CPH1和EFG1基因在游离态及生物膜态白念珠菌的表达差异

目的 检测游离态及不同时期生物膜态白念珠菌转录因子CPH1和EFG1的表达,探讨其在生物膜形成过程中的作用.方法 应用激光共聚焦显微镜观察白念珠菌质控株ATCC90028和临床分离株14215于聚乙烯片上黏附生长24 h后的生物膜形态.分别提取6株白念珠菌临床分离株13860、13874、14127、14371、14215、14533和质控株ATCC90028游离态以及早期(聚乙烯片上黏附生长4h)、中期(聚乙烯片上黏附生长12h)、晚期(聚乙烯片上黏附生长24 h)生物膜态的总RNA,应用荧光定量PCR测定其CPH1和EFG1基因的表达.结果 聚乙烯片上黏附生长24 h后,激光共聚焦显微镜下可见质控株ATCC90028多为单层的孢子细胞黏附;白念珠菌临床分离株14215形成菌丝态为主,具有三维结构的生物膜.相对于游离态,白念珠菌质控株ATCC90028在生物膜形成的早中晚期转录因子CPH1和EFG1表达均下调.临床分离株转录因子CPH1在游离态、生物膜形成的早中晚期时表达差异均无统计学意义(均P＜0.05).而与游离态相比,临床分离株转录因子EFG1基因的相对表达量在生物膜形成早期及中期均上调[0.141(0.029 ～ 0.212)、0.252(0.103 ～ 0.943)比0.077(0.018 ～ 0.113),均P＜0.05],在生物膜形成晚期则无明显改变(P＞0.05),相对表达量为0.091(0.024 ～ 0.354).结论 转录因子EFG1在白念珠菌临床分离株生物膜形成过程中有重要的调控作用.     

Clinical,neuroimaging and biochemical findings in patients and patient fibroblasts expressing ten novel GFM1 mutations

Pathogenic GFM1 variants have been linked to neurological phenotypes with or without liver involvement, but only a few cases have been reported in the literature. Here, we report clinical, biochemical, and neuroimaging findings from nine unrelated children carrying GFM1 variants, 10 of which were not previously reported. All patients presented with neurological involvement—mainly axial hypotonia and dystonia during the neonatal period—with five diagnosed with West syndrome; two children had liver involvement with cytolysis episodes or hepatic failure. While two patients died in infancy, six exhibited a stable clinical course. Brain magnetic resonance imaging showed the involvement of basal ganglia, brainstem, and periventricular white matter. Mutant EFG1 and OXPHOS proteins were decreased in patient's fibroblasts consistent with impaired mitochondrial translation. Thus, we expand the genetic spectrum of GFM1‐linked disease and provide detailed clinical profiles of the patients that will improve the diagnostic success for other patients carrying GFM1 mutations.     

补肾活血颗粒对帕金森病患者脑内神经递质多巴胺和5-羟色胺的影响

目的探讨补肾活血颗粒对帕金森病(PD)患者脑内多巴胺(DA)和5-羟色胺(5-HT)水平的影响。方法采用随机、单盲双模拟对照试验设计,将88例PD患者随机分成治疗组45例和对照组43例。其中治疗组服用补肾活血颗粒加西药安慰剂,对照组服用多巴丝肼片加中药安慰剂,疗程为3个月,治疗前后采用脑电超慢涨落图检测患者DA和5-HT水平。结果补肾活血颗粒组治疗后DA值和5-HT值分别为(5.7±0.54)和(19.6±9.1),分别与治疗前(4.2±0.57)和(15.4±7.5)比较,均有统计学差异(P<0.05),与对照组治疗后(3.4±0.42)和(14.0±8.1)比较,均有统计学差异(P<0.05)。结论补肾活血颗粒治疗PD的疗效机制可能与增加PD患者脑内DA和5-HT水平有关。     

EFG1和HGC1基因在白念珠菌菌丝相和酵母相的表达差异

目的比较白念珠菌双形态性的两个调控基因,即增强菌丝生长基因(Enhanced Filamentous Growth,EFG1)和菌丝G1细胞周期蛋白基因(hyphal G protein cycle1,HGC1)在菌丝相和酵母相中的表达情况,寻找调控菌丝表达的关键基因。方法分别提取白念珠菌菌丝相和酵母相的RNA,行半定量RT-PCR检测,比较EFG1和HGC1两个基因的RNA表达差异。结果EFG1在菌丝相和酵母相都有表达,差异无显著性意义,而HGC1在菌丝相有表达,在酵母相无表达。结论HGC1为菌丝特异基因。     

What Do Web Users Know about Skin Self-Examination and Melanoma Symptoms?

Background: Skin self-examination (SSE) may facilitate early diagnosis of melanoma at a potentially curablestage. Little data are available concerning the SSE frequency and knowledge about the symptoms of melanomain non-patient populations. The aim of our study was to assess the performance of skin self-examination,recognition of potential melanoma symptoms as well as behavior related to sun exposure among web users inPoland. Materials and Methods: A cross-sectional study was conducted among readers of a scientific portal.Invited respondents were asked to complete an online questionnaire. Finally, statistical analysis was conducted on4,919 surveys towards potential clinical signs of melanoma and SSE performance. Results: Approximately 60%of respondents had ever performed SSE in their life. Only 18.4 % declared performance on a regular, monthly,basis. Factors promoting this activity were established to be bigger place of residence, higher education andsensitive skin phototype, higher level of knowledge concerning melanoma, safe tanning rules and, especially, pastsurgical excision of naevi. Declared longer use of tanning beds was linked to understanding better the importanceof clinical features of melanoma. Awareness of hazardous behavior during sunbathing is associated with theattempts to change them. Conclusions: Regular SSE is not a common practice, whilst the knowledge about theclinical features of melanoma is varied. Therefore, constant pressure should be put on promotion of regular skinself-examination and teaching its proper techniques, including familiarity with the ABCD (asymmetry; border;color; diameter) rule and its extension of “EFG” (elevated, firm, progressive growth) criteria.     

Nonclinical regulatory considerations for wound-healing growth factors

Initial evaluation of the safety of wound-healing growth factors, whether manufactured by biotechnology or not, is dictated by the extent of knowledge of the physiologic, pharmacologic, and toxicologic effects, in vitro and in vivo in animals, and in man at the proposed dose and duration of administration. Prior to Phase 1 clinical study, products are studied to establish evidence of pharmacologic activity, understand the mechanism of action, evaluate the potential human risk, and establish a clinical study dose range. It is difficult to establish a generic plan and generic protocols for the preclinical development of wound-healing growth factors because the toxicologic concerns and suggested studies are tailored to the uniqueness of each product. The quantity of useful information which can be gained from preclinical studies is considered for each product on a case-by-case basis, taking into account the availability of a relevant model. Preliminary information regarding (1) production of the active moiety, (2) ingredients in the final formulation as it is to be marketed, (3) characterization of the growth factor, (4) the proposed dose and route of administration, (5) the known actions and effects, (6) the similarity to the endogenous growth factors, and (7) the proposed target clinical study population is needed to determine the most appropriate preclinical pharmacological and toxicologic studies. Use of this information and additional data relating the pharmacokinetic and toxicologic profiles will be discussed with respect to generalizations in study concepts for pharmacology and toxicology studies and individualization of these preclinical studies which may occur, based upon the uniqueness of the compound.     

脑涨落图检测精神分裂症患者无抽搐电休克治疗前后脑内神经递质功能的研究

目的探讨首发精神分裂症患者的神经递质功能特点及无抽搐电休克治疗对患者的神经递质功能的影响。方法采用脑涨落图仪(EFG)检测首发精神分裂症患者无抽搐电休克(MECT)治疗前后脑内神经递质功能。选取符合《中国精神障碍分类与诊断标准(第3版)》(CCMD-3)的首发精神分裂症患者24例,MECT治疗8~12次。在首次治疗前半小时,首次治疗之后半小时及24小时、末次治疗后24小时采用EFG检测脑内γ-氨基丁酸(GABA)、谷氨酸(Glu)、5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)、乙酰胆碱(Ach)六种神经递质的功率。在首次治疗前及疗程结束后24小时进行阳性与阴性症状量表(PANSS)测评。结果与治疗前比较,治疗后半小时患者的全部递质功率升高(P0.05),首次治疗与末次治疗后24小时,多巴胺功率降低(P0.05)。5-HT、Ach、NE、DA的功率与P分呈正相关(P0.05),GABA与G分、PANSS总评分呈负相关(P0.05),PANSS评分P分和PANSS总评分降低(P0.01)、G分降低(P0.05)。结论 MECT治疗能降低精神分裂症患者多巴胺功能。     

Influence of EGF/bFGF treatment on proliferation, early neurogenesis and infarct volume after transient focal ischemia

The persistence of neurogenesis in the adult mammalian forebrain suggests that endogenous precursors may be a potential source for neuronal replacement after injury or neurodegeneration. On the other hand basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) can facilitate neural precursor proliferation in the adult rodent subventricular zone (SVZ) and dentate gyrus. As the application of EGF and bFGF was found to boost neurogenesis after global ischemia, in this study we investigated whether a combined intracerebroventricular (i.c.v.) EGF/bFGF treatment over a period of 2 weeks affects the proliferation of newly generated cells in the endothelin-1 model of transient focal ischemia in adult male Sprague-Dawley rats as well. As assessed by toluidine blue staining, EGF/bFGF substantially increased the infarct volume in ischemic animals. Chronic 5'-bromodeoxyuridine (BrdU) i.c.v. application revealed an EGF/bFGF-induced increase in cell proliferation in the lateral ventricle 14 days after surgery. Proliferation in the striatum increased after ischemia, whereas in the dentate gyrus and in the dorsal 3rd ventricle the number of cells decreased. Analysis of the neuronal fate of these cells by co-staining with a doublecortin (DCX) antibody showed that the growth factors concomitantly nearly doubled early neurogenesis in the ipsilateral striatum in ischemic animals but diminished it in the dentate gyrus. Because of the increased infarct volume and unclear long-term outcome further modifications of a chronic treatment schedule are needed before final conclusions concerning the perspectives of such an approach can be made.     

补肾活血颗粒对帕金森病患者脑内多巴胺水平的影响

目的研究补肾活血颗粒对帕金森病(PD)患者脑内多巴胺(DA)水平的影响。方法采用双盲设计,将60例PD患者随机分成治疗组30例和对照组30例。两组均以西药为基础治疗,其中治疗组服用补肾活血颗粒,对照组服用安慰剂,每日2次。两组患者均以3个月为治疗观察期,疗程结束后带药随访6个月观察。采用脑电超慢涨落图(EFG)观察PD患者DA水平在入组时、3个月后、6个月后、9个月后的变化。结果对照组DA值在治疗9个月中逐渐下降,但不具有统计学意义(P>0.05)。治疗组无论在治疗观察期还是随访观察期中,DA数值都呈上升趋势,且具有统计学意义(P<0.05)。结论 PD患者脑DA水平随病情进展逐渐下降,补肾活血颗粒可以升高PD患者脑内DA水平,并且疗效稳定。     

Improving Evoked Response Audiometry With Special Reference To The Use Of Machine Scoring

The use of visual scoring of evoked response (ER) records to detect auditory threshold is reviewed, and it is concluded that current ER audiometry is not a reliable clinical tool because of substantial error compounded by subjectivity of score.

The mathematics underlying ER detection is reviewed. The critical part played by the signal-to-noise ratio (f) and techniques for enhancing f are discussed. The accepted techniques of averaging, segregation by EEG classification before averaging, and filtering are considered, along with two newly proposed techiques, fast periodic stimulation and correction of records by predictors averaging. These hold promise of enhancing the effective f by a factor of about 3 and reducing the lenght of test runs by an order of magnitude.

Self-normalization is introduced in order to define scores which are sensitive primarily to f rather than to these scores is relatively invariant from subject to subject since it depends on f alone. This simplifies normative studies, particularly for the no-ER condition for which f = 0, since estimates of type-II error, false positives, are independent of the subject.

Five machine scores are defined: (1) normalized peak-to-trough amplitudes; (2) Normalized rectified mean amplitudes; (3) the ratio of power of the ER to that of the background EEG; (4) the correlation coefficients between subsets in the same run; and (5) a combined measure based on (3) and (4). The sensitivity of each of these measures and their dependence on f are considered.

From the explorations thus far, it is concluded that machine scoring techiques are available which are at least as sensitive and reliable as visual scoring and which can be implemented by relatively simple, inexpensive special purpose computers. Furthermore, since machine scoring lends itself to a superior test strategy, it is concluded that machine scoring can greatly increase the sensitivity and reliability of ER audiometry. These conclusions apply without taking into account the vast improvements possible if the newly proposed techniques (fast periodic stimulation and correction by prediction) for enhancing f should prove successful.