Preliminary Findings on the Use of Targeted Therapy in Combination with Sodium Phenylbutyrate in Colorectal Cancer after Failure of Second-Line Therapy—A Potential Strategy for Improved Survival

Colorectal cancer (CRC) is the second leading cause of cancer death related mortality with 1.2 million new cases diagnosed annually worldwide. Despite remarkable advances in the treatment of resectable CRC, advanced disease that recurs following initial two lines of chemotherapy, remains incurable. Targeted therapies using a single agent or in combination with other drugs have been tested in a number of clinical trials, with only moderate improvement. Here we present preliminary findings of improved overall survival (OS) using a combination of sodium phenylbutyrate with various targeted and chemotherapeutic agents in stage IV CRC patients who had failed at least two lines of chemotherapy. Results suggest a strategy of simultaneous interruption of signal transduction involving EGFR (VEGF)?KRAS-ERK and PI3K-AKT pathways and interference with cell cycle, cancer cell metabolism, maintenance of cancerous stem cells, and promotion of apoptosis. In a group of 15 patients, median OS was higher compared to other third-line therapies (14.7 months compared to between 4.8 and 9.5 months in other studies). Given the understanding that our findings are preliminary, we propose the validation of our initial results using a well-designed phase I/II trial in recurrent advanced colorectal cancer.

Changing the paradigm：the potential for targeted therapy in laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.

Preliminary Findings on the Use of Targeted Therapy in Combination with Sodium Phenylbutyrate in Recurrent Advanced Pancreatic Cancer—A Potential Strategy for Improved Survival

Metastatic pancreatic cancer carries an estimated five-year survival rate of only 2%. Gemcitabine-based chemotherapy remains a first-line standard-of-care treatment for elderly patients with advanced pancreatic cancer. Combination chemotherapy FOLFIRINOX offers better results, but it is not recommended for the older patient population due to substantial toxicity. Standard-of-care second-line treatment is not yet established and is used in approximately 30% of patients since performance status is too low to consider further therapy. Targeted therapies with a single agent and in combinations have been tested in numerous clinical trials, but except for the combination of gemcitabine and erlotinib, have not yet proven efficacy. Here, we present preliminary findings of improved overall survival (OS) using a combination of sodium phenylbutyrate with various chemotherapeutic and targeted agents in stage IV A and B pancreatic cancer patients who failed at least one line of chemotherapy. The results suggest a strategy of simultaneous interruption of signal transmission involving multiple pathways in the second-line treatment that are believed to interfere with cell cycle, cancer cell metabolism, autophagy and maintenance of cancer stem cells and promote apoptosis. In this group of patients, median OS was higher compared to other second-line therapies (10.5 months compared to between 2.9 and 6.5 months in other studies, and in the best supportive care group, 2.3 months). Given the understanding that our findings are preliminary, we propose the validation of our initial results using a well-designed Phase I/II trial in recurrent advanced pancreatic cancer.

Preliminary Findings on the Use of Targeted Therapy with Pazopanib and Other Agents in Combination with Sodium Phenylbutyrate in the Treatment of Glioblastoma Multiforme

The most common and aggressive type of brain tumor is glioblastoma multiforme (GBM). The prognosis for GBM remains poor with a five-year survival rate between 1% and 2%. The prospects for patients with recurrent GBM (RGBM) are much worse, with the majority dying within 6 months. This publication provides a brief description of the treatment of 11 GBM patients treated with sodium phenylbutyrate (PB) in combination with pazopanib, m-TOR inhibitors, and other agents. The treatment was associated with tolerable side effects and resulted in objective responses in 54.5% of cases (complete response 18.2%, partial response 36.3%) and 27.3% cases of stable disease. The preferable treatment regimen consisted of PB, pazopanib, dasatinib, everolimus, and bevacizumab (BVZ). For various reasons not all patients were compliant with the treatment regimen. In patients who strictly complied with the treatment plan, all responded as CR or PR. Based on preliminary findings, the authors propose further phase I/II clinical trials with PB in combination with pazopanib, dasatinib, everolimus, and BVZ in patients with RGBM who failed standard surgery, radiation therapy and chemotherapy. With proper dose reductions, the treatment appears to be well-tolerated. Molecular profiling of patient subgroups with favorable genomic signatures may help to select patients for future studies.

Molecular genetics and targeted therapeutics in biliary tractcarcinoma

The primary malignancies of the biliary tract, cholangio-carcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates that molecularly targeted agents may provide new hope for improving treatment response in biliary tract carcinoma(BTC). In this article, we provide a critical review of the pathogenesis and genetic abnormalities of biliary tract neoplasms, in addition to discussing the current and emerging targeted therapeutics in BTC. Genetic studies of biliary tumors have identified the growth factors and receptors as well as their downstream signaling pathways that control the growth and survival of biliary epithelia. Target-specific monoclonal antibodies and small molecules inhibitors directed against the signaling pathways that drive BTC growth and invasion have been developed. Numerous clinical trials designed to test these agents as either monotherapy or in combination with conventional chemotherapy have been completed or are currently underway. Research focusing on understanding the molecular basis of biliary tumorigenesis will continue to identify for targeted therapy the key mutations that drive growth and invasion of biliary neoplasms. Additional strategies that have emerged for treating this malignant disease include targeting the epigenetic alterations of BTC and immunotherapy. By integrating targeted therapy with molecular profiles of biliary tumor, we hope to provide precision treatment for patients with malignant diseases of the biliary tract.

Preliminary Findings on the Use of Targeted Therapy in Combination with Sodium Phenylbutyrate in Advanced Malignant Mesothelioma: A Strategy for Improved Survival

Advanced malignant mesothelioma (MM) is among the most aggressive and difficult-to-treat diseases. Industrialization and exposure to asbestos is the main causative factor for the dramatic increase in the incidence of MM, which carries a poor prognosis and a median survival of less than 12 months. Combination chemotherapy offers only palliative results;however, targeted therapy carries more promise for future successful treatment. This paper presents preliminary findings of improved overall survival (OS) using a combination of sodium phenylbutyrate (PB) with various chemotherapeutic and targeted agents in advanced MM. The data suggest using a strategy of simultaneous interruption of signal transduction involving RAS-MEK-ERK, PI3K-AKT, mTOR, Merlin, and angiogenesis pathways and interference in cell cycle and epigenetic processes. Complete response was determined in 15.4% and stable disease in 46.2% in the group of 13 evaluable patients. Median OS for MM was higher compared to other treatments (17 months compared to between 6 and 12.1 months). The longest surviving patient continues to be in complete response and in excellent condition for over 12.5 years from the treatment start. These findings are only preliminary and validation of the results using a well-designed phase I/II trial in advanced MM is proposed.

“双碳”目标引领下家庭碳账户体系的构建对策及建议

碳账户体系建设是践行国家“双碳”目标的重要路径。随着个人碳账户的不断完善,开展家庭碳账户的试点探索,有助于个人碳账户应用体系与碳市场的建立与完善。从家庭碳账户体系构建的背景及意义出发,通过文献调研与实证调查等方法,分析个人碳账户存在问题及对家庭碳账户体系构建的启示。研究结果表明,个人碳账户建设存在多平台重复建设及标准不统一问题、公平性与合理性问题、信息准确性与偏差问题、以及减排政策框架的有效融合欠缺问题。在“双碳”目标引领下,应设立家庭碳户主并建立家庭碳共济总账户,整合碳账户平台并完善家庭碳账户数据信息,创新家庭碳普惠模式,以构建并完善家庭碳账户体系,促进全民参与绿色低碳生态文明行动。

Redox, immune and genetic biomarker system for personalized treatments in colorectal cancer

BACKGROUND Identifying biomarkers for the risk of developing degenerative processes linked to aging and colorectal cancer(CRC) onset that could improve clinical strategies.AIM To determine valid targets and a predictive biomarker's system of chronicization of inflammation for cancer treatment.METHODS A group of 147 CRC patients was studied. Clinical diagnosis was confirmed histopathologically, and patients were sub-typed using the pathological tumornode-metastasis classification. Thirteen colon adenoma patients and 219 healthy subjects were also studied. A system biology study on Thioredoxin1/CD30 redox-immune systems(Trx1/CD30), T helper cytokines and polymorphisms of killer immunoglobulin-like receptors, FcγRIIa-131 H/R and FcγRIIIa-158 V/F was carried out. Enzyme-linked immunosorbent assay was performed to analyze sera.Genetic study was executed by polymerase chain reaction sequence-specific primers and sequence-based typing method. Statistical analysis was performed by using the "Statgraphics software systems".RESULTS We found a positive increase between Trx1/RTrx1 levels and sCD30 level and increased age. With respect to the gender relationships, there were distinct differences. Females showed a primary relationship between transforming growth factor beta(TGFβ) with Trx1, whereas males had one with TGFβ and RTrx1. Trx1/CD30 controls the redox immune homeostasis, and an imbalance in the relationship between the Trx1/RTrx1 and sCD30 levels is linked to the onset and progression of tumor. This event happens through different gender-specific cytokine pathways. Our study demonstrated that the serum levels ofTrx1/RTrx1, TGFβ/interleukin(IL)6 and TGFβ/IL4 combinations and the sCD30,IFNγ and IL2 combination constitute a predictive gender specific biomarker system. This is relevant for clinical screening to detect the risk of the potential development or progression of a tumor.CONCLUSION Oxidative stress on Trx1/CD30 is a trigger of cancer disease, and the selected oxidation and immune products are a biomarker system for aging and cancer.

循证理念指导下的个性化护理对免疫联合靶向治疗肿瘤患者遵医行为及心理状态的干预效果

目的探讨循证理念指导下的个性化护理对免疫联合靶向治疗的肿瘤患者遵医行为和心理状态的影响。方法选取2021年1月—2023年1月医院接受免疫联合靶向治疗的120例肿瘤患者为研究对象,按照组间基本特征具有可比性的原则分为对照组与观察组,每组60例。对照组采用常规护理方式,观察组则采用循证指导下的个性化护理,比较两组患者护理前后生活质量、癌因性疲乏、自我感受负担、心理状态、营养指标、遵医行为及相关不良反应发生情况。结果护理前,两组生活质量评分、癌因性疲乏评分、自我感受负担比较,差异均无统计学意义(P>0.05)。护理后,观察组患者的生活质量评分高于对照组,差异有统计学意义(P<0.05);癌因性疲乏评分、自我感受负担中的情感负担和身体负担均低于对照组,差异有统计学意义(P<0.05),经济负担则与对照组相比差异无统计学意义(P>0.05)。护理前,两组心理状态、营养指标比较差异无统计学意义(P>0.05)。护理后,观察组患者的抑郁自评量表、焦虑自评量表评分低于对照组,差异有统计学意义(P<0.05),血红蛋白、血清白蛋白则高于对照组,差异有统计学意义(P<0.05);观察组遵医行为程度高于对照组,差异有统计学意义(P<0.05);观察组不良反应总发生率低于对照组,差异有统计学意义(P<0.05)。结论循证理念下的个性化护理能改善免疫联合靶向治疗的肿瘤患者的生活质量、癌因性疲乏、自我感受负担,缓解患者负面情绪与营养状态,进而提高患者遵医行为,并降低不良反应事件发生率。

结合多尺度融合和图匹配的行人重识别

由于行人遮挡、视角变化等因素影响,传统的行人重识别并不能准确表达遮挡行人的信息。针对该问题,提出一种基于多尺度融合和图匹配的网络模型。分为提取不同尺度的特征和基于拓扑结构匹配图像两个部分,将主干网络分为两个子分支分别提取全局特征并融合多个网络层面的局部特征;使用多头注意力机制学习相邻关键点的关系,基于拓扑结构匹配图像并预测相似度结果。使用ResNet-50作为主干网络,在Occluded-Duke数据集上的Rank-1和mAP分别是64.8%和59.9%,验证该模型在遮挡行人重识别中有一定程度的准确率提升。

基于人工智能的智慧养老精准服务问题研究

人工智能已成为引领新一轮科技革命和产业变革的重要驱动力,推动经济高质量发展的关键引擎。依托人工智能等现代信息技术,智慧养老模式正在为老年人提供实时、高效和低成本的服务。文章通过分析人工智能推动养老服务精准化的机理,包括数据采集、需求分析、服务供给和协同管理的精准化,设计了包含物联感知层、数据资源层和智慧应用层的智慧养老精准服务系统架构系统。应用结果表明,该系统能够有效整合多种智能化信息技术,精准捕捉并细致分析老年用户的需求,为他们提供个性化的养老服务,进而显著提升老年人的生活品质。

思政教育在专业人才培养中的角色与实践--以材料冶金学科研究生培养为例

随着科技的飞速发展,材料冶金技术处于持续迭代更新之中,在培养冶金类研究生过程中,持续学习和创新能力的培养方面离不开思政教育。本文以材料冶金学科研究生为例,深入探讨思政教育在专业人才培养中的角色与实践。通过实际案例讲授、学科交叉知识整合、个性化教学策略,探讨思政元素融入策略与实践路径。将思政教育与专业技能培养结合,培养学生创新思维与社会责任感,明确课程思政在综合素质目标培养中的作用,提出改进方向与措施,并基于教学反馈进行评价与展望,为高等教育改革提供借鉴,助力培养复合型人才。

医院调血脂药物的使用分析及思考

目的了解我院使用调血脂药物的患者人群、调血脂药物品种和剂量的选择、降脂目标达标情况,促进调血脂药物的合理使用。方法回顾性分析福建省惠安县医院2022年使用调血脂药物的患者100例,统计患者使用调血脂药物的品种及剂量,血脂水平、肌酸激酶、肝肾功能情况。结果低密度脂蛋白胆固醇(LDL-C)水平达到推荐目标值人数44例,动脉粥样硬化性心血管疾病(ASCVD)超高危患者的降脂目标达标率14.81%,极高危患者的达标率17.39%,中高危患者的达标率66.67%,低危患者的血脂水平达标率100%。结论ASCVD超高危患者和极高危患者的血脂水平达标不理想,与LDL-C推荐目标值认知不足,未能及时调整降脂药物的品种和剂量有关,建议综合评估患者情况,规范血脂管理,进行个体化指导用药。

肿瘤类器官在精准肺癌药物筛选中的研发与进展

背景:肺癌是全世界最常见且预后最差的恶性肿瘤之一,其发病率和死亡率长期位居恶性肿瘤前列。肺癌的异质性和耐药问题是导致其预后较差的原因之一。肺癌类器官是由患者来源的肿瘤细胞培养成的体外3D模型,可精准还原原发肿瘤的生物学特征,可用于肺癌的各项研究。目的:综述肺癌类器官在化疗、靶向治疗及免疫治疗药物敏感性检测中的应用和研究进展,分析其局限性,为推进肺癌的个性化精准医疗提供新的策略。方法:第一作者于2023年7月应用计算机在中国知网和PubMed数据库进行文献检索,文献发表时间为2013-2023年,以“类器官,肺癌类器官,肺癌实验模型,精准医疗,药物敏感性检测,化疗,靶向治疗,免疫治疗”为中文检索词,以“organoid,lung cancer organoid,lung cancer experimental model,precision medicine,drug sensitivity test,chemotherapy,targeted therapy,immunotherapy”为英文检索词,最终纳入84篇文献进行综述。结果与结论:①相较于传统肺癌研究模型仅能展现二维层面的细胞活动、缺乏细胞间交流互动及存在物种差异等缺陷,肺癌类器官培养细胞来源多样,培养介质不断被优化,能够从三维层面模拟细胞间互动的同时也能保留原发肿瘤的生物学特征,是一种拥有巨大潜力的新型研究模型,为支持其用于抗癌药物筛选提供了坚实基础。②肺癌类器官预测结果与患者实际临床结局高度一致,初步展现出对于指导抗癌用药的重要辅助意义:通过对常见化疗、靶向治疗和免疫治疗药物进行疗效预测和筛选,为患者定制个体化治疗策略;可避免不必要的药物试错和毒副反应;探索可行的替代药物或联合用药方案以改善耐药问题;指导罕见突变类型肺癌的精准治疗,弥补临床空白;通过比较不同药物活性,提供更加全面的药物评价。此外,需注意类器官可能出现内部异质性,故应尽可能多次取材检测,以提高结果的准确性。③肺癌类器官在药物筛选等实际应用中存在局限,如培养成功率及纯度不稳定、缺乏血管组织等。为弥补这些不足,需要改进培养条件、加速检测流程,以及发展多类器官系统,模拟药物在多个器官内的整体效应,这些改进将有助于更准确地评估药物的效果和毒性,提高肺癌治疗的精准性。

人才素质评价的一种要素指标设置法

针对人才评价的要素指标设置,一直处于众说纷纭的状态。为了系统描述各具特色的人性特征,本文以人性素质全貌的呈现为目标,对人的综合素质表征提出了一个具有8个类属约50个基础要素指标的模型体系,简称“8-50”要素体系。该体系对人的素质评价或人才选拔时考评点的选取,具有参考价值。

信息系统领域网络精准广告研究综述

网络精准广告是信息系统领域的重要论题,在实践中也有着深远意义,但目前缺少针对网络精准广告研究成果的系统梳理和分析。作者在大量文献收集和阅读的基础上,通过严谨的筛选方法对其中73篇具有代表性的英文文献进行系统地梳理,利用编码处理方法从发表时间、文献类型、研究方法和研究层面4个方面对国际上网络精准广告研究进行全面统计分析;并进一步运用文本数据挖掘,结合逐篇精读提炼出现有研究的主要主题并做深入分析。文献研究结果表明:(1)网络精准广告的研究数量呈上升态势,文献类型以期刊论文为主,研究方法以定量为主并呈现多元化趋势,研究层面从技术层面向用户行为层面延伸;(2)网络精准广告的研究可以提炼出6个主题,包括广告计划调度、广告匹配和分配、商业模式和系统框架、网络用户行为和模式分析、精准广告点击与效果以及用户个人隐私。

医科院校“基因导向”个体化用药教学现状经验及发展策略

目的探讨目前医科院校"基因导向"个体化用药的教学现状及发展策略。方法总结已有教学经验,探讨个体化用药教育现状;通过分析需要学习个体化用药知识的不同人群的特点,提出可行、可发展的普及个体化用药知识的教学策略。结果医科院校的必选课教育、高水平国际、国内专题会议的召开,以及针对在职人员的短期培训班都是在医务工作者中普及个体化用药知识的有效手段。结论随着遗传药理学研究成果向临床的不断转化,需要医务工作人员在医学实践中灵活掌握个体化用药知识,以上几种方法可以在更大范围人群中普及个体化用药知识,有利于医务工作人员在临床实践中合理用药。

一种基于行为的移动机器人目标人跟踪控制方法

针对室内复杂环境,对于智能服务移动机器人,设计一个连续稳定的目标人跟踪算法是必要的。为此提出一种室内环境下基于行为的移动机器人对运动目标人进行跟踪的控制方法,该方法综合优先级裁决方法与模糊行为融合法选取移动机器人的控制行为,较好地解决跟踪过程中存在多种行为以及行为冲突问题,在完成运动避障的同时保持对运动目标的跟踪。对避障行为模块提出声纳距离加权平均法求取障碍物距离信息,采用模糊逻辑法设计避障控制器。在不同的实验环境下做了大量的实验,结果表明,该算法能实时稳定地跟踪上指定的目标人,不仅能绕开障碍物,而且能保持给定的初始距离。

护士个人职业目标现状及影响因素研究

目的了解护士的个人职业目标现状并分析影响因素,为引导护士个人职业目标管理提供依据。方法在KRIF绩效考核模式的基础上设计护士个人职业目标调查工具,对726名护士进行调查。结果除学习本专业知识目标(74.8%)外,其他23个目标的选择率为0~36.1%。不同学历、科室、编制、职称、年龄、工龄护士的部分个人职业目标存在差异(P<0.05,P<0.01)。结论护士对个人职业目标的认识尚需提高,护理管理者应指导护士建立科学、合理的个人职业目标,关注护士的职业发展,促进护士成长和医院科室健康发展。

2021年非小细胞肺癌重要临床研究纵观与解读

尽管2021年新冠病毒仍在肆虐,非小细胞肺癌(non-small cell lung cancer,NSCLC)的临床研究并未止步。得益于肺癌治疗模式的进步,NSCLC患者的总生存时间和生活质量得到了显著改善。目前靶向治疗与免疫治疗的研究进展改变了术后辅助治疗的现状,建立了可手术NSCLC治疗新标准。局部晚期和晚期NSCLC同样有重要的研究进展,包括新的治疗模式、新的治疗药物等,均为临床治疗带来更多选择。相信在可预见的未来,这些疗法都将为NSCLC的治疗带来改变,并逐步走向肺癌“慢病化”的道路。因此,本文简要综述了2021年改变肺癌治疗临床实践的重要研究以及值得关注的研究进展。