简介:摘要目的探讨靶向B细胞淋巴瘤的分子探针131I-ch4E5的制备方法及其对荷人B细胞淋巴瘤裸鼠的抑瘤作用。方法采用Iodogen法用131I标记抗CD80的人-鼠嵌合抗体ch4E5,采用放射性薄层色谱扫描法测定标记率和放射化学纯度。(1)体外实验:在含细胞数为1×108、1×109、1×1010、5×1010、1×1011个/L的人B细胞淋巴瘤Raji细胞的离心管中分别加入131I-ch4E5溶液,同时设置非特异结合对照管,测量每管沉淀的放射性计数,计算Raji细胞与131I-ch4E5的特异性结合率。(2)体内实验:3只荷瘤裸鼠尾静脉注射7.4 MBq的131I-ch4E5,72 h后处死,分别取肿瘤、血等14种脏器或组织,分别计算肿瘤与正常组织的放射性比值(T/NT);将15只荷瘤裸鼠按随机数字表法分为3组,分别经尾静脉注射131I-ch4E5(131I-ch4E5组)、未标记的ch4E5(ch4E5组)及生理盐水(对照组),观察3组荷瘤裸鼠的肿瘤生长情况,给药后第15天计算肿瘤生长抑制率;之后处死荷瘤裸鼠取肿瘤组织,采用苏木精-伊红染色法做组织病理学检查。2组间的比较采用两独立样本t检验。结果131I-ch4E5的标记率为(84.2±2.4)%、放射化学纯度为(97.1±1.1)%。(1)体外实验:131I-ch4E5与Raji细胞的结合率随细胞数量的增加而升高,最大结合率为(38.2± 2.3)%。(2)体内实验:131I-ch4E5在荷人B细胞淋巴瘤裸鼠体内的分布具有靶向性,肿瘤与肌肉的T/NT最大为7.30;与ch4E5组、对照组比较,131I-ch4E5组肿瘤生长减慢,差异均有统计学意义(t=2.889、6.516,均P<0.05);给药后第15天,131I-ch4E5组肿瘤抑制率为71.7%、ch4E5组为43.4%。组织病理学检查结果同样显示131I-ch4E5的治疗效果更明显。结论自制分子探针131I-ch4E5的标记率及放射化学纯度高,且对荷人B细胞淋巴瘤裸鼠肿瘤生长有明显的抑制作用,为进一步研究131I-ch4E5在放射免疫治疗中的应用提供了实验依据。
简介:摘要目的探讨第3日(D3)4~5-细胞I、II及III级胚胎(4/I~5/III)囊胚的形成及移植对体外受精-胚胎移植(IVF-ET)临床结局的影响。方法回顾性分析2016年1月至2019年2月期间在解放军联勤保障部队第901医院采用IVF-ET助孕患者共884个周期的临床资料。比较4/I~5/III组间囊胚形成差异;根据囊胚移植周期中D3卵裂胚的情况,将4/I~5/III胚胎来源的164个囊胚移植周期设为A组,247个优质胚胎来源的囊胚移植周期设为B组,比较两组间的临床结局并分析4/I~5/III组间不同细胞数和评级对临床妊娠率及流产率的影响。结果4/I组的优质囊胚率(5.6%)高于4/II组(1.8%)(P=0.003)及4/III组(0.6%)(P<0.001);5/I组优质囊胚率(8.3%)分别高于4/II组、4/III组及5/III组(1.6%)(P均<0.001);5/II组优质囊胚率(8.4%)高于4/III组(P<0.001)。A组与B组在获卵数、成熟卵数、受精率、卵裂率、移植胚胎数、移植优质囊胚比、临床妊娠率、流产率、种植率及持续妊娠率差异均无统计学意义(P>0.05);A组D3优质胚胎率显著低于B组(P<0.001);A组平均移植周期次数高于B组(P=0.034);4-细胞和5-细胞来源的囊胚移植临床妊娠率分别为51.6%和50.0%,流产率分别为15.2%和26.8%;I+II级与III级胚胎来源的囊胚移植临床妊娠率分别为53.6%和41.2%,流产率分别为22.4%和21.4%,组间差异均无统计学意义(P>0.05)。结论4/I~5/III来源的囊胚能够获得与优质卵裂胚来源囊胚相近的临床结局;在4/I~5/III组间,细胞数和评级不会影响其囊胚的临床妊娠率及流产率,但5-细胞胚胎的囊胚形成率高于4-细胞胚胎。
简介:摘要目的探讨4D模板在125I粒子治疗晚期恶性肿瘤中的安全性及剂量研究。方法选取陕西省肿瘤医院胸外科自2018—2019年晚期恶性肿瘤患者98例,采用4D模板导航放射性125I粒子植入治疗。术前放疗计划、术中优化、术毕即刻剂量验证,术后评定植入剂量。观察治疗结果。结果98例肿瘤患者全部顺利完成粒子植入术,植入部位行外照射和未行外照射的大体肿瘤体积植入剂量分别为(12 489±414) cGy和(15 036±514) cGy,V100%分别为84.7%~94.1%和88.2%~93.7%;临床靶体积植入剂量分别为(7 450±621) cGy和(9 080±761) cGy。剂量植入质量评估优91%(89/98)、良7%(7/98)、中2%(2/98)、差0。疼痛患者症状缓解率为92%(36/39)。行外照射和未行外照射1、2年局控率分别为61%、36%和82%、54%(P=0.02)。48例肺部植入者气胸发生率为19%(9例),咯血发生率为10%(5例),其他部位植入者均未出现相应并发症。结论4D模板辅助125I粒子治疗恶性肿瘤安全有效,术中实时针道角度调节和剂量优化使植入剂量得到精准控制。
简介:摘要目的评价持续激活脊髓代谢型谷氨酸受体4(mGluR4)对神经病理性痛大鼠痛觉过敏的影响及其与抑制性G蛋白α(Gαi)的关系。方法清洁级健康雄性成年SD大鼠,体重200~250 g,取鞘内置管术成功的大鼠41只,采用随机数字表法分为4组:假手术组(Sham组,n=8)、假手术+mGluR4正性变构调节剂VU0155041组(Sham+V组,n=8)、神经病理性痛组(NP组,n=8)和神经病理性痛+VU0155041组(NP+V组,n=17)。采用脊神经根结扎(SNL)方法建立大鼠神经病理性痛模型。于SNL后第7天,Sham+V组和NP+V组鞘内注射VU0155041 500 nmol,10 μl,2次/d,连续7 d;Sham组和N注射等容量生理盐水。于SNL前、SNL后第7天、每次鞘内注射前后30 min、末次鞘内注射后24 h时测定50%缩足反应阈(PWT)。NP+V组于SNL前、SNL后第7天和末次鞘内注射后24 h时采用Western blot法检测脊髓mGluR4、Gαi1、Gαi2、Gαi3的表达。结果与Sham组比较,NP组和NP+V组SNL后第7天和末次鞘内注射后24 h时PWT降低(P<0.05);与NP组比较,NP+V组末次鞘内注射后24 h时PWT升高(P<0.05)。与SNL后第7天时比较,NP+V组末次鞘内注射后24 h时PWT升高(P<0.05),NP组差异无统计学意义(P>0.05)。与给药前比较,NP+V组每次鞘内给药后PWT均升高(P<0.01)。与SNL前比较,NP+V组SNL后第7天脊髓mGluR4和Gαi3表达下调(P<0.05);与SNL后第7天时比较,NP+V组末次鞘内注射后24 h时脊髓mGluR4和Gαi3表达上调(P<0.05)。结论持续激活脊髓mGluR4可减轻神经病理性痛大鼠已形成的痛觉过敏,机制可能与Gαi3有关。
简介:AbstractPhenuiviridae, a member of the Bunyavirales order, can lead to significant human morbidity and mortality. Various phenuiviruses target specific cellular proteins and have strategies to counteract the effects of type I interferon (IFN). Previous studies have shown that phenuiviruses infection inhibits the synthesis of type I IFNs, and viral nonstructural proteins (NSs) had been further identified as an IFN antagonist. This study found that the NSs proteins of Dabie bandavirus (DBV), Sandfly fever Sicilian virus (SFSV), and Uukuniemi virus (UUKV) can inhibit Sendai virus-induced activation of IFN-β promoter and phosphorylation of IFN regulatory factor 3 (IRF3). Moreover, detailed analysis revealed that the phenuivirus NSs protein could directly interact with retinoic acid inducible gene-I (RIG-I) and degrade it via a proteasome-dependent pathway. In short, this study demonstrate a novel mechanism of phenuiviruses to resist host antiviral immunity, which may help understand these pathogens and suggest novel therapeutic approaches.
简介:AbstractLeucine-rich repeats containing 4 (LRRC4, also named netrin-G ligand 2 [NGL-2]) is a member of the NetrinGs ligands (NGLs) family. As a gene with relatively high and specific expression in brain, it is a member of the leucine-rich repeat superfamily and has been proven to be a suppressor gene for gliomas, thus being involved in gliomagenesis. LRRC4 is the core of microRNA-dependent multi-phase regulatory loops that inhibit the proliferation and invasion of glioblastoma (GB) cells, including LRRC4/NGL2-activator protein 2 (AP2)-microRNA (miR) 182-LRRC4 and LRRC4-miR185-DNA methyltransferase 1 (DNMT1)-LRRC4/specific protein 1 (SP1)-DNMT1-LRRC4. In this review, we demonstrated LRRC4 as a new member of the partitioning-defective protein (PAR) polarity complex that promotes axon differentiation, mediates the formation and plasticity of synapses, and assists information input to the hippocampus and storage of memory. As an important synapse regulator, aberrant expression of LRRC4 has been detected in autism, spinal injury and GBs. LRRC4 is a candidate susceptibility gene for autism and a neuro-protective factor in spinal nerve damage. In GBs, LRRC4 is a novel inhibitor of autophagy, and an inhibitor of protein-protein interactions involving in temozolomide resistance, tumor immune microenvironment, and formation of circular RNA.
简介:AbstractEffective prophylactic and therapeutic interventions are urgentlyneeded to address the coronavirus disease 2019 (COVID-19) pandemic. Various antiviral drugs have recently been tested. Type I interferon (IFN) is a regulatory protein involved in the innate immune response, with broad-spectrum antiviral activities and the ability to directly block viral replication and support the immune response to eliminate virus infection. Insufficient virus-induced type I IFN production is characteristic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, because SARS-CoV-2 suppresses the IFN response by interacting with essential IFN signaling pathways. Exogenous type I IFN is recommended for treating COVID-19. Unexpectedly however, angiotensin converting enzyme-2 (ACE2) receptor, which acts as a SARS-CoV-2 receptor, was shown to be stimulated by IFN, raising doubts about the suitability of IFN use. However, further studies have excluded concerns regarding IFN administration. Type I IFNs, including IFN-α1b, have been used clinically as antiviral drugs for many years and have shown strong antiviral activity against SARS-CoV-2 in vitro. Preliminary clinical studies of type I IFNs, especially when delivered via aerosol inhalation, have demonstrated efficacy for the treatment and prevention of COVID-19. Randomized controlled trials of IFN for COVID-19 treatment are ongoing.
简介:摘要目的通过对1个家族性血尿家系进行遗传变异筛查,为家族性血尿病变提供遗传线索和证据。方法本研究纳入的研究对象为1个4代含20名成员的家族性血尿家系。对该家系进行临床资料和实验室检查结果的收集和整理,留取家系中11名成员的外周血并用盐析法提取DNA用于遗传分析。首先选取包括先证者在内的3名家系成员进行全外显子组测序,根据2015年美国医学遗传学与基因组学学会发布的序列变异解读指南进行遗传变异筛选。继而在家系成员中对筛选出的遗传变异位点进行实时荧光定量PCR和Sanger测序验证。结果该家系中6名女性患者有持续性血尿,2人因肾衰竭去世,2人因肾脏以外疾病去世,2人维持肾功能稳定。肾功能稳定2人中1人肾活检病理诊断为IgA肾病,电镜提示弥漫性基底膜病变,不除外Alport综合征。基因检测在家系中发现COL4A4基因(RefSeq NM_000092)的两个点突变,7号外显子c.G446T:p.G149V的变异,以及20号外显子c.G1249A:p.G417R的变异。结论通过对1个家族性血尿家系开展基因检测,发现COL4A4基因的两个新突变(7号外显子c.G446T:p.G149V和20号外显子c.G1249A:p.G417R的变异)与家族性血尿表型相关联。
简介:摘要目的探讨中青年甲状腺乳头状癌(PTC)患者131I治疗前细胞免疫状态预测首次131I治疗反应的价值。方法回顾性研究2018年3月至2019年4月于青岛大学附属医院接受过甲状腺全切除术及颈部淋巴结清扫术的中青年PTC患者150例[男46例、女104例,年龄(40.0±9.8)岁],所有患者术后1~2个月行131I治疗,且在131I治疗前1 d检测T淋巴细胞亚群(CD3+、CD4+、CD8+、CD4/CD8)和自然杀伤(NK)细胞,将其作为反映细胞免疫的指标。根据131I治疗后6~12个月的治疗反应将患者分为疗效满意(ER)组与非ER组,分析可能影响131I治疗反应的临床病理特征、治疗前刺激性甲状腺球蛋白(psTg)、首次131I剂量及细胞免疫指标(两独立样本t检验、Mann-Whitney U检验、χ2检验、多因素logistic回归分析),采用ROC曲线分析评估独立影响因素对非ER的预测价值。结果150例患者中,84例为ER组(56.00%),66例(44.00%)为非ER组。单因素分析示,2组患者在年龄(z=-2.86,P=0.004)、肿瘤M分期(χ2=13.64,P<0.001)、psTg(z=-8.94,P<0.001)、首次131I剂量(z=-7.60,P<0.001)、CD4+(t=2.50,P=0.014)、CD4/CD8(z=-2.22,P=0.027)方面的差异均有统计学意义;多因素分析示,psTg[比值比(OR)=1.27,95% CI:1.16~1.40,P<0.001]与CD4/CD8(OR=0.39,95% CI:0.15~0.99,P=0.048)为治疗反应的预测因素。psTg与CD4/CD8预测非ER的阈值分别为6.78 μg/L和1.67。结论PTC术后131I治疗前患者的细胞免疫状态对首次131I治疗反应具有一定的预测价值,当psTg高于6.78 μg/L、CD4/CD8低于1.67时提示治疗反应不佳。
简介:摘要4例男性患儿均表现为缺铁性贫血,其中2例伴有腹痛。胃镜组织活检病理诊断均符合胶原性胃炎表现,2例累及十二指肠。4例患儿均口服铁剂补铁,2例加用泼尼松口服治疗。1例患儿失访,另3例贫血症状均有改善,其中使用激素治疗的患儿胶原沉积减轻。