串联质谱技术在新生儿遗传代谢病筛查中的应用研究进展

近年来随着科学技术的发展,在新生儿遗传代谢病筛查过程中实施串联质谱技术的应用效果十分显著,其具有高敏感度和高特异性,还具有筛查时间短和筛查病种丰富的优势。串联质谱技术在国内外已广泛应用于新生儿疾病筛查中,该技术不但扩展了新生儿疾病筛查谱,也为疾病筛查开辟了新的领域。随着筛查技术的发展,人们对新生儿遗传代谢病的认识、诊疗也在不断更新中。串联质谱技术是出生缺陷防控的重要措施,本文对筛查结果的影响因素进行了总结。随着人们对各种遗传代谢性疾病机制认识的加深和质谱技术的日益成熟,串联质谱技术将会对更多的疾病进行筛查和诊断,临床应用意义重大。     

串联质谱技术筛查新生儿遗传代谢性疾病的价值

目的探析对新生儿遗传代谢性疾病采用串联质谱技术筛查的价值。方法 5020例新生儿均利用串联质谱技术对遗传性代谢性疾病进行筛查,分析筛查结果。结果相比于传统筛查技术,串联质谱技术筛查项目更多、筛查病种也更多,且筛查时间更短。结论在新生儿遗传性代谢性疾病筛查中,串联质谱技术的应用可以使筛查效率得到提升。     

新生儿游泳后足跟采血成功率提高的体会

<正>新生儿足跟采血是指在新生儿期,采集新生儿足跟3滴血用来进行新生儿遗传代谢性疾病的筛查,使这些疾病在临床症状出现之前及早诊断,从而早期治疗,预防婴儿智能低下及生长发育障碍。由于新生儿足底血液循环不丰     

高效液相-串联质谱技术在新生儿遗传代谢性疾病筛查中的应用价值

目的 探讨高效液相-串联质谱技术(HPLC-MS/MS)在新生儿遗传代谢性疾病筛查的应用价值。方法 选取我院就诊的301例新生儿,新生儿出生48 h～7 d内采集足底血制作血斑样本,采用HPLC-MS/MS技术对样本中多种氨基酸代谢、有机酸代谢和脂肪酸代谢进行筛查,初筛阳性结果患儿召回复查并做进一步诊断。结果 301例筛查样本中初筛可疑阳性21例(0.70%),召回20例进行复查,最终进行基因诊断确诊3种遗传代谢性疾病,其中1例甲基丙二酸血症(MMA),1例精氨酸血症,1例瓜氨酸血症。结论 HPLC-MS/MS技术应用于新生儿遗传代谢性疾病筛查,具有高效、准确、快速等优势,本地可能是此病的高发地区,大力推广新生儿遗传代谢性疾病筛查,做到早发现、早诊断、早治疗,对降低本地出生缺陷,提高人口素质有重大意义。     

广东省惠州市新生儿疾病筛查干预策略及实施效果分析

目的探讨开展新生儿先天性甲状腺功能减低症（CH）、苯丙酮尿症（PKU）、葡萄糖-6-磷酸脱氢酶缺乏症（G-6-PD）筛查的必要性和可行性,构建一套能早期发现、早期诊断、早期治疗先天性代谢性疾病的方法和干预策略。方法对广东省惠州市119847例新生儿进行先天性疾病筛查,筛查覆盖率为71．3％,成立新生儿疾病筛查领导小组及技术指导小组,建立健全新生儿疾病筛查网络及实行标准化管理,并对新生儿疾病筛查干预实施效果进行分析。结果119847衙中,确诊CH40例（0．03％）、PKU2例（0．0017％）、G-6-PD4326例（3．60％）。G-6-PD的发病率明显高于CH、PKU（χ^2=8．45,P〈0.05）;追踪率达91．6％,阳性召回率达76．8％;对42名患儿进行及时的治疗,避免了智力障碍的发生。缩论惠州市对新生儿三种先天性疾病的预防工作已有成效,需要进一步提高新生儿疾病筛查工作覆盖率。特别是农村地区。将新生儿疾病筛查工作纳入到新农合范围,提高出生人口素质。     

新生儿疾病筛查可疑阳性未召回调查分析

<正>新生儿疾病筛查是在新生儿时期对某些先天性缺陷性疾病进行筛查,通过快捷、简便、敏感的方法快速找出可疑病例,再加以进一步复查、确诊、治疗。遗传代谢性疾病(inherited metabolic diseases, IMD)又被称为先天代谢缺陷,属于临床疑难杂症。随着医疗技术的进步,IMD诊断和防治方法也越来越先进,对新生儿苯丙酮尿症(phenylketonuria PKU)、甲状腺功能减退症(congenital hypothyroidism CH)实施筛查,降低     

新生儿时期起病的遗传性代谢病2例并文献复习

目的：探讨新生儿期常见的遗传代谢性疾病临床特点及诊治经验。方法分析该科2例新生儿遗传代谢病资料,并结合近年来国内已报道的相同新生儿病例90例（其中甲基丙二酸血症70例,枫糖尿病20例）进行文献复习。结果92例均有喂养困难,76例在生后一周左右即发病,37例有母亲不明原因死胎、流产或同胞不明原因夭折、智力低下的家族史,92例均行血串联质谱或（和）尿气相色谱-质谱检测,49例MRI/CT有异常信号,67例死亡或放弃治疗。结论新生儿期遗传代谢性疾病如甲基丙二酸血症、新生儿枫糖尿病早期常表现喂养困难、反应差等,但无特异性,易被误诊,儿科医师应重视利用串联质谱和气相质谱技术进行遗传代谢病的筛查。     

新生儿疾病筛查中两种采血方法的探讨

新生儿疾病筛查是指通过特定的实验室对某些能够导致新生儿体格智能障碍、先天性、代谢性疾病及内分泌疾病进行群体筛查,使他们在临床症状尚未出现之前得以早诊断、     

关于开展汕尾市新生儿疾病筛查模式研究

目的探讨汕尾市新生儿疾病筛查对遗传代谢性疾病的控制作用。方法收集汕尾市妇幼保健院自2013年5月~2015年1月出生的1930例活产新生儿3d采集的足跟血滤纸干血斑标本,用实验室方法检测TSH、Phe、G6PD,筛查CH,PKU,G6PD缺乏症。对于出生缺陷患儿进行早期诊断、早期治疗。结果 1930例筛查新生儿中,CH,PKU,G6PD缺乏症3种遗传代谢缺陷病所引起的缺陷率为33.7‰。对筛查组CH及PKU缺陷儿治疗中智力发育水平进行评价和监测,与同期对照组比较,筛查组与非筛查组的缺陷儿转归差异有统计学意义(P0.001)。医护人员筛查必要性认知率及筛查相关知识认知率明显高于产妇及家属,两组比较差异有统计学意义(P0.05)。结论新生儿疾病筛查是防治残疾、提高人口素质的基本手段,可以起到早期诊断、干预的作用,从而减少新生儿的残疾发生率。     

序言

2019年12月以来,新型冠状病毒(Novel Coronavirus)感染的肺炎在武汉暴发。2020年1月12日,世界卫生组织(WHO)将这种致病病毒命名为"2019新型冠状病毒(2019-nCoV)"。2月7日,国家卫生健康委员会将新型冠状病毒感染的肺炎暂命名为"新型冠状病毒肺炎(Novel Coronavirus Pneumonia)",简称"新冠肺炎(NCP)"。2月11日,WHO将新型冠状病毒所致的疾病正式命名为"COVID-19"。国际病毒分类学委员会将新型冠状病毒正式命名为"SARS-CoV-2"。截至2020年2月28日,我国已累计报告新冠肺炎确诊病例78 959例,死亡2 791例。新冠肺炎疫情是新中国成立以来在我国发生的传播速度最快、感染范围最广、防控难度最大的一次重大突发公共卫生事件。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.