Tislelizumab in previously treated,locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors

Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

Factors predicting sensory and motor recovery after the repair of upper limb peripheral nerve injuries

OBJECTIVE： To investigate the factors associated with sensory and motor recovery after the repair of upper limb peripheral nerve injuries. DATA SOURCES： The online PubMed database was searched for English articles describing outcomes after the repair of median, ulnar, radial, and digital nerve injuries in humans with a publication date between 1 January 1990 and 16 February 2011. STUDY SELECTION： The following types of article were selected： （1） clinical trials describ- ing the repair of median, ulnar, radial, and digital nerve injuries published in English; and （2） studies that reported sufficient patient information, including age, mechanism of injury, nerve injured, injury location, defect length, repair time, repair method, and repair materials. SPSS 13.0 software was used to perform univariate and multivariate logistic regression analyses and to in- vestigate the patient and intervention factors associated with outcomes. MAIN OUTCOME MEASURES： Sensory function was assessed using the Mackinnon-Dellon scale and motor function was assessed using the manual muscle test. Satisfactory motor recovery was defined as grade M4 or M5, and satisfactory sensory recovery was defined as grade S3＋ or S4. RESULTS： Seventy-one articles were included in this study. Univariate and multivariate logistic regression analyses showed that repair time, repair materials, and nerve injured were inde- pendent predictors of outcome after the repair of nerve injuries （P 〈 0.05）, and that the nerve injured was the main factor affecting the rate of good to excellent recovery. CONCLUSION： Predictors of outcome after the repair of peripheral nerve injuries include age, gender, repair time, repair materials, nerve injured, defect length, and duration of follow-up.

Sciatic nerve repair using adhesive bonding and a modified conduit

When repairing nerves with adhesives, most researchers place glue directly on the nerve stumps, but this method does not fix the nerve ends well and allows glue to easily invade the nerve ends. In this study, we established a rat model of completely transected sciatic nerve injury and re- paired it using a modified 1 cm-length conduit with inner diameter of 1.5 mm. Each end of the cylindrical conduit contains a short linear channel, while the enclosed central tube protects the nerve ends well Nerves were repaired with 2-octyl-cyanoacrylate and suture, which complement the function of the modified conduit. The results demonstrated that for the same conduit, the av- erage operation time using the adhesive method was much shorter than with the suture method. No significant differences were found between the two groups in sciatic function index, motor evoked potential latency, motor evoked potential amplitude, muscular recovery rate, number of medullated nerve fibers, axon diameter, or medullary sheath thickness. Thus, the adhesive method for repairing nerves using a modified conduit is feasible and effective, and reduces the operation time while providing an equivalent repair effect.

METARO^(3):Metamorphic Relation Group for Automatic Program Repair

The application of metamorphic testing(MT)on automatic program repair(APR-MT)is used to generate a patch without test oracles by examining whether the input metamorphic relation(MR)is satisfied or not.However,the delivered patch is plausible since it may satisfy the input MR but violate other MRs.This inspires us to propose an improved approach to enhance the effectiveness of APR-MT with metamorphic relation group.Ourapproach involves three major steps.First,we formally define the repair process of APR-MT by building the model of automatic program repair and metamorphic testing separately.Then,we propose the advanced model of automatic program repair based on metamorphic relation group,named METARO^(3),which takes several MRs as input while only one MR is used in APR-MT.We additionally present two kinds of selection strategies to rank MRs in descending order of the fault detection capability,which helps shorten the repair time of finding a patch.To demonstrate the feasibility and procedure of our approach,an illustration example was conducted.The results show that METARO^(3) can improve the effectiveness of APR-MT significantly.

Optimal Coordination of Transportable Power Sources and Repair Crews for Service Restoration of Distribution Networks Considering Uncertainty of Traffic Congestion

This paper proposes a new method for service restoration of distribution network with the support of transportable power sources(TPSs)and repair crews(RCs).Firstly,a coupling model of distribution networks and vehicle routing of TPSs and RCs is proposed,where the TPSs serve as emergency power supply sources,and the RCs are used to repair the faulted lines.Considering the uncertainty of traffic congestion,the probability distribution of the travel time spent on each road is derived based on the Nesterov user equilibrium model,and a two-stage stochastic program is formulated to determine the optimal routings of TPSs and RCs.To efficiently solve the proposed stochastic mixed-integer linear program(MILP),a two-phase scenario reduction method is then developed to scale down the problem size,and an adaptive progressive hedging algorithm is used for an efficient solution.The effectiveness of the proposed methods and algorithms has been illustrated in a modified IEEE 33-bus system.

Component reallocation and system replacement maintenance based on availability and cost in series systems

Component reallocation(CR)is receiving increasing attention in many engineering systems with functionally interchangeable and unbalanced degradation components.This paper studies a CR and system replacement maintenance policy of series repairable systems,which undergoes minimal repairs for each emergency failure of components,and considers constant downtime and cost of minimal repair,CR and system replacement.Two binary mixed integer nonlinear programming models are respectively established to determine the assignment of CR,and the uptime right before CR and system replacement with the objective of minimizing the system average maintenance cost and maximizing the system availability.Further,we derive the optimal uptime right before system replacement with maximization of the system availability,and then give the relationship between the system availability and the component failure rate.Finally,numerical examples show that the CR and system replacement maintenance policy can effectively reduce the system average maintenance cost and improve the system availability,and further give the sensitivity analysis and insights of the CR and system replacement maintenance policy.

Random Search and Code Similarity-Based Automatic Program Repair

In recent years,automatic program repair approaches have developed rapidly in the field of software engineering.However,the existing program repair techniques based on genetic programming suffer from requiring verification of a large number of candidate patches,which consume a lot of computational resources.In this paper,we propose a random search and code similarity based automatic program repair(RSCSRepair).First,to reduce the verification computation effort for candidate patches,we introduce test filtering to reduce the number of test cases and use test case prioritization techniques to reconstruct a new set of test cases.Second,we use a combination of code similarity and random search for patch generation.Finally,we use a patch overfitting detection method to improve the quality of patches.In order to verify the performance of our approach,we conducted the experiments on the Defects4J benchmark.The experimental results show that RSCSRepair correctly repairs up to 54 bugs,with improvements of 14.3%,8.5%,14.3%and 10.3%for our approach compared with jKali,Nopol,CapGen and Sim Fix,respectively.

Android程序热修复技术及原理

随着移动互联网的普及和发展,人们对应用程序更新的敏感度越来越高,用户往往不愿意下载和安装大量的软件包。同时,传统的应用程序存在更新方式周期长、流程多,且需要用户主动更新,不能及时修复用户端的程序问题。为了解决以上问题,Android热修复技术应运而生。在不重新安装程序或更新版本的情况下,动态修复Android应用程序的代码和资源,提高了用户的体验和安全性。文章基于目前常见的热修复技术方案分析其实现原理,为软件开发者提供理论支撑,助力行业发展。

数据驱动的高校食堂智慧报修小程序设计与应用——以中国科学技术大学为例

随着科技的快速发展和社会的不断进步,高校食堂硬件设施不断增多,电话报修的矛盾日益凸显,难以满足日益增长的管理需求,迫切需要做好数字化转型。中国科学技术大学聚焦高校食堂场景的智慧报修小程序开发及应用过程,探讨如何实现维修工作的数据化、流程化、集约化和科学化管理,旨在为高校饮食服务管理者提供智慧报修小程序搭建的理论指导和实践经验,推动高校饮食服务管理的发展。

MMR、PD-L1在子宫内膜样癌中的表达及其与预后的相关性

目的探讨错配修复蛋白(MMR)、程序性死亡配体-1(PD-L1)在子宫内膜样癌(EEC)中的表达及其与预后的关系。方法收集2015年1月-2020年9月潍坊市人民医院病理科诊断的EEC组织标本90例、子宫内膜不典型增生组织30例、子宫内膜样癌旁组织30例及子宫内膜不典型增生旁组织10例,对不同子宫内膜组织中的MMR、PD-L1表达情况采用免疫组化法进行检测,分析MMR、PD-L1表达与患者临床病理特征关系及与预后的相关性。结果MMR缺失(dMMR)、PD-L1在EEC组织中表达高于不典型增生组织、子宫内膜不典型增生旁组织及EEC旁组织(检验水准<0.017);dMMR、PD-L1与EEC的年龄及淋巴结转移、FIGO分期、肌层浸润深度无关(P>0.05);PD-L1的表达在G3期较G1期表达上调(检验水准<0.017);PD-L1与dMMR呈正相关(P<0.05);dMMR、PD-L1与患者预后有关,dMMR、PD-L1阳性的患者预后更差,MMR可以作为影响EEC患者生存的独立因素(P<0.05)。结论dMMR、PD-L1在EEC发生发展过程中起协同作用。dMMR、PD-L1与患者预后有关。dMMR是影响EEC预后的独立因素,联合检测MMR、PD-L1可能为EEC预后评估提供理论依据。

基于变异和约束求解的程序缺陷自动修复方法

为能正确高效地生成修复补丁,针对Java程序中出现频率较高的条件语句相关缺陷修复问题,将启发式搜索方法与语义约束求解方法相结合,提出一个有针对性、更高效的解决方案。针对条件语句缺失错误,采用基于组件的程序合成技术,合成满足约束的候选条件语句;针对条件语句逻辑表达式错误,采用变异技术,生成候选逻辑表达式;针对条件语句逻辑表达式错误中,不能用变异技术修复的缺陷,使用基于组件的约束求解方法生成候选补丁。实验结果表明,所提方法有更高的补丁召回率和准确率。

资产负债表冲击:表现与修复路径

2023年以来,受地产行业低迷、信心不足与预期偏弱等因素影响,中国实体经济部门资产负债表受到一定冲击,且居民和企业部门更为明显,但现在断言中国陷入资产负债表衰退为时尚早。通过分析中国三部门资产负债表表现,发现影响中国资产负债表修复的三条逻辑主线:多重因素影响下居民行为函数发生变化带来超额储蓄、提前还贷、消费降级等现象;企业经营目标从利润最大化转向“求生存”,导致投融资下滑显著;债务约束下政府部门还本付息压力加大,扩表能力和意愿有限。而房地产的深度调整是这三者资产负债表变化的逻辑交点。最后,本文从短期调控和长期改革两方面提出修复路径与政策建议。

中职汽修专业构建职业技能“双链条式”质量评价体系的路径——以广西机电工程学校为例

升学与就业并重导向是当前职业教育热点话题,质量评价是难点问题。随着国家产业升级转型,汽车服务后市场对高素质技能型人才需求越来越大。当前国家构建职教升学通道,中职学生转为就业与升学双重导向。为适应新时期汽车服务行业发展,我们以广西机电工程学校为例,总结了当前中职汽车运用与维修专业职业技能质量评价存在的问题,包括评价主体片面、评价内容不全、标准不明确、评价方式单一、评价反馈应用效果不佳,提出职教高考和就业大背景下中职汽修专业以OBE成果导向法为理论依据优化人才培养方案,明确专业定位,重构课程体系,确定各阶段教学培养目标,形成学习成果链;以诊断改进为手段,理顺教学和实习工作机制,查找不足与完善,对教学过程实施诊断改进,形成诊改评价链条。通过构建以学习成果和诊改评价以基础的“双链条式”质量评价体系,以评促教而改,推进教学质量提升工作,促进学生“知识、能力、素养”协调发展,职业技能培养质量明显提升,为中职汽修学生升学和升学后过渡期提供能力保障。

行动导向教学法在汽车维护与保养课程中的应用

行动导向教学法是一种新型的教学方法,对于培养学生的实践能力和问题解决能力具有显著效果。然而在实际教学过程中,教学理念、教学环境、教学方法、教学设计等环节还存在诸多问题。文章从了解课程标准,分析课程内容;明确教学目标,选择教学方法;构建“双师”结构,优化教师队伍;激发学生兴趣,调动学生积极性;重视课前准备,提高课堂效率;创新教学手段,提高学生能力等方面进行了论述。后期经过一系列的教学实践,验证了该教学模式在汽车维护与保养课程教学中应用的有效性,希望在后期的教学开展中,能够不断创新教学手段,提升教学质量。

高职汽修专业“岗课赛证”融合实践研究——以江苏电子信息职业学院为例

培养高技术技能型人才是职业教育汽修专业的人才培养目标。文章结合“职教20条”和“三教”改革,对某职业院校汽修专业人才的“岗课赛证”融合现状与存在问题进行剖析,通过提出“五维三阶十环节”教学策略和4C教学设计法,进行了汽修专业“岗课”“课赛”和“课证”融合的实践探索。这对职业院校汽修相关专业的专业建设、课程改革等具有实践指导意义。

《材料加工工艺学》研究生课堂教学改革研究与实践

鉴于研究生课堂知识教育与课题研究教育之间不能有机衔接,以《材料加工工艺学》课程中模具零件表面强化及修复内容为例,实践课堂教学改革。教学模式由教师、学生共同完成,小组协作完成大作业,考核方式综合教师评价与学生评价,激发了研究生对课程内容的兴趣及主动学习的积极性,同时培养了学生自学、研究的热情,锻炼了研究生表达、交流、协作的能力,为较好地从课堂教学教育过渡到科研阶段打下基础。

伴有淋巴样间质的胃癌患者临床病理特征分析

目的 探讨伴有淋巴样间质的胃癌(GCLS)患者的临床病理特征、免疫表型、鉴别诊断及预后。方法 收集2016—2022年郑州大学第一附属医院收治的25例GCLS患者的临床及病理资料,行免疫组织化学染色及EB病毒编码的小RNA(EBER)原位杂交,并复习相关文献。结果 25例GCLS患者中男23例,女2例,年龄(59.20±12.41)岁。21例患者肿瘤位于近端胃,4例位于远端胃。显微镜下肿瘤细胞呈弥漫性、小巢状、条索状分布,局部可见发育不良的腺腔形成,部分病例可见腺管样结构,间质见大量淋巴细胞浸润。免疫组化结果显示,25例病例中,肿瘤细胞AE1/AE3均呈阳性表达(25/25,100%);间质中淋巴细胞CD3、CD20均呈阳性表达(25/25,100%),且CD3阳性细胞多于CD20阳性细胞;错配修复蛋白MSH2、MSH6、PMS2、MLH1肿瘤细胞表达均无缺失(25/25,100%)。25例病例中人表皮生长因子受体-2(HER2)表达均为阴性,其中14例HER2表达评分为0(14/25,56.00%),11例HER2表达评分为(1+)(11/25,44.00%)。所有病例细胞程序性死亡配体1(PD-L1)均呈阳性表达(25/25,100%),综合阳性评分(CPS)为50~70;其中18例以肿瘤细胞阳性表达为主(18/25,72.00%),7例以淋巴细胞、巨噬细胞阳性表达为主(7/25,28.00%)。原位杂交结果显示,25例病例中,肿瘤细胞EBER均呈阳性表达(25/25,100%)。随访3~72个月,24例无瘤存活,1例失访。结论 GCLS是一种少见的胃癌类型,与EB病毒感染和错配修复蛋白缺陷密切相关,其肿瘤微环境具有淋巴细胞丰富、PD-L1高表达等特点,PD-1/PD-L1抑制剂或许是未来治疗GCLS的一个有效手段。

基于可变修复水平的交通路网应急救援阶段恢复策略优化

重特大灾害往往会造成交通路段不同程度的损坏,使得交通路网陷入瘫痪,这不仅对人民生命财产安全带来隐患,更使得救援难度上升,因此恢复交通路网的连通性是首要任务。本文基于路段的可变修复水平提出应急救援阶段恢复策略优化模型,属于混合整数非线性规划问题,利用fmincon算法以及“蒙特卡罗模拟”进行1000万次循环得到最优派遣策略和恢复策略。通过算例分析,得出本文模型可以应用于大型交通路网修复工程并给出高效合理的救援策略,而且当实际中发生重大灾害后,对交通路网进行实际修复工作时,需要对实际路况进行评估,调整模型的参数从而使得模型效果达到最优。

基于数据流分析的过拟合补丁识别

自动程序修复技术可实现对软件缺陷的自动修复,并使用测试套件评估修复补丁.然而因为测试套件不充分,通过测试套件的补丁可能并未正确修复缺陷,甚至引入新的缺陷并产生波及效应,导致自动程序修复生成大量过拟合补丁.针对这个问题,本文提出了一种基于数据流分析的过拟合补丁识别方法,首先将补丁对程序的修改分解为对变量的操作,然后采用数据流分析方法识别补丁影响域,并根据补丁影响域选择针对性覆盖准则来识别目标覆盖元素,进而选取测试路径并生成测试用例实现对修复程序的充分测试,避免修复副作用的影响.本文在两个数据集上进行了评估,实验结果表明,基于数据流分析的过拟合补丁识别方法可有效提升自动程序修复的正确性.

不正确程序修复补丁识别

程序自动修复技术是保证软件质量、提高开发效率的有效手段.目前,大多数自动修复工具使用测试用例作为补丁正确性验证的最终方法,有限的测试用例难以对程序进行充分的测试,因此自动修复工具生成的补丁集合包含大量的不正确补丁.为了识别不正确补丁,我们采用对比缺陷修复前后成功测试的执行路径以及生成测试用例的方法来识别修复补丁的有效性,以解决自动修复工具精度低的问题.我们的方法评估了来自6个经典的自动修复工具生成的132个补丁,并成功地排除了80个不正确的补丁并且没有排除正确的补丁,这表明我们的方法可以有效地排除不正确补丁,并且提高自动修复工具的精度.