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??Periodic fever-aphthous stomatitis-pharyngitis-adenitis??PFAPA?? syndrome is the most frequent cause of recurrent fevers in childhood and presents with the cardinal symptoms of periodic fever??aphthous stomatitis??pharyngitis??and adenitis typically before 5 years old. The pathogenesis of PFAPA is still unknown and theories about the pathogenesis of PFAPA include faulty innate immunologic response with dysregulated T-cell activation. The potential hereditary nature of PFAPA is still disputed and the Mediterranean fever??MEFV?? gene mutation??implicated in familial Mediterranean fever??FMF????has a possible association with PFAPA. It appears to modify disease severity. Diagnostic criteria include the traditional clinical signs??as well as the following biomarkers??elevated C-reactive protein??vitamin D??CD64??C-X-C motif ligand 10??CXCL10?? and other nonspecific inflammatory mediators. Because PFAPA is self-limited and benign??there is no certain treatment model. Treatment for PFAPA includes a single dose of corticosteroids??tonsillectomy??and most recently??interleukin 1 inhibitors. Treatment options must be specific to the patient. More large cohort studies are needed to explore the inhereditary nature and specific biomarkers of PFAPA??to standardize the diagnosis and treatment process in order to improve the life quality of the children.     

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??Abstract?? Objective To accumulate knowledge of methylmalonic acidemia ??MMA?? screening by studying the clinical characteristics and laboratory characteristics of the disease. Methods The clinical manifestations and the results of laboratory tests of 95 cases of MMA were analyzed. Results The age of onset was from 1 day to 12 years. Six cases had the episodes of vomiting?? lethargy in 14 cases and recurrent difficulty with feeding in 4 cases?? seizures in 24 cases?? mental retardation and movement disorders in 18 cases?? dysarthria in 3 cases?? debilitation and BLE edemas in 10 cases?? jaundice in 7 cases?? complaints of precordium in 6 cases?? anaemia in 3 cases. The laboratory tests showed that the counts of white blood cells??WBC??were increased in 26 cases and the counts of red blood cells ??RBC??were decreased in 26 cases. The results of urine routine tests were abnormal in 37 cases. The results of renal function tests were abnormal in 18 cases. The results of hepatic function tests were abnormal in 17 cases. The results of myocardial enzyme were abnormal in 40 cases. The results of blood gas test were abnormal in 11 cases. The levels of glucose were decreased in 6 cases. The levels of lactic acid were increased in 62 cases. The levels of blood ammonia were increased in 50 cases. Remarkable elevation of urinary methymalonic concentration was confirmed in 97% patients by gas chromatography -mass spectrometry ??GC-MS??. Remarkable elevation of C3?? C3/C0 and C3/C2 concentrations was confirmed in 89% patients by liquid chromatography-tandem mass spectrometry ??LC-MS/MS??. Conclusion The main clinical features of MMA include lethargy?? seizure?? vomiting??developmental retardation or regradation?? hyperarmnonemia and hyperlactacidemia. Urine organic acids analysis by GS-MS and dry blood spots ??amino acids and acylcarnitine?? analysis by LC-MS/MS are very important to the diagnosis of MMA.     

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??Autism spectrum disorder??ASD??is a severe neurodevelopmental disease. At the present time, approved and recommended treatments for ASD are mainly based on rehabilitation and educational interventions. ASD is defined by core behavioural impairments, but gastrointestinal??GI?? symptoms are commonly reported. And the GI symptoms are considered to relate to the dysbiosis of gut microbiota and a disorder of the microbiota-gut-brain axis. The alterations of epithelial integrity, immune function and neurotransmitter lead to GI symptoms and autistic behaviors associated with dysbiosis of the gut microbiota. Probiotics can be useful to restore the microbiota balance in the intestine??to alleviate GI symptoms and ameliorate behavioural symptoms associated with some ASD. Although further research and rigorous clinical trial should be required to study the effect and mechanism of probiotics in the treatment of ASD??they can be considered potential effect on ASD.     

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??Adrenal insufficiency??AI?? is an uncommon clinical disorder that arises from an inadequate basal or stress level of plasma cortisol. The clinical findings of primary adrenal insufficiency??PAI?? are associated with deficient synthesis or release of glucocorticoids and frequent deficiency of mineralocorticoids. The presentation of adrenal insufficiency may be insidious and difficult to recognize??so it is important to diagnose adrenal insufficiency properly??for an unrecognized or untreated disorder sometimes might be fatal. Once suspected??the exact underlying diagnosis needs to be confirmed by a stepwise diagnostic approach??with an open eye for other differential diagnostic possibilities. The definite diagnosis should be supported by laboratory evaluation on the function of adrenocortical and HPA axis.     

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目的探讨中枢神经系统感染患儿脑脊液中胰岛素样生长因子(IGFs)的变化及意义。方法选择2001年2月至2003年6月在新乡医学院一附院治疗的化脓性脑膜炎患儿30例、病毒性脑炎30例,以非中枢神经系统疾病、非感染性疾病的患儿30例作对照组。脑脊液中胰岛素样生长因子Ⅰ(IGFⅠ)用放射免疫分析法检测,脑脊液中胰岛素样生长因子Ⅱ(IGFⅡ)用免疫放射分析法检测。结果(1)化脓性脑膜炎患儿脑脊液中IGFⅠ、IGFⅡ质量浓度均显著高于病毒性脑炎组及对照组(P<0.01);(2)化脓性脑膜炎患儿脑脊液中IGFⅡ的质量浓度与蛋白质浓度呈正相关(r=0.821,P<0.05),与葡萄糖浓度呈负相关(r=-0.742,P<0.01);(3)化脓性脑膜炎患儿脑脊液中IGFⅠ的质量浓度与蛋白质浓度呈正相关(r=0.862,P<0.01)。结论IGFs参与了化脓性脑膜炎的病理生理过程,并参与了脑脊液中葡萄糖和蛋白质的代谢。脑脊液中IGFⅠ、IGFⅡ的浓度可作为鉴别化脓性脑膜炎和病毒性脑炎的一项辅助指标。     

小儿哮喘及肺炎血浆白介素-18、-16、-4及IFN-γ水平的相关性研究及临床意义

目的探讨哮喘及肺炎患儿血浆白介素-18、-16、-4及IFNγ-水平的相关性及临床意义。方法哮喘患儿22例,肺炎患儿24例(重症组13例,普通组11例)。采用双抗体夹心酶联免疫吸附实验(SELISA)测定其血浆IL-18、IL-16、IL-4、IFNγ-水平。结果(1)哮喘组急性期血浆中IL-16低于非发作期(P<0.05)及对照组(P<0.01),非发作期高于对照组(P<0.01)。非发作期IL-4低于急性期及对照组(P<0.05)。血浆IL-18、IFNγ-无明显改变。急性期IL-18、IL-16、IL-4、IFNγ-水平存在相关性(P<0.01),IL-4与IFNγ-存在相关性(P<0.05)。(2)肺炎组急性期IL-18显著升高,重症组IL-18显著高于普通组(P<0.05)。重症组IL-16显著高于对照组(P<0.05)。各组间IL-4及IFNγ-无统计学差异(P>0.05)。急性期IL-18与IL-16、IL-4、IFNγ-之间存在高度相关性(P<0.01)。IL-16与IFNγ-存在相关性(P<0.05)。结论IL-18、IL-16、IL-4、IFNγ-参与了小儿哮喘和肺炎免疫病理过程。     

红-9-(2-羟基-3-壬基)腺嘌呤对低氧性肺动脉高压大鼠肺动脉压力和内源性腺苷的影响

目的 观察红-9-(2-羟基-3-壬基)腺嘌呤(EHNA)对低氧性肺动脉高压(HPH)大鼠肺动脉压力和内源性腺苷水平的影响,了解HPH与内源性腺苷水平的关系.方法　24只SD大鼠随机分为常氧组、低氧组和低氧+EHNA组,每组8只.低氧组和低氧+EHNA组大鼠每天置于含氧体积分数为(100±5) mL·L-1、二氧化碳体积分数<1 mL·L-1的大型玻璃箱中,在缺氧3 d后分别腹腔注射等量9 g·L-1盐水和EHNA(30 mg·kg-1·d-1)连续4 d.常氧组大鼠在自然空气条件下饲养.于实验第8天将大鼠麻醉,右颈外静脉插管,利用四道生理记录仪测定每只大鼠的平均肺动脉压(mPAP);完成压力测量后,左心室取血,采用高效液相色谱仪检测其血浆中腺苷水平.结果 低氧组mPAP水平[(16.50±2.43) mmHg,1 mmHg=0.133 kPa]及内源性腺苷水平[(24.75±3.08) mg·L-1]均显著高于常氧组[(11.25±1.75) mmHg,(11.50±2.05) mg·L-1](Pa＜0.01);低氧+EHNA组内源性腺苷水平[(8.58±1.90) mg·L-1]低于低氧组,而mPAP[(19.64±3.44) mmHg]显著高于低氧组(Pa＜0.01).结论　EHNA导致HPH大鼠肺动脉压力进一步升高,可能与其降低血浆内源性腺苷水平有关.     

Oculo-facio-cardio-dental syndrome caused by BCOR gene mutations: a case report北大核心CSCD

患儿女,足月儿,生后5h,因胎儿期发现心脏畸形,生后发绀1次入院。检查发现存在眼、面部、四肢、心脏多发畸形,全外显子基因检测显示BCOR基因存在致病性杂合突变c.2428C>T(p.Arg810^(*)),该患儿诊断为眼-面-心-牙综合征。住院期间予以辅助通气改善氧合、营养支持等治疗,生后1个月于外院行右室双出口矫治术,眼部病变于眼科随诊择期手术治疗。对于存在眼、面部、心脏多发畸形的新生儿应注意眼-面-心-牙综合征可能,需尽早完善基因检测明确诊断,同时积极给予眼及心血管方面的对症治疗,有助于改善患儿预后。     

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目的 研究白三烯D4是否参与调节支气管上皮细胞表达嗜酸性粒细胞趋化因子-3(eotaxin-3,Eot-3),探讨白三烯和支气管上皮细胞在气道变态反应性炎症中的作用.方法 用白三烯D4预处理支气管上皮细胞1h,然后用白细胞介素-4(IL-4)刺激细胞24h,RT-PCR法检测Eot-3在mRNA水平的表达;ELISA法检测细胞培养上清液中Eot-3蛋白的表达.结果 未经处理的支气管上皮细胞仅表达微量的Eot-3,用IL-4刺激细胞并培养24h后,在mRAN和蛋白水平的Eot-3表达明显增强,白三烯D4预处理细胞1h,可以使IL-4的这种诱导作用加强.结论 支气管上皮细胞不仅是一种屏障细胞,也是一种效应细胞,在炎症介质的刺激下能表达Eot-3,参与支气管炎症的产生.白三烯D4通过上调IL-4诱导Eot-3在上皮细胞的表达可能是其参与支气管哮喘嗜酸性粒细胞炎症的机制之一.     

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目的探讨6月龄内健康男婴睾酮、黄体生成素(LH)与促卵泡生成素(FSH)的血清浓度变化及意义。方法收集2010年4月至2011年10月重庆医科大学附属儿童医院6月龄内健康足月分娩男婴336名的血清标本,采用免疫化学发光法测定其睾酮、LH及FSH的浓度。结果睾酮于生后<1d达第一个高峰[(28.45±11.92)nmol/L];于10～<50d达第二个高峰[(8.41±3.83)nmol/L],峰值较第一个低,随后下降,4～6个月降至(0.48±0.45)nmol/L。LH、FSH于生后数月内均有短暂升高,以LH升高为主。LH、FSH在生后数天内保持在一个低浓度,随后开始升高,于10～<50d达高峰,之后下降,于4～6个月LH浓度降至(0.43±0.47)U/L,FSH浓度降至(0.48±0.51)U/L。结论男婴生后6个月内血清睾酮及促性腺激素浓度均有短暂升高,对男婴性腺发育有重要作用。     

哮喘患儿血浆白细胞介素-17、-10、-4及干扰素-γ的相关性及其临床意义

目的探讨哮喘患儿血浆IL17、IL10、IL4及IFNγ水平的相关性及其临床意义。方法哮喘患儿22例,正常对照20例。采用双抗体夹心酶联免疫吸附试验(SELISA)检测其血浆IL17、IL10、IL4及IFNγ水平。结果1.哮喘患儿急性期、缓解期血浆IL17均显著低于对照组(P均<0.01);而缓解期血浆IL17明显低于急性期(P<0.05)。2.哮喘患儿急性期血浆IL10显著高于缓解期及对照组(P均<0.01);缓解期与对照组比较无显著差异。3.哮喘患儿缓解期血浆IL4明显低于急性期及对照组(P均<0.05);急性期与对照组之间无显著差异。4.与对照组比较,哮喘患儿血浆IFNγ无明显改变。5.哮喘患儿急性期血浆中IL17、IL10、IL4、IFNγ水平之间均存在显著正相关(P均<0.01)。结论哮喘患儿T细胞因子水平的改变具有特殊性。糖皮质激素对IL17、IL10、IL4的分泌可能具有抑制作用。     

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目的研究肺炎支原体肺炎(MPP)患儿血清及诱导痰中白细胞介素-4(IL-4)及γ-干扰素(IFN-γ)质量浓度变化,探讨其在MPP发病机制中的作用。方法2003年2~8月对中国医科大学附属二院儿科住院的MPP患儿38例,用ELISA法测定38例血清及24例诱导痰中急性期及恢复期的IL-4及IFN-γ质量浓度。结果MPP患儿血清及诱导痰IL-4质量浓度急性期明显高于恢复期和正常对照组(P<0·01);IL-4/IFN-γ比值急性期高于恢复期和正常对照组(P<0·05)。MPP患儿急性期血清及诱导痰IL-4质量浓度重症组明显高于轻症组(P<0·01),急性期血清及诱导痰IL-4/IFN-γ比值重症组高于轻症组(P<0·05);诱导痰与血清两种标本检测结果一致,诱导痰中的质量浓度高于血清中的质量浓度,两者呈正相关。结论MPP患儿存在TH1/TH2功能紊乱,MPP患儿TH2反应占优势,IL-4及IFN-γ参与MPP患儿的免疫状态改变,在MPP发病机制中发挥一定作用。     

布地奈德对哮喘大鼠内源性H2S、CSE、CBS 体系的调节机制

目的：观察布地奈德对哮喘大鼠血浆硫化氢（H2S）含量和胱硫醚-γ-裂解酶（CSE）、胱硫醚-β-合成酶(CBS) mRNA的表达,探讨内源性H2S、CSE、CBS体系在哮喘发病机制中的作用。方法：Sprague-Dawley大鼠30只随机分成对照组、哮喘组、布地奈德组,每组10只。用鸡卵白蛋白（OVA）致敏与激发建立大鼠哮喘模型。分光光度法测定血浆H2S的含量,RT-PCR 法测定肺组织CSE、CBS mRNA的表达水平。结果：哮喘组血浆H2S的含量（61±16 μmol/L）显著低于对照组（84±15 μmol/L）（P0.05）。哮喘组肺组织CSE mRNA和CBS mRNA的表达水平显著低于对照组（P<0.01）,布地奈德组CSE mRNA和CBS mRNA表达显著低于对照组但高于哮喘组（均P<0.01）。相关性分析结果显示血浆H2S含量和支气管肺泡灌洗液(BALF)中炎症细胞总数表达呈显著负相关(n=30, r=-0.549,P<0.01)。结论：哮喘大鼠H2S、CSE、CBS的表达下降,它们的表达下降可能促进了炎症细胞在气道中的聚集,布地奈德改善哮喘炎症的机制可能部分通过内源性H2S、CSE、CBS体系起作用。［中国当代儿科杂志,2010,12（8）：654-657］     

儿童周期性发热-阿弗他口炎-咽炎-淋巴结炎综合征13例临床特点分析

目的 周期性发热-阿弗他口炎-咽炎-淋巴结炎（PFAPA）综合征是一种发病机制不明的多基因多因素自身炎症性疾病。该研究旨在分析儿童PFAPA综合征的临床特点。方法 回顾性分析13例PFAPA综合征患儿的临床资料。结果 13例均在3岁内起病,平均发病年龄（14±10）个月。13例均有周期性发热表现,年发作次数8~18次。发热间歇期平均（30±5）d。三大主要症状,即咽炎、颈淋巴结炎和阿弗他口炎的发生率分别为100%（13例）、85%（11例）和38%（5例）。发热期均伴白细胞、C反应蛋白、红细胞沉降率等炎性指标升高。13例中6例行医学全外显子基因测序,7例行自身炎症性疾病panel基因检测,6例（46%）检测出MEFV基因杂合突变。所有患儿的反复发热在不使用抗生素的情况下可逐渐退至正常。使用单剂量糖皮质激素治疗10例,治疗后当次发热均迅速缓解。使用西咪替丁治疗4例,2例有效。使用秋水仙碱4例,2例有效;2例因不良反应停用。扁桃体切除2例,1例已随访3年,无再次发作;1例仍有反复发作。结论 对于年幼起病的不明原因周期性发热伴咽炎、颈淋巴结炎和阿弗他口炎,伴有炎性指标升高,且对激素反应良好的患儿,临床医师应警惕PFAPA综合征;PFAPA综合征预后良好;早期诊断可避免患儿反复使用抗生素。     

迟发型3-羟基-3-甲基戊二酸尿症导致脑白质病

3-羟基-3-甲基戊二酸尿症是一种罕见的有机酸代谢病,病因为常染色体隐性遗传所导致的3-羟基-3-甲基戊二酰辅酶A裂解酶缺陷。患者通常在新生儿期至婴幼儿期发病。本研究报告1例晚发型3-羟基3-甲基戊二酸尿症导致的脑白质病。患儿为7岁男孩,急性起病,表现为头痛、困倦、呕吐, 进行性加重,一般化验发现肝损害、酮症、白细胞减少,脑磁共振扫描示双侧脑白质对称弥漫性病变。血液羟异戊酰肉碱、乙酰肉碱显著增高。尿液3-羟基-3-甲基戊二酸显著增高,3-甲基戊烯二酸、3-羟基戊二酸、甲基巴豆酰甘氨酸增高。经静脉滴注葡萄糖和左旋肉碱症状缓解。维持治疗半年后复诊,尿3-羟基3-甲基戊二酸降低,全身情况良好。     

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??Autoinflammatory syndromes are conditions caused by mutations of proteins??playing a important role in the regulation of the innate immunity??which leads to an uncontrolled inflammation. The understanding of the molecular mechanisms in these disorders discloses new molecular therapeutic targets. The good response to anti IL-1 drugs in cryopyrin-associated periodic syndromes??CAPS?? is the brightest example of the possibility to dampen inflammation with the blockade of a single cytokine??and IL-1 blockers have been used in the treatments of systemic juvenile idiopathic arthritis??sJIA????tumor necrosis factor??TNF?? receptor-associated periodic syndrome??TRAPS?? and familial Mediterranean fever??FMF??. Anti-TNF are needed in the control of long-term fever in TNF receptor-associated periodic syndrome??and anti-TNF agents are also useful in FMF with AA amyloidosis. Anti-TNF agents are the most common treatment for Blau syndrome??which relieve the joint symptoms. Many studies have demonstrated significant efficacy of anti IL-6 drugs in patients with sJIA. Due to their extreme rarity??there are few case reports on the response to anti IL-6 drugs in other autoinflammatory diseases.     

过敏性紫癜患儿血浆白细胞介素-17、-10、-4 及干扰素-γ水平的临床意义

目的 探讨过敏性紫癜(HSP)患儿血浆白介素(IL)-17、IL-10、IL-4及干扰素-γ(IFN-γ)水平的相关性及其临床意义。方法 HSP患儿21例,正常对照组20例。采用双抗体夹心酶联免疫吸附试验(SELISA)检测其血浆IL-17、IL-10、IL-4、IFN-γ水平。结果 1.HSP患儿急性期及缓解期血浆IL-17均明显下降(P<0.01,<0.05),急性期及缓解期比较无显著差异.2.HSP患儿急性期血浆IL-10水平显著升高(P<0.01),急性期及缓解期间无差异。3.HSP患儿血浆IFN-γ无明显改变(P>0 05)。4.HSP患儿急性期及缓解期血浆IL-4略升高,但无差异(P>0.05)。5.HSP患儿急性期血浆中IL-17、IL-10、IL-4、IFN-γ水平均存在显著相关性。结论HSP患儿血浆中存在T细胞因子分泌紊乱,且这种紊乱可能是HSP患儿发病的分子生物学基础。T细胞因子在HSP全身血管炎发生、发展中起作用。IL-10可能具有一定的保护作用。     

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??Objective??To investigate the correlations between plasma monocyte /macrophage chemoattractant protein and related parameters of insulin resisitance in children with simple obesity. Methods??70 children with simple obesity were enrolled as study group??30 healthy children as control group. Body mass index??BMI ??and waist circumference ??WC??were detected as indices of obesity .Plasma levels of macrophage inflammatory protein-1????MIP-1??????monocyte chemoattractant protein-1??MCP-1 ??were measured by ELISA.The rate of CD68 positive cells in blood were detected by flow cytometry??FCM???? Plasma levels of insulin ??adiponectin were measured by RIA?? Insulin resisitance index ??InRI?? were caculated by homeostasis model assessment of insulin resistance ??HOMA-IR??. The associations between MIP-1????MCP-1 levels and adiponectin and related parameters were analyzed with Pearson correlation analysis or partial correlation analysis??Results??The concentration of MIP-1?? and MCP-1 in plasma in children with simple obesity were higher than that in control group. There was a significant difference between the two groups ??P < 0. 05??. The rate of CD68 positive cells in blood of simple obesity had no significant difference between that in control group ??P > 0.05??.The concentration of MIP-1?? and MCP-1 in plasma had positive correlations with BMI and WC and InRI??P < 0. 05??. The concentration of adiponectin in plasma had negetive correlations with BMI and WC and InRI ??P < 0. 05??. The rate of CD68+ cell in blood had no correlation with BMI and WC and InRI??P < 0. 05??.Conclusion??We found that a differential low-grade inflammation is associated with obesity of children .The levels of MIP-1????MCP-1 in blood of obesity were associated with insulin resistance and abdominal obesity. The levels of plasma MIP-1????MCP-1??adiponectin may predict the onset of obesity related complications.     

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??Congenital adrenal hyperplasia??CAH??is mainly caused by 21-hydroxylase deficiency??21-OHD??. Nationwide neonatal screening for CAH caused by 21-OHD in China is based on measurement of 17-hydroxyprogesterone ??17-OHP?? levels from heel-stick blood samples on filter paper. The situation and methods of neonatal screening??confirmed diagnosis and therapeutic rule for CAH in China and other countries are described for the standardization of screening.