Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy(CAR–T)cell immunotherapy

Chimeric antigen receptor T-cesll therapy(CAR–T)has achieved groundbreaking advancements in clinical application,ushering in a new era for innovative cancer treatment.However,the challenges associated with implementing this novel targeted cell therapy are increasingly significant.Particularly in the clinical management of solid tumors,obstacles such as the immunosuppressive effects of the tumor microenvironment,limited local tumor infiltration capability of CAR–T cells,heterogeneity of tumor targeting antigens,uncertainties surrounding CAR–T quality,control,and clinical adverse reactions have contributed to increased drug resistance and decreased compliance in tumor therapy.These factors have significantly impeded the widespread adoption and utilization of this therapeutic approach.In this paper,we comprehensively analyze recent preclinical and clinical reports on CAR–T therapy while summarizing crucial factors influencing its efficacy.Furthermore,we aim to identify existing solution strategies and explore their current research status.Through this review article,our objective is to broaden perspectives for further exploration into CAR–T therapy strategies and their clinical applications.

Changing strategies for target therapy in gastric cancer

In spite of a worldwide decrease in the incidence of gastric cancer, this malignancy still remains one of the leading causes of cancer mortality. Great efforts have been made to improve treatment outcomes in patients with metastatic gastric cancer, and the introduction of trastuzumab has greatly improved the overall survival. The trastuzumab treatment took its first step in opening the era of molecular targeted therapy, however several issues still need to be resolved to increase the efficacy of targeted therapy. Firstly, many patients with metastatic gastric cancer who receive trastuzumab in combination with chemotherapeutic agents develop resistance to the targeted therapy. Secondly, many clinical trials testing novel molecular targeted agents with demonstrated efficacy in other malignancies have failed to show benefit in patients with metastatic gastric cancer, suggesting the importance of the selection of appropriate indications according to molecular characteristics in application of targeted agents. Herein, we review the molecular targeted agents currently approved and in use, and clinical trials in patients with metastatic gastric cancer, and demonstrate the limitations and future direction in treatment of advanced gastric cancer.

Research on Strategies for the Development of Selenium-enriched Tea in Ankang City of Shaanxi Province in the Context of Targeted Poverty Alleviation

As an important symbol of agricultural and sideline products in Ankang City,selenium-enriched tea affects the development of regional agricultural and sideline industries.In this paper,the development status and problems of the selenium-enriched tea products of Ankang were analyzed in terms of capital,technology,management and sales mode.This research is of positive significance to the development of selenium-enriched products and other agricultural and sideline products of health value,and plays a very important role in promoting the cultivation of village-level characteristic industries and the effective realization of targeted poverty alleviation.

Improving cancer therapy by combining cell biological, physical, and molecular targeting strategies

Successful cancer therapy depends on selective killing of tumor cells while sparing normal cells. Selectivity can be achieved through treatment strategies that target tumor cells. A recent report from the Li laboratory （1） describes an elegant strategy to selectively kill tumor cells by combining several targeting strategies based on cell biological, physical, and molecular （genetic） properties of tumor and normal cells that enhances tumor cell killing in vitro and in an in vivo tumor xenograft model. The idea of using a multiplex targeting approach is reminiscent of strategies in which several antibiotics are used to treat bacterial infections while minimizing the chance that rare antibiotic-resistant mutants will arise within a population.

Receptor tyrosine kinase-like orphan receptor 1:A novel antitumor target in gastrointestinal cancers

Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It has soluble and membrane-bound subtypes,with the latter highly expressed in tumors.ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms.Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis.Additionally,ROR1 may regulate the cell cycle,stem cell characteristics,and interact with other signaling pathways to affect cancer progression.This review explores the structure,expression and role of ROR1 in the development of gastrointestinal cancers.It discusses current antitumor strategies,outlining challenges and prospects for treatment.

Three-dimensional suboptimal guidance law for fly-over and shoot-down smart ammunition via virtual target

An optimal burst height is required for the fly-over and shoot-down smart ammunition with an EFP warhead at the instant of explosion which brings a special requirement to the miss distance of the terminal guidance law. In this paper, a guidance law based on the virtual target scheme is proposed. First, the practical pursuit-evasion issue between the ammunition and the target with specific miss distance is transformed into a virtuai pursuit-evasion problem with zero miss distance. Secondly, a complete three-dimensional pursuit-evasion kinematics model is established without any simplifications. And then, a suboptimal guidance law is designed based on the θ-D method which has constraints of the elevation and azimuth angular velocity of the virtual line of sight （LOS）. Finally, in order to verify the performance of the proposed guidance law, three test cases are conducted. Numericai results show that under the proposed terminal guidance law, the smart ammunition not only can fly above the target with an optimal burst height but also have a smaller normal acceleration on the terminal trajectory.

The inositol metabolism pathway as a target for neuroprotective strategies

Neurodegeneration is characterized by the progressive and permanent loss of neurons.Degeneration typically results in a debilitating loss of function in an otherwise healthy person.Neurodegenerative diseases have enormous direct health care costs,with some estimates for diseases.

Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors

Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto

Application of Learning Strategies in Self-access Environment

Since the 1970s, the studies of learning strategies and strategy training have made great achievements, but there are also many problems to be solved. Traditional teaching methodology emphasizes the knowledge and basic skills of the target language, ignoring the instruction of learning skills and strategies, which often results in ineffective learning in spite of much time and efforts. Of many factors that need to be considered, a very important one is that students aren't equipped with effective learning skills and strategies.

From basic researches to new achievements in therapeutic strategies of KRAS-driven cancers

Among the numerous oncogenes involved in human cancers, KRAS represents the most studied and best characterized cancerrelated genes.Several therapeutic strategies targeting oncogenic KRAS(KRASonc) signaling pathways have been suggested,including the inhibition of synthetic lethal interactions, direct inhibition of KRASonc itself, blockade of downstream KRASonc effectors, prevention of post-translational KRASonc modifications, inhibition of the induced stem cell-like program, targeting of metabolic peculiarities, stimulation of the immune system, inhibition of inflammation, blockade of upstream signaling pathways,targeted RNA replacement, and oncogene-induced senescence.Despite intensive and continuous efforts, KRASonc remains an elusive target for cancer therapy.To highlight the progress to date, this review covers a collection of studies on therapeutic strategies for KRAS published from 1995 to date.An overview of the path of progress from earlier to more recent insights highlight novel opportunities for clinical development towards KRASonc-signaling targeted therapeutics.

Three-dimensional coordinates test method with uncertain projectile proximity explosion position based on dynamic seven photoelectric detection screen

To objectively obtain the three-dimensional coordinates of the projectile fuze proximity explosion when projectile intersects the head of missile target, we propose a dynamic seven photoelectric detection screen test method, which is made up of six plane detection screens and a flash photoelectric dynamic detection screen. The three-dimensional coordinates calculation model of the projectile proximity explosion position based on seven plane detection screens with dynamic characteristics is established.According to the relation of the dynamic seven photoelectric detection screen planes and the time values,the analytical function of the projectile proximity explosion position parameters under non-linear motion is derived. The projectile signal filtering method based on discrete wavelet transform is explored in this work. Additionally, the projectile signal recognition algorithm using an improved particle swarm is proposed. Based on the characteristics of the time duration and the signal peak error for the projectile passing through the detection screen, the signals attribution of the same projectile passing through six detection screens are analyzed for obtaining precise time values of the same projectile passing through the detection screens. On the basis of the projectile fuze proximity explosion test, the linear motion model and the proposed non-linear motion model are used to calculate and compare the same group of projectiles proximity explosion position parameters. The comparison of test results verifies that the proposed test method and calculation model in this work accurately obtain the actual projectile proximity explosion position parameters.

Development of A Three-Dimensional Guidance System for Long-Range Maneuvering of A Miniature Autonomous Underwater Vehicle

The present paper introduces a three-dimensional guidance system developed for a miniature Autonomous Underwater Vehicle（AUV）. The guidance system determines the best trajectory for the vehicle based on target behavior and vehicle capabilities. The dynamic model of this novel AUV is derived based on its special characteristics such as the horizontal posture and the independent diving mechanism. To design the guidance strategy, the main idea is to select the desired depth, presumed proportional to the horizontal distance of the AUV and the target. By connecting the two with a straight line, this strategy helps the AUV move in a trajectory sufficiently close to this line. The adjacency of the trajectory to the line leads to reasonably short travelling distances and avoids unsafe areas. Autopilots are designed using sliding mode controller. Two different engagement geometries are considered to evaluate the strategy＇s performance： stationary target and moving target. The simulation results show that the strategy can provide sufficiently fast and smooth trajectories in both target situations.

纳米药物载体用于治疗胞内菌感染的研究进展

胞内菌能够逃避机体免疫并在宿主细胞内正常生长繁殖,比起胞外细菌更难清除,容易造成较为严重的感染。传统的抗生素治疗,药物无法突破宿主细胞膜的屏障,并且容易引起较强的毒副作用和多药耐药性。优良的纳米载体具有良好的生物相容性且易于修饰,有望通过构建纳米药物递送系统增强抗菌药物的细胞膜穿透性和胞内菌靶向性,在治疗胞内菌感染上具有巨大潜力和广阔前景。介绍了目前可用于治疗胞内菌感染的各种纳米颗粒,归纳总结了增强纳米药物递送系统治疗效果的机制和方法,阐述了目前在使用纳米药物递送系统治疗胞内菌感染时仍存在的问题,以期为构建更优良的纳米药物递送系统治疗胞内菌感染提供启发。

基于改进Faster RCNN的微操作空间目标检测算法

将Faster RCNN引入微操作系统的目标检测之中。针对微操作空间下待检测目标存在尺度变化和在显微镜放大倍数较小时,待检测目标尺度过小、特征不明显的问题,提出了一种基于改进Faster RCNN的微操作空间目标检测算法。使用在图像分类任务中性能优越的深度残差网络提取图像的特征。引入递归特征金字塔网络,对特征进行融合。改进区域建议网络的采样策略,对损失函数进行优化。实验结果表明:这种改进的Faster RCNN算法能有效解决由于目标尺度变化和目标尺度过小带来的问题。相比通用的目标检测算法,该算法的准确度更高,速度更快,具有实际应用价值。

基于多维空间离散基准的目标检测网络设计

针对目标检测网络中检测头的设计缺少依据,不能对不同数据集进行相应优化的问题,用一至四维的空间离散基准和正样本点(组)分配冲突率模型,提出了相应的设计依据。即基于位置的分配原则中,针对特定数据集的正样本点在4个回归量所组成的空间维度中的分布特点,在不高于指定的分配冲突率的条件下,以减少正负样本不均衡度和系统计算资源为目的,设计出具有最少点数检测头的规律。其本质是一个回归基准编码和正负样本分配设计的过程,进而实现检测性能与资源消耗之间的平衡。得出基于卷积目标检测网络检测头的回归基准可以采用4个回归中的任意组合,但需结合样本分配策略与数据集的正样本分配冲突率进行综合设计的结论。

基于改进人工势场法的潜航器避障策略

针对水下潜航器在复杂水下环境中面临的局部最优解困局及目标点不可达等避障挑战,提出了一种创新的基于改进人工势场法的避障策略。该策略首先通过融入随机扰动机制,显著提升了潜航器在动态环境中的路径探索能力与局部最优陷阱的逃逸能力;随后,为解决目标点不可达问题,策略中创新性地引入了目标调节因子,该因子通过精细调节引力与斥力的平衡关系,并优化引力分段函数的分界值及斥力影响半径,确保潜航器在接近目标时斥力渐减至零,从而实现了潜航器对目标点的精确、稳定到达。实验结果显示,所提策略避障成功率相较于传统人工势场法实现了显著提升,目标点到达率达到100%,验证了所提策略在复杂避障任务中的高效性与可靠性,也为水下潜航器自主导航技术探索了一条新的高效避障方法。

目标策略模式下知信行干预在脊柱内镜术后患者中的护理应用

目的 探讨目标策略模式下知信行干预在脊柱内镜术后患者中的护理应用。方法 选取2021年1月至2022年12月腰椎间盘突出症合并腰椎管狭窄症患者。2022年1月至12月60例为观察组。2021年1月至12月腰椎间盘突出症合并腰椎管狭窄症患者60例为对照组,对照组给予常规护理,观察组给予常规护理+目标策略模式下知信行干预。两组患者出院后继续予延续性护理共3个月,记录并比较护理前后两组患者自我效能评分、焦虑自评量表(SAS)评分、抑郁自评量表(SDS)评分、日本骨科协会(JOA)评分、生活质量各维度评分及护理满意度。结果 两组患者护理后的JOA评分与自我效能评分均升高,且观察组高于对照组(P<0.05),SAS评分、SDS评分均降低,且观察组低于对照组。两组患者护理后生活质量各维度评分均升高,且观察组高于对照组(P<0.05);观察组患者护理满意度为90.00%,明显高于对照组75.00%,差异有统计学意义(P<0.05)。结论 目标策略模式下知信行干预在脊柱内镜术后患者中具有良好的护理效果,能有效减少焦虑、抑郁情绪、提高患者的自我效能、腰椎功能及生活质量,且护理满意度高,具有临床应用价值。

双碳目标驱动体育用品制造业数字化战略变革:动力机制、现实瓶颈及纾解之策

加快推动体育用品制造业数字化战略变革是实现双碳战略目标的重要举措。运用文献资料等方法,研讨双碳目标驱动体育用品制造业数字化战略变革的动力机制、现实瓶颈及纾解之策。研究认为:推拉动力机制、内生外在动力机制、状态表现机制,主体响应机制形成数字化战略变革的动力机制,基于财政体制壁垒固化,财政政策体系不健全;绿色低碳发展理念不牢固,绿色生产消费法治体系不完善;碳数据管理平台缺位,碳市场交易体系不成熟;数字化复合型人才储备不足,数字技术创新能力薄弱瓶颈,提出推进财政体制改革,完善财政保障政策体系;树立绿色低碳理念,完善绿色生产消费法制体系;完善碳数据管理平台,健全碳市场、碳定价机制;培育复合型数字化人才,增强绿色低碳技术创新能力的纾解之策。

基于改进YOLOX的无人机航拍图像小目标检测算法

在无人机上运用目标检测技术具有广泛的应用前景,但和自然拍摄的图像不同,无人机航拍的图像更加复杂,且大多数为小目标。而现有的检测算法缺乏对小目标的特征提取能力,从而导致严重的误检和漏检问题。针对上述问题,提出一种基于YOLOX框架的高效的无人机小目标检测算法。首先,在特征融合网络中增加一层检测微小目标的特征融合结构,通过利用浅层特征图中丰富的位置信息和轮廓信息来加强网络对小目标的识别能力;同时,为了防止额外参数的增加,将减少头网络中的一层卷积层并缩减其通道数。其次,提出一种通道-空间注意力机制模块(Channel Spatial Attention Module,CSAM),利用最优的权重分配使网络聚焦于特征图中小目标密集的区域。最后,提出一种带位置引导的标签分配策略(LB-SimOTA),根据每个预测框和真实框的交并比(IOU)的大小,分别配以不同的权重,以改善网络中整体预测框的质量。在小目标居多的数据集VisDrone2019上的实验结果表明,文中提出的算法和YOLOX-S相比,针对车和人的检测精度提升了8.63%,检测速度FPS也可达到86,因此更适合在无人机对地面小目标检测的场景下部署。

肥胖症与脂肪性肝病协同诊疗模式的思考与探索

脂肪性肝病的两次更名均强调了代谢功能障碍在疾病发展中的潜在驱动作用,反映了脂肪性肝病的高度异质性。在“态靶理论”与“膏浊理论”指导下,该研究认为肥胖是脂肪性肝病发病及病程发展的关键因素,从肥胖症与脂肪性肝病的共病现状、共病机制、共治趋势等方面出发,进行肥胖症与脂肪性肝病共同防治的探讨。以减轻体重为中心,通过中药内服与中医外治结合、中医综合治疗与外科代谢手术结合、院内诊治与院外生活方式管理结合的系统性干预策略,实现脂肪性肝病与肥胖症的共同防治、共同管理,将脂肪性肝病及其并发症的防控关口前移,以此提高临床诊疗效果。