Prognostic significance of CDKN2A expression in colon adenocarcinoma: insights from TCGA analysis

Background:The cyclin-dependent kinase inhibitor 2a(CDKN2A)gene,identified as the multiple tumor suppressor gene,functions as a regulatory gene implicated in cancer pathogenesis.Its significance lies in its pivotal involvement in the genesis of various tumors;notwithstanding,the precise connection between CDKN2A and c olon adenocarcinoma(COAD)remains undisclosed.Methods:The objective of this research was to assess the predictive importance of CDKN2A in COAD by analyzing data from The Cancer Genome Atlas database.Logistic regression,signed rank test,Wilcoxon test,and Kruskal-Wallis test were used to examine CDKN2A expression levels and clinicopathological features.Univariate and multivariate Cox r egression analyses and Kaplan-Meier analysis found prognostic variables.Additionally,gene set enrichment analysis identified key CDKN2A expression pathways.The study additionally examined CDKN2A expression with tumor immune infiltration using The Cancer Genome Atlas data and single sample gene set enrichment analysis.Results:The results of this investigation indicated a substantial connection between higher CDKN2A expression and negative outcomes in terms of overall survival and disease-related survival among COAD patients.Gene set enrichment analysis indicated a tight link between CDKN2A and both the cell cycle and hedgehog signaling pathways.Subsequent evaluation employing single sample gene set enrichment analysis demonstrated a positive link between CDKN2A expression with infiltration by iDCs,whereas a negative correlation was detected with infiltration by helper T cells.Conclusion:In conclusion,the present study gives strong data supporting the predictive value of CDKN2A and its possible usefulness as a biomarker for COAD.Additionally,our results show a reasonable link between CDKN2A expression and immune influx in COAD,putting light on the role of CDKN2A in the control of the tumor microenvironment.Nevertheless,additional studies are needed to confirm the underlying mechanisms of these relationships and to discover the therapeutic possibilities of targeting CDKN2A in the treatment of COAD.

Amplification and Bioinformatics Analysis of vscN Gene from Vibrio alginolyticus

[Objectives]The paper was to clone and analyze bioinformatics of vscN gene from Vibrio alginolyticus.[Methods]A pair of specific primers was designed based on the vscN gene sequence of V.alginolyticus HY9901.The full length of vscN gene was amplified by PCR and bioinformatics analysis was performed.[Results]The vscN gene was 1323 bp in total,encoding 440 amino acids,with the theoretical molecular weight of 47.86 kD and the theoretical pI value of 5.89.The online prediction showed that there was no signal peptide and no transmembrane region in VscN.The amino acid sequence had 10 N-myristoylation sites,8 phosphorylation sites(2 protein kinase C phosphorylation sites,6 casein kinase II phosphorylation sites),1 amidation site,11 microbody C-terminal target signal sites,1 ATP/GTP binding site motif A(P ring),and 1 ATPaseαandβsubunit specific site.Homology analysis showed that the VscN protein of V.alginolyticus had high homology with that of V.antiquarius,with a similarity of 95.14%.Phylogenetic tree analysis showed that the VscN of V.alginolyticus was clustered into the same subgroup as that of V.diabolicus and V.antiquarius.Functional domain analysis of VscN protein showed that it had Pfam and AAA domains,and involved in the regulation of bacterial virulence.The three-dimensional structure model of VscN simulated by SWISS-MODEL software was similar to the structure of flagellate-specific ATPase FliH-FliI complex.[Conclusions]The results lay a foundation for further study on the regulatory mechanism of VscN protein on bacterial virulence.

Value of Texture Analysis on Gadoxetic Acid-enhanced MR for Detecting Liver Fibrosis in a Rat Model

Objective To explore the ability of texture analysis of gadoxetic acid-enhanced magnetic resonance imaging(MRI) T1 mapping images, as well as T1-weighted(T1 W), T2-weighted(T2 W) and apparent diffusion coefficient(ADC) maps for distinguishing between varying degrees of hepatic fibrosis in an experimental rat model.Methods Liver fibrosis in rats was induced by carbon tetrachloride intraperitoneal injection for 4–12 weeks(n = 30). In the control group(n = 10) normal saline was applied. The MRI protocol contained T2 W, diffusion weighted imaging, pre-and post-contrast image series of T1 W and T1 mapping images. METAVIR score was used to grade liver fibrosis as normal(F0), mild fibrosis(F1–2), and advanced fibrosis(F3–4). Texture parameters including mean gray-level intensity(Mean), standard deviation(SD), Entropy, mean of positive pixels(MPP), Skewness, and Kurtosis were obtained. Nonparametric Mann-Whitney U test was used to compare the average value of each texture parameter in each sequence for assessing the difference between F0 and F≥1 as well as F0–2 and F3–4. Receiver operating characteristic(ROC) curves were obtained to assess the diagnosing accuracy of the parameters for differentiating no liver fibrosis from liver fibrosis and rats with liver fibrosis grading F0–2 from those with grading F3–4. The area under ROC curve(AUC) was calculated to evaluate the diagnostic efficiency of texture parameters.Results Finally, 20 rats completed MR T1 mapping image scan. The pathologic staging of these 20 rats was no fibrosis(F0, n = 6), mild fibrosis(F1–2, n = 5) and advanced fibrosis(F3–4, n = 9). On pre-contrast T1 mapping image, Entropy was seen to be statistically significant higher in the F≥1 group than that in the F0 group at each spatial scaling factor(SSF) setting(P = 0.015, 0.015, 0.015, 0.013, 0.015 and 0.018 respectively to SSF = 0, 2, 3, 4,5, 6), and Mean of the F≥1 rats was statistically significant higher than that of the F0 rats at SSF 4, 5, 6(P = 0.004, 0.006, and 0.013, respectively). Entropy and Mean showed a moderate diagnostic performance in most SSF settings of T1 mapping pre-contrast images for differentiation of normal liver from liver fibrosis.Conclusion Certain texture features of gadoxetic acid-enhanced MR images, especially the Entropy of noncontrast T1 mapping image, was found to be a useful biomarker for the diagnosis of liver fibrosis.

盾构法联络通道T接头局部冻结加固效果及影响因素研究

为研究盾构法联络通道T接头局部冻结区域的薄弱位置,探究主隧道管片材料、洞门间隙注浆体热导率、是否注浆改良土体和冻结管环数等因素对局部冻结的影响,依托天津地铁10号线某联络通道T接头局部冻结加固工程,采用数值模拟对局部冻结温度场的分布规律进行分析。研究结果表明:1)对于沿洞门处的土体,联络通道顶底部冻结效果差于联络通道侧面;主隧道钢管片向主隧道底部比向顶部延伸的更长,因而联络通道底半环冻结效果略差于顶半环。2)影响局部冻结时间的主要因素为主隧道管片材料和洞门间隙注浆体的热导率。3)主隧道部分采用钢管片工况,钢管片起到通道壁后远近土体导热“桥梁”的作用;当洞门间隙注浆体的热导率较低(如0.93 W/(m·K))时,注浆体不能及时地向主隧道钢管片输送冷量,联络通道壁后近处土体中大量冻结冷量沿钢管片传递至远处土体,使通道壁后较近处土体温度较高,因而比主隧道全部采用钢筋混凝土管片工况冻结时间长。4)随着洞门间隙注浆体热导率的增大,其向主隧道管片输送冷量的效率得到提升,主隧道附近土体的冻结效果得到改善,冻结时长有所缩短;间隙注浆体热导率由0.93 W/(m·K)提升至1.8 W/(m·K)时,可以将主隧道部分采用钢管片工况冻结时间由17 d缩短至12 d,所需冻结时长相比主隧道全部采用钢筋混凝土管片工况反而缩短1 d,即主隧道部分采用钢管片工况的冻结时间对洞门间隙注浆体热导率的改变更为敏感。

肠道菌群情况与发声和多种运动联合抽动障碍患儿神经递质、神经功能及T细胞亚群的相关性分析

目的探讨发声和多种运动联合抽动障碍(又称抽动症)患儿肠道菌群分布情况与其神经递质、神经功能及T细胞亚群的相关性。方法以2020年5月—2023年5月南京中医药大学附属南京市中西医结合医院收治的97例抽动症患儿作为研究对象,通过耶鲁抽动症整体严重度量表(YGTSS)将所有患儿分为轻度组23例、中度组42例和重度组32例。采集所有患儿粪便样本,采用16S rRNA测序技术和Qiime软件进行肠道菌群α多样性分析[Chao1指数、observed species(Sobs)指数、Shannon指数、Simpson指数];测定T淋巴细胞亚群(CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))和神经递质[5-羟色胺(5-HT)、多巴胺(DA)、γ-氨基丁酸(GABA)、去甲肾上腺素(NE)]水平;评估两组儿童神经功能;采用Pearson相关性分析探讨患儿肠道菌群与神经递质、神经功能及T细胞亚群的关系。结果与轻度组相比,中度组和重度组的YGTSS评分的运动性抽动、发声性抽动、总分更高(P<0.05);轻度组、中度组和重度组患儿的Chao1、Sobs、Shannon和Simpson指数比较,经方差分析,差异均有统计学意义(P<0.05);与轻度组相比,中度组和重度组的α多样性更低(P<0.05);轻度组、中度组和重度组患儿的CD4^(+)、CD8^(+)和CD4^(+)/CD8^(+)比较,经方差分析,差异均有统计学意义(P<0.05);与轻度组相比,中度组和重度组的CD4^(+)和CD4^(+)/CD8^(+)更低,CD8^(+)更高(P<0.05);与轻度组相比,中度组和重度组的5-HT和DA更高,GABA、NE、神经功能评分更低(P<0.05)。根据Pearson相关性分析结果,患儿Chao1、Sobs、Shannon和Simpson指数与5-HT、DA呈负相关(P<0.05),与CD4^(+)、GABA、NE和神经功能评分呈正相关(P<0.05)。结论肠道菌群与抽动症患儿的神经递质、神经功能和T细胞亚群密切相关。

基于损伤因子的T形梁桥横向连接构件损伤识别

近年来,装配式T形梁桥在我国广泛应用,对桥梁易损位置横向连接构件损伤识别成为关注的热点问题.将T形梁桥的横隔梁简化成等刚度桥面板,采用弹簧体系模拟横向连接构件的受力变形,考虑横向连接构件剪力、横向力和翼缘板变形的影响,提出装配式T形梁桥横向连接构件损伤因子的理论计算式.将MATLAB理论计算、ANSYS数值模拟和实验的结果进行对比,验证损伤因子的有效性,并通过7种模拟工况和3种实际工况的对比,发现荷载作用位置越接近损伤横向连接构件,损伤识别的精确度越高.

基于多分析方法探讨近十年T细胞对类风湿关节炎影响的可视化分析

目的通过对近十年T细胞对类风湿关节炎(rheumatoid arthritis,RA)影响的文献进行多软件可视化分析,总结该领域的研究热点及前沿发展。方法在中国知网和Web of Science核心合集数据库检索2012-2022年关于T细胞对RA影响的中英文文献,运用CiteSpace、VOSviewer软件对其发文量、作者、关键词进行分析。结果中文文献519篇,英文文献861篇,结果显示2020-2022年中文发文量缓慢增加,英文发文量整体趋势较为平稳。关键词分析显示,预测该领域的未来研究聚焦于T细胞在RA中的发病机制、RA的骨破坏机制、疾病活动度、氧化应激等方面。结论T细胞对RA影响的研究关注度一直较高,研究价值大。但因国内外研究重点存在差异,团队间应良性互动、相互交流,以期揭示RA的内在机制,为靶向治疗提供理论依据。

老年急性缺血性脑卒中合并重症肺炎患者病原菌分布与T细胞亚群改变及预后

目的研究老年急性缺血性脑卒中合并重症肺炎(SP)者病原菌分布特点、T淋巴亚群改变及预后分析。方法将2021年3月至2023年3月新疆医科大学第一附属医院急救中心收治的150例老年急性缺血性脑卒中合并肺炎患者纳为研究对象,根据肺炎严重程度将其分为SP组与非SP(NSP)组,统计其临床资料、病原菌培养与药敏试验结果、外周血T淋巴细胞亚群占比以及患者28 d死亡率。采用SPSS 22.0软件进行数据分析。根据数据类型,组间比较分别采用t检验及χ^(2)检验。结果SP组患者平均年龄、美国国立卫生研究院卒中量表(NIHSS)评分、慢性阻塞性肺疾病(COPD)患病率、意识障碍发生率均高于NSP组,差异均有统计学意义(均P<0.05);两组卒中部位比较,差异有统计学意义(P<0.05)。70例SP患者中共培养出病原菌68株,其中革兰阴性菌占比88.24%(60/68),革兰阳性菌占比11.76%(8/68);检出率最高的三种病原菌分别为鲍氏不动杆菌(47.06%,32/68)、铜绿假单胞菌(14.71%,10/68)及肺炎雷克伯菌(13.24%,9/68)。鲍曼不动杆菌对复方新诺明及头孢哌酮/舒巴坦相对敏感。铜绿假单胞菌对妥布霉素及阿米卡星的灵敏性较高,对庆大霉素及喹诺酮类抗菌素相对灵敏,肺炎克雷伯菌对阿米卡星及亚胺培南的灵敏性最高。SP组患者CD3^(+)、CD4^(+)以及CD4^(+)/CD8^(+)水平低于存活组,CD8^(+)高于NSP组,差异均有统计学意义(均P<0.05)。SP组28 d死亡率为45.71%(32/70),高于NSP组的6.25%(5/80)(χ^(2)=31.290;P<0.05)。死亡者CD3^(+)、CD4^(+)以及CD4^(+)/CD8^(+)水平低于存活组,CD8^(+)高于存活者,差异均有统计学意义(P<0.05)。结论缺血性脑卒中合并SP将增加患者死亡风险,年龄、NIHSS评分、合并CODP及意识障碍可能是促进缺血性脑卒中一般肺炎向SP发展的相关因素,且免疫失衡还可能参与缺血性脑卒中SP发生相关机制,并增加患者死亡风险。

型钢混凝土T形截面剪力墙基于性能的变形限值研究

为更好地评估T形截面型钢混凝土(steel reinforced concrete,SRC)剪力墙变形性能,采用ABAQUS有限元软件对按照规范设计的324个T形截面SRC剪力墙构件的破坏形态和变形性能进行研究,根据收集的试验数据分析构件的破坏形态,提出T形截面SRC剪力墙的破坏形态划分准则;以构件的各材料应变极限值为准则来判别构件的性能状态,考虑轴压比、剪跨比、弯剪比、腹板暗柱配钢率、暗柱纵筋配筋率及箍筋暗柱特征值对构件变形性能的影响。对不同性能状态变形限值和参数进行线性回归分析,得到不同破坏类型下各性能状态位移角限值计算式;按规范ASCE 41修正各性能状态变形限值的失效概率,得到具有15%、20%、35%失效概率保证的各性能状态变形限值取值表。研究表明:剪跨比、轴压比对构件各性能状态位移角限值影响较大,暗柱腹板配钢率、纵筋配筋率及箍筋特征值对构件位移角限值影响相对较小,但能提高其延性。按规范ASCE 41修正后的位移角限值取值较为合理且有一定的安全储备。为T形截面SRC剪力墙基于性能的抗震设计与性能评估提供参考。

T/R组件过激励试验可靠性与失效机理研究

T/R组件作为通信系统的核心部件,在运行环境下其接收通道经常面临外界大功率强扰动信号。外界大功率强扰动信号是影响T/R组件可靠性的重要因素,鉴于此本文搭建T/R组件过激励测试试验平台,对T/R组件接收通道进行过激励试验,并借助金相显微镜及聚焦离子束等失效分析技术对试验后T/R组件开展失效分析研究。依据试验结果,确定了组件中接收通道在过激励下的失效部位、失效模式及失效机理,检验了典型T/R组件的抗扰动、耐功率、抗烧毁能力,为T/R组件的耐功率、抗烧毁设计提供借鉴和指导。

慢乙肝低病毒血症患者继续核苷(酸)类似物治疗的远期临床结局:一项系统评价和Meta分析

背景一线核苷(酸)类似物(nucleos(t)ide analogues,NAs)经治后发生低病毒血症(low-level viremia,LLV)的慢乙肝患者,继续使用NAs治疗的远期临床结局的研究尚缺乏.目的采用系统评价和Meta分析对慢乙肝经一线NAs治疗的LLV患者继续原NAs治疗和更换不同NAs治疗方案远期临床结局情况进行评价.方法经计算机检索PubMed、Embase、Web of Science、Cochrane Library数据库和中国知网(CNKI)、万方数据库,选取符合纳入标准的研究,使用R 4.3.1软件对纳入研究数据进行Meta分析.结果最终纳入11篇文献,涉及3153例慢乙肝LLV患者,其中7篇文献进行HBV DNA阴转率定量Meta分析,结果提示更换NAs方案组继续治疗24 wk[RR=4.23,95%CI(2.47,7.24),P<0.01]和48 wk[RR=2.90,95%CI(1.75,4.81),P<0.01]后HBV DNA阴转率明显高于继续原NAs方案组;纳入6篇文献进行HBeAg阴转率的定量Meta分析,更换NAs治疗方案组24 wk HBeAg阴转率高于继续原方案组[RR=2.31,95%CI(1.28,4.19),P<0.01],但48 wk两组HBeAg阴转率差异无统计学意义[RR=1.50,95%CI(0.88,2.54),P=0.13];纳入3篇文献进行终末期肝病发生率的定性系统评价,结果显示继续NAs治疗的LLV组患者远期终末期肝病发生率均高于维持病毒学应答(maintain virological response,MVR)组,差异均具有统计学意义(P<0.05).结论更换NAs治疗方案可提高慢乙肝LLV患者HBV DNA阴转率和HBeAg阴转率,但继续NAs方案治疗的慢乙肝LLV患者远期终末期肝病发生率较MVR患者高.

扩孔型T型钢梁柱连接节点抗震性能分析

高强螺栓连接的钢梁柱节点可通过增大螺栓孔的方式延续耗能来提升节点的抗震性能,为研究扩孔T型梁柱节点的抗震性能,对4个悬臂式T型梁柱节点低周往复加载试验展开数值模拟研究,利用ABAQUS中C3D8I实体单元建立有限元分析模型,分析T型连接件尺寸、螺栓规格、梁截面尺寸对扩孔T型连接节点的滞回性能、刚度退化及耗能性能的影响规律。结果表明:扩孔后的T型节点出现明显的滑移特征,滑移过程中可以耗散大量能量,4个扩孔T型梁柱节点的耗能能力均较常规孔节点有明显提升;对于初始转动刚度较低的常规孔构件,T型节点的耗能能力相对较弱,经扩孔处理之后,节点的耗能能力提升幅度更大;由于承载力机制的先后转变,扩孔之后的构件中期承载力小于常规孔构件,后期的极限承载力基本相同。

金属屋面系统新型T形连接件抗风性能分析

金属屋面系统对风荷载格外敏感,各屋面构件通过连接件固定,当风荷载较大时容易造成连接失效破坏.根据金属屋面与连接件在风荷载作用下的受力情况及破坏模式,提出一种可自由转动的扣嵌式新型连接件,由连接件的转动来抵消屋面变形及缓解温度应力,使整个屋面系统灵活可变,从而提高整个屋面板的抗风揭性能.通过ANSYS软件建立有限元模型,对新型连接件进行数值模拟分析,获得新型T形连接件的抗风承载力及抗风失效模式,并与原T形连接件进行对比分析,验证新型T形连接件对提高金属屋面系统抗风揭能力的有效性及合理性.

Differential Diagnostic Value of Texture Feature Analysis of Magnetic Resonance T2 Weighted Imaging between Glioblastoma and Primary Central Neural System Lymphoma

Objective To investigate the difference in tumor conventional imaging findings and texture features on T2 weighted images between glioblastoma and primary central neural system(CNS) lymphoma. Methods The pre-operative MRI data of 81 patients with glioblastoma and 28 patients with primary CNS lymphoma admitted to the Chinese PLA General Hospital and Hainan Hospital of Chinese PLA General Hospital were retrospectively collected. All patients underwent plain MR imaging and enhanced T1 weighted imaging to visualize imaging features of lesions. Texture analysis of T2 weighted imaging(T2 WI) was performed by use of GLCM texture plugin of ImageJ software, and the texture parameters including Angular Second Moment(ASM), Contrast, Correlation, Inverse Difference Moment(IDM), and Entropy were measured. Independent sample t-test and Mann-Whitney U test were performed for the between-group comparisons, regression model was established by Binary Logistic regression analysis, and receiver operating characteristic(ROC) curve was plotted to compare the diagnostic efficacy. Results The conventional imaging features including cystic and necrosis changes(P = 0.000), ‘Rosette' changes(P = 0.000) and ‘incision sign'(P = 0.000), except ‘flame-like edema'(P = 0.635), presented significantly statistical difference between glioblastoma and primary CNS lymphoma. The texture features, ASM, Contrast, Correlation, IDM and Entropy, showed significant differences between glioblastoma and primary CNS lympoma(P = 0.006,0.000, 0.002, 0.000, and 0.015 respectively). The area under the ROC curve was 0.671, 0.752, 0.695, 0.720 and 0.646 respectively, and the area under the ROC curve was 0.917 for the combined texture variables(Contrast, cystic and necrosis, ‘Rosette' changes, and ‘incision sign') in the model of Logistic regression. Binary Logistic regression analysis demonstrated that cystic and necrosis changes, ‘Rosette' changes and ‘incision sign' and texture Contrast could be considered as the specific texture variables for the differential diagnosis of glioblastoma and primary CNS lymphoma. Conclusion The texture features of T2 WI and conventional imaging findings may be used to distinguish glioblastoma from primary CNS lymphoma.

基于T-S模糊故障树的驱动电机冷却系统可靠性分析

车用驱动电机液压冷却系统存在故障机理不确定等问题。本文应用模糊数描述其故障概率和故障程度,建立驱动电机冷却系统的T-S模糊故障树模型,计算系统模糊可能性,分析各部件的概率重要度和关键重要度,找出影响系统可靠性的关键部件。

IVIM-DWI联合基于T2WI纹理分析术前鉴别直肠癌T2与T3分期的应用价值

目的探讨体素内不相干运动扩散加权成像(IVIM-DWI)和基于T_(2)WI纹理分析术前鉴别直肠癌T_(2)与T_(3)分期的价值。方法回顾性分析2016年6月至2023年5月于中国科学技术大学附属第一医院西区(安徽省肿瘤医院)就诊且经手术病理证实的105例直肠癌患者临床资料。根据术后病理T分期将患者分为T_(2)期组(n=57)和T_(3)期组(n=48)。所有患者均于术前行常规MRI及IVIM-DWI检查。测量患者癌灶的IVIM-DWI参数表观扩散系数(ADC)、D、D*和f,并提取T_(2)WI序列的三维纹理特征。比较两组患者IVIM-DWI参数和纹理参数的差异,建立纹理特征模型、IVIM-DWI和纹理特征参数的联合模型。用受试者工作特征(ROC)曲线评估各参数和模型术前对直肠癌T_(2)和T_(3)分期的鉴别效能。结果IVIM-DWI参数中,T_(2)期组D值大于T_(3)期组D值,T_(2)期组f值小于T_(3)期组f值,差异均有统计学意义(P<0.05),ADC值和D~*值的差异无统计学意义(P>0.05)。从T_(2)WI提取的1874个纹理参数中,筛选出4个具有统计学意义的纹理参数:firstorder_90Percentile、glrlm_LRLGLE、glszm_SZN和glszm_SAHGLE。D值、f值及4个纹理特征参数的曲线下面积(AUC)分别为0.705,0.664,0.840,0.740,0.801,0.656。纹理特征模型的AUC为0.952,联合模型的AUC为0.956。联合模型的AUC大于D值、f值及4个纹理特征参数的AUC,其灵敏度为93.9%,特异度为87.5%。结论IVIM-DWI联合基于T_(2)WI纹理分析对术前直肠癌的T_(2)期和T_(3)期具有良好的鉴别效能,一定程度上弥补常规MRI技术之不足。

Integration system research and development for three-dimensional laser scanning information visualization in goaf

An integration processing system of three-dimensional laser scanning information visualization in goaf was developed. It is provided with multiple functions, such as laser scanning information management for goaf, cloud data de-noising optimization, construction, display and operation of three-dimensional model, model editing, profile generation, calculation of goaf volume and roof area, Boolean calculation among models and interaction with the third party soft ware. Concerning this system with a concise interface, plentiful data input/output interfaces, it is featured with high integration, simple and convenient operations of applications. According to practice, in addition to being well-adapted, this system is favorably reliable and stable.

波形钢腹板梁T形接头焊接仿真分析与试验研究

为了解决波形钢腹板梁焊接温度场和残余应力分布尚不明确的问题,本文基于Simufact Welding软件建立三维有限元模型,对其T形接头的焊接温度场和残余应力进行了预测,并对模拟结果进行了试验验证。波形钢腹板梁的焊接温度场分布与熔池中心距离有关,距离熔池中心越近,温度梯度越大;焊接残余应力以纵向残余拉应力为主,而横向残余应力的应力水平相对较低,拉压应力共存;焊接速度和底板厚度的改变只会影响残余应力的峰值大小,不会影响残余应力的分布规律。结果表明:数值模拟结果和试验实测值吻合良好,数值模拟可靠。

双靶点嵌合抗原受体-T细胞治疗复发难治多发性骨髓瘤患者疗效和安全性的Meta分析

背景嵌合抗原受体(CAR)-T细胞免疫疗法已在多发性骨髓瘤(MM)中取得较好的疗效,最常见的靶点为B细胞成熟抗原(BCMA)。单靶点CAR-T细胞免疫疗法的缺点是会导致疾病抵抗和复发,可能与抗原逃逸有关。为此,改进开发了双靶点CAR-T细胞治疗复发难治多发性骨髓瘤(RRMM),此方面尚缺乏系统的临床分析。目的对RRMM患者应用双靶点CAR-T细胞免疫疗法治疗的有效性及安全性进行Meta分析。方法计算机检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方数据知识服务平台、维普网7个数据库中有关双靶点CAR-T细胞治疗RRMM的单组率研究,检索时限为建库至2023-02-06。由2名研究人员使用自制的数据表单来提取收集数据,并采用非随机对照试验方法学评价指标进行文献质量评价。采用R Studio软件进行数据分析。结果共纳入9篇文献,包括200例既往接受过多线治疗的RRMM患者。双靶点CAR-T细胞疗法根据不同靶点可分为4类:BCMA+CD19、BCMA+CD38,BCMA+跨膜剂与钙调节亲环素配体的相互作用者(TACI)、BCMA+人信号淋巴细胞激活分子家族成员7(CS1),其中BCMA+CD19靶点的研究较多。根据输注形式不同CAR-T细胞疗法可分为4类:双特异性CAR-T细胞、联合或序贯输注两种不同CAR-T细胞、双顺反子结构、共转导。Meta分析显示,双靶点CAR-T细胞治疗RRMM的总缓解率(ORR)为90.0%(95%CI=0.849~0.943),完全缓解率(CRR)为54.6%(95%CI=0.416~0.673),微小残留病(MRD)阴性率为75.6%(95%CI=0.489~0.952),髓外病变(EMD)总缓解率为55.1%(95%CI=0.234~0.851),最后一次随访时的复发率为29.7%(95%CI=0.141~0.454),最后一次随访时的生存率为75.6%(95%CI=0.554~0.915),3~4级细胞释放因子综合征(CRS)发生率为16.4%(95%CI=0.094~0.245),神经毒性(ICANS)发生率为4.0%(95%CI=0~0.120)。敏感性分析提示结果稳定。Egger's检验结果显示,ORR(P=0.03)及EMD总缓解率(P=0.02)提示存在一定的偏倚风险;CRR(P=0.53)、MRD阴性率(P=0.79)、最后一次随访时的复发率(P=0.71)、生存率(P=0.98)、3~4级CRS发生率(P=0.90)、ICANS发生率(P=0.30)提示不存在发表偏倚。结论双靶点CAR-T细胞免疫治疗RRMM显示出良好的疗效和安全性,未来需要多中心、大样本、更长随访期的研究来进一步评估其疗效和安全性。

基于最弱t-norm算法模糊贝叶斯网络土石坝渗漏风险分析

针对土石坝工程渗漏影响要素多,风险评估体系不完善的问题,提出一种基于最弱t-norm算法模糊贝叶斯网络的土石坝渗漏风险分析模型。首先基于土石坝渗漏破坏成因构建土石坝渗漏风险分析网络,再基于层次分析法和最弱t-norm聚合算法求解不同专家判断的相似性结果,最后将相似性结果转化为概率后代入贝叶斯理论计算水库渗漏破坏风险。以2005年英德尔水库渗漏破坏事件为例,计算得到该库渗漏破坏概率为0.08,属于不可接受风险,并通过反向诊断验证了该模型的可靠性与灵敏性优于传统算法。研究结果可为土石坝渗流风险分析与处置决策提供参考。