Essentials of cell physiology

Cell physiology and molecular genetics now provide the basis for the fundamental understanding of the mechanisms involved in normal and pathological physiology, modes of drug action, and risks involved in surgical procedures. Some explanations, often involving a single mutation in a protein are straightforward (e.g. cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis). Others may involve a constellation of effects (e.g. obesity) and surprisingly there still remain important areas lacking comprehensive explanation (e.g. the mode of action of general anaesthetics) or close to resolution but still lacking detail (aldosterone controlling both K and Na regulation in the kidney). The present article presents a concise summary of regulation of cell function, concentrating on the cell membrane and important organelles. Signalling and second messengers, together with the role of membrane channels and transporters constitute an important aspect of this, mediated via kinases and phosphatases. Cell volume regulation, reflecting swelling and oedema, are an important aspect of organ transplantation and brain function.     

La、hVAP-33、eIF2B γ和HCV IRES特异性小干扰RNA抑制HCV的复制和表达

目的 证实La自身抗原、33kD人类囊相关膜蛋白(hVAP-33)和真核细胞翻译起始因子第3亚单位(eIF2B γ)是HCV在细胞内的协同感染因子,通过抑制Huh7细胞内这些因子的表达可抑制HCV复制和表达. 方法 分别设计合成3条HCV内部核糖体进入位点(IRES)的小干扰RNA(siRNAs),转染Huh7-HCV细胞后筛选出其中沉默效率最高的1条.以HCV假病毒感染Huh7细胞后48 h,分别以上述HCV IRES siRNA和之前试验中已经筛选出的La、hVAP-33和eIF2B γ特异性siRNAs单独或者不同组合转染Huh7-HCV细胞,利用荧光定量PCR方法检测HCV核心基因并计算△△CT值(相对定量法),比较不同siRNAs及组合对目的基因沉默的效率;同时以Western blot观察HCV核心蛋白表达量的差异.结果 La自身抗原与IRES特异性siRNA共转染对HCV表达的抑制效率最高,使HCV核心蛋白基因相对表达量下降了约41％;4种基因特异性siRNAs 对HCV在Huh7细胞中的复制和表达均有不同程度的抑制作用,La、hVAP-33和eIF2Bγ特异性siRNAs分别与IRES siRNA联合均较其单独转染对目的基因的抑制效率高.结论 可以认为La自身抗原、hVAP-33和eIF2Bγ是HCV在宿主细胞内的协同感染因子,通过对Huh7细胞内协同感染因子及HCV IRES基因沉默后可以显著减少HCV的表达.     

48例小儿心脏术后体外膜肺氧合临床结果分析

目的:对阜外医院小儿心脏手术后,不同适应症下实施体外膜肺氧合(ECMO)治疗的效果及并发症情况进行分析,为更好的把握ECMO的临床适应症提出依据。方法:回顾性分析2004年12月至今48例小儿心脏术后ECMO的临床资料。结果:患儿年龄5 d～6岁;体质量3～17 kg。48例中脱离ECMO 30例(62.5%),最终治愈出院24例(50%)。心、肺功能持续不恢复及后期继发的急性肾衰竭是导致死亡的主要原因。结论:适应症的选择及治疗期间的并发症决定了ECMO总体的治疗效果。     

应用体外膜式人工肺氧合治疗体外循环脱机困难38例的临床经验

目的:总结心脏外科术后脱离体外循环机困难的患者接受体外膜式氧合(ECMO)治疗的临床经验。方法:2004年9月至2010年12月北京安贞医院共38例患者行ECMO治疗,男性29例,女性9例,年龄6个月～74岁,ECMO辅助时间6～280 h,平均65 h。结果:ECMO成功脱机20例(52.6%),其中14例(36.8%)痊愈,6例脱机后死亡;18例未能脱机均死亡。结论:ECMO对于体外循环脱机困难患者是一种有效的辅助措施,及早应用并积极防治ECMO并发症可提高院内生存率。     

3R疗法对阿尔茨海默病患者认知功能和血浆β淀粉样蛋白_(1-42)的影响

目的评价3R疗法对轻、中度阿尔茨海默病患者认知功能和血浆β淀粉样蛋白_(1-42)(Aβ_(1-42))的影响。方法选择轻、中度阿尔茨海默病患者34例,随机分为2组,每组17例。对照组给予药物常规治疗,治疗组在药物常规治疗基础上,采用3R疗法进行认知功能训练。测定血浆Aβ_(1-42),并进行神经心理学指标检查:简易智能状态检查量表、日常生活活动能力量表(ADL)、社会功能活动调查(FAQ)、神经精神量表(NPI)以及事件相关电位P300的基线评定,在开始实施训练后的第3、6个月时,分别对患者进行各项指标的评定与分析。结果治疗组经过3、6个月的3R治疗后,ADL、FAQ、NPI评分较治疗前明显减低,且明显低于对照组(P<0.05,P<0.01);P300潜伏期明显缩短,波幅明显增加(P<0.01);治疗组经过6个月的3R治疗后,血浆Aβ_(1-42)含量较治疗前明显下降,且较对照组明显下降(p<0.05)。结论 3R疗法能有效提高阿尔茨海默病患者生活自理能力、社会活动能力,从而延缓认知功能减退;3R治疗后,认知功能改善可能与血浆Aβ_(1-42)含量变化有关。     

左旋氨氯地平对血压控制不良患者微量白蛋白尿逆转作用的研究

目的观察不同联合治疗方案对高血压伴微量白蛋白尿(MAU)患者血压控制及白蛋白尿的逆转作用。方法选择使用血管紧张素转换酶抑制剂或血管紧张素Ⅱ受体拮抗剂后,血压仍>140/90 mm Hg(1 mm Hg=0.133 kPa)且MAU阳性的高血压患者94例,随机分为左旋氨氯地平组52例(2.5～5 mg/d)、氢氯噻嗪组42例(1 2.5～25 mg/d),干预12周。观察不同治疗方案对血压控制以及MAU的逆转作用。结果左旋氨氯地平组和氢氯噻嗪组干预1 2周后,血压达标分别为35例和27例(67.3%vs 64.3%,P>0.05)。MAU转阴率分别为53.8%和1 9.0%(P<0.01);血压<140/90 mm Hg同时MAU下降≥30%的比例分别为80.8%和64.3%(P<0.05)。结论肾素-血管紧张素阻滞剂联合钙拮抗剂或利尿剂(氢氯噻嗪)的治疗方案在血压降低以及达标率方面无显著差异。联合钙拮抗剂在降低MAU方面明显优于联合利尿剂方案。     

替罗非班对老年急性心肌梗死患者急诊直接介入治疗的应用价值

目的评价老年急性心肌梗死患者急诊直接PCI中简化应用血小板膜糖蛋白Ⅱb/Ⅲa受体拮抗剂替罗非班的价值。方法选择行急诊直接PCI的老年急性心肌梗死患者105例,随机分为替罗非班组57例和对照组48例。替罗非班组接受简化应用替罗非班方案(术前、术后使用,术中不使用),对照组不使用。分析2组的基线资料、即刻手术成功率、肌钙蛋白、出血和血小板减少情况,观察住院和随访30 d主要心脏不良事件及30 d LVEF。结果 2组患者均急诊直接PCI成功。替罗非班组冠状动脉造影时,梗死相关动脉前向血流明显优于对照组,24 h肌钙蛋白水平明显低于对照组(P<0.05),术后血小板计数比较差异无统计学意义(P>0.05)。2组患者住院及随访期间,均无主要心脏不良事件发生,2组患者出血情况比较差异无统计学意义(P>0.05)。替罗非班组30 dLVEF明显优于对照组(P<0.05)。结论老年急性心肌梗死患者急诊直接PCI简化应用替罗非班安全、有效。     

Topographic Distribution and Progression of Soft Drusen Volume in Age-Related Macular Degeneration Implicate Neurobiology of Fovea

PurposeTo refine estimates of macular soft drusen abundance in eyes with age-related macular degeneration (AMD) and evaluate hypotheses about drusen biogenesis, we investigated topographic distribution and growth rates of drusen by optical coherence tomography (OCT). We compared results to retinal features with similar topographies (cone density and macular pigment) in healthy eyes.MethodsIn a prospective study, distribution and growth rates of soft drusen in eyes with AMD were identified by human observers in OCT volumes and analyzed with computer-assistance. Published histologic data for macular cone densities (n = 12 eyes) and in vivo macular pigment optical density (MPOD) measurements in older adults with unremarkable maculae (n = 31; 62 paired eyes, averaged) were revisited. All values were normalized to Early Treatment Diabetic Retinopathy Study (ETDRS) subfield areas.ResultsSixty-two eyes of 44 patients were imaged for periods up to 78 months. Soft drusen volume per unit volume at baseline is 24.6-fold and 2.3-fold higher in the central ETDRS subfield than in outer and inner rings, respectively, and grows most prominently there. Corresponding ratios (central versus inner and central versus outer) for cone density in donor eyes is 13.3-fold and 5.1-fold and for MPOD, 24.6 and 23.9-fold, and 3.6 and 3.6-fold.ConclusionsNormalized soft drusen volume in AMD eyes as assessed by OCT is ≥ 20-fold higher in central ETDRS subfields than in outer rings, paralleling MPOD distribution in healthy eyes. Data on drusen volume support this metric for AMD risk assessment and clinical trial outcome measure. Alignment of different data modalities support the ETDRS grid for standardizing retinal topography in mechanistic studies of drusen biogenesis.