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1.
目的 探讨影响原发免疫性血小板减少症(ITP)患者树突状细胞功能异常的基因,为ITP治疗寻求新方法。 方法 随机选取ITP患者(ITP组)8例和同期入院体检健康者8例正常对照组为研究对象,分离外周单个核细胞并在体外诱导分化为单核细胞源性树突状细胞(moDCs),选取ITP组和正常对照组moDCs样本各3例,使用Illumina Hiseq平台进行转录组测序,并完成生物信息学分析。其他moDCs样本分为对照组、ITP组和ITP+雷帕霉素处理组,采用Western blotting法检测哺乳动物雷帕霉素靶蛋白复合体1(mTORC1)信号通路激活情况,采用流式细胞术检测moDCs表面分子表达,采用酶联免疫吸附(ELISA)法检测moDCs细胞因子分泌能力。 结果 差异性表达分析显示,与正常对照组相比,ITP组患者moDCs中有161个基因表达上调,320个基因表达下调,差异有统计学意义(P<0.05)。利用基因本体论(GO)和京都基因与基因组百科全书(KEGG)数据库对差异基因进行功能和分子通路注释,结果表明差异基因主要集中在T细胞分化、T细胞共刺激、T细胞活化等生物学过程和T细胞受体信号通路等信号途径。基因集富集分析(GSEA)显示,ITP组患者树突状细胞中mTORC1信号通路基因表达上调。进一步验证发现,ITP组患者moDCs中磷酸化哺乳动物雷帕霉素靶蛋白(mTOR)和mTORC1活化标志物磷酸化核糖体蛋白S6激酶(S6K)相对含量升高,同时ITP组患者moDCs共刺激分子CD80、CD86和促炎因子白介素6(IL-6)、白介素12(IL-12)的表达增加,而白介素10(IL-10)、转化生长因子-β(TGF-β)表达降低。使用mTORC1抑制剂雷帕霉素可以抑制moDCs共刺激分子CD80、CD86的表达和促炎因子IL-6、IL-12的分泌,并上调IL-10的表达,而对TGF-β的分泌无明显影响。 结论 ITP患者moDCs中mTORC1信号通路高度激活,使用mTORC1抑制剂雷帕霉素可以改善moDCs的免疫调节能力。因此,mTORC1信号通路可能是调节ITP患者moDCs功能异常的新靶点。  相似文献   
2.
ObjectiveAeromonas has recently been recognized as an emerging human pathogen. Aeromonas-associated diarrhea is a phenomenon occurring worldwide. This study was designed to determine the prevalence, genetic diversity, antibiotic resistance, and pathogenicity of Aeromonas strains isolated from food products in Shanghai.MethodsAeromonas isolates (n = 79) collected from food samples were analyzed using concatenated gyrB-cpn60 sequencing. The antibiotic resistance of these isolates was determined using antimicrobial susceptibility testing. Pathogenicity was assessed using β-hemolytic, extracellular protease, virulence gene detection, C. elegans liquid toxicity (LT), and cytotoxicity assays.ResultsEight different species were identified among the 79 isolates. The most prevalent Aeromonas species were A. veronii [62 (78.5%)], A. caviae [6 (7.6%)], A. dhakensis [3 (3.8%)], and A. salmonicida [3 (3.8%)]. The Aeromonas isolates were divided into 73 sequence types (STs), of which 65 were novel. The isolates were hemolytic (45.6%) and protease-positive (81.0%). The most prevalent virulence genes were act (73.4%), fla (69.6%), aexT (36.7%), and ascV (30.4%). The results of C. elegans LT and cytotoxicity assays revealed that A. dhakensis and A. hydrophila were more virulent than A. veronii, A. caviae, and A. bivalvium. Antibiotic resistance genes [tetE, blaTEM, tetA, qnrS, aac(6)-Ib, mcr-1, and mcr-3] were detected in the isolates. The multidrug-resistance rate of the Aeromonas isolates was 11.4%, and 93.7% of the Aeromonas isolates were resistant to cefazolin.ConclusionThe taxonomy, antibiotic resistance, and pathogenicity of different Aeromonas species varied. The Aeromonas isolates A. dhakensis and A. hydrophila were highly pathogenic, indicating that food-derived Aeromonas isolates are potential risks for public health and food safety. The monitoring of food quality and safety will result in better prevention and treatment strategies to control diarrhea illnesses in China.  相似文献   
3.
间隙连接蛋白(Cx)在保证细胞间物质信息传递及维持皮肤屏障稳态方面发挥着重要作用,其基因突变,甚至表达水平异常均会引起多种疾病,严重影响患者生活质量。在编码人类Cx家族的21个基因中,与Cx基因突变相关的临床伴随疾病至少有14种。其中,Cx43分布最广,不仅在大多数器官组织中均有报道,也是伤口愈合、皮肤角质化,以及皮肤肿瘤发展等重要生理病理过程中的关键调控节点。本文总结了近年来Cx43基因(GJA1)在皮肤屏障中的作用、GJA1基因突变相关皮肤疾病及其潜在致病机制这几个快速发展领域中的研究成果,以期为Cx43临床伴发疾病防治及相关研究提供参考。  相似文献   
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5.
 目的 探讨分析鹦鹉热衣原体肺炎患者的临床表现及辅助检查结果特征,以提高对该病的认识。方法 回顾性分析某医院2019年6月- 2021年8月经宏基因组二代测序(mNGS)诊断鹦鹉热衣原体肺炎的9例患者临床资料。结果 9例患者中男性7例,女性2 例,包含1例妊娠36+2周孕妇;年龄25~70岁,中位年龄63岁;临床主要表现为高热(9例)、咳嗽(9例)、咳痰(7例)。白细胞计数正常8例,淋巴细胞计数降低9例,CRP升高9例,ESR升高9例,PCT正常4例,门冬氨酸氨基转移酶和丙氨酸氨基转移酶升高6例。9例患者胸部 CT均表现为斑片或斑片实变影。经血及肺泡灌洗液mNGS确诊后使用多西环素、莫西沙星、左氧氟沙星、阿奇霉素单药治疗方案,疗程14~21 d,均好转出院。结论 鹦鹉热衣原体肺炎临床表现多样、诊断困难,mNGS检测可以快速明确病原学诊断,有助于及时启动特异性抗感染治疗,可减少抗菌药物的使用,改善预后。  相似文献   
6.
AIM: To investigate the clinical characteristics and genetic features of a Bietti crystalline dystrophy (BCD) proband in a Chinese family. METHODS: A Chinese female diagnosed with BCD complicated by bilateral choroidal neovascularization (CNV) and her parents underwent complete ophthalmic examinations, including fundus autofluorescence (AF), fundus photography (FP), fundus fluorescein angiography (FFA), visual field testing, full-field electroretinography (ERG), optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). The sequencing of the CYP4V2 gene was performed to the whole family. RESULTS: Bilateral tiny glittering crystal-like deposits and differing extent of atrophy of the retinal pigment epithelium (RPE) were found in the posterior pole of her fundus. The diffuse hypo-fluorescence shown on AF images and window defects shown on FFA both indicated the atrophy of the RPE and choriocapillaris. OCT showed the thinning of the RPE and choriocapillaris layer, ellipsoid zone (EZ) band defect and CNV in both eyes. OCTA images proofed bilateral type 2 CNV. The visual field test showed central and paracentral scotoma. ERG showed a slightly decreased b-wave in scotopic ERG. Gene sequencing identified three mutations of the CYP4V2 gene, c.802_807del, c.810delT, and c.1388G>A. The mutation c.1388G>A was a novel substitution mutation. CONCLUSION: The novel mutation c.1388G>A may be a possible cause that could induce the clinical phenotype of BCD.  相似文献   
7.
Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient.  相似文献   
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9.
《Molecular therapy》2022,30(1):32-46
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10.
《Molecular therapy》2022,30(1):209-222
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