基于支持向量机神经母细胞瘤血清蛋白质标记物的检测及临床应用

目的 寻找神经母细胞瘤特异血清蛋白标记物,构建初步诊断模型,并探讨其临床应用价值.方法 收集47例神经母细胞瘤患儿血清标本,30例其它恶性实体肿瘤患儿血清标本以及健康儿童血清标本10例;用ZUCI-Protein Chip Data Analyze System分析软件进行数据处理;经留一法交叉验证,分类器评价模型的预测效果.结果 构建3个模型并筛选出10个蛋白标记物,能够成功区分神经母细胞瘤和健康儿童蛋白质谱的差异,表达模型的敏感性为100%,特异性为100%,区分神经母细胞瘤术前和术后蛋白质潜差异表达模型的敏感性为100%,特异性为100%,区分神经母细胞瘤与其它小儿恶性实体肿瘤血清蛋白质指纹图谱模型的敏感性为88.89%.特异性为100%.结论 用SELDI-TOF-MS及生物信息学技术并结合支持向量机(SVM)初步建立的模型可作为神经母细胞瘤的另一种特异性强、敏感性高的辅助检查手段.     

影响肾母细胞瘤预后的因素

３２０例肾母细胞瘤获远期随访２３５例。依治疗时间及治疗方法不同分无化疗组、化疗组、规律化疗组。规律化疗组预后好的组织结构（ＦＨ）８１例，四年无瘤生存Ⅰ期９５．８％，Ⅱ期８３．３％，Ⅲ期６３．６％，Ⅳ期４０．０％；预后差的组织结构（ＵＨ）１２例，四年无瘤生存Ⅰ期５０．０％，Ⅲ期１６．７％。在病理组织分型和一定的临床分期情况下，合理的综合治疗特别是规律性化疗是影响肾母细胞瘤预后的重要因素。     

增殖细胞核抗原在肾母细胞瘤中的表达及其临床意义

为明确增殖细胞核抗原在肾母细胞瘤中的表达及其临床意义。对３５例肾母细胞瘤采用免疫组化染色进行回顾性研究。结果；３５例肾母细胞瘤采用免疫组化染色进行回顾性研究。结果；３５例肾母细胞瘤中ＰＣＮＡ表达阳性者１２例，其中Ⅱ级５例，Ⅲ级４例，Ⅳ级３例，阳性率为３４．２９％，其阳性率随临床分期升高而增加，ＰＣＮＡ阳性者其Ｓ期细胞指数及增殖指数均显著高天ＰＣＮＡ阴性者，而其五年生存率，１６．６７％，则显著低于Ｐ     

血管内皮生长因子-C在儿童实体肿瘤生长转移中的表达

目的探讨血管内皮生长因子-C(VEGF-C)在儿童实体肿瘤神经母细胞瘤及肾母细胞瘤中的表达。方法对33例神经母细胞瘤和30例肾母细胞瘤标本进行VEGF—C免疫组织化学分析,神经母细胞瘤Ⅲ期8例,Ⅳ期25例,远处转移25例,其中淋巴结转移5例,组织病理满意型(FH)20例,组织病理不满意型(UFH)13例;肾母细胞瘤Ⅰ Ⅱ期15例,Ⅲ Ⅳ期15例,远处转移12例,肾门、腹主动脉旁淋巴结受累5例,FH22例,UFH8例。结果神经母细胞瘤Ⅲ期VEGF-C阳性率37.5%(3/8),Ⅳ期32%(8/25),FH45%(9/20),UFH30.8%(4/13),远处转移32%(8/25),淋巴结转移66.7%(4/6),肾母细胞瘤Ⅰ Ⅱ期26.7%(4/15),Ⅲ Ⅳ期40%(6/15),FH27.3%(6/22),UFH25%(2/8),远处转移33.3%(4/12),淋巴结转移60%(3/5)。VEGF-C的表达与肿瘤的临床分期及病理类型无显著意义,而与淋巴结的转移存在显著意义(P<0.05)。结论VEGF-C的表达与肿瘤淋巴结的转移存在密切相关。     

胆道闭锁血清蛋白质标记物的检测

目的 寻找特异性诊断胆道闭锁的血清蛋白标记物.方法 应用表面增强激光解吸电离飞行时间质谱(SELDI-TOF-MS)技术检测28例血清标本(胆道闭锁7例,先天性胆总管囊肿7例,婴肝综合征3例,正常对照11例)的蛋白质质谱表达,结合生物信息学方法(SVM)分析数据.结果 筛选出m/z位于3403、2108、2111、2131、2823的5个蛋白质标记物区分肝胆疾病和正常对照小儿的血清蛋白指纹图谱模型,敏感性94.1%,特异性81.8%;筛选出m/z位于3403蛋白质标记物区分胆道闭锁和正常对照小儿的血清蛋白指纹图谱模型,敏感性100%,特异性100%;筛选出m/z位于3403、4796的2个蛋白质标记物区分胆道闭锁和其他肝胆疾病的血清蛋白指纹图谱模型,敏感性71.4%,特异性80.0%.结论 应用SELDI-TOF-MS结合SVM构建的胆道闭锁血清蛋白指纹图谱模型为胆道闭锁的早期诊断方法开拓了新方向,值得进一步研究.     

肾母细胞瘤诊治10年回顾

目的 对10年中收治的小儿肾母细胞瘤的发病特点和诊治进行回顾分析,讨论影响肾母细胞瘤治疗和预后的因素.方法 统计10年期间69例肾母细胞瘤患儿的临床资料,包括患儿性别,发病年龄,临床表现和分期,病理分型和治疗手段,并将患儿分别以临床分期和病理分型进行分层,用Kaplan-Meier进行单因素生存分析.结果平均发病年龄(3.25±2.78)岁,发现腹部包块为主要起病症状,其中Ⅰ期18例,Ⅱ期25例,Ⅲ20例,Ⅳ期6例.治疗手段为患肾切除,NWTSG的化疗方案和有限病例的放疗.随访时间4～123个月,平均生存时间(41±30.9)个月.生存率:总体生存率78.2%,其中Ⅰ期患儿100%,Ⅱ期患儿76%,Ⅲ期患儿70%,Ⅳ期患儿50%.Kaplan-Meier生存分析表明,Ⅰ期、Ⅱ期、Ⅲ期三组患儿的生存时间差别无统计学意义,但明显高于Ⅳ期组患儿(LogRank法,P=0.04).预后良好组织类型(FH)组生存率为86.9%,其中Ⅰ期为100%,Ⅱ期93.3%,Ⅲ期72.7%,Ⅳ期50%;预后不良组织类型(UH)组总体生存率为65.2%,Kaplan-Meier生存分析生存表明,二组的生存时间具有显著性差异(Log Rank法,P=0.004).结论 临床分期,病理类型和治疗手段是影响肾母细胞瘤患儿预后的重要因素.     

肾母细胞瘤切除术中探查对侧肾脏是必须的吗?

目的：探讨肾母细胞瘤切除术中对侧肾脏探查的必要性。方法：1979年10月至1994年12月，共81例肾母细胞瘤患儿均于术前接受B超、CT和IVU检查，所有患儿均在本院接受手术并化和放疗。15例患儿接受了MRI成像检查。结果：76例患儿术前诊断和为单侧或双侧（仅3例）肾母细胞瘤，与手术结果完全一致，4例患儿术前怀疑为神经母细胞瘤，1例疑为畸胎瘤。3例双侧者均为小肿瘤侧半肾切除和大肿瘤侧全肾切除，单侧者均未探查对侧肾脏。术后病理证实为肾母细胞瘤。根据NWTS的分期标准，Ⅰ期34例，Ⅱ期23例，Ⅲ期15例，Ⅳ期6例，Ⅴ期3例，结果：78例单侧患儿随访6－20年，5年生存率为79．49％，患儿死于转移，复发和化疗或放疗并发症，无一例患儿发现有对侧肾母细胞瘤。结论：肾母细胞瘤切除术中无必要探查对侧肾脏。     

小儿肾母细胞瘤146例分析

目的总结小儿肾母细胞瘤的治疗经验,以期改进肾母细胞瘤的治疗方法,改善。肾母细胞瘤患儿的预后。方法回顾性分析本院近20年来收治的146例。肾母细胞瘤患儿的临床资料。结果146例中,Ⅰ期62例,Ⅱ期32例,Ⅲ期33例,Ⅳ期17例,Ⅴ期2例：71例随访时间〉5年,共死亡11例,无瘤存活60例,总治愈率84．5％（60／71）,其中Ⅰ期97．3％（37／38）,Ⅱ期83．3％（10,12）,Ⅲ期72．7％（8／11）,Ⅳ期55．5％（5／9）。对术前评估手术切除困难或有远处转移的48例进行术前化疗5周,其中41例一般情况明显改善,肿瘤缩小;4例肿瘤体积增大;3例下腔静脉瘤栓患儿死亡;45例行手术完整切除肿块。结论采取综合治疗后小儿肾母细胞瘤的治愈率得到明显提高,其中手术加规范的化疗起关键作用。     

肾母细胞瘤手术与肿瘤局部复发的关系

目的 探讨肾母细胞瘤手术后肿瘤局部复发与手术的关系。方法 1994年1月-1999年12月经手术病理证实肾母细胞瘤35例，年龄11个月-9岁。术后按照国际肾母细胞瘤研究组织（MWTS）Ⅲ-V期放化疗方案治疗并随访。结果 肿瘤复发7例（I期1例，Ⅱ期2例，Ⅲ期4例），复发发生在术后2个月-3年。术中肿瘤破溃6例中4例局部复发；未作淋巴结活检2例局部复发；间变型肾母细胞瘤3例复发。结论 术中肿瘤破溃则复发率高，对巨大肾母细胞瘤术中应仔细操作，避免破溃。必须作腹主动脉旁及肾门淋巴细胞结病理检查，明确临床分期，针对性性放化疗，是提高患儿存活率的重要手段。     

儿童节细胞神经母细胞瘤血清特异性蛋白的筛选与鉴定

目的构建更为完善的儿童节细胞神经母细胞瘤(GNB)的早期诊断血清蛋白质指纹图谱模型。方法入选30例GNB术前患儿及30例正常对照儿童,采集血清标本;以弱阳离子交换磁珠芯片(MB-WCX)处理血清,用表面增强激光解析电离飞行时间质谱(SELDI-TOF-MS)筛选方法检测和分析蛋白m/z峰值,筛选特异性蛋白,通过基质辅助激光解析电离飞行时间质谱(MALDI-TOF/TOF)方法对特异性蛋白进行鉴定。结果 SELDI-TOF-MS质谱筛选GNB术前患儿与正常对照儿童得到m/z峰位于5 920的蛋白标记物,该标记物在GNB术前患儿中高表达(6 180.6±2 328.0),相比正常对照儿童(419.1±493.3),差异有统计学意义(P0.05);经MALDI-TOF/TOF鉴定,该蛋白标记物为类载脂蛋白C-Ⅲ(Apo C-Ⅲ)。结论 m/z峰位于5 920的蛋白标记物考虑为儿童GNB特异性标记物,其有助于儿童GNB的早期诊断。     

Bibliometric data: a disaster for many non-American biomedical journals

Bibliometric data published by the Institute of Scientific Information in Philadelphia (ISI), and which was previously discussed in Acta Paediatrica , has increasingly been used despite all the relevant and severe criticism that has been raised against this method of evaluating individual research results and grading scientific journals. It is obvious that the present trend regarding the use of bibliometric data as a basis for priorities and funding of research and for the promotion of individual scientists favours American-oriented research projects at the expense of those that are based on concepts of predominantly European relevance.

Conclusion: For the future of non-American research, it is important that no single super-power, i.e. the USA, should dominate scientific priorities. The condition for efficient European competition is that European Centres with high levels of competence for creative research and training of scientists from all over the world are established. In addition, it is important that the results of European research are published in prestigious European journals, as was the situation before World War II.     

The importance of different immunosuppressive regimens in the development of posttransplant diabetes mellitus

Solid-organ transplantation is the optimal long-term treatment for most patients with end-stage organ failure. After solid-organ transplantation, short-term graft survival significantly improved (1). However, due to chronic allograft nephropathy and death with functioning graft, long-term survival has not prolonged remarkably (2). Posttransplant immunosuppressive medications consist of one of the calcineurin inhibitors in combination with mycophenolate mofetil (MMF) or azathioprine (Aza) and steroids. All of them have different adverse effects, among which posttransplant diabetes mellitus (PTDM) is an independent risk factor for cardiovascular (CV) events and infections causing the death of many transplant patients and it may directly contribute to graft failure (3). According to the criteria of the American Diabetes Association (4), diabetes mellitus (DM) is defined by symptoms of diabetes (polyuria and polydipsia and weight loss) plus casual plasma glucose concentration ≥ 11.1 mmol/L or fasting plasma glucose (FPG) ≥ 7.0 mmol/L or 2-h plasma glucose level ≥ 11.1 mmol/L following oral glucose tolerance test (OGTT). This metabolic disorder occurring as a complication of organ transplantation has been recognized for many years. PTDM, which is a combination of decreased insulin secretion and increased insulin resistance, develops in 4.9/15.9% of liver transplant patients, in 4.7/11.5% of kidney recipients, and in 15/17.5% of heart and lung transplants [cyclosporine A (CyA)/tacrolimus (Tac)-based regimen, respectively] (5). Risk factors of PTDM can be divided into non-modifiable and modifiable ones (6), among which the most prominent is the immunosuppressive therapy being responsible for 74% of PTDM development (7). Emphasizing the importance of the PTDM, numerous studies have determined the long-term outcome. On the basis of these studies, graft and patient survival is tendentiously (8) or significantly (9, 10) decreased for those developing PTDM.     

alpha -SMOOTH MUSCLE ACTIN DISTRIBUTION IN THE PULMONARY VASCULATURE COMPARING HYPOPLASTIC AND NORMAL FETAL LUNGS

We investigated the intra-acinar pulmonary vascular muscularization in the developing human fetal lung between the 17th and 24th gestational weeks, that is, during the canalicular phase of lung development. Fifteen hypoplastic and 25 normal developed lungs were included in this study using monoclonal alpha -smooth muscle (sm) actin antibodies for smooth muscle detection. Computer-aided image analysis was performed for morphometrical measurements and statistical evaluation. Alphasm-actin-immunoreactive intra-acinar vessels down to a luminal diameter of less than 10 mu m were detected in hypoplastic as well as in normally developed lungs. Crucial differences presented as follows: significantly higher density of intra-acinar vessels, especially due to alpha -sm-actin-negative vessels less than 30 mu m in luminal diameter, in the control group; significantly higher alpha -sm-actin immunoreactivity per section unit as well as per vessel in the hypoplastic lung group. As suggested by others, alpha-sm-actin-positive cells of the intra-acinar vessel wall in the developing human lung were demonstrated to be smooth muscle cells, their immediate precursors, and pericytes. We conclude that the increased alpha -sm-actin immunoreactivity represents muscularization of the vessel wall in functional terms and may be regarded as one structural cause among others for the establishment of persistent fetal circulation in hypoplastic lungs.     

Whole-body mineral measurements in Swedish adolescents at 17 years compared to 15 years of age

Aim: To provide reference data for bone mineral variables in 15- and 17-y-old adolescents and to analyse the relationships between these variables and measures of bone and body size, gender, puberty, growth, various lifestyle and environmental factors and socioeconomic background.

Methods: In the same 321 randomly selected adolescents (147 boys and 174 girls) living in two different regions of Sweden, the total bone mineral content (TBMC), bone area (BA) and total bone mineral density (TBMD) were assessed by dual-energy X-ray absorptiometry at ages 15 and 17 y. The effects of bone and body size, gender, growth, sexual maturity, physical activity, region of domicile, social conditions, food habits, smoking and alcohol intake on TBMC and TBMD were examined in multivariate analyses.

Results: In the 15-y-old adolescents, BA, height, gender, physical activity, maturity and weight explained 91% and 48%, of the variance in TBMC and TBMD, respectively. In similar analyses in the 17-y-olds, the corresponding figures were 92% and 62%, respectively, when BA, height, growth, physical activity, gender and region emerged as significant in the model. In all these analyses, BA explained most of the variance in TBMC and TBMD. No significant reduction of variance was found when different measures of social conditions, smoking, food habits, alcohol or dietary intakes of energy, calcium or vitamin D were included in the models. The reason why region of domicile had a significant impact on TBMC in the 17-y-olds is not known. The fact that the normal fluoride concentration in drinking water (1.1 mg/L) is 10 times higher in the region where TBMC was higher than in the other region is an interesting observation.

Conclusion: Almost 90% of the variance in TBMC and 50% of that in TBMD was explained by measures of bone and body size and only a few percent by gender, physical activity, Tanner stage, growth and region of domicile.     

VARICELLA ZOSTER VIRUS INFECTIONS IN THE PEDIATRIC STEM CELL TRANSPLANT PATIENT

Varicella zoster virus (VZV), a member of the human herpesvirus family, causes the clinical syndromes of chickenpox during primary infection and shingles on later reactivation. In immunocompromised patients, including those undergoing hematopoietic stem cell transplantation, VZV can produce life-threatening infections. The most serious forms of VZV infection involve hematogenous dissemination of the virus to vital organs, such as the lung, brain, and liver. Advances in immunoprophylaxis, antiviral chemotherapy, and vaccine development have provided effective tools to limit the morbidity and mortality previously associated with VZV infection in hematopoietic stem cell transplant patients. In this review, we discuss virologic aspects of VZV, pathogenesis of VZV infection, methods of viral diagnosis, clinical manifestations of infection in both normal and immunocompromised patients, and available preventative and therapeutic measures.     

The potential role of rapamycin in pediatric transplantation as observed from adult studies

Although pediatric patient and renal graft survival rates have shown marked improvements during the past decade, the persistent toxicities of immunosuppressive drugs and chronic allograft attrition remain major obstacles in transplant therapy. Results in adult patients suggest that complete steroid withdrawal is possible in the majority of recipients under treatment with a cyclosporin A-rapamycin (CsA RAPA) regimen. Furthermore, preliminary studies suggest that a marked reduction in the dose of CsA may be possible under the umbrella of RAPA coverage. The gain in immunosuppressive efficacy afforded by RAPA has not only been obtained without an increased morbidity owing to infectious or neoplastic causes, but also with the potential for reducing the incidence and/or progression of chronic rejection.     

GENETICS OF CARNEY COMPLEX AND RELATED FAMILIAL LENTIGINOSES, AND OTHER MULTIPLE TUMOR SYNDROMES

Carney complex is a multiple endocrine neoplasia (MEN) syndrome that affects the adrenal cortex, the pituitary and thyroid glands, and the gonads. The complex is also associated with skin and mucosa pigmentation abnormalities and myxoid and other neoplasms of mesenchymal and neural crest origin. Thus, this syndrome also belongs to another group of genetic disorders, the lentiginoses (or lentigenoses), which include the Peutz-Jeghers, LEOPARD, arterial dissections and lentiginosis, and Laugier-Hunziker syndromes, Cowden disease and Ruvalcaba-Myhre-Smith (Bannayan-Zonana) syndrome and the centrofacial, benign patterned and segmental lentiginoses, all of which can be associated with a variety of developmental defects. The inheritance of Carney complex, just like that of the other MENs and the lentiginoses, is autosomal dominant. Genetic loci or genes have been identified for Carney complex, Peutz-Jeghers and Ruvalcaba-Myhre-Smith syndromes, but not for other lentiginoses. Elucidation of the molecular defects responsible for these disorders is expected to shed light on aspects of early neural crest differentiation, the regulation of pigmentation, the development of autonomous endocrine function, and endocrine and nonendocrine tumorigenesis.     

All you ever wanted to know about infant formulas (but were afraid to ask)

The World Health organisation recommends breast feeding infants for the first six months of life. When this breast feeding does not occur either through parental choice or medical need, infant formulas will be required. There is a bewildering array of formulas on the UK market for many different requirements. When faced with an unsettled infant many parents (and health care professionals) will experiment with the infant formula available and often attend the paediatric clinic looking for help and advice. It is therefore essential that paediatricians understand what milks are available and what the key differences between different products are. This review attempts to provide a simple guide through many of the formulations currently available in the UK; and offers advice for the dietary management of the child with extra calorie requirements, infants with cow's milk protein allergy, gastro oesophageal reflux disease, apparent unresolved hunger and infantile colic. Whatever the underlying condition, there is likely to be an infant formula that is suitable in this generation of ever expanding formulations.     

Génétique des schizophrénies : mise en perspective des schizophrénies à début précoce et autres pathologies du développement

Schizophrenia (SCZ) is a severe brain disorder characterized by hallucinations, delusions, flat and/or inappropriate affect and cognitive impairment. The lifetime risk is about 0.5% with heritability of 65–85%. The prevalence of early-onset schizophrenia (defined here as before 15 years of age) has not been well studied, but is likely to be 5–10% of all cases. The rarity of early-onset SCZ has made it difficult to study. We focus on genetic studies of adults with schizophrenia, highlighting results for early-onset schizophrenia where available. Prior to the past 5 years, studies failed to find replicable association or linkage between SCZ and specific genes when appropriate statistical corrections for multiple testing were used. Many false positive results were probably reported using the candidate gene approach. Recently, the development of single nucleotide polymorphism (SNP) “chips” has permitted large genome-wide association study (GWAS) analyses that suggest that across all age groups, a proportion of genetic risk can be attributed to a large number of common SNP, each with a very small effect on risk (odds ratios of 1.1 or less). The greatest known genetic effect is conferred by the 1.5–3 Mb 22q.11.2 deletions, which occurs in ∼ 1/4000–1/6000 births with SCZ developing in 20–30% of carriers. Large SNP and aCGH microarray studies have now identified associations between SCZ and other rare, large copy number variations (CNV, insertions and deletions) with high odds ratios (5–10), including deletions of 1q21, 2p16.3 (neurexin-1 gene), 3q29 and 15q13.3, and duplications of 16p11.2. Some of these CNV are also associated with autism or other developmental disorders as well as epilepsy or intellectual deficiency, suggesting some overlap in the mechanisms that contribute to risks of these disorders. Based on preliminary data from larger-scale analyses in progress, approximately 1–2% of cases carry a CNV that has been clearly associated with SCZ (ORs 4–12). Whole exome and genome sequencing studies of large adult samples will be the next steps to identify rarer SCZ-associated mutations, including point mutations and smaller as well as rarer CNV. Genetic findings are beginning to contribute to an understanding of biological mechanisms of SCZ risk and may lead to new approaches to treatment.     

INACTIVATION OF PULMONARY SURFACTANT AND THE TREATMENT OF ACUTE LUNG INJURIES

Inactivation of pulmonary surfactant may be important in acute lung injury and acute respiratory distress syndrome. Treatment of surfactant dysfunction by instilling exogenous surfactants may improve gas exchange and pulmonary mechanics. Surfactants used for treatment vary in their attributes and effects, so when various surfactants are considered for therapy, resistance to inactivation is an important consideration. Animal models of acute lung injury exist in which the relative merits of surfactants can be compared. We hypothesize that the surfactants most resistant to inactivation in vitro will be the ones that are most effective in treatment of animal models of acute lung injury. Surfactants with higher concentrations of surfactant proteins (specifically A, B, and C) are more resistant to inactivation. Nonionic polymers mimic surfactant proteins in preventing surfactant inactivation under some conditions. Adding nonionic polymers to surfactant containing minimal amounts of SP-B and SP-C markedly improves lung function of animals with lung injury. Making surfactants more "inactivation-proof" may improve surfactant therapy of acute lung injuries.