DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

Imperative for long-term management and surveillance in Kawasaki disease

Kawasaki disease(KD)is a significant pediatric vasculitis known for its potential to cause severe coronary artery complications.Despite the effectiveness of initial treatments,such as intravenous immunoglobulin,KD patients can experience long-term cardiovascular issues,as evidenced by a recent case report of an adult who suffered a ST-segment elevation myocardial infarction due to previous KD in the World Journal of Clinical Cases.This editorial emphasizes the critical need for long-term management and regular surveillance to prevent such complications.By drawing on recent research and case studies,we advocate for a structured approach to follow-up care that includes routine cardiac evaluations and preventive measures.

Systematic comparison of Kawasaki disease Z-score formulas:Enhancing diagnostic accuracy and clinical applicability across populations

This study aims to evaluate the performance of six distinct Z-score formulas in diagnosing coronary artery dilation in Kawasaki disease(KD)patients,with a focus on their clinical applicability across diverse populations.A retrospective analysis was conducted using comparative statistical methods to assess the sensitivity and specificity of each formula.The Kobayashi and Dallaire formulas demonstrated the highest sensitivity in China,particularly in younger patients with prolonged fever duration.Our findings provide evidence-based recommend-ations for selecting Z-score formulas to optimize diagnostic precision in KD patients.

Helicobacter pylori infection and gastric microbiota:Insights into gastric and duodenal ulcer development

Helicobacter pylori(H.pylori)infection plays a critical role in gastric diseases,impacting the microbiota structure in gastric and duodenal ulcers.In their study,Jin et al utilized metagenomic sequencing to analyze mucosal samples from patients with ulcers and healthy controls,revealing significant changes in microbial diversity and composition.This article reviews their findings,emphasizing H.pylori’s role in gastric ulcers and the need for further research on its impact on duodenal ulcers.We evaluate the study’s strengths and limitations,suggesting future research directions to enhance our understanding of H.pylori’s contribution to ulcerative diseases.

Addressing functional constipation in children:A call for comprehensive and collaborative management

Functional constipation(FC)is the most common gastrointestinal disorder in children,with a global prevalence of 14.4%based on Rome IV criteria.This editorial explores the multifactorial pathogenesis and diagnostic complexity of FC,emphasizing the importance of early and accurate diagnosis.Effective management of FC hinges on child-oriented toilet training and the use of osmotic laxatives,particularly polyethylene glycol.Emerging therapies,including probiotics,serotonin 5-HT4 receptor agonists,chloride channel activators,and herbal remedies,offer promising options but require further research.Lifestyle modifications,such as adequate fiber and fluid intake and physiotherapy,are crucial in supporting pharmacological treatments.For intractable cases,a multidisciplinary approach involving pediatric specialists,nutritionists,physiotherapists,and psychologists is essential.This comprehensive strategy aims to improve the quality of life for children with FC and their families through continuous research,education,and collaborative care.

列车荷载作用下压实花岗岩残积土累积变形特性试验研究

为研究列车荷载作用下应力及湿化条件对压实花岗岩残积土累积变形特性的影响,以围压、动应力幅值、含水率为变量,对压实花岗岩残积土进行循环空心扭剪和循环定向加载试验。结果表明:循环扭剪应力路径下主应力轴旋转效应增加了试样的累积变形量,甚至改变了累积变形的发展模式,该影响程度随试样含水率的增大而增大;试样的累积应变发展速率在加载初期(N<100)时完成大幅度衰减,围压增大可加快累积应变发展速率的衰减,动应力幅值的增加会延长累积应变发展速率的衰减时间,循环扭剪加载时试样的累积应变发展速率衰减程度小于循环定向加载试验,含水率越高该效应越显著。通过预测模型能够对两种动力加载应力路径下的稳定型和发展型累积应变发展曲线能够进行拟合,对压实花岗岩残积土的累积变形作出较好预测。

双线盾构隧道近距离下穿施工对既有线路影响分析

为研究新建双线隧道近接下穿施工对既有隧道的影响,以大连市地铁5号线下穿2号线工程为依托,通过有限元软件建立盾构穿越施工的三维数值模型,研究了新建隧道穿越对既有运营隧道拱顶、拱底竖向位移及附加应力的变化规律,并分析了新旧隧道净距、土仓压力、注浆压力等因素对既有线路的影响。研究结果表明:新建双线盾构隧道使既有隧道拱顶、拱底产生不同的沉降槽曲线,拱顶沉降小于拱底,新建左线穿越对既有隧道的影响要大于新建右线,约占最终沉降量的87%;既有隧道的附加应力整体表现为受拉,且随着开挖的推进其取值区间不断扩大,拱顶部位应力持续增大;既有线路竖向位移随新旧隧道净距增大而增加,在注浆压力上同样表现出该趋势,但既有线路竖向位移并不随土仓压力的改变而发生显著变化。研究结果可为类似工程提供参考。

干旱区骏枣根系分布和土壤养分关系分析

【目的】研究干旱区骏枣吸收根和输导根分布特征及其与土壤养分的关系。【方法】以阿拉尔垦区6年生骏枣为试材,采用剖面挖掘和分层取样法,使用WinRHIZO根系分析系统测定骏枣不同直径的根系根长、根表面积和根体积指标,并测定不同生长期(0~60 cm深度)土壤的碱解氮、速效磷、速效钾含量,分析根系分布与土壤养分的相关性。【结果】各土壤空间,吸收根根长密度始终高于输导根,根体积则相反。垂直方向上,吸收根和输导根根长密度和根表面积密度均随土层加深而下降,0~20 cm土层根系最密集,吸收根根长密度和根表面积密度占比分别为77.1%、76.5%,输导根占比为76.0%、74.6%。水平方向上,吸收根在0~20 cm和20~40 cm水平距离土壤密集分布,根长密度占比为20.0%~20.7%,根表面积密度占比20.0%~22.2%,输导根占比分别为21.8%~22.1%,18.4%~23.8%;40~140 cm水平距离土壤吸收根根长密度和根表面积密度占比8.8%~14.4%,输导根为8.7%~14.5%,吸收根根长密度和根表面积密度均随水平距离增加缓慢下降,输导根表现为上升下降往复变化,存在差异性。吸收根和输导根根长密度和根表面积密度与展叶期土壤碱解氮、幼果期碱解氮和速效磷相关系数大于0.820,吸收根根长密度和根表面积密度与展叶期土壤速效磷相关系数大于0.809,均表现极显著正相关性,根长密度和根表面积密度与速效钾成负相关关系,相关性不显著。【结论】骏枣根系分布较浅,0~20 cm深度、0~40 cm水平距离的土壤根系分布较为密集,是水分和养分利用的重要区域,根系在垂直方向分布与展叶期和幼果期土壤中的碱解氮和速效磷含量密切相关。

库尔勒香梨的光能截获率及冠层结构优化

【目的】调查库尔勒香梨5种树形的冠层结构,分析不同树形冠层内的光照分布差异,建立光截获量日变化模型,计算光能截获率,明确库尔勒香梨冠层结构的调控方法和目标参数,为高光效树形培育提供参考依据。【方法】以不同树形的库尔勒香梨为试材,测定冠层结构参数和不同部位的光合有效辐射(photosynthetic effective radiation,PAR),基于象限思维构建三维空间,绘制光分布图,建立光能截获评价指标体系,计算光截获量和光能截获率,通过相关性分析和主成分分析,明确影响光能截获的主要冠层结构和调控方法。【结果】(1)大圆柱形的地径、平均枝粗较大,存在枝干比失调的主枝。圆柱形冠层上下的分枝数和枝粗更加均匀。窄圆柱形的分枝数、枝总长、平均枝长显著低于圆柱形。矮圆柱形的树高显著降低,其余参数与窄圆柱形相似。细长纺锤形的地径、平均枝长、平均枝粗、平均枝角、平均枝间距显著低于圆柱形,但短枝占比显著增加。(2)离主干距离和高度是影响冠层光截获量(light interception,LI)的主要因素,离主干100 cm处的平均光截获量(average light interception,ALI)显著提高,达到572μmol·m^(-2)·s^(-1),约为内膛的2倍,220 cm以下的光照条件均较差。南、北、东南、西南侧为高光区,西、东、东北、西北侧为低光区,ALI日变化可以大致分为5个时段。(3)树形变窄、变矮,可显著增加内膛ALI,显著增加各层或部分层次的ALI,显著增加所有或部分方位的ALI,显著增加部分时段的ALI。(4)细长纺锤形的单日累积光截获量(cumulative light interception,CLI)为22.2 mol·m^(-2),群体CLI为3 712 mol/667 m^(2),光能截获率(light interception rate,LIR)为35.6%,显著高于其他树形,其低光区占比(proportion of low light area,PLL)为50.9%,显著低于其他树形。(5)与光能截获率显著正相关的冠层结构参数有5个,显著负相关的冠层结构参数有15个。【结论】短枝占比是影响库尔勒香梨光能截获率的最主要参数,枝长是影响低光区占比的最主要参数。控制树高和冠幅可以提高光能截获率和光照分布的均匀度。细长纺锤形的冠层光分布更加均匀,光能截获率最高,可保持较多的分枝数和较大的短枝占比,降低平均枝长,改善冠层光照水平。

儿童重症肺炎支原体肺炎与重症肺炎链球菌肺炎的临床特征对比分析

目的 对比重症肺炎支原体肺炎(MPP)与重症肺炎链球菌肺炎(SPP)的临床特征。方法 回顾性分析2015年1月—2020年1月收治的77例重症MPP和40例重症SPP患儿,对比两组患儿的一般情况、临床表现、辅助检查等资料。结果 重症MPP患儿组男性48例(62.3%),年龄为44(24~78)月。重症SPP患儿组男性22例(55.0%),年龄为14(9~25)月。96.1%(74/77)的重症MPP患儿与80.0%(32/40)的重症SPP患儿在入院前使用抗生素(P=0.007)。与重症SPP患儿相比,重症MPP患儿出现发热、高热比例较高,出现喘息、神经系统症状比例较低(P均<0.05)。重症SPP患儿更易在肺部闻及湿啰音、哮鸣音,且双侧均出现体征患儿比例更高(P均<0.05)。与重症SPP患儿相比,重症MPP患儿WBC较低、LDH水平较高,胸部CT更易出现支气管充气征(均P<0.05)。两组患儿支气管镜镜下表现及肺泡灌洗液常规检查结果的差异无明显统计学意义(P均>0.05)。结论 重症MPP与重症SPP患儿临床特征常不典型,年龄、发热、高热、喘息、肺部体征、神经系统表现、外周血白细胞计数、外周血乳酸脱氢酶水平等对临床鉴别有提示作用。

不同干燥方法对合欢花药材化学成分及其抗氧化活性影响

建立测定合欢花药材中槲皮苷、异槲皮苷和槲皮素3种黄酮类成分含量测定的方法。通过化学成分含量及其抗氧化活性测定,探讨不同干燥方法对不同规格合欢花药材的影响,为合欢花药材的初加工工艺选择提供参考。通过晒干、阴干、蒸汽杀青后烘干、微波杀青后烘干、烘干(30、50、70、90℃)、冷冻干燥的方式对两种规格合欢花药材进行干燥处理,采用紫外分光光度法、高效液相色谱法、比色法和ABTS法、DPPH法等检测样品中总黄酮、异槲皮苷、槲皮苷、槲皮素含量及抗氧化活性。利用主成分分析、聚类分析和相关性分析对干燥后不同规格样品进行综合评价。研究结果表明,不同干燥处理合欢花药材样品化学成分和抗氧化活性结果存在显著差异。相关性分析表明,槲皮苷含量和总黄酮含量呈显著正相关(P<0.05),槲皮苷含量可作为总黄酮含量大小的评价指标,与O_(2)^(-)自由基清除能力呈正相关但不显著。槲皮苷含量和总黄酮含量与其他四种抗氧化指标呈显著正相关(P<0.05)或极显著正相关(P<0.01),槲皮素含量与ABTS自由基清除能力呈显著正相关(P<0.05),推测槲皮苷和槲皮素是2种合欢花类药材主要抗氧化活性物质。不同干燥方法对2种规格合欢花药材影响显著,盛开的合欢花适合宜采用70℃烘干处理,花蕾期的合欢米宜采用冷冻干燥处理,合欢花和合欢米均不宜采用阴干处理。本研究为2种合欢花类药材初加工方法的选择提供实验依据。

黄芩抗斑马鱼焦虑的作用及靶向GABA受体的分子对接研究

目的:研究黄芩50%乙醇提取物对1-(3-氯苯基)哌嗪盐酸盐(mCPP)致焦虑的斑马鱼焦虑状态的治疗作用及可能的作用机制。方法:抗焦虑研究:选取受精后10、30 d的斑马鱼分为空白组、模型组(0.1 nmol/L mCPP)、给药组(不同浓度黄芩提取物+0.1 nmol/L mCPP),Zebralab软件分析斑马鱼的平均移动距离。采用分子对接软件Autodock Vina分析黄芩中的12种主要成分与γ-氨基丁酸A型受体(GABAAR)的结合能,初步确定潜在的活性组分。结果:黄芩50%乙醇提取物对mCPP诱导的受精后10、30 d斑马鱼焦虑均有抑制作用,其中受精后30 d斑马鱼空白组、模型组(0.1 nmol/L mCPP)和给药组(200µg/mL+0.1 nmol/L mCPP)的平均移动距离分别为3633、4280、3894 mm,说明200µg/mL黄芩提取物可以减缓0.1 nmol/L mCPP对受精后30 d龄斑马鱼的焦虑行为。同时斑马鱼的焦虑行为符合趋触性。11种黄芩活性成分与GABAAR结合能强于原配体地西泮的结合能(-7.2 kcal/mol),白杨素的结合力最强(-8.8 kcal/mol),主要成分黄芩素、黄芩苷、汉黄芩素和汉黄芩苷的结合力也较强,分别为-8.3、-7.7、-8.3、-7.3 kcal/mol。预测黄芩苷等黄酮类成分是黄芩治疗焦虑主要物质基础。结论:黄芩具有抗斑马鱼焦虑的确切疗效,其活性机制可能与黄芩黄酮类成分激活GABAAR有关。

Relationship between Kawasaki disease and abdominal pain

This editorial presents an analysis of an article recently published in the World Journal of Clinical Cases.Kawasaki disease(KD)is a well-known pediatric vasculitis characterized by fever,rash,conjunctivitis,oral mucosal changes,and swelling of the extremities.This editorial aims to delve into the intricate relationship between KD and abdominal pain,drawing insights from recent research findings to provide a comprehensive understanding and potential avenues for future investigation.

Application of artificial intelligence in the diagnosis and treatment of Kawasaki disease

This editorial provides commentary on an article titled"Potential and limitationsof ChatGPT and generative artificial intelligence(AI)in medical safety education"recently published in the World Journal of Clinical Cases.AI has enormous potentialfor various applications in the field of Kawasaki disease(KD).One is machinelearning(ML)to assist in the diagnosis of KD,and clinical prediction models havebeen constructed worldwide using ML;the second is using a gene signalcalculation toolbox to identify KD,which can be used to monitor key clinicalfeatures and laboratory parameters of disease severity;and the third is using deeplearning(DL)to assist in cardiac ultrasound detection.The performance of the DLalgorithm is similar to that of experienced cardiac experts in detecting coronaryartery lesions to promoting the diagnosis of KD.To effectively utilize AI in thediagnosis and treatment process of KD,it is crucial to improve the accuracy of AIdecision-making using more medical data,while addressing issues related topatient personal information protection and AI decision-making responsibility.AIprogress is expected to provide patients with accurate and effective medicalservices that will positively impact the diagnosis and treatment of KD in thefuture.

结果部位不同光照条件对梨果实品质的影响

为促进新疆主干形梨树的推广应用,以库尔勒香梨、玉露香梨和新梨7号树冠内膛遮荫果实及光照良好外部果实为试验材料,对比分析了不同光照条件对果实品质的影响。结果表明,与树冠内膛遮荫果实相比,外部光照良好的库尔勒香梨、玉露香梨和新梨7号果实亮度值(L^(*))分别显著提高了12.87%、7.24%和6.02%;红绿色度值(a^(*))值分别显著提高了62.88%、46.02%和18.88%,果面色泽好,颜色红;单果重、纵横径有一定提高,但不存在显著性差异;可溶性总糖、可溶性固形物及咀嚼性显著提高,果实的蔗糖、果糖、VC、硬度和有机酸等品质指标有一定改善,但不存在显著性差异。可见,树体外部光照条件良好的果实品质优于内膛遮荫果实,在生产中,应当加强修剪,改善果实光照条件。

SCL整合教学法在本科生肾内科教学中的应用探索-以慢性肾衰竭为例

目的分析SCL教学法应用于肾内科教学理论中的教学效果。方法随机整群抽取山西医科大学2022届临床五年制本科A班(观察组)和2021届临床五年制本科B班(对照组)学生作为研究对象。观察组36人采用SCL教学法,对照组32人采用传统授课。通过比较两组教学后的随堂考试成绩、综合应用能力、自主学习能力及教学满意度,以评估SCL整合教学法的教学效果。结果对比随堂考试成绩,观察组学生随堂考试成绩高于对照组,差异有统计学意义(P<0.05);在学生综合能力、自主学习能力评分方面,观察组学生均高于对照组,差异有统计学意义(P<0.05);观察组学生教学满意度各项评分,包括教学方式、课堂积极性、课堂氛围、学习效率、课堂目标实现度均高于对照组,差异有统计学意义(P<0.05)。结论SCL整合教学法运用于肾内科的理论教学,可以促进学生自我学习与互相讨论相结合,激发学生的学习兴趣和注意力,提高学生的理论成绩和综合素养,获得较高的满意度。

制冷站双目标权重自适应非线性预测控制

针对传统制冷站控制系统易产生振荡,且无法实现系统性能整体优化的问题,本文提出一种制冷站非线性预测控制策略,优化目标函数设计为满足建筑冷量需求的同时,尽可能提高系统整体能效.为解决上述两个优化目标之间的矛盾关系,本文采用模糊逻辑设计了优化目标权重自适应模块,实时求取权重因子最优解;针对非线性系统在线优化求解困难问题,本文提出了基于神经网络的非线性滚动优化算法,采用神经网络作为反馈优化控制器,并将系统优化目标函数作为在线寻优性能指标,结合Euler-Lagrange方法和随机梯度下降法对控制器权值和阈值进行在线寻优,算法计算量小,占用存储空间适中,便于采用低成本的现场控制器实现制冷站预测控制.仿真实验结果表明,本文所提出的预测控制策略与PID控制相比,在未加入优化目标函数权重自适应模块情况下,系统平均能效比提高约32.5%;进行优化目标函数权重自适应寻优后,系统平均能效提高约39.43%.

Cavitation cloud impingement and scattering motion of jet in rock breaking process

The cavitation cloud impingement of the jet in the rock breaking process was experimentally investigated to reveal the jet erosion mechanism in drilling of petroleum exploitation. Serial erosion tests and flow visualization were performed, where the cavitation cloud motion in the erosion crater was obtained with the designed transparent specimen. Various erosion patterns were identified in the whole erosion process based on the eroded specimen topography. The shallow eroded crater with a shrinking erosion area is generated by the combination of impinging and scattering cavitation clouds. The increase of l_(d) promotes the development of cavitation cloud σ_(c) but reduces the impingement frequency f_(d), suggesting that the jet aggressive ability is enhanced when the balance between σ_(c) and f_(d) is reached. The cavitation cloud motion in the erosion crater was investigated with the transparent specimen. The erosion in the crater at shorter exposure periods T_(e) is generated by the combination of impingement and restricted scattering of cavitation clouds. With the continuous development of the erosion damage, the jet's aggressive ability is diminished due to the erosion expansion on sandstone, where the cavitation clouds impinge on the target and then collapse and vanish without restricted scattering.

考虑平衡气体效应的乘波体特征线设计方法及气体模型影响

乘波体在高空高超声速飞行时,流场温度急剧升高,气体热力学性质发生改变,其气动特性与采用完全气体模型得到的结果存在差异,因此在飞行器设计中开展真实气体效应影响研究具有重要的工程价值。本文针对锥导乘波体设计提出了一种考虑平衡气体效应的特征线方法(Method of characteristic, MOC),基于不同半锥角和不同流动捕获曲线生成了不同外形的乘波体,并使用快速估算方法估算平衡气体条件和完全气体条件下各乘波体的气动特性和几何特征参数,研究了不同气体模型对乘波体设计结果的影响。研究结果表明,高马赫数下基于平衡气体模型设计得到的乘波体升阻比、容积率和俯仰力矩系数等特性参数相比完全气体结果存在差异,并且平衡气体效应对不同外形乘波体的影响程度和影响规律不同。

高超声速带奇性轴外形热流准确预示的混合算法研究与应用

准确的热流预示在超/高超声速复杂流动数值模拟是一个难点问题。当计算网格中出现奇性轴时,进一步增加了准确流场模拟、热流计算的难度。本文针对奇性轴在有限差分计算中出现的流场结构不稳定、热流预测误差大等难题,在通量重构方法的基础上,结合基于守恒变量的重构方法,提出了一种采用高精度格式计算带奇性轴问题的混合算法。该算法在奇性轴附近使用基于守恒变量的重构方法,有效反映奇性轴附近流场分布对奇性轴计算的影响,能够有效解决奇性轴问题。采用该混合算法并对比应用WENO3‑JS和高分辨率WENO3‑PRM^(2)_(1,1)格式,本文对高超声速球头、HB‑2、球钝锥及Apollo等外形绕流问题进行了数值模拟,结果表明:新方法能够有效解决含奇性轴问题计算中的流场结构不稳定问题,并且可以实现准确的热流预示。