MyD88和TICAM1基因多态性及其交互作用与儿童社区获得性肺炎的关联研究

目的 探讨髓样分化因子88(myeloid differentiation factor 88,MyD88)和Toll样受体衔接分子1(Toll-like receptor adaptor molecule 1,TICAM1)基因的单核苷酸多态性及其交互作用与儿童社区获得性肺炎（community-acquired pneumonia,CAP）的相关性。方法 前瞻性采用改良多重高温连接酶检测反应技术对2015年8月—2017年9月在延安大学医学院第二附属医院儿科就诊的375例CAP患儿和306例健康体检儿童的MyD88和TICAM1基因的9个标签位点进行分型,并采用logistic回归分析评价各位点基因型及其交互作用与儿童CAP的关联。结果 TICAM1基因rs11466711T/C位点多态性与儿童CAP易感性密切相关（P<0.05）;rs35747610G/A位点AA基因型可显著降低CAP患儿并发脓毒症的风险（P<0.05）;rs6510826G/A位点AA基因型与CAP患儿急性期C反应蛋白水平的增高显著关联（P<0.05）。MyD88基因rs7744A/G位点GG...     

肿瘤坏死因子基因多态性与儿童淋巴瘤关系的研究

目的利用SNaPshot SNP分型技术检测儿童淋巴瘤患者肿瘤坏死因子α(TNF-α)基因-308 G/A位点及淋巴毒素(LTα)基因+252 A/G位点的单核苷酸多态性(SNP),探讨TNF基因多态性与儿童淋巴瘤临床特征及预后的关系。方法收集2004年7月-2011年7月在我院血液科确诊的儿童淋巴瘤患者血样,提取基因组DNA,用SNaPshot SNP分型技术检测TNF-α基因-308G/A位点及LTα基因+252 A/G位点的单核苷酸多态性,分析TNF-α/LTα基因多态性与淋巴瘤患儿的临床特征及预后的关系。结果 62例淋巴瘤患儿中,非霍奇淋巴瘤51例,霍奇金病11例,TNF-α-308位点与LTα+252位点基因存在遗传连锁不平衡现象。将含2个及以上TNF或LTα高产位点的基因型定义为高危型,少于2个高产位点的基因型定义为低危型。对56例随访治疗的淋巴瘤患儿以Kaplan-Meier方法进行生存分析,高危型组和低危型组5年无事件生存率(EFS)分别为47%、75%(Log-rank检验,P=0.045),差异有显著性;对51例非霍奇金淋巴瘤患儿分析,高危型组和低危型组的5年EFS分别为53.5%、71.4%(Log-rank检验,P=0.288),差异无显著性。结论 TNF-α-308位点和LTα+252位点多态性联合危险度分型可能与儿童淋巴瘤预后有关。     

过敏性紫癜患儿血浆纤维蛋白原水平及基因多态性的研究

目的 探讨过敏性紫癜(HSP)患儿血浆纤维蛋白原水平及β纤维蛋白原基因FGB-455G/A、-148C/T、-448G/A基因多态性的相关性.方法 采集528例HSP患儿及180例健康儿童末梢血标本,应用PCR限制性片段长度多态性(FGB-RFLP)技术,检测FGB-455G/A、-148C/T、-448G/A基因型,并检测158例HSP患儿和100例健康儿童的血浆纤维蛋白原水平.结果 HSP患儿FGB-455G/A位点的GG型和-448G/A位点的GG型出现频率比健康儿童明显增高,差异有统计学意义(P ＜ 0.01).HSP患儿FGB-455G/A位点的G等位基因、-148C/T 位点的C等位基因、-448G/A位点的G等位基因出现频率较健康儿童明显增高,差异有统计学意义 (P ＜ 0.05).FGB-455G/A位点GG基因型发生HSP的相对危险性(OR)为2.39(95%CI,1.66 ～ 3.39);HSP患儿的血浆纤维蛋白原水平较健康儿童明显增高,差异有统计学意义(P ＜ 0.01);FGB-455G/A位点GG基因型HSP患儿的纤维蛋白原水平明显高于AG + AA基因型,差异有统计学意义(P ＜ 0.05).结论 HSP发病可能与β纤维蛋白原FGB-455G/A和-488A/G基因多态性及其水平相关;FGB-455A/G位点GG基因型可能是HSP的危险基因.     

柯萨奇-腺病毒受体基因-968G/A多态性与柯萨奇病毒性心肌炎的关系

目的 探讨柯萨奇-腺病毒受体(CAR)基因.968G/A多态性与中国南方汉族人群柯萨奇病毒性心肌炎的关系.方法 收集病毒性心肌炎患儿280例,将其中CVB-IgM阳性130例作为心肌炎组,并选择同期130名健康儿童作为对照组,采用聚和酶链反应-限制性内切酶片断长度多态性(PCR-RFLP)、DNA测序等方法 检测2组CAR基因-968G/A多态性,采用酶联免疫吸附法(ELISA)测定两组血清CAR水平.结果 心肌炎组GG基因型和G等位基因频率均显著高于对照组(P<0.05).心肌炎组血清CAR水平明显高于对照组(P<0.01),CAR基因-968G/A多态位点中含G等位基因(GG+GA)者血清CAR水平和CVB感染率均显著高于非G等位基因(AA)携带者(P均<0.05).结论 CAR基因-968G/A多态性可能与中国南方汉族人群柯萨奇病毒性心肌炎有关,G等位基因是柯萨奇病毒性心肌炎的易感基因.     

IL-1β-511T基因rs16944多态性与热性惊厥的关联研究

目的 致热因子白细胞介素1（IL-1β）基因多态性是否参与热性惊厥（FS）的发病目前仍存在争议,该研究将探讨中国北方汉族儿童热点基因IL-1β-511T 的单核苷酸（SNP）rs16944 多态性与 FS 发病的关联性。方法 用 SNaPshot SNP 分型技术对 141 例单纯型 FS 患儿和 130 例健康对照进行 IL-1β-511T 基因rs16944 位点分型,比较该 SNP 基因型和等位基因频率的差异。结果 与对照组相比,病例组rs16944 多态性的基因型和等位基因频率差异均无统计学意义（P>0.05）;rs16944 多态性3 种基因型 A/A、A/G、G/G 的FS 患儿的临床特征比较,显示首次惊厥的年龄（χ2=19.491,Pχ2=9.317,Pχ2=26.798,P结论 IL-1β-511T 基因 rs16944 多态性与北方汉族儿童单纯FS 的发病无关联,但其基因型不同可能与患儿FS 的发生及预后有关。     

逆转录-PCR-变性梯度凝胶电泳法检测葡萄糖-6-磷酸脱氢酶基因缺陷女性携带者

目的：探讨应用逆转录-PCR-变性梯度凝胶电泳法(RT-PCR-DGGE)对葡萄糖-6-磷酸脱氢酶(G6PD)基因缺陷女性携带者人群进行分子诊断的可行性。方法：对54例G6PD基因缺陷可疑携带女性的血液标本,应用外周血提取总RNA并逆转录成cDNA;针对已报道的中国人群17种突变位点,以cDNA为模版,分段设计6对DGGE引物,PCR扩增、DGGE筛查分型,必要时进行测序验证。结果：54例可疑标本共检出1例1024C/T、20例1376G/T、12例1388G/A ,共检出杂合突变标本33例,总检出率为61.1%。结论： RT-PCR-DGGE对G6PD基因缺陷女性携带者人群具有较高的检出率,具有临床诊断意义。［中国当代儿科杂志,2009,11（8）：613-616］     

TNF-α-308G/A和IL-6-174G/C基因多态性与呼吸道合胞病毒毛细支气管炎的相关性

目的：探讨肿瘤坏死因子(TNF)-α-308G/A、白细胞介素(IL)-6-174G/C基因多态性与呼吸道合胞病毒((RSV) 毛细支气管炎易感性的关系。方法：应用聚合酶链反应 限制性酶切片段长度多态性技术（PCR-RFLP）检测150例RSV毛细支气管炎患儿(病例组)和120例正常对照儿童(对照组)TNF-α-308G/A和IL-6-174G/C的基因多态性。结果：①病例组TNF-α-308位点GG、GA、AA基因型频率分别为68.0%、28.0%、4.0%,G、A等位基因型频率分别为82.0%,18.0%;对照组TNF-α-308位点GG,GA,AA基因型频率分别为80.8%,19.2%,0,G、A等位基因型频率分别为90.4%,9.6%;两组基因型及等位基因频率差异有显著性意义,病例组A等位基因的频率明显高于对照组(χ2=5.665,7.726,均P＜0.05);与G等位基因携带者相比,A等位基因携带者患RSV毛细支气管炎的风险增加了2.071倍(OR=2.071, P＜0.05);②病例组和对照组IL-6-174G/C位点均只见GG基因型。结论：TNF-α-308A等位基因与RSV毛细支气管炎的易感性相关,其可能是影响RSV毛细支气管炎发病的一个重要候选基因;温州地区汉族儿童未发现IL-6-174G/C基因多态性。［中国当代儿科杂志,2009,11（10）：821-824］     

ALOX5启动子区基因多态性与儿童哮喘易感性及白三烯受体拮抗剂药效关系研究

目的观察ALOX5启动子区-1708 SNP及位于-176/-147的Sp1/Egr1结合位点重复序列多态性与儿童哮喘易感性、临床特征及白三烯受体拮抗剂(LTRA)药效的关系。方法选取2016年10月至2018年1月沈阳军区总医院儿科243例哮喘患儿为病例组,以同期体检的228例非哮喘儿童为对照组,应用聚合酶链反应(PCRs)、测序法对纳入对象ALOX5-1708及Sp1/Egr1结合位点基因分型,收集各项临床资料并予抗哮喘治疗,分析基因多态性与临床特征及LTRA药效关系。结果 (1)病例组Sp1/Egr1结合位点重复序列非5/5基因型频率明显高于对照组(OR=1.485,95%CI=1.018-2.167,χ2=4.225,P=0.040)。(2)中重度组G/A+A/A型及G/A型频率均高于轻度组(χ2=4.832、4.565,P=0.028、0.033),中重度组4/6型频率低于5/5型,而5/6型频率则高于5/5型(χ2=3.643、3.888,P=0.056、0.049)。结论 ALOX5 Sp1/Egr1结合位点重复序列多态性可能与儿童哮喘发病及严重程度、过敏及其家族史、LTRA效果有关;ALOX5-1708位点多态性可能与哮喘严重程度、肺功能指标及LTRA效果有关。     

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目的研究T细胞免疫球蛋白域黏蛋白域蛋白-1(TIM-1)启动子-1454G/A基因多态性与儿童过敏性紫癜(HSP)的相关性,探讨HSP的遗传易感因素。方法2008年3月至2009年2月安徽医科大学第一附属医院、安徽省立儿童医院住院HSP患儿143例,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析、基因测序等技术测定HSP患儿和178名正常儿童(对照组)的TIM-1基因多态性,计算基因型和等位基因频率,比较各组间关系。结果HSP组基因型及等位基因频率与对照组比较差异无统计学意义(P>0.05),但63例伴肾脏损害者即紫癜性肾炎(HSPN)组与80例不伴肾脏受累组-1454G/A3个基因型间比较差异有统计学意义(P<0.05),且HSPN患儿携带-1454G等位基因频率增高(OR2.375,95%CI1.168～4.830,P<0.05)。结论TIM-1基因启动子-1454G/A基因多态性可能与HSP易感性无关联,但携带-1454G等位基因的患儿出现HSPN风险增高,提示TIM-1基因多态性可能在决定HSP患儿肾脏受累遗传易感性方面有重要作用。     

T细胞免疫球蛋白域黏蛋白域蛋白-1-1454位点基因多态性与儿童过敏性紫癜的关系研究

目的研究T细胞免疫球蛋白域黏蛋白域蛋白-1(TIM-1)启动子-1454G/A基因多态性与儿童过敏性紫癜(HSP)的相关性,探讨HSP的遗传易感因素。方法2008年3月至2009年2月安徽医科大学第一附属医院、安徽省立儿童医院住院HSP患儿143例,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析、基因测序等技术测定HSP患儿和178名正常儿童(对照组)的TIM-1基因多态性,计算基因型和等位基因频率,比较各组间关系。结果HSP组基因型及等位基因频率与对照组比较差异无统计学意义(P0.05),但63例伴肾脏损害者即紫癜性肾炎(HSPN)组与80例不伴肾脏受累组-1454G/A3个基因型间比较差异有统计学意义(P0.05),且HSPN患儿携带-1454G等位基因频率增高(OR2.375,95%CI1.168～4.830,P0.05)。结论TIM-1基因启动子-1454G/A基因多态性可能与HSP易感性无关联,但携带-1454G等位基因的患儿出现HSPN风险增高,提示TIM-1基因多态性可能在决定HSP患儿肾脏受累遗传易感性方面有重要作用。     

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.     

Resurgence of measles in Singapore: profile of hospital cases

OBJECTIVE: To ascertain the profile of cases of measles seen at a general hospital during a recent outbreak that occurred despite a measles vaccination program. METHODOLOGY: A retrospective study from January 1991 to March 1998. All patients with measles (ICD code 055. 9) seen at the emergency unit or as inpatients were included. RESULTS: There were 87 cases identified. The diagnosis was clinical in all and proven serologically in 71%. Eighty-five per cent of the cases occurred between January 1997 and March 1998. There was a bi-modal age distribution with peaks in the very young (相似文献   

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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     

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.     

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.     

A profile of respiratory symptoms in urban and rural South Australian school children

This report describes the cross-sectional analyses of data from the first year of a longitudinal study using questionnaire and respiratory function data over a 5 year period from a sample of rural South Australian school children. The cumulative or lifetime prevalences of respiratory symptoms were estimated in 825 rural and 1261 urban school children aged between 5 and 15 years in order to determine if the prevalence rates differed between rural and urban school children. The study found the overall cumulative prevalence of asthma and/or wheezy breathing (AWB) to be 24.1% in the rural school children compared to 27.6% in the urban school children. Most children developed AWB symptoms before the age of 7 years, with 20% reporting moderately severe symptoms and 10% having more than one attack per fortnight. The cumulative prevalence of bronchitis, loose/rattly cough (BLRC) differed significantly between the rural school children (34.1%) and urban school children (47.9%). The BLRC symptoms preceded the development of AWB in many cases. Urban school children also reported a higher prevalence of atopic conditions.     

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.     

Hauttemperaturen verschiedener Körperoberflächenareale des Rumpfes bei Säuglingen

Summary In two groups of infants (3–53 weeks old) skin temperatures were controlled in different areas of the trunk—i.e.: regions of sternum, lungs, heart, liver, spleen, kidneys—at different room-temperatures (group I: 21–25°C; group II: 29–32°C). Rectal temperatures of some probands in both groups also had been controlled simultaneously. A definite change in the reaction to heat was proofed in different periods of the first year of life. In higher environmental temperatures the skin temperature was almost constant at every controll-point of the skin, even in older infants. In lower environmental temperatures the skin temperatures lowered continuously with age till 7. to 9. moth. From 10. to 12. month the lowering of skin temperature discontinued. The rectal temperatures were relatively constant in all infants. Only in infants from 7. to 12. month, whose skin temperatures were controlled in lower as well as in higher environmental temperatures, a tendency to higher rectal temperatures was proofed in warmer environmental temperatures.The significance of these results is discussed.

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Untersuchungen mit Unterstützung durch die Deutsche Forschungsgemeinschaft.