High-dose methotrexate and zanubrutinib combination therapy for primary central nervous system lymphoma

In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.

Status of Renal and Liver Function in Rheumatoid Arthritis (RA) Patients of Chattogram, Bangladesh Treated with Methotrexate (MTX)

Rheumatoid Arthritis (RA) is a chronic autoimmune disorder that is usually manifested as inflammation in multiple joints and several extra-articular symptoms, involving the liver, kidney, eye, skin, blood, blood vessels, heart, lungs, nervous system, and other organs. Methotrexate (MTX) is the anchor drug that treats RA. As renal and liver abnormalities are more common during disease conditions as well as during the treatment period, we tried to find out if there is any impact of MTX in these organs during the treatment of RA patients. Once the disease complications are developed, it is quite difficult to reverse the disease, and treatment in this situation is not very effective. Consequently, patients suffer a lot. So, early evaluation of renal and liver function is essential for the treatment of RA patients and it might also help prevent different complications which are usually very frequently observed. This was a cross-sectional study. A total of 150 RA patients treated with MTX were evaluated for the study where female and male respondents were 115 and 35 respectively. In this study, we found that 82% of RA patients had creatinine levels ≤ 1.1 mg/dL although the normal range of serum creatinine is below 1.4 mg/dL. Usually, a 15% increase in Serum creatinine level from the baseline is considered renal impairment. We found 4% of such cases. Moreover, 2% of RA patients had creatinine levels above the normal range of 1.4 mg/dL and those patients were hypertensive as well. So, a total (4 + 2 = 6)% had renal impairments. Among them, 5% had diabetes mellitus. On the other hand, the ultrasonogram (USG) of RA patients with kidney disease showed signs of renal parenchymal disease and 3% of RA patients having renal problems whose serum creatinine level was within the normal range showed signs of chronic kidney disease (CKD). On the other hand, 2% of RA patients showed signs of hepatic parenchymal disease. In this study, 69% of RA patients had ALT levels ≤ 50 mg/dL, 23% had 50 - 100 mg/dL, and 5% had 101 - 150 mg/dL. The remaining 3% of RA patients had ALT levels above 150 mg/dL. All those patients with ALT levels above 100 mg/dL used Nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly. Different parameters of liver and renal function should be monitored strongly in RA patients treated with MTX and NSAIDs. MTX should not be given for a prolonged period without monitoring renal and liver function. As MTX, Diabetes Mellitus, Hypertension, etc., may cause renal complications, we could not concretely conclude which one is the actual causative agent.

ADS-B信号在对流层大气波导中的传播性能

对流层大气环境存在特殊大气结构“大气波导”,可形成电波超视距传播或产生雷达盲区等。目前,通过雷达、GNSS信号等可以对大气波导进行一定程度的反演探测,但均存在一定的不足。ADS-B信号具有应用范围广、信号密度大、实时性高等特点,为此提出利用ADS-B信号受到不同大气环境影响后能量损耗不同的特点对ADS-B信号与对流层大气环境关联性进行分析研究。以武汉地区ADS-B信号数据为例,基于抛物方程传播理论对路径损耗进行仿真分析,并进行了实验验证。结果表明:ADS-B接收信号与仿真结果存在线性相关性并给出线性表述,为后续利用ADS-B信号反演大气波导提供参考依据。

基于ADE优化的IPMSM全速域无传感器控制

为了实现内置式永磁同步电机(IPMSM)全速域的无传感器控制和切换速域的平滑过渡,提出了一种基于自适应差分进化(ADE)算法优化的复合控制方法。分别在零低速域、中高速域采用旋转高频电压注入法和滑模观测器法来对电机转速和转子位置进行估算,并在切换速域采用基于ADE算法的权重系数优化法来实现上述两种控制方法的平滑切换,从而实现IPMSM全速域无传感器控制。仿真结果表明:提出的复合控制方法能够实现电机全速域的无感控制和切换速域的平滑过渡,且具有良好的稳定性。

Conservative management of cervical pregnancy with intramuscular administration of methotrexate and KCl injection: Case report and review of the literature

We report the case of a cervical pregnancy successfully treated with intramuscular injection of methotrexate(MTX) and intramniotic administration of potassium chloride. A 41-year-old woman was admitted to our Department with the suspicion of ectopic pregnancy. Transvaginal ultrasound revealed empty endometrialcavity, gestational sac within the cervical canal and embryonic echo measuring crown rump length 1.5 mm. Serum beta human chorionic gonadotropine(β-HCG) was measured 28590 IU/L. No cardiac activity was detected. The diagnosis of a cervical pregnancy was made. Patient was treated with intramuscular administration of methotrexate(50 mg/m2) in combination with ultrasoundguided intramniotic injection of KCl(2 meq/mL). Gradual decrease of β-HCG levels as well as ultrasound observation of collapsed gestational sac was observed. No curettage was necessitated. Patient was discharged on day 10 th and was set in follow-up on a weekly basis. β-HCG values were measured < 10 IU/L on 56 th day after MTX administration. Intramuscular administration of MTX may be effective in treatment of cervical pregnancy without additional interventional measures.

Degradation of methotrexate by UV/peroxymonosulfate:Kinetics,effect of operational parameters and mechanism

Methotrexate(MTX)is one of the most consumed anti-cancer drugs in the pharmaceutical market around the world.The widespread occurrence of MTX in aquatic environment through hospital effluent has attracted increasing concern due to its potential to induce water pollution.In the present study,the degradation of MTX in aqueous medium was investigated by UV-activated peroxymonosulfate(PMS).A significant improvement in degradation rate by increasing UV intensity and PMS concentration while the decrease in degradation efficiency with the increase of solution p H and initial concentration of MTX was observed.The proposed UV/PMS process could achieve more than 90%MTX degradation in 30 min with a good mineralization degree(65%).A pseudofirst order kinetic model was employed and successfully predicted the degradation of MTX.The effect of other operational parameters such as the initial concentration of the targeted compound,dosage of oxidant(PMS),solution p H and UV intensity on the degradation rate were investigated.At the last,the main transform intermediates were identified using LC–MS and possible degradation pathways were proposed.The results show that UV/PMS can be used as an efficient technology to treat pharmaceuticals such as methotrexate containing water and wastewater.

Temporal profiles of synaptic plasticity-related signals in adult mouse hippocampus with methotrexate treatment

Methotrexate, which is used to treat many malignancies and autoimmune diseases, affects brain functions including hippocampal-dependent memory function. However, the precise mechanisms underlying methotrexate-induced hippocampal dysfunction are poorly understood. To evaluate temporal changes in synaptic plasticity-related signals, the expression and activity of N-methyI-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, extracellular signal-regulated kinase 1/2, cAMP responsive element-binding protein, glutamate receptor 1, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor were examined in the hippocampi of adult C57BL/6 mice after methotrexate （40 mg/kg） intraperitoneal injection. Western blot analysis showed biphasic changes in synaptic plasticity-related signals in adult hippocampi following methotrexate treatment. N-methyI-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, and glutamate receptor 1 were acutely activated during the early phase （1 day post-injection）, while extracellular signal-regulated kinase 1/2 and cAMP responsive element-binding protein activation showed biphasic increases during the eady （1 day post-injection） and late phases （7-14 days post-injection）. Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression increased significantly during the late phase （7-14 days post-injection）. Therefore, methotrexate treatment affects synaptic plasticity-related signals in the adult mouse hippocampus, suggesting that changes in synaptic plasticity-related signals may be associated with neuronal survival and plasticity-related cellular remodeling.

基于AD与TRIZ的加工中心主轴松拉刀机构优化设计

数控加工中心在加工过程中常出现主轴松刀力不足或无法松刀的现象。针对此问题,通过TRIZ系统组件分析明确现有松拉刀机构各组件间作用关系,利用因果链分析得出影响松刀的根本原因,最终应用TRIZ理论中的物场模型分析方法和AD独立性原理提出优化设计方案。根据新方案计算出实际工况下的主轴松刀力和螺杆强度,并对松刀杆进行建模和仿真。结果表明:最大位移量为6.995μm,最大应力为45.24 MPa,符合结构设计要求。最后,经过现场实物测试,当液压力为5 MPa时,松刀行程、松刀力以及打刀量均符合生产要求,验证了优化设计方案的合理性。

基于改进型多斜Ⅲ技术的7位半AD转换器设计

高精度测试仪器在环境试验中扮演着重要角色,而积分型AD转换器被广泛的应用在高精度测试仪器中。针对传统型积分型AD转换器转换速率较低的问题,提出了一种提高转换速率的改进型多斜ⅢAD转换器,详细的介绍了其原理和设计思路。该转换器以单片机与CPLD一同控制积分型ADC,在积分末尾利用单片机片内ADC测量积分器的残留电压,以达到提高转换速率的目的。经理论分析该AD转换器比传统型转换速率快836倍,分辨率可达到31位,在±10V直流电压测量中可实现7位半分辨率。

基于FPGA与AD9786的调制解调电路的设计

谐振式光学陀螺因其高理论精度、小型化以及高稳定性受到了国内外的强烈关注。针对于谐振式光学陀螺检测信号微弱的特点,需要对该信号进行调制解调,以实现陀螺的稳定输出,设计了一种基于FPGA和AD9786的高精度模拟信号源,该信号以FPGA作为核心控制单元,AD9786作为数模转换器,实现16位的高精度DA转换,通过上位机实现指令的通信过程,可实现不同频率的交流信号。该实验结果表明,该系统符合陀螺测试系统调制解调要求,通过上位机对不同输出信号进行测试,且测试结果无纹波时输出噪声Vrms269μV,交流信号精度达到0.01%,最高频率可达到2M,稳定性高。

基于AD7616的16通道数据采集系统设计

针对传统数据采集系统因通道不足或数据量过大,无法满足多通道同步采集的问题,设计了一种基于AD7616的16通道数据采集系统。系统以Xilinx系列FPGA作为主控芯片,ADI公司的AD7616作为模数转换芯片,DDR3 SDRAM作为缓存单元。介绍了各个模块硬件的设计思路,重点介绍了FPGA控制AD7616模数转换模块、DDR3 SDRAM缓存模块的软件程序设计,并对系统的多通道采样功能、同步性能以及实际水下超声信号的采集能力进行了实验验证,结果表明,系统可以完成水下超声信号的多通道同步采集。

基于动态离散模型的机场ADS-B攻击威胁影响研究

随着航空业信息技术的发展,空中交通管制系统面临着多种网络攻击的威胁。广播式自动相关监视(ADS-B)系统因其明文广播的数据传输方式,存在着被网络攻击的安全问题。依据“等待降落-降落-停泊-排队起飞-起飞”的航班运行全流程,建立了WLPQD动态离散模型,研究机场流量和航班延误。模型引入了系统冗余能力、处理速率等参数,模拟了攻击场景;通过受影响飞机数量和延误时间等指标研究了机场航班延误的传播影响。模型展示了ADS-B消息注入攻击对降落、起飞航班造成的延误,提出了两种攻击缓解方法。结果表明,延误规模的大小与攻击强度呈现正相关,且攻击对起飞航班的延误影响更大;提升对“幽灵飞机”和合法飞机的处理速率都可提升机场系统的抗毁性,但前者对提升机场系统冗余能力的效果更加显著。所做研究为机场系统抵御网络攻击、增强抗毁性提供了决策分析的参考依据。

采用AD654芯片的直流电压传感器及其温度漂移补偿

提出一种基于电压-频率变换的光电式电压传感器及电压传感信号温度漂移的补偿方法。电压传感系统主要包括电阻分压器、电压-频率变换芯片、发光二极管、光纤、光电探测与信号处理单元等。利用两块AD654型芯片分别作为被测电压和温度传感单元,通过对两路光传感信号进行非线性数据拟合等方式实现了对电压传感信号温度漂移的实时补偿。实验测量了0.6 kV~5.0 kV范围内的直流电压,并实现了电压传感信号的温度漂移补偿,在-40℃~+60℃的温度范围内,电压传感信号温度漂移的平均相对误差约为±0.7%。

CHEMOTHERAPY FOR ADVANCED NASOPHARYNGEAL CARCINOMA WITH METHOTREXATE, VINCRISTINE, CISPLATIN AND ADRIAMYCIN

Objective: To evaluate the efficacy and toxicity of M-VCA (methortrexate 30 mg/m2, vincristine 2 mg, cisplatin 70 mg/m2, adriamycin 30 mg/m2) combination chemotherapy for advanced nasopharyngeal carcinoma. Methods: Thirty-five patients with advanced nasopharyngeal carcinoma, including 11 patients with untreated local advanced nasopharyngeal carcinoma and 24 patients with local-regional recurrent or metastatic nasopharyngeal carcinoma, received the chemotherapy of M-VCA. The cycle was repeated on day 22 for two cycles. All patients completed the chemotherapy courses. Results: The overall response rate was 75%, with untreated local advanced nasopharyngeal carcinomas 11/11(100%), local-regional recurrent nasopharyngeal carcinomas 12/18(67%), lung metastases 8/9(89%), bone metastases 5/9(56%), and liver metastases 1/2(50%). The main side effects included mild to moderate degree alopecia, nausea/vomiting, and neutropenia. Conclusion: M-VCA is well tolerated and has good efficacy for advanced nasopharyngeal carcinoma and is worth investigating further.

面向Ad-Hoc协作的局部观测重建方法

在多智能体强化学习的研究中,如何进行Ad-Hoc协作,也就是说如何适应种类和数量变化的队友,是一个关键问题。现有方法或者有很强的先验知识假设,或者使用硬编码的规则进行合作,缺乏通用性,无法泛化到更一般的Ad-Hoc协作场景。为解决该问题,提出一种面向Ad-Hoc协作的局部观测重建算法,利用注意力机制和采样网络对局部观测进行重建,使得算法认识到并充分利用不同局面中的高维状态表征,实现了在Ad-Hoc协作场景下的零样本泛化。在星际争霸微操环境和Ad-Hoc协作场景上与代表性算法的性能进行对比与分析,验证了算法的有效性。

情境目标和Ad hoc关联影响言语产生的语义效应

干扰词与目标词之间的语义关联性是影响言语产生中语义效应性质的关键因素。相比其他语义关联类型,Ad hoc关联是一种较为特殊的概念联系类型。考察情境目标和Ad hoc关联对语义效应的影响,结果表明:与其他语义关联性相比,Ad hoc关联对语义效应的影响既有共性,又有差异。共性表现在:Ad hoc关联抑制图片命名,产生语义干扰效应,这种效应发生在图片命名早期(SOA从-200ms至0ms)。差异表现在:Ad hoc关联的语义干扰效应的产生要以情境目标提示为前提,有情境目标提示时,Ad hoc关联效应非常显著;无情境目标提示时,Ad hoc关联效应消失。不同语义关联类型产生不同语义效应的根源在于类别概念结点是否得到激活。

Dose-individualization Efficiently Maintains Sufficient Exposure to Methotrexate without Additional Toxicity in High-dose Methotrexate Regimens for Pediatric Acute Lymphoblastic Leukemia

Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.

ADS-B系统导频同步算法研究及改进

针对ADS-B接收模块中,低功率信号匹配滤波器输出信号检测峰值低,且报文接收误包率较高的问题,研究和改进了导频同步算法。通过理论分析其原理,合理设计了匹配滤波器参数以实现接收性能改善,验证了基于互相关检测的前导脉冲序列检测方法,优化了匹配滤波器互相关检测延时模型,使得抽样时刻为最大值。仿真结果表明,与初始的模块匹配滤波器相比,所设计的匹配滤波器有效提高了低功率下的峰值,且能够有效降低误包率。

维生素AD联合锌剂治疗呼吸道合胞病毒肺炎的效果

目的:研究维生素AD联合锌剂治疗呼吸道合胞病毒肺炎(RSVP)的效果。方法:选取2022年7月—2023年10月深圳市龙华区妇幼保健院收治的200例RSVP患儿作为研究对象,随机分为A组、B组、C组、D组,各50例。A组给予常规治疗;B组在常规治疗基础上单独给予维生素AD治疗;C组在常规治疗基础上单独给予锌剂治疗;D组在常规治疗用药基础上,予以维生素AD及锌剂的联合治疗。比较四组临床疗效、症状改善时间、免疫功能指标及不良反应发生情况。结果:D组总有效率高于A组、B组及C组,差异有统计学意义(P<0.05)。D组退热、喘息改善时间均早于A组,咳嗽、气促及肺部哮鸣音改善时间均早于A组、B组、C组,且C组咳嗽改善时间早于A组、B组,B组、C组气促及肺部哮鸣音改善时间均早于A组,差异有统计学意义(P<0.05)。治疗后,四组免疫球蛋白E(IgE)、免疫球蛋白A(IgA)、免疫球蛋白G(IgG)均高于治疗前,且D组均高于A组、B组、C组,B组、C组均高于A组,差异有统计学意义(P<0.05)。四组药物不良反应总发生率比较,差异无统计学意义(P>0.05)。结论:维生素AD联合锌剂治疗RSVP患儿的效果较好,能够有效改善其临床症状及机体的免疫功能,且安全性较高。

基于链式存储结构的ADS-B信号解码系统设计与实现

针对传统ADS-B信号解码系统的问题,如解码准确率低、数据传输速率小和解码实时性差,本文基于AD9361和Xilinx的Zynq-7000通用软件无线电平台提出了解决方案。该方案通过提高ADS-B信号采样率来提高解码准确率,并进行原理阐述和验证。此外,为了应对采样率增加导致的数据量增加问题,引入了链式存储结构作为DMA的缓存区域。实验结果表明,与传统解码系统相比,本文提出的系统识别并解码ADS-B信号的准确率提高了10%。链式存储结构的引入提高了数据处理速度,满足飞机航迹实时显示需求。此外,该系统的数据传输速率最高可达到682 Mb/s,满足高速数据传输的需求。