[Comparison study on the differential expression of miRNAs in rat pulmonary fibrosis induced by nanosized SiO(2) and microsized SiO(2)].

Objective: To explore the correlation between expression level of miRNAs and pulmonary fibrosis on the basis of comparison the differential expression of miRNAs in rat pulmonary fibrosis induced by nano SiO(2) and micron SiO(2). Methods: Thirty-six healthy male SD rats weighting 180-220 g were randomly divided into 3 groups. They were instilled intratracheally with 1 ml suspension of saline, 25 mg/ml nanosized SiO(2) and microsized SiO(2) particles and sacrificed at 60 d and 90 d postexposure from each group with six rats. The change of pathological morphology and ultrastructure of lung were observed by optical and transmission electron microscopy. The differentially expressed microRNAs in lung tissue of the rats after instilled intrachcally nanosized SiO(2) and microsized SiO(2) particles at 60 d and 90 d were determined by Illumina HiSeq 2 000 sequencing technique. Target prediction for miRNAs was conducted by databases of Target-scan. Function-significant enrichment analysis and signal pathway analysis for predicted target genes were respectively conducted by the GO and the KEGG, then target genes related to pulmonary fibrosis were screened out. Results: Light microscope examination showed that wide bronchi, vessels, interlobular septa and slight fibrous connective tissue proliferation at 60 d and 90 d postexposure in 25 mg/ml nanosized SiO(2) group. A few fused nodules at 30 d postexposure, a lot of fused nodules at 60 d postexposure, fibrous cell nodules and compensatory emphysema around alveolar at 90 d postexposure in 25 mg/mL microsized SiO(2) group were observed. Electron microscopy demonstrated swelling and vacuolar degeneration of osmiophilic lamellar bodies in type Ⅱ alveolar epithelial cells, collagen fiber and elastic fiber hyperplasia in pulmonary interstitial at 60 d, 90 d postexposure in 25 mg/ml nanosized SiO(2) group. Increased and vacuoloid changed osmiophilic lamellar bodies in type Ⅱ alveolar epithelial cells, collagen fiber and elastic fiber hyperplasia in the interstitial at 60 d, 90 d postexposure in 25 mg/ml microsized SiO(2) group were observed. Comparing to saline control group, the number of miRNA up-regulated expression was 50, 70, and down-regulated expression was 22 and 24 at 60 d, 90 d postexposure in 25 mg/ml nanosized SiO(2) group respectively. There were 91,70 miRNAs up-regulated expression and 34,78 miRNAs down-regulated expression at 60 d, 90 d postexposure in 25 mg/ml microscale SiO(2) group. The common miRNA of differential up-regulated expression are miRNA-18a and miRNA-702-3p, down-regulated expression are miRNA-541, miRNA-127 and miRNA-379 both in nanosized SiO(2) and microscale SiO(2) group. The target genes related to pulmonary fibrosis were CTGF, IGF, BMP7, FGF7, TGF-ß RIII, IGF1R and TGF-ß1 respectively. Their biologic functions are to regulate signal pathway of TGF-ß, MAPK and Wnt, and activation of fibroblast. Conclusion: These findings suggested that same dose of nanosized SiO(2) particles could cause mainly characterized by pulmonary interstitial fibrosis differing from silicotic nodule caused by microsized SiO(2). miRNA-18a, miRNA-702-3p, miRNA-541, miRNA-127 and miRNA-379 may play a role in the process of pulmonary fibrosis in nanosized SiO(2) and microscale SiO(2) by regulating its target genes.

Cytotoxicity and DNA damage in mouse macrophages exposed to silica nanoparticles.

Silica (SiO2) nanoparticles are being progressively applied in various applications, including cosmetics, food technology, and medical diagnostics. Although crystalline SiO2 is a known carcinogen, the carcinogenicity of SiO2 nanoparticles remains unclear. Here, we assessed the cytotoxic effects and DNA injury induced by exposure to various dosages of SiO2 nanoparticles at 0-2400 mg/mL (0-3200 mg/mL microscale SiO2 as positive control) for 24 h using RAW264.7 cells, followed by methyl tetrazolium (MTT) assay. Cells were also treated by 31.25, 125, and 500 mg/mL SiO2 nanoparticles (500 mg/mL microscale SiO2 as positive control) for 24 h and examined by single cell gel electrophoresis assay (SCEG) and flow cytometry. Outstanding dose-related decline in cell viability was observed with enhancing dosages of SiO2 nanoparticles by MTT assay. The inhibitory concentration 50% of SiO2 nanoparticles and microscale SiO2 was 16690 and 5080 mg/mL, respectively. The comet rate (comet%), length of tail, the percentage in DNA tail (TDNA%) and olive tail moment (OTM) induced by SiO2 nanoparticles were significantly increased in comparison with control and microscale SiO2 at 500 mg/mL. 500 mg/mL SiO2 nanoparticles and microscale SiO2 caused a significant increase in apoptosis rate, decreased proliferation index and increased cell proportions in G0/G1 phases by contrast to the negative control (P < 0.05). This indicates that SiO2 nanoparticles are more cytotoxic than microscale SiO2 particles; they induce DNA injury, increase apoptosis, and decrease the proliferation index in RAW264.7 cells. DNA injury and apoptosis may be involved in reducing cell proliferation.

Correlation between dynamic recrystallization and formation of rare earth texture in a Mg-Zn-Gd magnesium alloy during extrusion.

The trace addition of rare earth (RE) elements in Mg alloys can modify the extrusion texture, leading to the formation of RE texture and thus improved formability. The interrupted extrusion experiment as well as electron back-scatter diffraction (EBSD) characterization was conducted in Mg-1.5Zn-0.5Gd (wt.%) alloy to unveil the dominant dynamic recrystallization (DRX) mechanism and its correlation with the formation of RE texture during extrusion. The results indicate that continuous DRX (CDRX) dominated the microstructural development. Fresh DRXed grains with 30° [0001] grain boundaries preferentially nucleated in unDRXed grains with [10[Formula: see text]0] basal fiber orientation via CDRX, showing preferred selection of [2[Formula: see text][Formula: see text]0] basal fiber orientation rather than RE texture orientation. Consequently, CDRX contributed to the weakening of [10[Formula: see text]0] basal fiber texture and had a more significant effect on the formation of [2[Formula: see text][Formula: see text]0] basal fiber component than that of RE texture component. Besides, the preferred growth of recrystallized grains with RE texture orientation was confirmed to occur during static annealing after extrusion, which is inferred as the key reason for the formation of RE texture in dilute Mg-RE alloys.

Size-manipulable synthesis of single-crystalline BaMnO3 and BaTi1/2Mn1/2O3 nanorods/nanowires.

We report a size-manipulable synthesis of single-crystalline nanorods/nanowires of barium manganite (BaMnO(3)) and barium titanium manganite (BaTi(1/2)Mn(1/2)O(3)) by using the composite-hydroxide-mediated approach. The synthesis cleanly yields nanorods with a hexagonal perovskite structure. Typical nanorods have widths ranging between 50 and 100 nm, and the lengths can be easily controlled by time and temperature or by adding a small amount of water during the synthesis process. Resistance measurement shows that a phase transition happened at 58 K on BaMnO(3). The photoluminescence spectrum of BaTi(1/2)Mn(1/2)O(3) presents two emission peaks at wavelengths of 465 and 593 nm, corresponding to blue and green fluorescence. The ability to synthesize nanorod manganites of a desired length should enable detailed investigations of the size-dependent evolution of magnetism, magnetoresistance, nanoscale phase separation, and realization of a nanodevice of magnetic sensors.

Synthesis and electrical transport of single-crystal NH4V3O8 nanobelts.

Monoclinic NH(4)V(3)O(8) single-crystalline nanobelts with widths of 80-180 nm, thicknesses of 50-100 nm, and lengths up to tens of micrometers have been synthesized at large scale in an ammonium metavanadate solution by a templates/catalysts-free route. Such nanobelts grow along the direction of [010]. The individual NH(4)V(3)O(8) nanobelt exhibits nonlinear, symmetric current/voltage (I/V) characteristics, with a conductivity of 0.1-1 S/cm at room temperature and a dielectric constant of approximately 130. The dominant conduction mechanism is based on small polaron hopping due to ohmic mechanism at low electric field below 249 V/cm due to Schottky emission at medium electric field between 249 and 600 V/cm and due to the Poole-Frenkel emission mechanism at high field above 600 V/cm.

Interlaboratory comparison of analytical methods for residual ethylene oxide in medical device materials.

An interlaboratory comparison of four gas chromatographic test procedures for the quantification of ethylene oxide in an acrylic polymer was conducted by thirteen laboratories. The procedures included extractions with water, acetone, and N,N-dimethylformamide, and headspace gas analysis. The results of this study, using only the data from the labs that did not deviate from the procedure, showed that the average estimated total coefficient of variation ranged from 8 to 22% for the four different methods. Each of the methods is suitable for use as a reference test method for determining residual ethylene oxide in polymeric materials.

Equivalence in test assay method comparisons for the repeated-measure, matched-pair design in medical device studies: statistical considerations.

In medical device clinical studies, including therapeutic device and in vitro test assay method studies, the investigator is frequently interested in demonstrating the equivalence of clinical response, generally in continuous measurements, between a standard assay method and a new assay method over various occasions or times. The new assay method may be less invasive or more convenient or cheaper to use than the standard assay method. In this paper, several statistical approaches are discussed, including various repeated-measure regression models, the simultaneous 95% confidence interval for paired mean differences derived from Hotelling's multivariate T2 analysis for repeated-measure, paired data, repeatability and reproducibility studies, and concordance correlation coefficient.

Statistical considerations for survival analysis from medical device clinical studies.

Appropriate statistical methods are presented to estimate the 95% lower confidence limit of true event-free probability, with heavy censoring in the small sample size situation, and to compare crude probability, linearized rate, and life-table probability. The problem of survival experience extrapolation beyond the last observed follow-up is also discussed.

Application of CUSUM technique and beta-binomial model in monitoring adverse drug reactions.

The cumulative sum (CUSUM) technique is applied to monitor spontaneous reports of adverse drug reactions (ADRs). The beta-binomial model, as suggested by Moussa (2), was used to fit the observed proportion of upper gastrointestinal bleeding, perforation, and ulcer (UGIBPU) for drug A, a nonsteroidal anti-inflammatory drug (NSAID). ADRs reported directly by physicians and manufacturers from the third quarter of 1982 through the fourth quarter of 1985 were analyzed. The model estimates the proportion of UGIBPUs for drug A, expressed as a fraction of all UGIBPUs for NSAIDs. To illustrate the procedure, estimated mean proportion of UGIBPUs for drug A and all NSAIDs was computed for directly reported physician and manufacturer ADRs. The beta-binomial model leads to estimates of 0.096 for directly reported physician ADRs compared to 0.039 for directly reported manufacturer ADRs. The difference is statistically significant (p < 0.025) by the method of maximum likelihood applied to the beta-binomial model. Moussa also suggested the use of this model for signaling important new ADRs. For these data on NSAIDs, the CUSUM method is less likely to signal an alarm than the approaches suggested by Mandel (5) and Patwary (4).

Statistical applications for in vitro diagnostic tests and other medical device clinical trials.

Some statistical methods applied to in vitro diagnostic tests for the three primary indications (screening, diagnosis, and monitoring) are discussed. Various examples with practical statistical applications are presented, including test for k by k ordered categorical matched-pair data for screening of cervical cancer, receiver operating characteristic (ROC) curve for diagnosis or screening, and the Cox time-to-event model to estimate relative risk of first cancer progression by monitoring carcinoembryonic (CEA) levels for stage IV breast cancer patients.

Survival and projection analyses of the effect of radiation on beagle dogs.

The Cox proportional hazard model is used to identify important covariates related to survival for this beagle dog study. The Weibull and the Gompertz parametric probability models are used to fit the survival curves for 1680 beagle dogs given whole body Co-60 gamma radiation or sham irradiation and held for life-span observation. Deaths from cancer and noncancer are the primary diagnoses. Of dogs dying from cancer, female dogs showed significantly greater cancer mortality (p < 0.0001) than did males, and irradiated dogs had significantly greater cancer mortality (p = 0.022) than did the unexposed dogs, by either the Weibull or the Cox model. However, there were no sex and exposure differences in mortality for dogs dying from noncancer causes. The fitted Weibull and Gompertz models have been successful in projecting the actual mortality experience in this experiment and could be used for similar life-span experiences.

The FDA report on intraocular lenses.

Clinical studies of intraocular lenses (IOLs) as investigational devices have been regulated in the United States by the Food and Drug Administration (FDA) since February 9, 1978. As of August 1982, data have been collected on more than one million IOLs implanted. During the last 12 months of the study, 409,000 IOLs were implanted. Visual acuity of 20/40 or better at one year after surgery was present in 85% of over 45,000 cases reviewed. Increasing patient age, surgical problems, postoperative complications, and adverse reactions were factors that reduced the visual acuity. The current trend in the USA is for implantation of the posterior chamber and anterior chamber IOLs.