简介:[摘要]嵌合抗原受体T(CAR-T)细胞治疗被认为是治疗复发或难治性肿瘤,特别是血液系统恶性肿瘤的有效方法。尽管最初批准的抗CD19 CAR-T疗法取得了令人印象深刻的结果,但也经历了高复发率和耐药性等挫折,促使人们需要发现更有效的工程CAR-T细胞用于治疗。CAR-T细胞在结构和制造方面的创新导致了疗效和持久性的显著改善,特别是随着第四代CAR-T细胞的发展。与免疫调节剂配对,第四代和下一代CAR-T细胞的使用将不会因为细胞毒效应而受到限制,将成为克服肿瘤微环境的有效工具。本文综述了CAR-T细胞结构在胞外区、跨膜区和胞内区的最新变化,结合创新的制造技术和改进的细胞来源,展望了CAR-T细胞治疗的未来发展前景。
简介:摘要:面对高盐高碱的复杂地质环境,对混凝土质量和耐久性能有更高的要求,本论文旨在研究高性能混凝土T梁施工工艺,尽量采用“就地取材,优化施工,降低成本,绿色环保”的原则。生产高性能混凝土,满足施工要求以及恶劣环境下对耐久性的要求,同时最大程度降低混凝土成本,使用绿色环保的工业副产品。减少对环境的污染, 采用在中国标准基础上结合ACI、BS相关标准,发挥中国技术优势结合两者差异, 在巴基斯坦技术落后的情况下选择合理有效的合格施工材料,制定合理的配合比,来生产高性能混凝土,满足了现场施工要求、优化了T梁施工方案。
简介:摘要:某特大桥在钢桁拱预拼场里程方向配置2台MQ150t/10t-40.5m门式起重机配合施工,门式起重机起吊重量为150t/10t,跨度40.5m,高度30m。门吊拆除采用在中线上搭设支架,支架上布置千斤顶,松开大梁螺栓,在采用吊机将大梁下放至指定地点,而后依次拆除。本文以大里程侧龙门吊为例详细介绍了龙门吊支架法拆除的施工方法和质量控制要点。
简介:摘要:本文通过比较羽绒蓬松度新旧测试标准的差异,对蓬松度仪,搅拌棒,前处理箱以及前处理过程进行比较,并着重对新旧标准测定所得到的数值进行了比较和分析。
简介:【摘要】目的 骨关节炎(Osteoarthritis,OA)是一种累及关节软骨及非软骨组织的骨关节高发病,具有症状进行性加重的特点,严重影响患者生活质量,早期诊断及治疗成为临床工作亟待解决的问题。T2 mapping作为一项磁共振的新技术,可以针对损伤组织中各成分含量的改变进行定量分析,从而检测出早期OA的软骨变性。三维梯度回波T2*加权脂肪抑脂(three-dimensional Gradient recalled echo T2*weighted imaging fat suppression,3D GRE T2*WI fs)是在GRE T2*WI基础上研发的扫描序列,扫描时间较常规PD抑脂像节省了65秒的时间,可大范围、无间隔连续薄层扫描。本研究旨在评估T2 mapping及3D GRE T2*WI抑脂像在髋关节OA诊断中的应用价值及其临床意义。
简介:AbstractThere is increasing evidence that cell-free DNA (cfDNA) in spent culture media (SCM) can be amplified for genetic testing. Therefore, this paper reviews the characteristics of cfDNA, including its fragment size, amount, origin, as well as some factors affecting the success rate of its amplification, together to provide researchers with a more comprehensive perspective on embryonic cfDNA. The origin of cfDNA in SCM is complicated and poses challenges to the interpretation of genetic test results. Advanced molecular techniques should distinguish between embryonic and contaminated DNA to maximize the success rate of amplification and analysis. Recent data showed that the type of culture medium, assisted hatching or not, the type of amplification kit, and fresh or thawed embryos were not related to the success rate of amplification, but the length of culture time might affect the success rate. The longer culture time, the more cfDNA is available in the SCM. Then we focused on the concordance between trophectoderm (TE), inner cell mass, whole embryo, and embryonic cfDNA. Despite successful amplification, the concordance between TE and embryonic cfDNA was low. In summary, non-invasive genetic testing using SCM could represent a major advance in future single embryo selection, however, contamination and timing for media collection are key factors affecting the results, and current non-invasive cfDNA testing should not be directly applied to clinical practice. Further research is needed to improve the methods used for testing techniques and genetic analysis to achieve greater accuracy and trace its origins before it can be used in the clinics.
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简介:AbstractBackground:Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis.Methods:Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq).Results:TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown- TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation.Conclusion:TPCN2 might be a potential protective factor against SLE.
简介:AbstractBackground:Gene promoter methylation is a major epigenetic change in cancers, which plays critical roles in carcinogenesis. As a crucial regulator in the early stages of B-cell differentiation and embryonic neurodevelopment, the paired box 5 (PAX5) gene is downregulated by methylation in several kinds of tumors and the role of this downregulation in esophageal squamous cell carcinoma (ESCC) pathogenesis remains unclear.Methods:To elucidate the role of PAX5 in ESCC, eight ESCC cell lines, 51 primary ESCC tissue samples, and eight normal esophageal mucosa samples were studied and The Cancer Genome Atlas (TCGA) was queried. PAX5 expression was examined by reverse transcription-polymerase chain reaction and western blotting. Cell apoptosis, proliferation, and chemosensitivity were detected by flow cytometry, colony formation assays, and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays in ESCC cell lines with PAX5 overexpression or silencing. Tumor xenograft models were established for in vivo verification.Results:PAX5 methylation was found in 37.3% (19/51) of primary ESCC samples, which was significantly associated with age (P = 0.007) and tumor-node-metastasis stage (P = 0.014). TCGA data analysis indicated that PAX5 expression was inversely correlated with promoter region methylation (r = -0.189, P = 0.011 for cg00464519 and r = -0.228, P = 0.002 for cg02538199). Restoration of PAX5 expression suppressed cell proliferation, promoted apoptosis, and inhibited tumor growth of ESCC cell lines, which was verified in xenografted mice. Ectopic PAX5 expression significantly increased p53 reporter luciferase activity and increased p53 messenger RNA and protein levels. A direct interaction of PAX5 with the p53 promoter region was confirmed by chromatin immunoprecipitation assays. Re-expression of PAX5 sensitized ESCC cell lines KYSE150 and KYSE30 to fluorouracil and docetaxel. Silencing of PAX5 induced resistance of KYSE450 cells to these drugs.Conclusions:As a tumor suppressor gene regulated by promoter region methylation in human ESCC, PAX5 inhibits proliferation, promotes apoptosis, and induces activation of p53 signaling. PAX5 may serve as a chemosensitive marker of ESCC.
简介:摘要目的介绍1.5 T MR加速器的临床剂量调试方法和结果。方法中国医学科学院肿瘤医院于2019年5月安装1台医科达Unity型1.5 T MR加速器,使用磁场兼容测量设备对其进行剂量调试。调试项目包括绝对剂量校准、数据采集和计划系统模型验证。结果磁场下绝对剂量校准需要使用磁场修正因子修正,参考条件下的绝对剂量为87 cGy。将采集的射束数据和计划系统计算结果进行γ分析(3%/2 mm),标准野测试例剂量验证平均通过率为96.41%,TG119测试例为98.24%,美国休斯敦肿瘤放疗和成像质控中心(IROC)端对端测试例为97.5%(7%/4 mm)。结论计划系统模型和射束采集数据具有良好的一致性;标准野和TG119测试例剂量验证结果达到AAPM TG218号报告的通用容差限值要求,端对端测试例验证结果满足IROC中心标准。
简介:摘要:本文以杭绍甬高速绍兴侧预制梁场为研究对象,从其T梁预制施工过程的实际需求出发,对重点工序运用了智能化控制系统,为公路施工企业进行生产智能化转型提供参考。
简介:摘 要:小学语文作业设计作为语文教学中的一个主要环节,它与课堂教学、课外活动一起构成了完整的小学语文教学体系。它是检测学生课堂教学效果的一种重要手段,对学生的语文学习起到一个导向作用。在“双减”政策的背景下,通过“T字法”作业设计,帮助学生形成初步阅读策略,从而提高学生的阅读能力。