肠道菌群失调在儿童非酒精性脂肪肝中的研究进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)已成为儿童最主要的一种慢性肝病,与成人相比,儿童NAFLD进展迅速,预后不良.多项研究证实肠道菌群失调在NAFLD的发病机制中发挥着重要作用.肠道内微生物的发展可追溯至宫内胎儿期,微生物的多样性主要发生在儿童期.目前对儿童NAFLD药物治疗的探索仍在进行中.调节肠道菌群可以改善肝脏氧化应激和炎性损伤状态,从而改善机体的代谢异常及延缓NAFLD患者肝病进展,这对预防和治疗儿童NAFLD有重要的临床意义.     

单纯性肥胖患儿非酒精性脂肪肝病与胰岛素抵抗

目的探讨单纯性肥胖(肥胖)儿童发生非酒精性脂肪肝病(NAFLD)的情况及与胰岛素抵抗(IR)、血脂、体质量指数(BMI)、腰臀比(WHR)的关系。方法选择肥胖儿童90例,年龄2.5～14.3岁。其中NAFLD 24例(NAFLD组),无NAFLD 66例(无NAFLD组)。另选35例年龄、性别与其相匹配的健康儿童为健康对照组。清晨空腹测量其体质量、身高、腰围和臀围,计算BMI和WHR,同时静脉采血检测其血清胰岛素(FINS)、糖(FBG)、胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和ALT、AST等,计算稳态模型胰岛素抵抗指数(HOMA-IR=FINS×FBG/22.5),并做肝胆等部位超声检查。结果 NAFLD占肥胖儿童的26.67%;NAFLD组儿童BMI、WHR最高,其次为无NAFLD组,差异均有统计学意义(Pa<0.001);3组儿童FINS和HOMA-IR值差异均有统计学意义(Pa<0.001),NAFLD组最高,其次为无NAFLD组,均明显高于健康对照组,但FBG无明显差异;NAFLD组血清TG、LDL-C和TC水平明显高于无NAFLD组和健康对照组(Pa<0.01);HOMA-IR值与BMI、WHR、血TG、LDL-C呈正相关(r=0.402、0.256、0.239、0.180,P=0.000、0.004、0.008、0.046);BMI、WHR诊断NAFLD的受试者工作特征(ROC)曲线下面积分别为0.805和0.765(Pa=0.000)。结论肥胖儿童NAFLD的发生与IR,血TG、LDL-C、TC升高及BMI、WHR增高关系密切,BMI、WHR对儿童肥胖NAFLD具有一定的诊断价值。控制体质量,减少腰围,可减轻IR,阻止NAFLD的发生、发展。     

上海市闵行区儿童青少年非酒精性脂肪肝病7年患病率横断面调查

背景：儿童非酒精性脂肪肝病（NAFLD）导致成年后心血管病发病风险明显增加,而目前我国儿童青少年一般人群NAFLD患病率研究十分有限,长期变化趋势亦不明确。目的：描述儿童青少年NAFLD患病流行趋势。设计：横断面调查。方法：以上海市闵行区2014至2020年参加健康体检的住校学生为调查对象。将ALT水平高于一般人群性别和年龄别P97.5水平定义为疑似NAFLD,依此估计疑似NAFLD患病率（简称患病率）。根据全国标准分别以BMI和腰围定义一般性肥胖和腹型肥胖。通过计算平均年度变化百分比（AAPC）及其95%CI行描述NAFLD患病率逐年变化幅度,趋势性检验Logistic回归分析,并校正BMI和腰围。主要结局指标：NAFLD患病率。结果：NAFLD总体患病率为5.1%,从2014年至2020年上升了2.5倍（2.1%到7.4%）,NAFLD患病率逐年上升（Ptrend<0.001）,AAPC为0.9%（95%CI：0.1%~1.7%）,且男孩高于女孩（6.3% vs 3.7%）。在体重正常人群中NAFLD患病率为1.9%,7年中呈逐年上升趋势（Ptrend<0.001）。调整BMI和腰围后,NAFLD患病率逐年上升的趋势仍显著（Ptrend<0.001）。结论：上海儿童青少年人群NAFLD患病率呈现每年上升近1.0%的趋势,调整BMI和腰围因素后,NAFLD患病率逐年上升的趋势仍然存在。提示除肥胖外,儿童人群防控NAFLD需进一步关注其他可干预危险因素的作用。     

儿童青少年腰围身高比与非酒精性脂肪肝病关系的回顾性分析

背景：肥胖是导致儿童青少年人群非酒精性脂肪肝病（NAFLD）发生的重要原因之一,腰围身高比（WHtR）是反映内脏脂肪和评价儿童青少年心血管代谢风险的简单而准确的体格测量指标,但WHtR 与NAFLD的关系研究十分有限。 目的：分析儿童青少年WHtR与NAFLD的关系。 设计：常规体检数据的回顾性分析。 方法：以所有参加上海市闵行区2014至2020年住校学生健康体检的学生为研究对象,将血清ALT水平高于一般人群性别和年龄别第97.5百分位数水平定义为疑似NAFLD（简称NAFLD）。基于全国数据提示心血管代谢风险聚集的WHtR作为切点值,以男孩和女孩WHtR分别≥0.481和≥0.456定义为WHtR升高;以非条件二分类Logistic回归模型,校正年龄、性别等协变量后,分析WHtR升高与NAFLD的关系。通过计算AUC、敏感度、特异度、阳性预测值和阴性预测值,评价WHtR升高对NAFLD的区分效果。 主要结局指标：WHtR与NAFLD的关联性。 结果：与WHtR正常组相比,NAFLD患病率在 WHtR升高人群中显著升高（16.2% vs 2.3%, P<0.001）,且随着年龄的增长呈现上升趋势。在WHtR升高人群中,男孩NAFLD患病率高于女孩（21.6% vs 11.0%,P<0.001）,而在WHtR正常人群中男孩和女孩的NAFLD患病率接近（2.3% vs 2.2%, P=0.71）。WHtR升高人群NAFLD的发生风险增加 71%,校正的OR =1.71,95% CI：1.26~2.31,P=0.001。分层分析结果显示WHtR升高分别能增加男孩77%（OR=1.77,95% CI：1.19~2.63,P=0.005）和女孩69% （OR=1.69,95% CI：1.05~2.71,P=0.005）的NAFLD发生风险 。WHtR升高区分NAFLD的AUC为0.73（95% CI：0.71~0.76）,敏感度63.2%、特异度83.4%、阳性预测值16.8%和阴性预测值97.7%。 结论：儿童青少年WHtR升高与NAFLD的发生独立相关;学校和社区等基层医疗保健机构要重点关注WHtR升高的人群,除了血压、糖脂代谢异常以外,还需特别关注NAFLD的患病情况。     

A cross-sectional study on the prevalence rate and influencing factors of nonalcoholic fatty liver disease in overweight/obese children北大核心CSCD

目的 调查医院就诊的超重/肥胖儿童非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)的患病率,并探讨NAFLD发生的影响因素,为超重/肥胖儿童NAFLD的预防提供依据。方法 招募2019年6月-2021年9月在湖南省儿童医院就诊的超重/肥胖儿童作为研究对象,调查NAFLD患病率,并采用logistic回归分析探讨NAFLD,包括单纯性脂肪肝(non-alcoholic fatty liver,NAFL)和非酒精性脂肪肝炎(non-alcoholic steatohepatitis,NASH)发生的影响因素。采用受试者操作特征曲线分析评价影响因素对NAFL及NASH的预测价值。结果 共纳入844例超重/肥胖儿童,年龄为6~17岁。NAFLD患病率为38.2%(322/844),其中NAFL和NASH患病率分别为28.8%(243/844)和9.4%(79/844)。多因素logistic回归分析显示,腰臀比(waist-to-hip ratio,WHR)增加及低高密度脂蛋白胆固醇血症与NAFL和NASH的发生有关(P<0.05)。受试者操作特征曲线分析显示:WHR和高密度脂蛋白胆固醇联合检测预测NAFL的曲线下面积为0.653 (95%CI:0.613~0.694);二者联合检测预测NASH的曲线下面积为0.771 (95%CI:0.723~0.819)。结论 医院就诊的超重/肥胖儿童NAFLD的患病率较高;WHR和高密度脂蛋白胆固醇与NAFLD的发生有关,二者联合检测对NAFLD的发生具有一定的预测价值。     

腰围预测肥胖儿童非酒精性脂肪性肝病的价值

目的探讨腰围预测肥胖儿童发生非酒精性脂肪性肝病(NAFLD)的价值。方法2003-06—2006-09对浙江大学医学院附属儿童医院儿科197例9~14岁肥胖儿童进行腰围、体质指数(BMI)测定,作肝脏B超检查、血清肝酶测定,并与正常对照组比较。同时对肥胖儿童进行腰围、BMI与脂肪肝严重程度、血清ALT水平的相关性分析,以及腰围、BMI诊断肥胖儿童发生NAFLD曲线下面积的ROC分析。结果肥胖组腰围[(91.99±11.03)cm]显著大于正常对照组[(66.27±4.76)cm],BMI、肝酶水平也显著高于正常对照组。197例9~14岁肥胖患儿中诊断为NAFLD者147例,占74.62%;肥胖组NAFLD患儿腰围、BMI均大于非NAFLD患儿。肥胖患儿腰围、BMI与脂肪肝严重程度、血清ALT水平均呈正相关(r=0.478、0.356、0.302、0.205,均P<0.01);腰围和BMI诊断NAFLD的ROC曲线下面积分别为0.767、0.717(均P<0.01)。结论9~14岁肥胖儿童NAFLD发生与腰围密切相关,腰围、BMI对肥胖儿童发生NAFLD有一定的预测价值。     

儿童脂肪性肝病命名探析

肥胖是多种重大慢性疾病的危险因素, 其中肝脏疾病尤其是脂肪性肝病的发生与肥胖密切相关。非酒精性脂肪性肝病(NAFLD)已成为我国儿童青少年慢性肝病的最常见类型, 给社会造成了严重的经济和公共卫生负担。随着对疾病研究的深入, 2020年国际共识小组建议将NAFLD更新为代谢障碍相关脂肪性肝病(MAFLD)。而为了积极防控肥胖基础上的脂肪肝大流行, 本文提出在儿童中应用"肥胖相关脂肪性肝病(OAFLD)"这一新名称。本文将从儿童脂肪性肝病疾病命名的背景与机制出发, 探讨NAFLD、MAFLD、OAFLD在儿童青少年中应用的优劣。     

鼠李糖乳杆菌与儿童非酒精性脂肪肝病研究进展

非酒精性脂肪肝病(NAFLD)已成为儿童最常见的慢性肝病之一,其疾病谱包括非酒精性单纯性脂肪肝、非酒精性脂肪性肝炎及其相关肝纤维化、肝硬化和肝细胞癌。在肥胖儿童中,至少有50%的儿童表现出一定程度的NAFLD。在NAFLD进展中起主要作用的是游离脂肪酸水平增加和胰岛素抵抗,致使肝细胞中三酰甘油过度聚积。鼠李糖乳杆菌是目...     

肥胖儿童非酒精性脂肪肝病与心血管疾病的相关性

目的：探讨肥胖儿童非酒精性脂肪肝病（NAFLD）与心血管疾病(CVD)的关系。方法：231例肥胖儿童以及24例非肥胖儿童(对照组)进行临床、生化指标及颈动脉内膜-中层厚度（IMT）各项检查,根据诊断标准将231例肥胖儿童分为肥胖无肝脏损伤组（OCWLD）75例和NAFLD组156例。比较各组儿童临床、生化各项指标及IMT。结：果NAFLD组患儿IMT为0.066±0.021 cm,显著高于OCWLD组和对照组（分别为0.060±0.011 cm,0.037±0.007 cm,均P＜0.05）,OCWLD组亦显著高于对照组,P<0.05。NAFLD组患儿高血压、高脂血症患病率分别为39.7%和40.4%,明显高于OCWLD组（分别为22.7%,29.3%）和正常对照组（分别为4.2%,12.6%）（P<0.05）。经逐步线性回归分析显示IMT与BMI、NAFLD、ALT呈正相关（调整R2=0.316,P<0.01）。结论：肥胖儿童NAFLD的出现不仅是CVD发生的早期标志,而且是CVD发生的早期状态。NAFLD的早期诊断和治疗是预防心血管疾病发生发展的关键。［中国当代儿科杂志,2010,12（7）：547-550］     

肥胖及伴非酒精性脂肪肝病儿童血清脂联素与代谢综合征的相关性

目的 研究肥胖及伴非酒精性脂肪肝病(NAFLD)儿童、青少年的血脂代谢特征及血清脂联素水平与代谢综合征(MS)的关系.方法 采用典型整群抽样方法选取北京市海淀区中等水平的4所小学和4所中学的7～18岁儿童及青少年,在知情同意的前提下,进行问卷、身体测量、腹部B超脂肪肝检查及血生化检测.从中选取各项调查资料完整的609例作为研究对象,其中单纯肥胖儿童280例,肥胖伴NAFLD儿童65例(肥胖伴NAFLD组),正常体质量儿童264例作为健康对照组.经统计分析,正态分布测量数据以x±s表示;血清三酰甘油(TG)、脂联素、AIX和AST生化指标呈偏态分布,以几何均数和四分位间距(P25～P75)表示,经自然对数转化为正态分布后进行分析.采用方差分析,Logistic回归分析等.结果 肥胖组及肥胖伴NAFLD组体质量指数(BMI)及腰围(WC)显著高于健康对照组,3组间差异有统计学意义(P＜0.001);3组儿童的空腹血浆葡萄糖、血脂、脂联素及转氨酶水平比较差异均有显著统计学意义;肥胖伴NAFLD组儿童的AIX、AST明显升高;控制可能的影响因素年龄、性别后进行多因素Logistic回归分析显示,与单纯肥胖组比较,肥胖伴NAFLD组MS及组分高TG、高血压的检出率明显增加,罹患MS的相对风险增加尤为显著(P＜0.001).结论 肥胖及肥胖伴NAFLD对儿童、青少年的肝功能和血脂代谢均造成危害,其血清脂联素水平随肥胖程度的增加析降低,脂联素作为胰岛素的增敏激素,连接脂肪组织和整体糖代谢,脂联素可作为MS的评估指标之一.     

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

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.     

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孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%～5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相     

Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte-proliferative disorders corresponding to chronic active Epstein-Barr virus infection

A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.     

LUTEINIZING HORMONE RECEPTOR MUTATIONS IN DISORDERS OF SEXUAL DEVELOPMENT AND CANCER

Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.     

Personality profiles and heart rate variability (vagal tone) in children with recurrent abdominal pain

The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.     

Understanding infant formula

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 healthcare professionals) will experiment with the infant formula available and then 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.     

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.