简介:目的观察不同剂量的ATP终止不同年龄组阵发性室上性心动过速(PSVT)时复律时间、长间歇及其副作用。方法以静脉给药,将56例随机分为青年组(A组)、中年组(B组)和老年组(C组)。结果56例PS—VT全部中止.各组复律时间无差异。结论C组长间歇延长、副作用和剂量有关,C组用量宜从最低剂量开始。
简介:摘要本文利用ATP程序,针对某地一地区的35kV电网,对中性点不同接地方式下的间歇性弧光接地过电压进行了仿真。根据仿真结果,提出了一种新型中性点接地方式中性点经消弧线圈并联电阻接地方式,该方式能有效地降低弧光接地过电压,保障电网的安全、稳定、可靠运行。
简介:AbstractIntroduction:Darier’s disease is a rare autosomal dominant skin disorder caused by mutations in ATP2A2. Recently, the high prevalence of neuropsychiatric symptoms is frequently reported in Darier’s disease patients.We present a case of patient with concurrence of Darier’s disease and depression and detected the mutations in ATP2A2.Case presentation:A 29-year-old man presented with a 15-year history of brown, harsh keratotic papules on his scalp, face, neck, trunk, axilla, ingunia and upper limbs. Meanwhile, he had persistent depression. He was diagnosed as Darier’s disease according to clinical manifestations and result of histological examination. We sequenced all coding regions of ATP2A2. The mutation c.2993_2994del (p. Val998Alafs*33) in exon 20 of ATP2A2 was detected.Discussion:Darier’s disease has been associated with several extracutaneous manifestations, in particular neuropsychiatric morbidity. Likely gene disrupting mutations in ATP2A2 was reported to have a close relationship to Darier’s disease cases with reported co-occurring neuropsychiatric features. Consistent with the previous reports, an likely gene disrupting mutations was detected in our patient with concurrence of DD and depression.Conclusion:The psychiatric disorders in patients with Darier’s disease should be well appreciated .The underlying mechanism in correlation between the mutation in ATP2A2 and neuropsychiatric phenotypes in Darier’s disease remain unclarified and warrants further investigation.
简介:AbstractImportance:The phenotypes of ATP1A3 gene mutations are diverse. Relapsing encephalopathy with cerebellar ataxia and fever-induced paroxysmal weakness and encephalopathy (FIPWE) are considered non-classical phenotypes caused by p.Arg756 mutations of ATP1A3.Objective:To summarize the clinical manifestations, treatment, and follow-up of Chinese patients with p.Arg756 mutations of ATP1A3.Methods:We analyzed the clinical features, treatment, and genotypes of eight children with p.Arg756 mutations of ATP1A3 who were treated in Beijing Children’s Hospital from January 2014 to December 2019.Results:Eight patients (six boys and two girls) were included; seven had been misdiagnosed with encephalitis. The age of onset ranged from 0.8 to 4.5 years. All patients had encephalopathy and had at least one episode of FIPWE. Cerebellar ataxia was present in nine episodes. Reversible splenial lesions of the corpus callosum were found in two patients in the acute phase. Three types of heterozygous ATP1A3 mutations were found: c.2267G > T (p.R756L) (patient 3 [P3]), c.2266C > T (p.R756C) (P2 and P4), and c.2267G > A (p.R756H) (P1, P5, P6, P7, and P8). Six mutations were de novo; two mutations were inherited. Both patients with p.R756C and one patient (P7) with p.R756H had four episodes of severe ataxia as the main manifestations. However, in the other three episodes, limb weakness was more prominent than ataxia. P5 with p.R756H exhibited overlap with FIPWE and rapid-onset dystonia-parkinsonism.Interpretation:Acute encephalopathy followed by febrile disease was characteristic of the disease in patients with p.Arg756 mutations of ATP1A3. However, the weakness and ataxia were variable. Phenotypic crossover and overlap were observed among these patients.
简介:摘要目的探究肝豆状核变性(Wilson disease,WD)妊娠期患者围产期管理,以及探索通过对患者羊水、脐带血基因检测确定其后代遗传病因和胎儿患病的可能性。方法在围产期精细化管理方面,对1例2019年3月因眼涩眼胀、视力下降于首都医科大学附属北京友谊医院眼科就诊时发现K-F环,肝病科进一步诊断WD的孕妇行人工流产一次,并于2020年10月再次妊娠后进行包括妇产科、肝病中心、麻醉科、消化科、营养科等多学科会诊和孕期规范化治疗;二次妊娠后提取患者静脉血、羊水和脐带血基因组,采用Sanger测序进行ATP7B基因变异分析。结果通过多学科协作管理,该患者在妊娠合并肝硬化、门静脉高压、脾大伴功能亢进、血小板减少、贫血、食管胃底静脉曲张等多种合并症的情况下顺利产子。新生儿表型正常,阿氏评分10-10-10。测序发现该患者存在ATP7B p.Arg778Leu 和p.Val890Met,为数据库已报道的错义杂合变异,ACMG分级为致病性变异。羊水和脐带血的检测结果显示胎儿仅p.Arg778Leu单杂合变异,仅携带母亲一个致病突变位点,预测不会出现肝豆状核变性的临床表型。结论围产期多学科协作管理对WD患者顺利妊娠具有重要保护意义。对患者羊水和脐带血的遗传学筛查有利于早期发现胎儿WD。
简介:摘要目的总结儿童肝豆状核变性(WD)的临床表型及ATP7B基因变异类型特征,探讨其对WD早期诊断的临床意义。方法回顾性分析2010年1月至2021年6月就诊于广州市妇女儿童医疗中心的316例WD患儿的临床资料。收集患儿一般情况、临床表现、实验室检查、影像学检查、ATP7B基因变异特征等资料。根据诊断时有无临床症状分为无症状组和有症状组,组间比较采用χ²检验、t检验或Mann-Whitney U检验。结果316例WD患儿中男199例、女117例,确诊年龄为5.4(4.0,7.6)岁。无症状组261例(82.6%),年龄4.9(3.9,6.4)岁;有症状组55例(17.4%),年龄9.6(7.3,12.0)岁,主要症状为肝肾功能、神经和皮肤损伤。所有WD患儿中,95.9%(303/316)确诊时肝功能异常;98.1%(310/316)血清铜蓝蛋白低于200 mg/L;97.7%(302/309)24 h尿铜含量超过40 μg;仅7.4%(23/310)角膜K-F环阳性和8.2%(23/281)头颅磁共振成像提示豆状核异常信号,且均有肝肾功能或神经损伤等症状。无症状组WD患儿血清丙氨酸转氨酶(ALT)水平高于有症状组,铜蓝蛋白和24 h尿铜含量均低于有症状组[(208±137)比(72±78)U/L,(55±47)比(69±48)mg/L,103(72,153)比492(230,1432)μg,t=9.98、-1.98、Z=-4.89,均P<0.001]。314例患儿完成ATP7B基因检测,共检测到107种变异类型,其中10种新发变异,检测到3例患儿携带第10~11号外显子杂合缺失。无症状组患儿携带错义变异的比例显著高于有症状组[81.5%(422/518)比69.1%(76/110),χ²=8.47,P<0.05]。携带c.2333G>T纯合变异的WD患儿(106例)的血清铜蓝蛋白水平显著低于不携带者(208例)[(23±5)比(61±48)mg/L,t=-2.34,P<0.001]。结论ALT升高是儿童WD早期诊断的重要线索,而血清铜蓝蛋白和24 h尿铜含量是儿童WD早期诊断的特异性指标。需结合Sanger测序和多重连接依赖探针扩增技术等多种检测技术明确WD的基因诊断。
简介:摘要2例散发性偏瘫性偏头痛患儿,例1,男,5岁10月龄,因“反复惊厥发作5年余,行为异常20 d”入院。例2,男,4岁6月龄,因“反复惊厥发作3年余,发热伴右侧肢体活动受限1 d”入院。2例患儿均无相关家族史,早期表现为热性惊厥,随年龄增长,在发热等诱因下出现先兆头痛伴急性脑病发作。基因检测均为ATP1A2基因错义变异,分别为c.2143G>A(p.Gly715Arg)、c.2563G>A(p.Gly855Arg)。
简介:摘要目的探究ATP6V1C1在肝细胞癌(HCC)表达情况及功能。方法本研究为基础研究,利用来自癌症基因组图谱数据库基因表达总库(GEO)测序数据,找出HCC差异表达基因(P<0.01,|logFc|≥1),进一步利用来自于癌症基因组图谱(TCGA)在线数据UALCAN、Timer分析ATP6V1C1在HCC不同分期的表达情况及不同表达水平的预后情况,The Human Protein Atlas分析正常肝组织与肿瘤组织免疫组化。TCGA数据库包含女性患者121例,男性患者281例,年龄16~81岁,数据分析后台自行完成。KEGG信号了解ATP6V1C1对相关通路的影响。构建pcDNA3.1(+)-ATP6V1C1载体,购买siRNA干扰片段体外研究ATP6V1C1对肝细胞癌的影响。统计学方法采用独立样本t检验。结果生物信息学分析提示ATP6V1C1在多种癌症中上调(P<0.05),ATP6V1C1的表达水平与HCC的肿瘤分级有关,在肝癌患者中,ATP6V1C1表达上调患者相对下调患者预后更差(P<0.05)。过表达ATP6V1C1后明显促进HCC细胞的侵袭、迁移、增殖及克隆形成能力,同时,干扰ATP6V1C1抑制HCC细胞的侵袭、迁移、增殖及克隆形成能力。结论ATP6V1C1在HCC中表达与预后相关,这个研究为HCC提供了新的可能诊断及治疗靶标。
简介:摘要目的观察胺碘酮和ATP治疗阵发性室上速的临床疗效。方法回顾性分析2010-2015年阵发性室上性心动过速者176例,给予ATP5mg弹丸式用药不能顺利转复窦律的,随机分两组,一组给予胺碘酮注射液150mg入液以1mg/min.Kg静脉应用,持续两小时后再次给ATP5mg复律。另一组间隔五分钟ATP计量翻倍复律。结果胺碘酮联合ATP治疗PSVT获得明显疗效且无明显不良反应,转复率明显高于单用ATP者,尤其是反复发作多次用药物复律的患者转复律明显高,有显著性差异,且应用胺碘酮者转复过程中HR、SDP、SBP均较用药前改善,不良反应发生率明显少于单用ATP者。结论胺碘酮联合ATP治疗阵发性室上性心动过速可获得明显疗效且无明显不良反应,但转复时间较长,反复PSVT发作单用ATP效果不理想,未合并血流动力学紊乱的患者可采用此法。
简介:目的:构建表达基因编辑钙探针(GECIs)的细胞系HeLa-GECIs,探究细胞应答外界ATP刺激中钙离子在细胞内的响应和变化。方法:分别用能够直接通过荧光强度反映细胞胞浆内和线粒体内钙离子相对浓度的2种钙探针cyto-GCaMP6和4mt-GCaMP6感染HeLa细胞,获得2种表达钙离子探针的HeLa细胞系;在感染了2种腺病毒探针24h后,用共聚焦荧光显微镜检测荧光探针在HeLa细胞内的表达情况;在表达2种钙探针的细胞的培养基中加入外源ATP,用Time-lapse成像动态观测技术观察HeLa细胞内钙离子对外环境中ATP的响应。结果:共聚焦荧光显微镜观察,确定95%以上的细胞表达了对应的钙离子指示荧光探针;Time-lapse成像动态观测技术观察发现,在细胞培养基中加入ATP后,细胞胞浆钙探针荧光强度瞬时(3~6s)升至10倍,200s后逐渐降低到基础水平;线粒体钙到达峰值(4倍)的时间稍滞后(5~8s),并且回落更慢,300s时至1.5倍。在ATP受体P2X7抑制剂A438079预处理的实验组,上述胞浆钙和线粒体钙浓度上升不明显。结论:构建了能在活体细胞内通过荧光探针实时监测钙离子响应胞外ATP刺激的细胞实验体系,为进一步深入探究ATP等危险信号导致细胞的炎性损伤机制奠定了基础。
简介:目的:研究刺五加叶皂苷(ASS)对心肌线粒体ATP敏感性钾通道(mitoKATP)和细胞膜ATP敏感性钾通道(sarcolKATP)的作用,探讨ASS对缺血心肌保护作用的机制.方法:用酶解法获取兔心室肌细胞,激光扫描共聚焦显微镜观察ASS对mitoKATP的作用,全细胞膜片钳技术观察ASS对sarcolKATP的作用.结果:对照组观察10min线粒体荧光强度无明显变化.ASS30、100和300mg·L-1组均可见用药后线粒体荧光强度明显增加,分别增加(14.8±3.6)%、(30.4±4.3)%和(38.4±5.7)%.3μmol·L-1格列本脲不影响线粒体荧光强度,但可以阻断ASS对线粒体荧光强度的作用.而对照组、ASS10、100和300μmol·L-1组的IK-ATP峰值无明显差异.结论:ASS对mitoKATP有开放作用,而对sarcolKATP没有作用.ASS通过开放mitoKATP产生心肌保护作用.