BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants signif...BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.展开更多
Two X-type chromophores, 2-[4-(4,5-di(4-nitrophenyl) imidazolyl) phenyl]-4,5-di(4-methoxyphenyl)-imidazole (DNPIPDMOPI), 2-[4-(4,5-di(4-nitrophenyl)-imidazolyl) phenyl]-4,5-di(4-aminophenyl)-imidazole (DNPIPDAPI), wer...Two X-type chromophores, 2-[4-(4,5-di(4-nitrophenyl) imidazolyl) phenyl]-4,5-di(4-methoxyphenyl)-imidazole (DNPIPDMOPI), 2-[4-(4,5-di(4-nitrophenyl)-imidazolyl) phenyl]-4,5-di(4-aminophenyl)-imidazole (DNPIPDAPI), were synthesized and characterized. The results show that they possess good nonlinearity, considerable blue-shifted absorption (385 nm and 379 nm in THF) and high decomposition temperature (377 'C and 405 'C). These mean that the X-type chromophores possess a rather good nonlinearity-transparency-thermal stability trade-off. The multi-step corona-poling technique at elevated temperature and in-situ SHG measurements were used to obtain and evaluate the poled films of these chromophores doped in PMMA. The largest SHG signals appeared at 110-120°C, which are 12.5 pm/V and 16.7 pm/V respectively. The dependence of poling induced orientation stability on temperature was measured by depoling experiments and the results indicate that the poling-induced orientation of the films is stable at about 100°C. Theoretic analyses imply that better orientation stability arises from the X-type structure of chromophore. The X-type chromophore has two crossed intramolecular CT, both β xxx and β xyy can contribute to the second-order susceptibility, and the ratio of the tensorial components (γ= β xyy /β xxx ) is about 1/3, so the orientation decay of the films induced by rising temperature will provide a certain compensation for the contribution of β xyy of chromophores.展开更多
A new type of ultra-lightweight metallic lattice structure (named as the X-type structure) is reported. This periodic structure was formed by two groups of staggered struts in the traditional pyramid structure, and fa...A new type of ultra-lightweight metallic lattice structure (named as the X-type structure) is reported. This periodic structure was formed by two groups of staggered struts in the traditional pyramid structure, and fabricated by folding expanded metal sheet along rows of offset nodes and then brazing the folded structure (as the core) with top and bottom facesheets to form sandwich panels. The out-of-plane compressive and shear properties of the X-type lattice sandwich structure were investigated experimentally and compared to those of the sandwich having a pyramidal truss core. It is found that the formation of the 2-dimensional staggered nodes can effectively make the X-type structure more resistant to inelastic and plastic buckling under both compression and shear loading than the pyramidal lattice truss. Obtained results show that the compressive and shear peak strengths of the X-type lattice structure are about 30% higher than those of the pyramidal lattice truss having the same relative density.展开更多
The expanded metal sheets were folded with 11% work-hardening. These were sub- sequently used with resistance welding to construct X-type lattice truss sandwich panels having a core relative density of 0.17. The sandw...The expanded metal sheets were folded with 11% work-hardening. These were sub- sequently used with resistance welding to construct X-type lattice truss sandwich panels having a core relative density of 0.17. The sandwich panels were tested in uniaxial compression and, for comparison, the method of finite elements was employed to simulate the measured compressive stress-strain curves. The peak compressive strength was 32% higher than that of pyramidal core sandwiches. The enhanced mechanical properties of the work-hardened X-Type lattice structures mainly originate from the contribution of straight struts with low degree of curvature and work hardening, rather than the two-dimensional staggered nodes.展开更多
基金Supported by the National Natural Science Foundation of China,No.81573507,No.81473283,No.81173131,and No.81320108027Guangdong Provincial Key Laboratory Construction Foundation,No.2017B030314030+1 种基金The National Key Research and Development Program,No.2016YFC0905003the 111 Project,No.B16047
文摘BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.
基金This work was supported by the National Natural Science Foundation of China (No. 90201005).
文摘Two X-type chromophores, 2-[4-(4,5-di(4-nitrophenyl) imidazolyl) phenyl]-4,5-di(4-methoxyphenyl)-imidazole (DNPIPDMOPI), 2-[4-(4,5-di(4-nitrophenyl)-imidazolyl) phenyl]-4,5-di(4-aminophenyl)-imidazole (DNPIPDAPI), were synthesized and characterized. The results show that they possess good nonlinearity, considerable blue-shifted absorption (385 nm and 379 nm in THF) and high decomposition temperature (377 'C and 405 'C). These mean that the X-type chromophores possess a rather good nonlinearity-transparency-thermal stability trade-off. The multi-step corona-poling technique at elevated temperature and in-situ SHG measurements were used to obtain and evaluate the poled films of these chromophores doped in PMMA. The largest SHG signals appeared at 110-120°C, which are 12.5 pm/V and 16.7 pm/V respectively. The dependence of poling induced orientation stability on temperature was measured by depoling experiments and the results indicate that the poling-induced orientation of the films is stable at about 100°C. Theoretic analyses imply that better orientation stability arises from the X-type structure of chromophore. The X-type chromophore has two crossed intramolecular CT, both β xxx and β xyy can contribute to the second-order susceptibility, and the ratio of the tensorial components (γ= β xyy /β xxx ) is about 1/3, so the orientation decay of the films induced by rising temperature will provide a certain compensation for the contribution of β xyy of chromophores.
基金Supported by the National Basic Research Program of China ("973" Project) (Grant No. 2006CB601202)the National Natural Science Foundation of China (Grant Nos. 10632060,10825210)+1 种基金the National "111" Project of China (Grant No. B06024)the National High-Tech Research and Development Program of China ("863" Project) (Grant No. 2006AA03Z519)
文摘A new type of ultra-lightweight metallic lattice structure (named as the X-type structure) is reported. This periodic structure was formed by two groups of staggered struts in the traditional pyramid structure, and fabricated by folding expanded metal sheet along rows of offset nodes and then brazing the folded structure (as the core) with top and bottom facesheets to form sandwich panels. The out-of-plane compressive and shear properties of the X-type lattice sandwich structure were investigated experimentally and compared to those of the sandwich having a pyramidal truss core. It is found that the formation of the 2-dimensional staggered nodes can effectively make the X-type structure more resistant to inelastic and plastic buckling under both compression and shear loading than the pyramidal lattice truss. Obtained results show that the compressive and shear peak strengths of the X-type lattice structure are about 30% higher than those of the pyramidal lattice truss having the same relative density.
基金supported by the National Basic Research Program of China(No. 2011CB610300)the National Science Foundation for Young Scientists of China(No. 11102152)+1 种基金the Fundamental Research Funds for Xi'an Jiaotong University(No. xjj2011007)the National 111 Project of China (No. B06024)
文摘The expanded metal sheets were folded with 11% work-hardening. These were sub- sequently used with resistance welding to construct X-type lattice truss sandwich panels having a core relative density of 0.17. The sandwich panels were tested in uniaxial compression and, for comparison, the method of finite elements was employed to simulate the measured compressive stress-strain curves. The peak compressive strength was 32% higher than that of pyramidal core sandwiches. The enhanced mechanical properties of the work-hardened X-Type lattice structures mainly originate from the contribution of straight struts with low degree of curvature and work hardening, rather than the two-dimensional staggered nodes.
