ALK阳性非小细胞肺癌靶向治疗耐药机制及治疗管理的研究进展

目前,肺癌仍是世界上最常见的恶性肿瘤,位居癌症死亡原因的第1位,随着靶向治疗的发展,死亡率已显著降低。间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)作为对治疗有显著反应的非小细胞肺癌(non-small cell lung carcinoma,NSCLC)基因型,发展至今已有三代针对其靶位的间变性淋巴瘤激酶酪氨酸激酶抑制剂(anaplastic lymphoma kinase-tyrosine kinase inhibitors,ALK-TKIs),新一代的ALK-TKIs比上一代具有更为广泛的作用位点覆盖范围及更强的药物组织穿透能力。发展前路可观,但仍无法规避耐药问题,随着多种ALK抑制剂应用及联合治疗的选择增多,新的耐药后突变、复合突变以及其他多种耐药机制已逐渐被关注。与此同时,相关早期诊断及预后标志物也被发掘证实。NSCLC耐药机制及检测手段在不断更新,治疗以基于基因依赖性的个体化治疗为主,以期通过对多种耐药方式的介入,使得NSCLC逐渐转变为慢性病。本文归纳介绍了ALK抑制剂应用于NSCLC的现状及耐药机制,耐药后治疗策略及诊断和预后标志物的进展,旨在为ALK阳性NSCLC的诊治及耐药后管理策略提供参考依据。

Hydrogen storage behavior of Mg-based alloy catalyzed by carbon-cobalt composites

The composites comprised of Co nanoparticle and C nanosheet were prepared though a high-temperature carbonization reaction.The catalysis of Co@C composites on the hydrogen storage behavior of Mg_(90)Ce_(5)Y_(5)alloy was investigated in detail by XRD,SEM,TEM,PCI,and DSC method.Because of the synergistic catalytic function of C and Co in C@Co nanocomposites,the Mg_(90)Ce_(5)Y_(5)alloy with 10 wt.%C@Co shows the excellent hydrogen absorption and desorption performances.Time for releasing hydrogen reduces from 150 min to 11 min with the addition of the C@Co composites at the temperature of 300℃.Meanwhile,the dehydrogenation activation energy also declines from 130.3 to 81.9 kJ mol^(-1)H_(2)after the addition of the C@Co composites.This positive effect attributes to the C layer with the high defect density and the Co nanoparticles,which reduces the energy barriers for the nucleation of Mg/MgH_(2)phase and the recombination of hydrogen molecule.Besides,the C@Co composites also improve the activation property of the Mg_(90)Ce_(5)Y_(5)alloy which was folly activated in the first cycle.Moreover,the temperature for initial dehydrogenation and the endothermic peak of the alloy hydride were also decreased.Although the addition of the C@Co composites increases the plateau pressures and decreases the value of the decomposition enthalpy,these differences are so small that the improvement on thermodynamics can hardly be seen.

CO_2 sensing properties and mechanism of PrFeO_3 and NdFeO_3 thick film sensor

The CO_2 sensing of PrFeO_3 and NdFeO_3 sensors were investigated. Experimental results show that the resistances for PrFeO_3 and NdFeO_3 in CO_2 gas are larger than those in air and the responses for PrFeO_3and NdFeO_3 sensors increase with an increase in room-temperature relative humidity. When exposed to1000 ppm CO_2, the response of PrFeO_3 thick film based on nano-powders annealed at 700℃can reach8.44 at 160℃for the background of wet air with 58%of room-temperature relative humidity (RH),which is much larger than the corresponding value (3.03) in wet air with 25%RH. The sensing response S of NdFeO_3 thick-film sensor based on nano-powders annealed at 600℃to 3000 ppm CO_2 at the operating temperature 200℃can reach 2.36 for the background of wet air with 72%RH, which is larger than the corresponding value (1.83) in the air with 25%RH. Compared with other CO_2 sensing materials, the PrFeO_3 sensor has larger response at lower operating temperature for CO_2 gas and may be used as a new CO_2 sensing material.

Extraordinary simultaneous enhancement of the coercivity and remanence of dual alloy HRE-free Nd-Fe-B sintered magnets by post-sinter annealing

Post-sinter annealing process plays an important role in the microstructures and magnetic properties of the Nd-Fe-B sintered magnets.In this paper,systematically investigated are the magnetic properties and microstructures of the as-sintered and post-sinter annealed Nd-Fe-B magnets with Pr-Fe-Ga boundary addition.Two choice consecutive annealing methods are adopted at high and low temperatures,namely the 1 st annealing at 880℃ for 2 h and then the 2^(nd) annealing at 440℃ for 3 h.It is exceptional to find out that both the remanence and coercivity are improved after 2^(nd) annealing process for this type of magnet.The coercivity is hugely increased from 10.09 kOe for the as-sintered sample to 17.19 kOe for the 2^(nd) annealed magnet,with a significant increment of 70.37%in coercivity.The extraordinary magnetic properties of B_(r)=14.44 kGs,H_(cj)=17.19 kOe and(BH)_(max)=51.08 MGOe are obtained for the designated Nd-Fe-B sintered magnets without heavy rare earth(HRE)elements manufactured by dual alloy method.The Curie temperature is monotonically decreased from 634 K to 602 K while the c-axis alignment degree is optimized after annealing.Microstructural observation and analysis indicate that the elemental distribution patterns are altered after the 2^(nd) annealing.The diffusion of the aggregate(Pr,Nd,Cu,Ga)-rich phase from triple junctions into the grain boundary regions is ascribed to the formation of thin and continuous grain boundary layer,which is critical to improve the microstructures and magnetic properties.

Linearly shifting ferromagnetic resonance response of La_(0.7)Sr_(0.3)MnO_(3) thin film for body temperature sensors

Human body temperature not only reflects vital signs,but also affects the state of various organs through blood circulation,and even affects lifespan.Here a wireless body temperature detection scheme was presented that the temperature was extracted by investigating the out-of-plane(OP)ferromagnetic resonance(FMR)field of 10.2 nm thick La_(0.7)Sr_(0.3)MnO_(3)(LSMO)film using electron paramagnetic resonance(EPR)technique.Within the range of 34-42℃,the OP FMR field changes linearly with the increasing or decreasing temperature,and this variation comes from the linear responses of magnetization to the fluctuant temperature.Using this method,a tiny temperature change(<0.1℃)of organisms can be detected accurately and sensitively,which shows great potential in body temperature monitoring for humans and mammals.

Phase evolution,hydrogen storage thermodynamics,and kinetics of ternary Mg_(98)Ho_(1.5)Fe_(0.5) alloy

Rare earth elements and transition metals have been found to improve the hydrogen storage characteristics of magnesium-based alloys.This study investigated the Mg-Ho-Fe(MHF) ternary alloy prepared using the vacuum induction melting technique.X-ray diffraction(XRD),scanning electron microscopy(SEM),transmission electron microscopy(TEM),pressure-composition-temperature(PCT),and differential scanning calorimetry(DSC) were used to analyze the alloy's phase transitions,microstructure,thermodynamics,and kinetic properties.The results reveal that the Mg_(98)Ho_(1.5)Fe_(0.5) alloy forms a solid solution with Ho and Fe in the magnesium matrix.Upon hydrogen absorption,the activated alloy transforms into a mixture of Mg/MgH_(2) phases and nanoscale HoH_(2) phases.Notably,only the MgH_(2) phase decomposes during hydrogen desorption,while the HoH_(2) phase remains unchanged,exhibiting a positive catalytic effect.The alloy demonstrates excellent hydrogen absorption kinetics,achieving a capacity of 5.56 wt% H_(2) within 10 min at 360℃,owing to the combined catalytic effects of Ho and Fe.The activation energy for hydrogen desorption is found to be 135.87 kJ/mol,which is lower than that of the activation energies of pure MgH_(2) and MgFe alloys,indicating an enhancement in desorption kinetics.Moreover,the enthalpy and entropy changes for hydrogen absorption and desorption are determined to be-70.51 kJ/mol H_(2),-125.62 J/(K·mol) H_(2),72.83 kJ/mol H_(2),and 128.95 J/(K·mol) H_(2),respectively.Furthermore,it is worth noting that the thermodynamic properties of the alloy are improved due to the catalytic effect of Ho and Fe.