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《Cancer cell》2021,39(9):1214-1226.e10
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Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established. Thus, future research on LNPs will focus on addressing the following: expanding the scope of drug delivery to different constituents of the human body, expanding the number of diseases that can be targeted, and studying the change in the pharmacokinetics of LNPs under physiological and pathological conditions. This review article provides an overview of recent advances aimed at expanding the application of LNPs, focusing on the pharmacokinetics and advantages of LNPs. In addition, analytical techniques, library construction and screening, rational design, active targeting, and applicability to gene editing therapy have also been discussed. 相似文献
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BackgroundTumor mutation burden (TMB) as a prognostic marker for immunotherapy has shown prognostic value in many cancers. However, there is no systematic investigation on TMB in papillary thyroid carcinoma (PTC).MethodsBased on the somatic mutation data of 487 PTC patients from The Cancer Genome Atlas (TCGA), TMB was calculated, and we classified the samples into high-TMB (H-TMB) and low-TMB (L-TMB) groups. Bioinformatics methods were used to explore the characteristics and potential mechanism of TMB in PTC.ResultsHigh TMB predicts shorter progression-free survival (PFS) (P < 0.001). TMB was positively correlated with age, stage, tumor size, metastasis, the male sex and tall cell PTC. Compared to the L-TMB group, the H-TMB group presented with lower immune cell infiltration, a higher proportion of tumor-promoting immune cells (M0 macrophages, activated dendritic cells and monocytes) and a lower proportion of antitumor immune cells (M1 macrophages, CD8+ T cells and B cells). Additionally, the characteristics displayed by different TMB groups were not driven by critical driver mutations such as BRAF and RAS.ConclusionsPTC patients with high TMB have a worse prognosis. By stratifying PTC patients according to their TMB, advanced PTC patients who are candidates for immunotherapy could be selected. 相似文献
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目的探究肿瘤坏死因子-α(Tumornecrosis factor-α,TNF-α)-308基因对导管相关性脓毒症(Catheter related sepsis,CRS)患者病情的影响,旨在为临床治疗CRS提供科学依据。方法选取2017年7月-2018年10月于浙江大学医学院附属杭州市第一人民医院接受治疗的86例CRS患者为研究对象,按照是否并发多器官功能障碍综合征将患者分为试验组和对照组,对照组共48例,未并发多器官功能障碍综合征,试验组共38例,并发多器官功能障碍综合征,分析两组患者TNF-α-308基因多态性差异,使用多因素Logistic回归分析CRS患者并发多器官功能障碍综合征的危险因素。结果试验组GA基因型频率34.21%、AA基因型频率50.00%、高G等位基因频率18.42%均高于对照组,GG基因型频率52.63%、A等位基因频率28.95%均低于对照组,差异均具有统计学意义(P<0.05);多因素Logistic回归分析结果显示,低GG基因型频率、低G等位基因频率、高GA基因型频率、高AA基因型频率、高A等位基因频率是CRS患者并发多器官功能障碍综合征的危险因素(P<0.05)。结论TNF-α-308基因与CRS患者病情密切相关,GG基因型频率和G等位基因频率降低,GA基因型频率、AA基因型频率、A等位基因频率升高会加重患者的病情,增加多器官功能障碍综合征的发生风险,临床上应该加以重视。 相似文献
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应用拷贝数变异测序(copy number variation sequencing,CNV-seq)技术鉴别来源不明的胎儿标记染色体,明确其遗传物质的来源,并探讨此技术在产前诊断中的应用价值。讨论Pallister-Killian综合征(Pallister-Killian syndrome,PKS)的临床特征及遗传学特点,提高对此类罕见染色体疾病的认识。该病例因在妊娠中期超声发现胎儿异常而行羊水穿刺进行CNV-Seq检测,同时分析胎儿和父母的核型。羊水CNV-Seq结果示该样本12号染色体p13.33-p11.1处检测到拷贝数为3.5、片段大小为34.70 Mb的嵌合重复区域;羊水染色体核型结果为47,XY,+i(12)(p10)[58]/46,XX[42],综合上述结果考虑为PKS。通过结合超声结果,综合应用染色体G显带核型分析和CNV-seq技术能准确确认染色体异常片段来源,在产前有效诊断PKS患者。 相似文献
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《Diagnostic and interventional imaging》2020,101(12):821-830
PurposeTo compare morphological imaging features and CT texture histogram parameters between grade 3 pancreatic neuroendocrine tumors (G3-NET) and neuroendocrine carcinomas (NEC).Materials and methodsPatients with pathologically proven G3-NET and NEC, according to the 2017 World Health Organization classification who had CT and MRI examinations between 2006-2017 were retrospectively included. CT and MRI examinations were reviewed by two radiologists in consensus and analyzed with respect to tumor size, enhancement patterns, hemorrhagic content, liver metastases and lymphadenopathies. Texture histogram analysis of tumors was performed on arterial and portal phase CT images. images. Morphological imaging features and CT texture histogram parameters of G3-NETs and NECs were compared.ResultsThirty-seven patients (21 men, 16 women; mean age, 56 ± 13 [SD] years [range: 28-82 years]) with 37 tumors (mean diameter, 60 ± 46 [SD] mm) were included (CT available for all, MRI for 16/37, 43%). Twenty-three patients (23/37; 62%) had NEC and 14 patients (14/37; 38%) had G3-NET. NECs were larger than G3-NETs (mean, 70 ± 51 [SD] mm [range: 18 - 196 mm] vs. 42 ± 24 [SD] mm [range: 8 - 94 mm], respectively; P = 0.039), with more tumor necrosis (75% vs. 33%, respectively; P = 0.030) and lower attenuation on precontrast (30 ± 4 [SD] HU [range: 25-39 HU] vs. 37 ± 6 [SD] [range: 25-45 HU], respectively; P = 0.002) and on portal venous phase CT images (75 ± 18 [SD] HU [range: 43 - 108 HU] vs. 92 ± 19 [SD] HU [range: 46 - 117 HU], respectively; P = 0.014). Hemorrhagic content on MRI was only observed in NEC (P = 0.007). The mean ADC value was lower in NEC ([1.1 ± 0.1 (SD)] × 10−3 mm2/s [range: (0.91 - 1.3) × 10−3 mm2/s] vs. [1.4 ± 0.2 (SD)] × 10−3 mm2/s [range: (1.1 - 1.6) × 10−3 mm2/s]; P = 0.005). CT histogram analysis showed that NEC were more heterogeneous on portal venous phase images (Entropy-0: 4.7 ± 0.2 [SD] [range: 4.2-5.1] vs. 4.5 ± 0.4 [SD] [range: 3.7-4.9]; P = 0.023).ConclusionPancreatic NECs are larger, more frequently hypoattenuating and more heterogeneous with hemorrhagic content than G3-NET on CT and MRI. 相似文献
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目的 检测分析被诊断为X连锁视网膜色素变性(XLRP)的三个中国家系内的基因突变。设计 基因研究。研究对象 三个中国XLRP家系共27位受试者(其中18人为男性)。方法 由同一医生收集家系成员的详细临床资料并进行眼部检查,采集三个家系的先证者及有条件采血者的外周静脉血,提取基因组DNA。应用PCR技术扩增RPGR和RP2基因的全部外显子和内含子交界区序列,包括RPGR基因15号外显子开放阅读框,产物直接测序进行突变分析。主要指标 临床特征及基因测序结果。结果 基因筛查证实了两个RPGR基因的新型无义突变(c.1541C>G;p.S514X 和 c.2833G>T;p.E945X) 及一个错义突变(c.607G>C;p.A203P)。基因型-表型的相关性分析表明家系3患者在接近ORF15下游位置存在突变,这种突变导致视锥细胞功能的早期丧失。ORF15无义突变的女性携带者临床表型重,呈现出部分显性遗传的特点。结论 本研究证实了三种RPGR基因的新型突变,这一结果扩展了RPGR的突变谱及表型谱。 相似文献
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