液相色谱-串联质谱法监测不同负荷方案替考拉宁治疗骨髓炎患者的血药浓度比较

目的建立并验证液相色谱-串联质谱法(LC-MS/MS)检测替考拉宁血浆浓度,并分析我院不同负荷方案骨髓炎患者的替考拉宁谷浓度(C_(min))达标情况。方法建立LC-MS/MS法测定替考拉宁的C_(min),考察方法的专属性、标准曲线、精密度与回收率、基质效应和稳定性。收集43例接受替考拉宁治疗的骨髓炎患者,根据给药方案不同分为2组:试验组A患者接受3次负荷剂量400 mg,q12h,试验组B患者接受6次负荷剂量400 mg,q12h,同时进行治疗药物监测(TDM)。两组均于第4天维持剂量给药前30 min采样,检测患者替考拉宁C_(min)值,比较两组替考拉宁C_(min)达标情况。结果血浆中替考拉宁标准曲线方程为Y=0.0324X+0.000886(r=0.9964),在0.20~50.00μg·m L^(-1)内线性关系良好;质控样本的准确度为94.71%~112.50%内;日内、日间RSD为3.17%~15.19%;提取回收率为81.22%~91.26%;基质效应为93.54%~119.78%。临床应用中,试验组A负荷剂量后替考拉宁平均C_(min)为(8.32±4.76μg·mL^(-1),C_(min)≥10μg·mL^(-1)比例仅为25.90%;试验组B负荷剂量后替考拉宁平均C_(min)为(19.58±7.78)μg·mL^(-1),16例患者C_(min)均≥10μg·mL^(-1);两组平均C_(min)差异有统计学意义(P<0.0001)。结论建立的LC-MS/MS方法适用于替考拉宁常规TDM。临床应用中,低频次负荷方案下替考拉宁C_(min)达标情况较差,而TDM指导的高频次负荷方案下替考拉宁C_(min)达标情况更优。研究表明替考拉宁TDM的重要性,尤其是针对感染高危患者人群。

Targeting mTOR network in colorectal cancer therapy

The mechanistic target of rapamycin(mTOR)integrates growth factor signals with cellular nutrient and energy levels and coordinates cell growth,proliferation and survival.A regulatory network with multiple feedback loops has evolved to ensure the exquisite regulation of cell growth and division.Colorectal cancer is the most intensively studied cancer because of its high incidence and mortality rate.Multiple genetic alterations are involved in colorectal carcinogenesis,including oncogenic Ras activation,phosphatidylinositol 3-kinase pathway hyperactivation,p 53 mutation,and dysregulation of wnt pathway.Many oncogenic pathways activate the mTOR pathway.mTOR has emerged as an effective target for colorectal cancer therapy.In vitro and preclinical studies targeting the mTOR pathway for colorectal cancer chemotherapy have provided promising perspectives.However,the overall objective response rates in major solid tumors achieved with single-agent rapalog therapy have been modest,especially in advanced metastatic colorectal cancer.Combination regimens of mTOR inhibitor with agents such as cytotoxic chemotherapy,inhibitors of vascular endothelial growth factor,epidermal growth factor receptor and Mitogen-activated protein kinase kinase(MEK)inhibitors are being intensively studied and appear to be promising.Further understanding of the molecular mechanism in mTOR signaling network is needed to develop optimized therapeutic regimens.In this paper,oncogenic gene alterations in colorectal cancer,as well as their interaction with the mTOR pathway,are systematically summarized.The most recent preclinical and clinical anticancer therapeutic endeavors are reviewed.New players in mTOR signaling pathway,such as nonsteroidal anti-inflammatory drug and metformin with therapeutic potentials are also discussed here.

Recurrent coronal jets observed by SDO/AIA

In this paper,we carried out multiwavelength observations of three recurring jets on 2014November 7.The jets originated from the same region at the edge of AR 12205 and propagated along the same coronal loop.The eruptions were generated by magnetic reconnection,which is evidenced by continuous magnetic cancellation at the jet base.The projected initial velocity of jet2 is~402 km s^(-1).The accelerations in the ascending and descending phases of jet2 are not consistent,the former is considerably larger than the value of g_(⊙) at the solar surface,while the latter is lower than g_(⊙).There are two possible candidates of extra forces acting on jet2 during its propagation.One is the downward gas pressure from jet1when it falls back and meets with jet2.The other is the viscous drag from the surrounding plasma during the fast propagation of jet2.As a contrast,the accelerations of jet3 in the rising and falling phases are constant,implying that the propagation of jet3 is not significantly influenced by extra forces.

Structural and Rheological Properties of PP/EPR/PE Alloys

Linear and non-linear rheological properties were examined for in-reactor alloy samples composed of isotactic polypropylene(iPP),ethylene-propylene rubber(EPR),and polyethylene(PE).The samples were prepared through two-or three-stage sequential polymerization,where iPP,as the majority,was synthesized in the first stage,and either EPR or PE,as the minority,was synthesized in the second or third stage.Above Tm of both PE and iPP,the linear viscoelasticity shows two relaxation processes,where the fast and slow processes are attributable to the relaxation of the iPP component and that of the EPR/PE domains,respectively.Both the damping behavior upon applying the step-strain measurements and the shear-thinning behavior under the shear-rate sweep measurements are strongly related to the different degrees of nonlinearity of the two relaxation processes.

Interaction of brassinosteroid and cytokinin promotes ovule initiation and increases seed number per silique in Arabidopsis

Ovule initiation is a key step that strongly influences ovule number and seed yield.Notably,mutants with enhanced brassinosteroid(BR)and cytokinin(CK)signaling produce more ovules and have a higher seed number per silique(SNS)than wild-type plants.Here,we crossed BR-and CKrelated mutants to test whether these phytohormones function together in ovule initiation.We determined that simultaneously enhancing BR and CK contents led to higher ovule and seed numbers than enhancing BR or CK separately,and BR and CK enhanced each other.Further,the BR-response transcription factor BZR1 directly interacted with the CK-response transcription factor ARABIDOPSIS RESPONSE REGULATOR1(ARR1).Treatments with BR or BR plus CK strengthened this interaction and subsequent ARR1 targeting and induction of downstream genes to promote ovule initiation.Enhanced CK signaling partially rescued the reduced SNS phenotype of BR-deficient/insensitive mutants whereas enhanced BR signaling failed to rescue the low SNS of CK-deficient mutants,suggesting that BR regulates ovule initiation and SNS through CK-mediated and-independent pathways.Our study thus reveals that interaction between BR and CK promotes ovule initiation and increases seed number,providing important clues for increasing the seed yield of dicot crops.

Effect of Short-Range Ordering on the Strength-Ductility Synergy of Fine-Grained Cu–Mn Alloys at Different Temperatures

Uniaxial tensile tests were carried out at room temperature(RT)and 250℃,respectively,to investigate the effect of shortrange ordering(SRO)on the mechanical properties and deformation micromechanism of fine-grained(FG)Cu–Mn alloys with high stacking fault energy.The results show that at RT,with the increase in SRO degree,the strength of FG Cu–Mn alloys is improved without a loss of ductility,and corresponding deformation micromechanism is mainly manifested by a decrease in the size of dislocation cells.In contrast,at a high temperature of 250℃,the SRO degree becomes violently enhanced with increasing Mn content,and the deformation microstructures thus transform from dislocation cells to planar slip bands and even to deformation twins,significantly enhancing the work hardening capacity of the alloys and thus achieving a better strength-ductility synergy of FG Cu–Mn alloys.

非缠结对称缔合链在蠕变过程中的动力学行为研究

首先介绍具有摩擦系数分布的Rouse链的动力学分析方法,并检验了其应用于预测未缠结缔合高分子动力学行为的可行性.之后利用上述方法研究不同缔合点数量的高分子链分别在固定应变速率的启动剪切(start-up)和固定应力的蠕变(creep)测试过程中,链段的取向函数随时间的变化行为.阐明了缔合体系在蠕变条件下,高分子链从链段相对独立的运动到整链协同运动的转变机制.

The Latest Research Progress of New Self-Repairing Energetic Compositest

This review summarizes research progress in self-repairing energetic composites based on the design of chemical structure of binders and the introduction of self-repairing properties between composite interfaces.Researchers have prepared the polyurethane-urea binder and the GAP self-repairingbinder based on the disulfide bond,the polyurethane binder and FTPB-PDMl binder based on the Diels-Alder reaction,and the polyurethane binderbased on dynamic photocroslinking reaction.In addition,PVDF-coHFP/EMIOTf/graphene achieves the self-repairing behavior of the polymer bondedexplosive(PBX).The future development of elf-repairing energetc composites is proposed.lt is pointed out that the mechanical properties,processingproperties and energy properties should be improved together with the introduction of self-repairing properties,and the energetic composites whichcan be repaired in various ways should be prepared.