[Study on the method of detection of benzene exposure biomarkers by solid phase extraction-gas chromatography-tandem mass spectrometry].

Objective: A gas chromatography-tandem mass spectrometry detection method for benzene and its metabolites was established to provide methodological support and theoretical basis for the study of benzene toxicity mechanism. Methods: In August 2019 to March 2020, the animal model of containing high concentration of benzene by inhalation of poison through the respiratory tract of mice was established, taken the blood of mice after dyeing the poison, and the HLB solid phase extraction method was used to extract and purify the samples. The gas chromatography-tandem mass spectrometry detection method was used to qualitative and quantitative analysis of the target substances. After separated by HP-17MS capillary chromatographic column, the compounds were ionized with EI ion source, mass spectrometry detection was carried out by selective ion scanning method (SIM) , and quantification was carried out by external standard curve method. Results: Benzene and its metabolites (phenol, catechol, hydroquinone and m-trihydroxybenzene) in blood could be effectively separated and quasi deterministic and quantitative by this method. The regression equations and correlation coefficients of this method for detecting benzene and its metabolites were: benzene: y=3252.1x+1540, r=0.9993; phenol: y=2046.5x+1423, r=0.9991; catechol: y=1853.9x+945, r=0.9993; hydroquinone: y=1891.5x+840, r=0.9992; m-trihydroxybenzene: y=1052.4x+655, r=0.9991. The detection limits for benzene, phenol, catechol, hydroquinone and m-trihydroxybenzene were 0.03, 0.03, 0.05, 0.05 and 0.10 µg/g, respectively. And the lower limits of quantification were 0.10, 0.10, 0.15, 0.15 and 0.30 µg/g, respectively. The intra-assay precision interval was 2.64%-10.06%, the inter-assay precision interval was 1.37%-10.17%, and the spike recovery rate was 89.8%-102.3%. This method could be used to quantitatively detect benzene, phenol, catechol, hydroquinone and m-trihydroxybenzene in the blood of benzene-infected mice. Conclusion: Solid phase extraction-gas chromatography-mass spectrometry can be used for qualitative and quantitative detection of benzene and its metabolites (phenol, catechol, hydroquinone and m-trihydroxybenzene) accurately.

Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience.

BACKGROUND: Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. METHODS: This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. RESULTS: Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). CONCLUSIONS: Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed.

Fracture liaison services for osteoporosis in the Asia-Pacific region: current unmet needs and systematic literature review.

The analysis aimed to identify the treatment gaps in current fracture liaison services (FLS) and to provide recommendations for best practice establishment of future FLS across the Asia-Pacific region. The findings emphasize the unmet need for the implementation of new programs and provide recommendations for the refinement of existing ones. The study's objectives were to evaluate fracture liaison service (FLS) programs in the Asia-Pacific region and provide recommendations for establishment of future FLS programs. A systematic literature review (SLR) of Medline, PubMed, EMBASE, and Cochrane Library (2000-2017 inclusive) was performed using the following keywords: osteoporosis, fractures, liaison, and service. Inclusion criteria included the following: patients ≥ 50 years with osteoporosis-related fractures; randomized controlled trials or observational studies with control groups (prospective or retrospective), pre-post, cross-sectional and economic evaluation studies. Success of direct or indirect interventions was assessed based on patients' understanding of risk, bone mineral density assessment, calcium intake, osteoporosis treatment, re-fracture rates, adherence, and mortality, in addition to cost-effectiveness. Overall, 5663 unique citations were identified and the SLR identified 159 publications, reporting 37 studies in Asia-Pacific. These studies revealed the unmet need for public health education, adequate funding, and staff resourcing, along with greater cooperation between departments and physicians. These actions can help to overcome therapeutic inertia with sufficient follow-up to ensure adherence to recommendations and compliance with treatment. The findings also emphasize the importance of primary care physicians continuing to prescribe treatment and ensure service remains convenient. These findings highlight the limited evidence supporting FLS across the Asia-Pacific region, emphasizing the unmet need for new programs and/or refinement of existing ones to improve outcomes. With the continued increase in burden of fractures in Asia-Pacific, establishment of new FLS and assessment of existing services are warranted to determine the impact of FLS for healthcare professionals, patients, family/caregivers, and society.

Concentrations of minerals in pig feed ingredients commonly used in China.

Mineral concentrations were determined in 13 different feed ingredients commonly used in swine diets. Ingredients included corn and 4 corn co-products: corn gluten feed, corn gluten meal, corn germ meal, and corn distillers dried grains with solubles (DDGS). Wheat, wheat bran, and wheat shorts were also included, and 5 oilseed meals including soybean meal, rapeseed meal, sunflower meal, cottonseed meal, and peanut meal were used as well. Corn grain contained 88.7% dry matter (DM) and 0.46% K (DM basis). Greater concentrations of DM, ash, Ca, P, nonphytate P, Cu, Fe, Mn, and Zn were observed in corn gluten feed, corn DDGS, and corn germ meal compared with corn grain (P < 0.05). In general, minerals in corn DDGS were approximately three times greater than in corn grain and about 90% of the total P in corn DDGS was in the nonphytate bound form. Corn gluten meal had the least concentrations (P < 0.05) of most minerals, but the greatest (P < 0.05) concentrations of Fe (373.55 mg/kg, DM basis), Cu (11.88 mg/kg, DM basis), and Se (0.92 mg/kg, DM basis). On a DM-basis, concentrations of DM, Ca, P, phytate bound P, and Fe in wheat grain were 88.2%, 0.10%, 0.34%, 0.16%, and 53.48 mg/kg, respectively. Wheat bran contained more (P < 0.05) K, Mg, Cl, Fe, Zn, and Mn compared with wheat and wheat shorts. On a DM-basis, 2.72% K was observed in soybean meal, which was more (P < 0.05) than in the other oilseed meals. However, rapeseed meal had the greatest (P < 0.05) concentration of ash (9.37%), Ca (1.01%), P (1.05%), and Fe (526.49 mg/kg) among the oilseed meals, but only 16.2% of the total P in rapeseed meal was non-phytate P. In contrast, more than 50% of the P in soybean meal and peanut meal was non-phytate P. The least (P < 0.05) concentration of Cu (6.73 mg/kg, DM basis) was observed in rapeseed meal and the greatest (P < 0.05) concentration (32.75 mg/kg) was analyzed in sunflower meal. Concentrations of most minerals in soybean meal, rapeseed meal, sunflower meal, cottonseed meal, and peanut meal varied considerably compared with published values. In conclusion, the concentration of minerals in 13 commonly used feed ingredients were analyzed and results indicated considerable variation among and within feed ingredients for most minerals, which for some minerals may be a result of differences in minerals in the soil in which the ingredients were grown, but processing likely also contributes to differences among ingredients.

Effect of low temperatures on BAX and BCL2 proteins in rats with spinal cord ischemia reperfusion injury.

We evaluated changes in BAX and BCL2 expression levels after spinal cord ischemia/reperfusion injury (SCII) and hypothermia during operations in rats. Eighty rats were divided into four groups: Group A (N = 20, 18°C); Group B (N = 20, 28°C); Group C (N = 20, room temperature); and Group D (N = 20, sham operation control). Spinal cord ischemia was induced for 90 min. Hypothermia was induced 15 min before, and maintained during ischemia, followed by heating to normothermia for 30 min after reperfusion. Motor function of the lower limbs was evaluated according to the Tarlov score at 72 and 168 h. For each rat, spinal cord samples were taken at 6, 24, 72 h, and 1 week to evaluate the histopathological changes, neuronal apoptosis, and BAX and BCL2 expression levels. Compared with normothermia, hypothermia significantly improved hind limb function; Group B achieved a higher score than Group A. Group D showed no neurologic deficiency, while the other groups showed various degrees. Group C exhibited greater neuronal apoptosis, higher BAX expression, but lower BCL2 expression than the other groups. Compared with Group A, BAX was expressed less and BCL2 more in Group B, and there was less apoptosis in Group B. Hypothermia preserves hind limb motor function and reduces neuronal death, thereby protecting rats from SCII. The spinal cord may be protected from SCII by inhibition of BAX and activation of BCL2. However, deep hypothermia may inhibit the expression of BCL2, resulting in a worse outcome than mild hypothermia.

NF-κB Enhances Androgen Receptor Expression through 5'-UTR Binding in Gingival Cells.

Dihydropyridine-induced gingival overgrowth (DIGO) is a side effect observed in patients treated for hypertension. The disease is aggravated by inflammation. Nifedipine (Nif), a dihydropyridine, causes gingival overgrowth by increasing the expression of the androgen receptor (AR). Furthermore, the proinflammatory cytokine interleukin 1ß (IL-1ß) induces collagen α1(I) expression through the AR in DIGO fibroblasts. These observations prompted us to investigate whether and how nuclear factor kappa B (NF-κB) affects AR expression in DIGO. Therefore, gingival fibroblasts obtained from the tissues of patients with DIGO and healthy subjects were stimulated with IL-1ß, Nif, or both. mRNA and protein expression was detected with real-time polymerase chain reaction and Western blotting. High correlation coefficients were observed for the mRNA expression of the AR, connective tissue growth factor, and collagen α1(I) induced by both drugs. Western blot analysis showed that IL-1ß and Nif increased and activated NF-κB more in DIGO cells than in healthy cells. An electrophoretic mobility shift assay demonstrated that the promoter and 5'-untranslated regions (5'-UTRs) of the AR gene contains 3 binding sites for the NF-κB p65 subunit. A chromatin immunoprecipitation assay revealed that the NF-κB p65 subunit was associated with AR 5'-UTRs in gingival fibroblasts. A site-directed mutagenesis study indicated that a mutation of NF-κB binding sites reduced Nif- and IL-1ß-induced AR promoter activities. Collectively, these data indicate that NF-κB is an essential transcriptional regulator of AR gene expression and thus plays a crucial role in collagen overproduction in DIGO fibroblasts.

Effects of inclusion levels of wheat bran and body weight on ileal and fecal digestibility in growing pigs.

The objective of this study was to determine the effects of graded inclusions of wheat bran (0%, 9.65%, 48.25% wheat bran) and two growth stages (from 32.5 to 47.2 kg and 59.4 to 78.7 kg, respectively) on the apparent ileal digestibility (AID), apparent total tract digestibility (ATTD) and hindgut fermentation of nutrients and energy in growing pigs. Six light pigs (initial body weight [BW] 32.5±2.1 kg) and six heavy pigs (initial BW 59.4±3.2 kg) were surgically prepared with a T-cannula in the distal ileum. A difference method was used to calculate the nutrient and energy digestibility of wheat bran by means of comparison with a basal diet consisting of corn-soybean meal (0% wheat bran). Two additional diets were formulated by replacing 9.65% and 48.25% wheat bran by the basal diet, respectively. Each group of pigs was allotted to a 6×3 Youden square design, and pigs were fed to three experimental diets during three 11-d periods. Hindgut fermentation values were calculated as the differences between ATTD and AID values. For the wheat bran diets, the AID and ATTD of dry matter (DM), ash, organic matter (OM), carbohydrates (CHO), gross energy (GE), and digestible energy (DE) decreased with increasing inclusion levels of wheat bran (p<0.05). While only AID of CHO and ATTD of DM, ash, OM, CHO, GE, and DE content differed (p<0.05) when considering the BW effect. For the wheat bran ingredient, there was a wider variation effect (p<0.01) on the nutrient and energy digestibility of wheat bran in 9.65% inclusion level due to the coefficient of variation (CV) of the nutrient and energy digestibility being higher at 9.65% compared to 48.25% inclusion level of wheat bran. Digestible energy content of wheat bran at 48.25% inclusion level (4.8 and 6.7 MJ/kg of DM, respectively) fermented by hindgut was significantly higher (p<0.05) than that in 9.65% wheat bran inclusion level (2.56 and 2.12 MJ/kg of DM, respectively), which was also affected (p<0.05) by two growth stages. This increase in hindgut fermentation caused the difference in ileal DE (p<0.05) to disappear at total tract level. All in all, increasing wheat bran levels in diets negatively influences the digestibility of some nutrients in pigs, while it positively affects the DE fermentation in the hindgut.

Prediction of digestible and metabolizable energy content of rice bran fed to growing pigs.

Two experiments were conducted to determine the digestible energy (DE) and metabolizable energy (ME) content of 19 rice bran samples and to develop prediction equations for DE and ME based on their chemical composition. The 19 rice bran samples came from different rice varieties, processing methods and regions. The basal diet was formulated using corn and soybean meal (74.43% corn and 22.91% soybean meal and 2.66% vitamins and minerals). The 19 experimental diets based on a mixture of corn, soybean meal and 29.2% of each source of rice bran, respectively. In Exp. 1, 108 growing barrows (32.1±4.2 kg) were allotted to 1 of 18 treatments according to a completely randomized design with 6 pigs per treatment. The treatment 1 was the control group which was fed with basal diet. The treatments 2 to 18 were fed with experimental diets. In Exp. 2, two additional rice bran samples were measured to verify the prediction equations developed in Exp. 1. A control diet and two rice bran diets were fed to 18 growing barrows (34.6±3.5 kg). The control and experimental diets formulations were the same as diets in Exp. 1. The results showed that the DE ranged from 14.48 to 16.85 (mean 15.84) MJ/kg of dry matter while the ME ranged from 12.49 to 15.84 (mean 14.31) MJ/kg of dry matter. The predicted values of DE and ME of the two additional samples in Exp. 2 were very close to the measured values.

Influence of sirolimus-induced TGF-ß secretion on mouse Treg cell proliferation.

We examined the effects of co-culturing CD4+ CD25+ Treg cells with sirolimus or cyclosporin A on Treg cell proliferation and differentiation and on transforming growth factor-ß (TGF-ß) and Foxp3 expression. CD4+ CD25+ Treg cells were harvested from mononuclear cells of spleens of C57BL/6 mice using immunomagnetic beads and divided into control, sirolimus, and cyclosporine groups. Following a 96-h co-culture, Treg cells were assayed by flow cytometry. FoxP3 and TGF-ß mRNA levels and secretion were assayed by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Smad protein of the TGF-ß signaling pathway was assayed by western blot and its effect on CD4+ CD25+ FoxP3+ Treg cell proliferation was determined. Sirolimus-promoted differentiation and proliferation was examined using a TGF-ß neutralizing antibody. Sirolimus-treated CD4+ T cell TGF-ß secretion increased 2.5X over control levels (P < 0.01), but that of the cyclosporine group decreased marginally (P > 0.05). The CD4+ cell proportion decreased significantly (41.25 vs 69.22%, P < 0.01) and slightly (65.21 vs 69.22, P > 0.05) in the cyclosporine and sirolimus groups, respectively. T cell Foxp3 mRNA expression was significantly higher in the sirolimus-treated than in the cyclosporine (53.7 vs 40.2%, P < 0.05) and control groups (P < 0.01), but was significantly lower in the cyclosporine group than in controls (23.6 vs 40.2%, P < 0.01). Overall, sirolimus promoted CD4+ CD25+ Treg cell proliferation and growth in vitro, whereas cyclosporin A inhibited proliferation. Sirolimus might promote CD4+ CD25+ FoxP3+ regulatory T cell proliferation by inducing TGF-ß secretion in vivo.

Effect of prenatal exposure to LPS combined with pre- and post-natal high-fat diet on hippocampus in rat offspring.

OBJECTIVE: Prenatal exposure to lipopolysaccharide (LPS) or high-fat diet (HFD) results in hippocampal impairment and cognitive deficits in offspring rats. What is not clear is how prenatal exposure to LPS combined with pre- and post-natal HFD would affect the hippocampus in offspring rats. METHODS: 32 pregnant rats were randomly divided into four groups, including control group; LPS group (pregnant rats were injected with LPS 0.4 mg/kg intraperitoneally on the 8th, 10th and 12th day of pregnancy); HFD group (maternal rats had HFD during pregnancy and the lactation period, and their pups also had HFD up to the third month of life); LPS+HFD group (rats were exposed to the identical experimental scheme with LPS group and HFD group). The serum IL-6 and TNF-alpha concentration was measured in three-month-old offspring rats in all groups. Hippocampal morphology and expressions of glial fibrillary acidic protein (GFAP), Tau and synaptophysin (SYP) in offspring rats were measured. RESULTS: Serum IL-6 and TNF-alpha concentration in the HFD group increased significantly compared with the control group, LPS group and LPS+HFD group. Compared with the control group and the LPS+HFD group, cells in the LPS and HFD groups were smaller and arranged in disorder, and cell membrane was not complete, nucleoli and nuclear heterochromatin stained darkly with hematoxylin. GFAP and Tau expression in the hippocampus of the LPS and HFD groups increased significantly compared with the control group and LPS+HFD group. SYP expression in the LPS and HFD groups decreased significantly compared with the control group and HFD group, increased in the LPS+HFD group. CONCLUSION: Prenatal exposure to LPS combined with pre- and post-natal HFD result in a protective effect on the hippocampus in offspring rats, and it might be a benefit from the predictive adaptive response to prenatal inflammation.

Determination and prediction of digestible and metabolizable energy from the chemical composition of chinese corn gluten feed fed to finishing pigs.

Two experiments were conducted to determine the digestible energy (DE) and metabolizable energy (ME) contents of corn gluten feed (CGF) for finishing pigs and to develop equations predicting the DE and ME content from the chemical composition of the CGF samples, as well as validate the accuracy of the prediction equations. In Exp. 1, ten CGF samples from seven provinces of China were collected and fed to 66 finishing barrows (Duroc×Landrace×Yorkshire) with an initial body weight (BW) of 51.9±5.5 kg. The pigs were assigned to 11 diets comprising one basal diet and 10 CGF test diets with six pigs fed each diet. The basal diet contained corn (76%), dehulled soybean meal (21%) and premix (3%). The ten test diets were formulated by substituting 25% of the corn and dehulled soybean meal with CGF and contained corn (57%), dehulled soybean meal (15.75%), CGF (24.25%) and premix (3%). In Exp. 2, two additional CGF sources were collected as validation samples to test the accuracy of the prediction equations. In this experiment, 18 barrows (Duroc×Landrace×Yorkshire) with an initial BW of 61.1±4.0 kg were randomly allotted to be fed either the basal diet or two CGF containing diets which had a similar composition as used in Exp. 1. The DE and ME of CGF ranged from 10.37 to 12.85 MJ/kg of dry matter (DM) and 9.53 to 12.49 MJ/kg of DM, respectively. Through stepwise regression analysis, several prediction equations of DE and ME were generated. The best fit equations were: DE, MJ/kg of DM = 18.30-0.13 neutral detergent fiber-0.22 ether extract, with R(2) = 0.95, residual standard deviation (RSD) = 0.21 and p<0.01; and ME, MJ/kg of DM = 12.82+0.11 Starch-0.26 acid detergent fiber, with R(2) = 0.94, RSD = 0.20 and p<0.01. These results indicate that the DE and ME content of CGF varied substantially but the DE and ME for finishing pigs can be accurately predicted from equations based on nutritional analysis.

Rapid diagnosis of Naja atra snakebites.

BACKGROUND: The clinical diagnosis of snakebites is critical and necessary in many parts of the world, especially in Southeastern Asia, where venomous snakebites are a burden on public health. It is difficult to define or recognize the species of venomous snake because of the overlapping clinical manifestations of envenomations. A quick and reliable method for identifying the snake species is necessary. We designed and tested a strip of lateral flow system for the diagnosis of cobra snake bites in Taiwan. METHODS: We developed a kit based on an immunochromatographic method for rapid detection of cobra (Naja atra) venom in human serum. The test and control lines composed of 1 mg/ml polyclonal duck antivenom and 0.5 mg/ml goat anti-rabbit immunoglobulin antibody solutions, respectively, were coated on nitrocellulose strips. Colloidal gold was conjugated with rabbit polyclonal anti-cobra venom antibodies. From July 2007 to December 2012, we used the kit to test serum from snakebite patients and to examine the agreement between our rapid test and the currently used sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Our kit was able to detect cobra venom in serum samples in 20 minutes with a detection limit of 5 ng/ml. An absence of cross-reactivity with other non-cobra venoms from Taiwan was noted in vitro. A total of 88 snakebite patients (34 cobra and 54 other non-cobra) were tested. The sensitivity of the strips based on the ELISA results was 83.3% and the specificity was 100%. There was a strong agreement between the results of the ELISA and immunochromatographic strips (κ = 0.868). DISCUSSION AND CONCLUSIONS: This data indicates that an immunochromatographic strip might be suitable for cobra venom detection and could be used as a quick diagnostic tool in cases of N. atra snakebite.

Intra-grain perpendicular percolated L11 CoPt thin films.

Ultrathin percolated high-Ku magnetic films with thicknesses of 2 nm are realized simply by using sputter deposition and post annealing. L11 CoPt:MgO, with Ku on the order of 10(7) erg cm(-3), was deposited on a MgO(111) substrate at 350 °C, followed by post annealing to induce complete segregation of the added MgO dopants. The optimized film shows significant enhancement of the out-of-plane coercivity, approximately an order of magnitude greater than that of the CoPt binary film, a remanence ratio close to unity, considerably reduced in-plane magnetization, sharp perpendicular magnetic reversal, and reduced surface roughness in the range of a few angstroms. Microstructure results indicate that MgO precipitates into grains within the interconnected L11 grains after appropriate post annealing. The MgO grains, with sizes in the range 2-7 nm, form coherent interfaces to the CoPt matrix and penetrate through the whole depth of the film. The development of ideal non-magnetic domain wall pinning sites explains the optimization of the perpendicular magnetic properties. The advantages of a simple fabrication process, a thin film layer structure, and remarkable enhancement of the magnetic characteristics demanded by ultrahigh-density recording reveal its potential for practical applications.

Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome.

Recently, mutations of the additional sex comb-like 1 (ASXL1) gene were identified in patients with myelodysplastic syndrome (MDS), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, ASXL1 mutations were identified in 106 (22.7%) of the 466 patients with primary MDS based on the French-American-British (FAB) classification and 62 (17.1%) of the 362 patients based on the World Health Organization (WHO) classification. ASXL1 mutation was closely associated with trisomy 8 and mutations of RUNX1, EZH2, IDH, NRAS, JAK2, SETBP1 and SRSF2, but was negatively associated with SF3B1 mutation. Most ASXL1-mutated patients (85%) had concurrent other gene mutations at diagnosis. ASXL1 mutation was an independent poor prognostic factor for survival. Sequential studies showed that the original ASXL1 mutation remained unchanged at disease progression in all 32 ASXL1-mutated patients but were frequently accompanied with acquisition of mutations of other genes, including RUNX1, NRAS, KRAS, SF3B1, SETBP1 and chromosomal evolution. On the other side, among the 80 ASXL1-wild patients, only one acquired ASXL1 mutation at leukemia transformation. In conclusion, ASXL1 mutations in association with other genetic alterations may have a role in the development of MDS but contribute little to disease progression.

Integration of cytogenetic and molecular alterations in risk stratification of 318 patients with de novo non-M3 acute myeloid leukemia.

Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1, CEBPA, IDH2, RUNX1, WT1, ASXL1, DNMT3A and FLT3, that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis (P<0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.

Gate length scaling effect on high-electron mobility transistors devices using AlGaN/GaN and AlInN/AlN/GaN heterostructures.

Compared to AlGaN/GaN HEMT with 0.15 µm T-gate length, the AlInN/AlN/GaN one exhibits much higher current density and transconductance of 1558 mA/mm at Vd = 2 V and 330 mS/mm, respectively. The high extrinsic ft and fmax of 82 GHz and 70 GHz are extracted from AlInN/AlN/GaN HEMT. Besides, we find that the transconductance roll-off is significant in AlGaN/GaN, but largely improved in AlInN/AlN/GaN HEMT, suggesting that the high carrier density and lattice-matched epitaxial heterostructure is important to reach both large RF output power and high operation frequency, especially for an aggressively gate length scaling.

Drug reaction with eosinophilia and systemic symptoms syndrome associated myocarditis: a survival experience after extracorporeal membrane oxygenation support.

WHAT IS KNOWN AND OBJECTIVE: Myocarditis that develops because of the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening disease. We report a case of DRESS-associated myocarditis with cardiac failure that required extracorporeal membrane oxygenation (ECMO) for cardiovascular support. CASE SUMMARY: A 14-year-old boy experienced DRESS-associated myocarditis after anticonvulsive therapy with carbamazepine, clonazepam and phenytoin. The clinical signs included hypotension, cardiac arrhythmia and poor left ventricular (LV) performance. Laboratory investigations showed elevated levels of cardiac enzymes. Systemic corticosteroid pulse therapy for 3 days was administered for treating the DRESS syndrome. The patient required inotropic drugs including dopamine, dobutamine and milrinone because of refractory hypotension and poor LV function. He was placed on ECMO support, and intra-aortic balloon pumping was initiated because of poor response to inotropic drugs and stasis of blood flow in the ventricle on hospital day 17. Plasma exchanges for four separate times over 8 days were also performed during ECMO support on day 22. His condition stabilized 13 days after ECMO support was initiated. The patient was discharged on hospital day 50, and the seizure was controlled by the oral form clonazepam, phenobarbital, topiramate and levetiracetam. Three months later, an echocardiogram showed mild dilated cardiomyopathy. WHAT IS NEW AND CONCLUSION: Drug reaction with eosinophilia and systemic symptoms-associated fulminant myocarditis is a life-threatening disease. Traditionally, systemic corticosteroid administration, plasmapheresis, intravenous immunoglobulin infusion and ventricular assist device implantation have been used for the treatment of this disease. To our knowledge, this is the first case of DRESS-associated fulminant myocarditis treated successfully with ECMO support. However, echocardiogram should be followed regularly because dilated cardiomyopathy may be the late sequela.

Butyrate induces reactive oxygen species production and affects cell cycle progression in human gingival fibroblasts.

BACKGROUND AND OBJECTIVE: Short-chain fatty acids, such as butyric acid and propionic acid, are metabolic by-products generated by periodontal microflora such as Porphyromonas gingivalis, and contribute to the pathogenesis of periodontitis. However, the effects of butyrate on the biological activities of gingival fibroblasts (GFs) are not well elucidated. MATERIAL AND METHODS: Human GFs were exposed to various concentrations of butyrate (0.5-16 mm) for 24 h. Viable cells that excluded trypan blue were counted. Cell cycle distribution of GFs was analyzed by propidium iodide-staining flow cytometry. Cellular reactive oxygen species (ROS) production was measured by flow cytometry using 2',7'-dichlorofluorescein (DCF). Total RNA and protein lysates were isolated and subjected to RT-PCR using specific primers or to western blotting using specific antibodies, respectively. RESULTS: Butyrate inhibited the growth of GFs, as indicated by a decrease in the number of viable cells. This event was associated with an induction of G0/G1 and G2/M cell cycle arrest by butyrate (4-16 mm) in GFs. However, no marked apoptosis of GFs was noted in this experimental condition. Butyrate (> 2 mm) inhibited the expression of cdc2, cdc25C and cyclinB1 mRNAs and reduced the levels of Cdc2, Cdc25C and cyclinB1 proteins in GFs, as determined using RT-PCR and western blotting, respectively. This toxic effect of butyrate was associated with the production of ROS. CONCLUSION: These results suggest that butyrate generated by periodontal pathogens may be involved in the pathogenesis of periodontal diseases via the induction of ROS production and the impairment of cell growth, cell cycle progression and expression of cell cycle-related genes in GFs. These events are important in the initiation and prolongation of inflammatory processes in periodontal diseases.

Insulator, semiclassical oscillations and quantum Hall liquids at low magnetic fields.

Magneto-transport measurements are performed on two-dimensional GaAs electron systems to probe the quantum Hall (QH) effect at low magnetic fields. Oscillations following the Shubnikov-de Haas (SdH) formula are observed in the transition from the insulator to QH liquid when the observed almost temperature-independent Hall slope indicates insignificant interaction correction. Our study shows that the existence of SdH oscillations in such a transition can be understood based on the non-interacting model.