Acute liver failure in Chinese children:a multicenter investigation

BACKGROUND: Currently, no documentation is available regarding Chinese children with acute liver failure(ALF). This study was undertaken to investigate etiologies and outcomes of Chinese children with ALF.METHODS: We retrospectively enrolled 32 pediatric patients with ALF admitted in five hospitals in different areas of China from January 2007 to December 2012. The coagulation indices, serum creatinine, serum lactate dehydrogenase,blood ammonia and prothrombin activity were analyzed; the relationship between these indices and mortality was evaluated by multivariate analysis.RESULTS: The most common causes of Chinese children with ALF were indeterminate etiology(15/32), drug toxicity(8/32),and acute cytomegalovirus hepatitis(6/32). Only 1 patient(3.13%)received liver transplantation and the spontaneous mortality of Chinese children with ALF was 58.06%(18/31). Patients who eventually died had higher baseline levels of international normalized ratio(P=0.01), serum creatinine(P=0.04), serum lactate dehydrogenase(P=0.01), blood ammonia(P<0.01) and lower prothrombin activity(P=0.01) than those who survived.Multivariate analysis showed that the entry blood ammonia was the only independent factor significantly associated with mortality(odds ratio=1.069, 95% confidence interval 1.023-1.117,P<0.01) and it had a sensitivity of 94.74%, a specificity of 84.62%and an accuracy of 90.63% for predicting the death. Based on the established model, with an increase of blood ammonia level,the risk of mortality would increase by 6.9%.CONCLUSIONS: The indeterminate causes predominated in the etiologies of ALF in Chinese children. The spontaneous mortality of pediatric patients with ALF was high, whereas the proportion of patients undergoing liver transplantation was significantly low. Entry blood ammonia was a reliable predictor for the death of pediatric patients with ALF.

Hot deformation behaviors of a 9Cr oxide dispersion-strengthened steel and its microstructure characterization

The hot deformation behaviors of a 9 Cr oxide dispersion-strengthened(9 Cr-ODS) steel fabricated by mechanical alloying and hot isostatic pressing(HIP) were investigated. Hot compression deformation experiments were conducted on a Gleeble 3500 simulator in a temperature range of 950–1100°C and strain rate range of 0.001–1 s^(-1). The constitutive equation that can accurately describe the relationship between the rheological stress and the strain rate of the 9 Cr-ODS steel was established, and the deformation activation energy was calculated as 780.817 kJ/mol according to the data obtained. The processing maps of 9 Cr-ODS in the strain range of 0.1–0.6 were also developed. The results show that the region with high power dissipation efficiency corresponds to a completely recrystallized structure. The optimal processing conditions were determined as a temperature range of 1000–1050°C with strain rate between 0.003 and 0.01 s^(-1).

Phycocyanobilin accelerates liver regeneration and reduces mortality rate in carbon tetrachloride-induced liver injury mice

AIM: To investigate the hepatoprotective effects of phycocyanobilin(PCB) in reducing hepatic injury and accelerating hepatocyte proliferation following carbon tetrachloride(CCl4) treatment.METHODS: C57BL/6 mice were orally administered PCB 100 mg/kg for 4 d after CCl4 injection, and then the serum and liver tissue of the mice were collected at days 1, 2, 3, 5 and 7 after CCl4 treatment. A series of evaluations were performed to identify the curative effects on liver injury and recovery. Aspartate aminotransferase(AST), alanine aminotransferase(ALT), albumin and superoxide dismutase(SOD) were detected to indirectly assess the anti-inflammatory effects of PCB. Meanwhile, we detected the expressions of hepatocyte growth factor, transforming growth factor alpha(TGF-α), TGF-β, tumor necrosis factor-alpha(TNF-α) and interleukin-6(IL-6), the factors which are associated with inflammation and liver regeneration. The protein expressions of proliferating cell nuclear antigen(PCNA), TNF-α and cytochrome C were detected by western blot. Furthermore, the survivalrates were analyzed of mice which were administered a lethal dose of CCl4(2.6 mg/kg)with or without PCB.RESULTS:In our research,PCB showed a strongly anti-inflammatory effect on CCl4-induced liver injury in mice.The ALT was significantly decreased after CCl4 treatment from day 1(P<0.01)and the AST was significantly decreased from day 2(P<0.001).Both albumin and liver SOD were increased from day2(P<0.001 and P<0.01),but serum SOD levels did not show a significant increase(P>0.05).PCB protected the structure of liver from the injury by CCl4.TUNEL assay showed that PCB dramatically reduced the number of apoptotic cells after CCl4 treatment compared to the control(101.0±25.4 vs 25.7±6.4,P<0.01).The result of western blotting showed that PCB could increase PCNA expression,decrease TNF-αand cytochrome C expression.Furthermore,data shows that PCB could improve the survival rate of acute liver failure(ALF)mice which were injected with a lethal dose of CCl4(60.0%vs 20.0%).CONCLUSION:Our study indicated that PCB could be an ideal candidate for reversing acute liver injury or ALF.

Effect of heat treatment processing on microstructure and tensile properties of Ti-6Al-4V-10Nb alloy

Effects of heat treatment processing on the microstructure and mechanical properties of Ti-6Al-4V-10Nb alloy were investigated. The microstructures were investigated by SEM, TEM and XRD, and the mechanical properties were evaluated by tensile tests at room and elevated temperatures. The results indicate that the lath-like and globular primary α phase, secondary α phase and β phase are obtained after forging and heat treatment processing. The size of secondary α phase is much smaller than that of primary α phase. After heat treatment, the volume fraction of primary α phase is decreased, and that of secondary α phase is increased. With the increase of solution temperature, the volume fraction of primary α phase is gradually decreased, and that of secondary α phase is obviously increased. The yield strength and tensile strength of Ti-6Al-4V-10Nb alloy are significantly enhanced with the solution temperature increasing.

Effect of indium addition on the microstructural formation and soldered interfaces of Sn-2.5Bi-1Zn-0.3Ag lead-free solder

The microstructural formation and properties of Sn-2.5Bi-xln-lZn-0.3Ag （in wt%） alloys and the evolution of soldered interfaces on a Cu substrate were investigated. Apart from the relatively low melting point （about 195C）, which is close to that of conventional eutectic Sn-Pb solder, the investigated solder presents superior wettability, solderability, and ductility. The refined equiaxial grains enhance the me- chanical properties, and the embedded bulk intermetallic compounds （IMCs） （Cu6Sn5 and CusZns） and granular Bi particles improve the joint reliability. The addition of In reduces the solubility of Zn in the 13-Sn matrix and strongly influences the separation and growth behaviors of the IMCs. The soldered interface of Sn-2.5Bi-xln-lZn-0.3Ag/Cu consists of Cu-Zn and Cu-Sn IMC layers.

Effects of aluminum and titanium on the microstructure of ODS steels fabricated by hot pressing

Three oxide-dispersion-strengthened(ODS)steels with compositions of Fe-14Cr-2W-0.2V-0.07Ta-0.3Y_2O_3(wt%,so as the follows)(14Y),Fe-14Cr-2W-0.2V-0.07Ta-1Al-0.3Y_2O_3(14YAl),and Fe-14Cr-2W-0.2V-0.07Ta-0.3Ti-0.3 Y_2O_3(14YTi)were fabricated by hot pressing.Transmission electron microscopy(TEM)was used to characterize the microstructures and nanoparticles of these ODS steels.According to the TEM results,14Y,14YAl,and 14YTi ODS steels present similar bimodal structures containing both large and small grains.The addition of Al or Ti has no obvious effect on the microstructure of the steels.The spatial and size distribution of the nanoparticles was also analyzed.The results indicate that the average size of nanoparticles in the 14YTi ODS steel is smaller than that in the 14YAl ODS steel.Nanoparticles such as Y_2O_3,Y_3Al_5O_(12) and YAlO_3,and Y_2Ti_2O_7 were identified in the 14Y,14YAl,and 14YTiODS steels,respectively.

Morphology and quantitative analysis of O phase during heat treatment of hot-deformed Ti_2AlNb-based alloy

A 1040°C-hot-deformed Ti_2AlNb-based alloy solution-treated at 950°C and aged at different temperatures was quantitatively investigated. The microstructure, size of the phase, and microhardness of the deformed alloys were measured. The results indicated that the microstructure of the deformed Ti_2AlNb-based alloy specimens comprise coarse O lath, fine O lath, equiaxed O/α_2, and acicular O phase. More O phase was generated in the deformed alloy after heat treatment because the acicular O phase was more likely to nucleate and grow along the deformation-induced crystal defects such as dislocations and subgrain boundaries. After deformation and subsequent heat treatment, the acicular O phase of the resultant alloy became finer compared to that of the undeformed alloy, and the acicular O phase became coarser and longer with the elevated aging temperature, while the width of the O lath exhibited unobvious variations. The hot deformation facilitated the dissolution of the O lath but accelerated the precipitation of the acicular O phase. When the 950°C-solution-treated deformed Ti_2AlNb-based alloy was then aged at 750°C for different periods, the phase content was nearly invariable, O and B2 phases eventually reached equilibrium, and the microstructure became stable and homogeneous.

Crust-derived felsic magmatism in the Emeishan large igneous Province:New evidence from zircon U-Pb-Hf-O isotope from the Yangtze Block,China

Numerous intrusive bodies of mafic–ultramafic to felsic compositions are exposed in association with volcanic rocks in the Late Permian Emeishan large igneous province(ELIP),southwestern China.Most of the granitic rocks in the ELIP were derived by differentiation of basaltic magmas with a mantle connection,and crustal magmas have rarely been studied.Here we investigate a suite of mafic dykes and Ⅰ-type granites that yield zircon U-Pb emplacement ages of 259.9±1.2 Ma and 259.3±1.3 Ma,respectively.The εHf(t)values of zircon from the DZ mafic dyke are–0.3 to 9.4,and their corresponding TDM1 values are in the range of 919–523 Ma.The εHf(t)values of zircon from the DSC Ⅰ-type granite are between–1 and 3,with TDM1 values showing a range of 938–782 Ma.We also present zircon O isotope data on crust-derived felsic intrusions from the ELIP for the first time.The δ18O values of zircon from the DSC Ⅰ-type granite ranges from 4.87‰to 7.5‰.The field,petrologic,geochemical and isotopic data from our study lead to the following salient findings.(i)The geochronological study of mafic and felsic intrusive rocks in the ELIP shows that the ages of mafic and felsic magmatism are similar.(ii)The DZ mafic dyke and high-Ti basalts have the same source,i.e.,the Emeishan mantle plume.The mafic dyke formed from magmas sourced at the transitional depth between from garnet-lherzolite and spinel-lherzolite,with low degree partial melting(<10%).(iii)The Hf-O isotope data suggest that the DSC Ⅰ-type granite was formed by partial melting of Neoproterozoic juvenile crust and was contaminated by minor volumes of chemically weathered ancient crustal material.(iv)The heat source leading to the formation of the crust-derived felsic rocks in of the ELIP is considered to be mafic–ultramafic magmas generated by a mantle plume,which partially melted the overlying crust,generating the felsic magma.

Effect of cold rolling and first precipitates on the coarsening behavior of γ″-phases in Inconel 718 alloy

The coarsening behaviors of γ″-phase particles in Inconel 718 alloy aged at 750, 800, and 850℃ were investigated by scanning electron microscopy（SEM）. Detailed observations and quantitative measurements were conducted to characterize the coarsening behavior of the γ″-phase under various aging conditions. The experimental results indicate that the existence of the δ-phase retards the formation and coarsening of the γ″-phase, without influencing its final particle size or amount. Moreover, when cold rolled with a reduction of 50%, the dimensions of the γ″ particles in Inconel 718 alloy decrease with increasing aging time. Furthermore, the coarsening behavior of the γ″-phase in the Inconel 718 alloy after a normal aging treatment（sample A） and that of the primary δ-phase（sample B） follow the Lifshitz–Slyozov–Wagner（LSW） diffusion-controlled growth theory; the thus-obtained activation energies for the γ″-phase are 292 k J·mol^-1 and 302 k J·mol^-1, respectively.

Epigenetic regulation in cardiac fibrosis

Cardiac fibrosis represents an adoptive response in the heart exposed to various stress cues. While resolution of the fibrogenic response heralds normalization of heart function, persistent fibrogenesis is usually associated with progressive loss of heart function and eventually heart failure. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix proteins, a process the epigenetic machinery plays a pivotal role. In this minireview, we summarize recent advances regarding the epigenetic regulation of cardiac fibrosis focusing on the role of histone and DNA modifications and non-coding RNAs.

Effect of microstructure variation on the corrosion behavior of high-strength low-alloy steel in 3.5wt% NaCl solution

The effect of microstructure variation on the corrosion behavior of high-strength low-alloy（HSLA） steel was investigated. The protective property of the corrosion product layer was also explored. Experimental results reveal that the type of microstructure has significant effect on the corrosion resistance of HSLA steel. The measurement results of weight loss, potentiodynamic polarization curves, and electrochemical impedance spectroscopy indicate that the steel with acicular ferrite microstructure exhibits the lowest corrosion rate. Martensite exhibits a reduced corrosion resistance compared with polygonal ferrite. It is found that the surface of the acicular ferrite specimen uniformly covered by corrosion products is seemingly denser and more compact than those of the other two microstructures, and can provide some amount of protection to the steel; thus, the charge transfer resistance and modulus values of the acicular ferrite specimen are the largest. However, corrosion products on martensite and polygonal ferrite are generally loose, porous, and defective, and can provide minor protectiveness; thus, the charge transfer resistance values for polygonal ferrite and martensite are lower.

Effect of deformation twinning on high-temperature performance of cold-rolled S31042 steel

Influence of deformation twinning on high-temperature instantaneous performance of cold-rolled S31042 steel was investigated by optical microscopy, scanning electron microscopy, transmission electron microscopy, and high-temperature tensile test. An increasing number of deformation twins have formed as the cold rolling reduction degree increases during the cold rolling process. During the tensile process at 700 ℃, M23C6 particles generated along the deformation twin boundaries, and NbCrN nanoparticles dispersedly precipitated throughout the austenite grains. For the high-temperature tensile sample subjected to cold reduction for 80%, it is observed from the fractured cross section that numerous defor-mation twin boundaries were decorated by discontinuous M23C6 particles. Therefore, austenite grains were divided into several independent zones by the deformation twins, and the grains were refined. Due to the grain refinement strengthening and precipitation strengthening, the high-temperature temporal strength of the 80% cold-rolled sample was significantly improved, and simultaneously, this sample exhibited favorable high-temperature elongation.

Glioma stem cells and neural stem cells respond differently to BMP4 signaling

Malignant glioma is a highly heterogeneous and invasive primary brain tumor characterized by high recurrence rates,resistance to combined therapy,and dismal prognosis.Glioma stem cells(GSCs)are likely responsible for tumor progression,resistance to therapy,recurrence,and poor prognosis owing to their high self-renewal and tumorigenic potential.As a family member of BMP signaling,bone morphogenetic protein4(BMP4)has been reported to induce the differentiation of GSCs and neural stem cells(NSCs).However,the molecular mechanisms underlying the BMP4-mediated effects in these two cell types are unclear.In this study,we treated hGSCs and hNSCs with BMP4 and com-pared the phenotypic and transcriptional changes between these two cell types.Phenotypically,we found that the growth of hGSCs was greatly inhibited by BMP4,but the same treatment only increased the cell size of hNSCs.While the RNA sequencing results showed that BMP4 treatment evoked significantly transcriptional changes in both hGSCs and hNSCs,the profiles of differentially expressed genes were distinct between the two groups.A gene set that specifically targeted the proliferation and differentiation of hGSCs but not hNSCs was enriched and then validated in hGSC culture.Our results suggested that hGSCs and hNSCs responded differently to BMP4 stimulation.Understanding and investigating different responses between hGSCs and hNSCs will benefit finding partner factors working together with BMP4 to further suppress GSCs proliferation and stemness without disturbing NSCs.

Interferon-beta inhibits human glioma stem cell growth by modulating immune response and cell cycle related signaling pathways

Malignant Glioma is characterized by strong self-renewal potential and immature differentiation potential.The main reason is that malignant glioma holds key cluster cells,glioma stem cells(GSCs).GSCs contribute to tumorigenesis,tumor progression,recurrence,and treatment resistance.Interferon-beta(IFN-β)is well known for its anti-proliferative efficacy in diverse cancers.IFN-βalso displayed potent antitumor effects in malignant glioma.IFN-βaffect both GSCs and Neural stem cells(NSCs)in the treatment of gliomas.However,the functional comparison,similar or different effects of IFN-βon GSCs and NSCs are rarely reported.Here,we studied the similarities and differences of the responses to IFN-βbetween human GSCs and normal NSCs.We found that IFN-βpreferentially inhibited GSCs over NSCs.The cell body and nucleus size of GSCs increased after IFN-βtreatment,and the genomic analysis revealed the enrichment of the upregulated immune response,cell adhesion genes and down regulated cell cycle,ribosome pathways.Several typical cyclin genes,including cyclin A2(CCNA2),cyclin B1(CCNB1),cyclin B2(CCNB2),and cyclin D1(CCND1),were significantly downregulated in GSCs after IFN-βstimulation.We also found that continuous IFN-βstimulation after passage further enhanced the inhibitory effect.Our study revealed how genetic diversity resulted in differential effects in response to IFN-βtreatment.These results may contribute to improve the applications of IFN-βin anti-cancer immunotherapy.In addition,these results may also help to design more effective pharmacological strategies to target cancer stem cells while protecting normal neural stem cells.