The clinical value of hepatic extracellular volume fraction using routine multiphasic contrast-enhanced liver CT for staging liver fibrosis.

AIM: To investigate the value of hepatic extracellular volume fractions (fECVs) measured using routine liver computed tomography (CT) evaluating liver fibrosis (LF). MATERIALS AND METHODS: A total of 60 patients (male:female ratio, 39:21; mean age, 42.4 years) histologically diagnosed with LF underwent routine liver CT. Absolute enhancement (in Hounsfield units) of the liver parenchyma (Eliver) and aorta (Eaorta) 3 minutes after contrast medium administration was calculated using precontrast and equilibrium phase scans. The fECV was calculated using the following equation: fECV (%)=Eliver× (100 - haematocrit [%])/Eaorta. Correlation between fECV and LF stage was evaluated using the Spearman correlation coefficient. The fECVs were compared between each stage of LF. The diagnostic performance of fECV was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: The difference among the groups was statistically significant (p<0.05). The fECVs were significantly different (p<0.05) between F0 versus F4, F1 versus F4, and F2 versus F4. The fECVs showed a significant correlation with pathological LF staging (r=0.468, p=0.001). The sensitivity and specificity were 0.76 and 0.68 for severe LF (F≥3); and 0.89 and 0.63 for cirrhosis (F=4). The areas under the ROC curve (AUCs) for F≥3 and F=4 were 0.757 and 0.775, respectively. CONCLUSIONS: Calculation of fECV during routine contrast-enhanced liver CT may provide a non-invasive means of assessing LF.

Phylogenetic relationships of Pseudohynobius (Urodela, Hynobiidae) inferred from DNA barcoding analysis.

As a proven tool, DNA barcoding can identify species rapidly and unambiguously. In this study, we used mtDNA cyt b, COI, and 16s rRNA sequences of six species of Pseudohynobius, Protohynobius puxiongensis, Liua shihi, Ranodon sibiricus, and Pachyhynobius shangchengensis, to reconstruct the phylogenetic relationships using Bayesian inference and maximum likelihood methods. Approximate lineage divergence times were also estimated, the divergence between them was calculated to have taken place mainly in Miocene. Our results showed that: 1) Ps. guizhouensis is an independent and valid species that is a sister species to Ps. kuankuoshuiensis; 2) five Pseudohynobius species formed a monophyletic group; 3) Ps. tsinpaensis is different from L. shihi, and should be classified as belonging to the Liua genus; and 4) Pr. puxiongensis is the sister lineage to all Pseudohynobius species, and should therefore be named Pseudohynobius puxiongensis.

Identification of conservation units of the hynobiid salamander Pachyhynobius shangchengensis.

The evolutionary significant units (ESUs) of the salamander Pachyhynobius shangchengensis (Hynobiidae) in the Dabieshan mountains, southeastern China, were identified based on mitochondrial DNA data. We used methods for detecting cryptic species, such as the minimum spanning tree, the automatic barcode gap discovery, and the generalized mixed Yule-coalescent model; geographical partitioning was also used to identify the ESUs. A total of four ESUs were identified.

Bursts of Terahertz Radiation from Large-Scale Plasmas Irradiated by Relativistic Picosecond Laser Pulses.

Powerful terahertz (THz) radiation is observed from large-scale underdense preplasmas in front of a solid target irradiated obliquely with picosecond relativistic intense laser pulses. The radiation covers an extremely broad spectrum with about 70% of its energy located in the high frequency regime over 10 THz. The pulse energy of the radiation is found to be above 100 µJ per steradian in the laser specular direction at an optimal preplasma scale length around 40-50 µm. Particle-in-cell simulations indicate that the radiation is mainly produced by linear mode conversion from electron plasma waves, which are excited successively via stimulated Raman scattering instability and self-modulated laser wakefields during the laser propagation in the preplasma. This radiation can be used not only as a powerful source for applications, but also as a unique diagnostic of parametric instabilities of laser propagation in plasmas.

Population genetic structure and historical demography of the ground beetle Chlaenius costiger in the Tsinling-Dabashan Mountains of central China.

Population genetic structure and demographic history of the ground beetle Chlaenius costiger (Coleoptera: Carabidae) in the Tsinling-Dabashan Mountains of central China were estimated using mitochondrial DNA sequences (Cox1-tRNALeu-Cox2) of 144 individuals from 16 local populations. The high haplotype diversity was accompanied by low nucleotide diversity. Phylogenetic analysis (Bayesian inference) of the 43 haplotypes revealed no phylogeographic structure. Analysis of molecular variance suggested that most of the variation was attributed to within population variation (79.26%). Mantel test results showed a significant correlation between the genetic distance and geographical distance of the populations with a correlation coefficient equal to 0.216964 (P = 0.0471 < 0.05), indicating the presence of isolation by distance. Spatial AMOVA and PERMUT analyses showed no phylogeographic structure. Gene flow calculated through the number of migrants was high between many pairs of populations. The results of a neutrality test, mismatch distribution analyses, and Bayesian skyline plot analysis together showed a demographic expansion. The estimated expansion time of the whole sampled population was 0.125 million years. The complex topography in the Tsinling-Dabashan Mountains area led to the high level of genetic diversity, and migratory flight resulted in the high level of gene flow, leading to the lack of a phylogeographic structure.

Genetic diversity and historical demography of the narrow-range endemic Alpine toad, Scutiger liupanensis, in the Liupan Mountains of central China.

The genetic diversity and historical demography of the narrow-range endemic Alpine toad, Scutiger liupanensis, in the Liupanshan National Forest Park of central China were estimated using cytochrome b and cytochrome c oxidase subunit I (COI) from 85 individuals from five local populations. Both the haplotype diversity (Hd) and the nucleotide diversity (Pi) were very high. Phylogenetic analysis of the 63 haplotypes revealed two major clades, and an analysis of molecular variance attributed most of the variation to within populations. Mantel tests did not reveal an isolation by distance pattern of genetic divergence between populations, and SAMOVA showed no phylogeographic structure. The results of neutrality tests, mismatch distribution analyses, and allelic frequency spectra suggest that a sudden demographic expansion occurred, and that high genetic variation is beneficial to the survival and development of this species.

Diagnostic value of magnetic resonance elastography for detecting and staging of hepatic fibrosis: a meta-analysis.

AIM: A meta-analysis was performed to evaluate the diagnostic value of magnetic resonance elastography (MRE) in detecting and staging hepatic fibrosis. MATERIALS AND METHODS: A systematic search of PubMed, EMBASE, Web of Science, and Cochrane Library Database up to October 2013 was undertaken to find studies on the evaluation of MRE in patients suspected of hepatic fibrosis. Data from the articles were analysed using Meta-disc 1.4 and Stata 12.0 software. The sensitivity, specificity, and area under the summary receiver operating characteristic (ROC) curve (AUROC) were pooled for all stages of hepatic fibrosis (F ≥ 1, F ≥ 2, F ≥ 3, and F = 4). Publication bias was assessed through the Deeks' funnel plot asymmetry tests. RESULTS: Thirteen studies comprising 989 patients met the inclusion criteria. The pooled sensitivity and specificity for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4 were 0.87 (95% CI = 0.84-0.89) and 0.92 (95% CI = 0.87-0.96), 0.87 (95% CI = 0.84-0.90) and 0.92 (95% CI = 0.89-0.95), 0.88 (95% CI = 0.85-0.91) and 0.91 (95% CI = 0.88-0.93), 0.91 (95% CI = 0.87-0.94) and 0.92 (95% CI = 0.89-0.94), respectively. The pooled AUROC for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4 were 0.9502, 0.9663, 0.9644, and 0.9768, respectively. The non-significant slope of Deeks' funnel plot asymmetry tests indicated that no significant bias was found. CONCLUSIONS: MRE has a high diagnostic accuracy for the quantitative detection and staging of hepatic fibrosis.

Note: A new angle-resolved proton energy spectrometer.

In typical laser-driven proton acceleration experiments Thomson parabola proton spectrometers are used to measure the proton spectra with very small acceptance angle in specific directions. Stacks composed of CR-39 nuclear track detectors, imaging plates, or radiochromic films are used to measure the angular distributions of the proton beams, respectively. In this paper, a new proton spectrometer, which can measure the spectra and angular distributions simultaneously, has been designed. Proton acceleration experiments performed on the Xtreme light III laser system demonstrates that the spectrometer can give angle-resolved spectra with a large acceptance angle. This will be conductive to revealing the acceleration mechanisms, optimization, and applications of laser-driven proton beams.

Prolonged cell cycle delay in radioresistant human cell lines transfected with activated ras oncogene and/or simian virus 40 T-antigen.

Normal human diploid cell strains were transfected with an activated Ha-ras oncogene (EJ ras) and/or SV40 T-antigen. Clones expressing SV40 T-antigen alone or in combination with ras protein p21 were significantly radioresistant (D0 = 1.68-2.73 Gy) compared with their parent cells or clones transfected with the neo gene only (D0 = 1.20-1.35 Gy). This radioresistant phenotype persisted in postcrisis, immortalized cell lines. Cell cycle perturbations after X irradiations were studied in four immortalized, radioresistant cell lines transfected with EJ-ras plus SV40 T or SV40 T alone as well as in two nontransfected parental cell strains. Exponentially growing cells were exposed to various doses of X radiation and the distributions within the cell cycle were determined by flow cytometry. The time of onset and duration of division delay were also measured by cell counting. All cells underwent a dose-dependent G2 arrest; the duration of this division delay was proportional to radiation dose. The radioresistant cell lines had a longer arrest in G2 phase of the cell cycle compared to that of the parental cell strains. These data suggest that a prolonged cell cycle delay may be one of the factors involved in the radioresistance acquired by transfection of human diploid cells with SV40 T-antigen.

Transformation and radiosensitivity of human diploid skin fibroblasts transfected with SV40 T-antigen mutants defective in RB and P53 binding domains.

A series of human diploid fibroblast cell clones were developed by DNA transfection with either wild-type SV40 T-antigen (SV40 T) or T-antigen mutants defective in its various functional domains. Cell clones expressing the wild-type SV40 T were significantly radioresistant as compared with clones transfected with the neo gene only (D0 = 192 +/- 13 vs 127 +/- 19). This radioresistance persisted in post-crisis, immortalized cell lines. A series of mutants with point or deletion mutations within each functionally active domain of SV40 T were also examined for their ability to alter radiosensitivity and induce morphological transformation. Cell clones transfected with T-antigen mutants defective in nuclear localization or origin binding showed increased radioresistance similar to clones transfected with wild-type T-antigen, and expressed morphological changes characteristic of SV40 T-transfected cells. A retinoblastoma susceptibility gene (RB) binding defective mutant showed moderately increased radioresistance (D0 = 174 +/- 10). However, cell clones transfected with three different p53 binding defective mutants showed no change in radiosensitivity (D0 = 132 +/- 5) as compared with neo gene transfected controls. Transfection with T-antigen mutants defective in either the RB or p53 binding domain yielded no morphological alterations characteristic of transformation. These data suggest that the SV40 T/p53 complex may be of importance in the radioresistance phenotype.

Transformation and radiosensitivity of human diploid skin fibroblasts transfected with activated ras oncogene and SV40 T-antigen.

Three normal human diploid cell strains were transfected with an activated Ha-ras oncogene (EJ ras) or SV40 T-antigen. Multiple clones were examined for morphological alterations, growth requirements, ability to grow under anchorage independent conditions, immortality and tumorigenicity in nude mice. Clones expressing SV40 T-antigen alone or in combination with ras protein p21 were significantly radioresistant as compared with their parent cells or clones transfected with the neo gene only. This radioresistant phenotype persisted in post-crisis, immortalized cell lines. Cells transfected with EJ ras alone showed no morphological alterations nor significant changes in radiosensitivity. Cell clones expressing ras and/or SV40 T-antigen showed a reduced requirement for serum supplements, an increase in aneuploidy and chromosomal aberrations, and enhanced growth in soft agar as an early cellular response to SV40 T-antigen expression. The sequential order of transfection with SV40 T-antigen and ras influenced radio-sensitivity but not the induction of morphological changes. These data suggest that expression of the SV40 T-antigen but not activated Ha-ras plays an important role in the radiosensitivity of human diploid cells. The radioresistant phenotype in SV40 T transfected cells was not related to the enhanced level of genetic instability seen in pre-crisis and newly immortalized cells, nor to the process of immortalization itself.

Suppression of phorbol ester-enhanced radiation-induced malignancy in vitro by protease inhibitors is independent of protein kinase C.

X-irradiation and the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) act in a synergistic manner to increase the yield of transformed C3H10T1/2 cells in vitro. TPA modulated both translocation from the cytosol to the plasma membrane, and down regulation of protein kinase C (PKC) after prolonged (48 h) TPA exposure. N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), antipain, and soybean-derived Bowman-Birk inhibitor, protease inhibitors that suppress transformation of C3H10T1/2 cells, had no effect on these TPA-mediated alterations of PKC activity, suggesting that protease inhibitors suppress TPA-stimulated promotion in vitro via a PKC-independent pathway. Several experiments were performed to determine whether non-toxic concentrations of the PKC inhibitors, N-p-tosyl-L-lysine chloromethyl ketone (TLCK), TPCK, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), or 1-(5-isoquinoline-sulfonyl)-2-methyl-piperazine (H-7), modulated the movement of cells from a quiescent state into the cell cycle. TPCK and the combination of H-7 and W-7 lowered DNA synthesis when cells were stimulated to divide by TPA. Because other protease inhibitors that slow transformation in vitro did not have the same suppressive effect on DNA synthesis, the inhibitory pathway that suppresses carcinogenic activity is likely to be different from the suppression of DNA synthesis.

Gonadal dose measurement in diagnostic nuclear medicine using thermoluminescent dosimeters.

Instead of using the Medical Internal Radiation Dose Committee (MIRD) concept to calculate the gonadal dose during diagnostic examination using radiopharmaceuticals, measurements of gonadal doses using thermoluminescent dosimeters were studied. The results obtained are comparable with that calculated using the MIRD concept. Five frequently used examinations were investigated, viz., liver, brain, thyroid, bone scintigraphy and cholescintigraphy. The calibration of thermoluminescent dosimeters are fully described, and the experimental techniques are also fully presented.