts. The tight-seal cell clamp technique was used. In the current clamp condition, Fle prolonged significantly the atrial action potential (APD) with frequency dependence. Delayed outward K+ current and outward tail current were specifically inhibited by Fle in a frequency- and concentration-dependent fashion. Fle inhibited Ik more strongly as the membrane potential became more positive from +10 mV to +60 mV. The value of Ik was attenuated to 973 pA from 1105 pA of control and the value of tail current was reduced to 113 pA from 288 pA of control at 60 mV. The drug did not affect the holding current. The effects of Fle on the action potential and transmembrane ionic currents strongly suggested that the main mechanism of action of this agent was to inhibit the voltage-dependent potassium current. In the voltage clamp condition, Fle affected neither the conventional L type Ca2+ current nor the Ik1 current significantly. Our research proved that Fle was not completely consistent with the class Ic agents, because Fle could markedly increase the APD in the experiment.

Electron microscopic and immunohistochemical findings in a case of olfactory neuroblastoma.

A case of olfactory neuroblastoma is reported. Light microscopic examination showed various arrangements of poorly differentiated tumour cells forming either uniform sheets or convoluted cords of multiple cell layers orientated toward a richly vascular stroma. Electron microscopic examination showed the presence of abundant cytoplasmic filaments and processes, and dense core endocrine vesicles ranging from 100-160 nm in diameter in both the perinuclear region and tumour cell processes. Immunohistochemical staining was positive in most of the tumour cells for neuron specific enolase, and in a few cells for S-100 protein, vimentin, and serotonin, but staining for desmin and keratin produced no reaction.

[Pulmonary tumors induced by diethylnitrosamine in mice].

High incidence pulmonary tumors induced in the mice by diethylnitrosamine were studied as to their morphology and pathogenesis. Under the light microscope, the induced pulmonary adenomas may be divided into three types: solid, papillary and mixed adenomas. Ultrastructural study showed that some adenomas were derived from the Type II pneumonocytes, some from Clara cells and more than a half of the adenomas possessed the common features of both. The author terms the latter bi-phase differentiated adenoma, which is characterised by the presence of a lot of the lamellar bodies and electron dense granules in the cytoplasm as well as transitional from between the two. The bi-phase differentiated adenoma is firstly considered as originating form the Clara cells, secondly from the anaplastic cells in the bronchiolar epithelium. Ultrastructural study indicates that the lamellar bodies are probably derived from the multivesicular bodies and/or electron dense granules. The malignant change of the adenomas goes into malignancy resembling the bi-phase differentiated adenomas in the ultrastructure. The lung carcinomas of the mice are similar to those which occur in the human being.