血清AFP-L2与NIPT联合超声NT值在胎儿异常染色体筛查中的应用价值

目的探讨血清甲胎蛋白异质体L2(AFP-L2)、无创产前基因检测(NIPT)技术联合超声胎儿后颈部透明层的厚度(NT)值对24~28^(+6)胎儿染色体异常筛查的价值。方法选取2021年9月至2022年9月于医院接受早期孕检确认染色体异常的孕妇120例纳入染色体异常组,选取同期接受正常孕检且已完成胎儿染色体异常筛查的孕妇120名作为健康志愿者。对所有受检孕妇分别采取超声检查NT、血清AFP-L2检查、NIPT技术单独检测及三者联合检测。比较4种检测方式的阳性、阴性检出情况,以及4种检测方式对提高胎儿染色体异常筛查的诊断效能。结果与健康志愿者比较,染色体异常组胎儿AFP-L2检查水平较低,NT厚度较高(P<0.05)。与超声检查比较,血清AFP-L2检查、NIPT检查、联合检查阳性预测值、阴性预测值较高(P<0.05);与血清AFP-12检查比较,超声检查阳性预测值、阴性预测值较低,NIPT检查、联合检查阳性预测值、阴性预测值较高;与NIPT检查比较,血清AFP-12检查、超声检查阳性预测值、阴性预测值较低,联合检查阳性预测值、阴性预测值较高(P<0.05)。与超声检查比较,血清AFP-L2检查、NIPT检查、联合检查灵敏度、特异度和准确率较高(P<0.05);NIPT检查技术对于性染色体异常的总阳性预测值(PPV)为92.24%;对于54,X(含嵌合体)、54,XXX、54,XXY、54,XYY、性染色体微缺失微重复的PPV分别为49.05%、79.15%、85.55%、43.19%、57.69%。与血清AFP-12检查比较,超声检查灵敏度、特异度和准确率较低,NIPT检查、联合检查灵敏度、特异度和准确率较高,与NIPT检查比较,超声检查、血清AFP-12检查灵敏度、特异度和准确率较低,联合检查灵敏度、特异度和准确率较高(P<0.05)。结论通过超声检查、血清AFP-L2检查、NIPT技术对胎儿染色体不正常进行筛查,提高对胎儿染色体异常筛查的准确率,降低误诊率,具有良好的诊断效能。超声、血清AFP-L2检查联合NIPT技术对胎儿染色体异常筛查具有重要意义。

低成瘾性阿片类镇痛药物研发现状和趋势

阿片类药物在疼痛治疗中发挥重要作用,但其在有效控制各类型急性和慢性疼痛的同时,也带来非医疗目的用药和药物成瘾的风险,造成阿片类药物危机。阿片受体在中枢神经系统广泛分布,介导复杂的生物学效应。阿片类镇痛药物的不良反应如呼吸抑制、依赖和成瘾等严重限制了其临床应用。目前,低成瘾性阿片类镇痛药物研发策略主要包括防滥用新制剂、靶向外周的阿片受体激动剂、阿片受体G蛋白信号通路偏向性激动剂、阿片受体异聚体激动剂和阿片受体多功能配体等,大部分正在进行非临床或临床研究,有一些新制剂药物已经上市。但这些措施在产生镇痛或其他治疗益处的同时,仍在一定程度上保留了传统阿片类镇痛药物的潜在滥用风险和其他不良反应,如何将镇痛作用与成瘾潜能完全分离面临重大挑战。因此,新型低成瘾性阿片类镇痛药物的研发仍需更多努力。

Three-dimensional simulation of long-wavelength free-electron lasers with helical wiggler and ion-channel guiding

A three-dimensional simulation of a steady-state amplifier model of a long-wavelength free-electron laser （FEL） with realizable helical wiggler and ion-channel guiding is presented. The set of coupled nonlinear differential equations for electron orbits and fields of TE 11 mode in a cylindrical waveguide are solved numerically by the Runge–Kutta algorithm with averages calculated by the Gaussian quadrature technique. Self-fields and space-charge effects are neglected, and the electron beam is assumed to be cold and slippage is ignored. The parameters correspond to the Compton regime. Evolution of the radiation power and growth rate along the wiggler is studied. Ion-channel density is chosen to obtain optimum efficiency. Simulations are preformed for the FEL operating in the neighborhood of 35 GHz and 16.5 GHz for the electron beam energies of 250 keV and 400 keV, respectively. The result of the saturated efficiency was found to be in good agreement with the simple estimation based on the phase-trapping model.

Gain calculation of a free-electron laser operating with a non-uniform ion-channel guide

Amplification of an electromagnetic wave by a free electron laser （FEL） with a helical wiggler and an ion channel with a periodically varying ion density is examined. The relativistic equation of motion for a single electron in the combined wiggler and the periodic ionbchannel fields is solved and the classes of possible trajectories in this configuration are discussed. The gain equation for the FEL in the low-gain-per-pass lirnit is obtained by adding the effect of the periodic ion channel. Numerical calculation is employed to analyse the gain induced by the effects of the non-uniform ion density. The variation of gain with ion-channel density is demonstrated. It is shown that there is a gain enhancement for group I orbits in the presence of a non-uniform ion-channel but not in a uniform one. It is also shown that periodic ion-channel guiding is used to reach the maximum peak gain in a low ion-channel frequency （low ion density）.

Anti-proliferative and anti-angiogenic activities of ion-channel modulators:In-ovo,in-vitro and in-vivo study

Objective:Angiogenesis is the development of new blood vessels.The ion channels on endothelium play a vital action in cell proliferation and so in the related angiogenesis.We aimed to investigate the anti-angiogenic effects of Mefloquine(Cl-channel blocker) and4-Aminopyridine(K+ channel blocker).Methods:The anti-angiogenic activities of Mefloquine and 4-Aminopyridine(4-AP)were investigated by in-vivo(sponge implantation method),in-vitro(aortic ring assay)and in-ovo(CAM,Chick Chorioallantoic membrane) methods.The standard antiangiogenic drug used was Bevacizumab.Results:In the CAM assay,both the ion channel blockers exhibited noticeable antiangiogenic activity at the concentrations of 10-5M and 10-4M where they significantly exhibited ant proliferative activity by inhibiting the new blood vessel formation.For the further confirmation anti-angiogenic activity was evaluated in vitro and in vivo.In Rat aortic ring assay reduction in the area of sprouts were observed with 40 m M of 4-AP and7 m M of Mefloquine.A significant reduction in weight of sponges,number of blood vessels formed and hemoglobin content were observed at 4.2 mg/kg of 4-AP and 20 mg/kg and 30 mg/kg of Mefloquine.Conclusions:These scientific findings indicate the use of Mefloquine and 4-Aminopyridine in pathological situations involving excessive angiogenesis.Negative regulation of cell volume,cell migration and proliferation of blood vessels may be the underlying molecular mechanisms.

阿片受体最新研究进展

作为一类经典镇痛药物,阿片类药物广受医学界关注。除了疼痛调制和成瘾,阿片受体还广泛参与各种生理以及病理活动。阿片受体是体内最错综复杂的神经递质系统。3种不同的阿片受体通过在大脑及其他器官的交叉分布调节着阿片类药物的功能作用。由于目前阿片受体在大脑内的功能尚未清楚,以至于阿片类药物更为广泛的临床应用受限。随着人类对阿片受体亚型及晶体结构的发现及了解,阿片类药物的使用范围将会更广泛,应用效果将会更精准。

Safety-Critical System Reliability Modeling and Their Analyses in Terms of Effects of Component Failure Modes

New models of safety-critical systems are built here. In these systems, when components fail, different defect states have different effects, hence need different ways to measure. In the models, there are two kinds of failure modes of the components： one could be called failed-safe, and the other may be named failed- dangerous In practice, the so-called failed-dangerous components may lead a system to peril. However, failed-safe components will not. Reliability and safety issues are analyzed using Ion-Channel modeling theory to get count of repairs and time duration before the system becomes dangerous. In the closing section a numerical example is presented to illustrate the results obtained in the paper.

Dispersion relation and growth rate for a corrugated channel free-electron laser with a helical wiggler pump

The effects of corrugated ion channels on electron trajectories and spatial growth rate for a free-electron laser with a one-dimensional helical wiggler have been investigated. Analysis of the steady-state electron trajectories is performed by solving the equations of motion. Our results show that the presence of a corrugated channel shifts the resonance frequency to smaller values of ion channel frequency. The sixth-order dispersion equation describing the coupling between the electrostatic beam mode and the electromagnetic mode has also been derived. The dispersion relation characteristic is analyzed in detail by numerical solution. Results show that the growth rate of instability in the presence of corrugated ion channels can be greatly enhanced relative to the case of an uniform ion channel.

Heteromeric and Homomeric Geranyl Diphosphate Synthases from Catharanthus roseus and Their Role in Monoterpene Indole Alkaloid Biosynthesis

Catharanthus roseus is the sole source of two most important monoterpene indole alkaloid （MIA） anti- cancer agents： vinblastine and vincristine. MIAs possess a terpene and an indole moiety derived from terpenoid and shikimate pathways, respectively. Geranyl diphosphate （GPP）, the entry point to the formation of terpene moiety, is a product of the condensation of isopentenyl diphosphate （IPP） and dimethylallyl diphosphate （DMAPP） by GPP synthase （GPPS）. Here, we report three genes encoding proteins with sequence similarity to large subunit （CrGPPS.LSU） and small subunit （CrGPPS.SSU） of heteromeric GPPSs, and a homomeric GPPSs. CrGPPS.LSU is a bifunctional enzyme producing both GPP and geranyl geranyl diphosphate （GGPP）, CrGPPS.SSU is inactive, whereas CrGPPS is a homomeric enzyme forming GPP. Co-expression of both subunits in Escherichia coil resulted in heteromeric enzyme with enhanced activity producing only GPR While CrGPPS.LSU and CrGPPS showed higher expression in older and younger leaves, respectively, CrGPPS.SSU showed an increasing trend and decreased gradually. Methyl jasmonate （MelA） treatment of leaves sig- nificantly induced the expression of only CrGPPS.SSU. GFP localization indicated that CrGPPS.SSU is plastidial whereas CrGPPS is mitochondrial. Transient overexpression of AmGPPS.SSU in C. roseus leaves resulted in increased vindoline, immediate monomeric precursor of vinblastine and vincristine. Although C. roseus has both heteromeric and homomeric GPPS enzymes, our results implicate the involvement of only heteromeric GPPS with CrGPPS.SSU regulating the GPP flux for MIA biosynthesis.

Electron acceleration in the inverse free electron laser with a helical wiggler by axial magnetic field and ion-channel guiding

Electron acceleration in the inverse free electron laser （IFEL） with a helical wiggler in the presence of ion-channel guiding and axial magnetic field is investigated in this article. The effects of tapering wiggler amplitude and axial magnetic field are calculated for the electron acceleration. In free electron lasers, electron beams lose energy through radiation while in IFEL electron beams gain energy from the laser. The equation of electron motion and the equation of energy exchange between a single electron and electromagnetic waves are derived and then solved numerically using the fourth order Runge-Kutta method. The tapering effects of a wiggler magnetic field on electron acceleration are investigated and the results show that the electron acceleration increases in the case of a tapered wiggler magnetic field with a proper taper constant.

Exercise and Ion-Channel Remodeling in Vascular Smooth Muscle During Hypertension:Therapeutic Implications

Myogenic contraction of vascular smooth muscle cells(VSMCs)in resistance arteries and arterioles plays a critical role in regulating peripheral resistance.Ion channels expressed in VSMCs control ion influx or efflux from the plasma membrane and endoplasmic reticulum to regulate membrane potential,which contributes to the regulation of vascular tone.With the depolarization of VSMC membranes,an elevation of intracellular calcium ion(Ca^(2+))concentration is mediated by voltage-gated Ca^(2+)channels and can trigger a vasoconstrictive response.In addition,potassium ion(K^(+))efflux through K^(+)channels can hyperpolarize VSMCs,resulting in vasodilation.However,in the pathophysiological progression of diseases such as hypertension,VSMCs undergo a wide range of pathological changes,among them is"electrical remodeling",which refers to changes in ion channels.Under physiological or pathological conditions,exercise has a profound impact on the human body,and ion channels are an essential target of the beneficial adaptive responses.This review provides insight on the physi-ological function of ion channels in VSMCs,including Cav1.2 channels,voltage-gated K^(+)channels,large-conductance Ca^(2+)-activated K^(+)channels,and inward-rectifier K^(+)channels,and the changes of these ion channels during hypertension.Focus is given to the effects of exercise on these ion channels and its implications in disease treatment.

酸敏感离子通道在大鼠岩神经节神经元的表达

目的:探讨酸敏感离子通道(acid-sensing ion channels,ASICs)的四种亚型即ASIC1a、ASIC1b、ASIC2a和ASIC3是否表达于大鼠岩神经节(petrosal ganglion)神经元。方法:采用常规免疫组化法(PV法),观察正常大鼠岩神经节神经元是否表达ASIC1a、ASIC1b、ASIC2a和ASIC3。结果:在正常大鼠岩神经节神经元,可见ASIC1a、ASIC1b、ASIC2a和ASIC3表达;ASIC1a与ASIC2a,ASIC3与ASIC1b,ASIC3与ASIC1a,ASIC3与ASIC2a在岩神经节神经元上共表达。结论:正常生理情况下,大鼠岩神经节神经元均表达ASIC1a、ASIC1b、ASIC2a和ASIC3;ASICs亚型之间的共表达提示,在岩神经节可能存在ASICs异聚体的方式。

Recent development in NMDA receptors

Purpose To identify the structure and the function of NMDA receptors, to understand the modulatory mechanism of some endogenous and exogenous compounds on NMDA receptors, and to provide theoretical basis for developing new drugs that modulate NMDA receptors Data sources A total of 24 originally identified articles were selected Study selection A total of 24 articles were selected from several hundred original articles or reviews. The content of selected articles are in accordance with our purpose and the authors are authorized scientists in the study on NMDA receptors.Data extraction After careful review of the selected papers, the meaningful results and conclusions were extracted using scientific criteria and our experience in the research of NMDA receptors.Results NMDA receptor contains at least five subunits. They were designated as the NR1 (ζ1), NR2A (ε1), NR2B (ε2), NR2C (ε3), and NR2D (ε4). A unique feature of NMDA receptor is the requirement for both glutamate and the co agnist glycine for the efficient gating. NMDA receptor is modulated by a number of endogenous and exogenous compounds. Mg 2+ not only blocks the NMDA channel in a voltage dependent manner but also potentiates NMDA induced responses at positive membrane potentials. Na +, K + and Ca 2+ not only pass through the NMDA receptor channel but also modulate the activity of NMDA receptors. Zn 2+ blocks the NMDA current in a noncompetitive and a voltage independent manner. It has been demonstrated that polyamines do not directly activate NMDA receptors, but instead act to potentiate or inhibit glutamate mediated responses. The activity of NMDA receptors is also strikingly sensitive to the changes in H + concentration, and partially inhibited by the ambient concentration of H + under physiological conditions.Conclusions NMDA receptors are glutamate regulated by ion channels that are permeable to Ca 2+ , Na +, K + and are sensitive to voltage dependent Mg 2+ block This channel complex contributes to excitatory synaptic transmission at sites throughout the brain and the spinal cord,and is modulated by a number of endogenous and exogenous compounds NMDA receptors play a key role in wide range of physiologic and pathologic processes Five NMDA receptor subunits have now been characterized in both rat and mouse brain

甲胎蛋白异质体3与AFP比值对原发性肝癌患者超选择性肝动脉栓塞治疗效果的预测价值

目的探讨甲胎蛋白异质体3与AFP比值(AFP-L3%)对原发性肝癌(PLC)患者超选择性肝动脉栓塞治疗效果的预测价值。方法行超选择性肝动脉栓塞治疗的PLC患者212例,依据治疗后3个月近期疗效分为有效组(98例)和无效组(114例),于术前和术后30 d检测血清中甲胎蛋白(AFP),计算AFP-L3%,分析其对PLC患者超选择性肝动脉栓塞治疗效果的预测价值。结果超选择性肝动脉栓塞治疗PLC的总有效率为46.23%(98/212)。有效组肿瘤病灶直径小于无效组(P<0.05)。两组术后30 d,血清AFP水平和AFP-L3%均较术前降低(P<0.05),有效组上述指标降低程度大于无效组(P<0.05)。ROC曲线分析显示,术前AFP和AFP-L3%预测PLC经超选择性肝动脉栓塞治疗有效的AUC分别为0.715[95%CI(0.646~0.783),P<0.05]和0.673[95%CI(0.602~0.745),P<0.05],术后30 d为0.625[95%CI(0.547~0.703),P<0.05]和0.852[95%CI(0.803~0.900),P<0.05]。结论术后30 d,AFP-L3%对PLC患者超选择性肝动脉栓塞治疗疗效的预测价值优于AFP。

P2X受体内源性异源三聚体的研究进展

离子通道型嘌呤能受体P2X是一类可被胞外ATP激活的配体门控阳离子通道,以同源或异源三聚体的形式行使功能。它们广泛分布于全身各组织,参与多种生理病理学过程,是一类重要的新药靶标。由于P2X异聚体的研究较同聚体复杂,一定程度上阻碍了其特异性靶向药物的研发。本文就P2X异聚体的成员分类、亚基组成计量学、参与的生理病理过程以及相关靶向药物研发进行了综述。