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目的观察1型糖尿病患儿血管内皮损害标志物—内皮素(ET)和血管性假血友病因子(von Wille-brand因子,vWF)的变化,分析其与尿白蛋白排泄率(UAER)的关系,从而筛查出更敏感的早期诊断糖尿病肾病(DN)的指标。方法收集1998-06—2005-06在山东省立医院就诊的4~18岁1型糖尿病患儿40例,根据UAER分为正常白蛋白尿组(A组)25例和微量白蛋白尿组(B组)15例,同时以年龄、性别、身高1∶1匹配的健康儿童作为对照组,分别检测其血糖(FBG)、糖化血红蛋白(HbA1c)、血浆ET和vWF的变化,并分析其相关性。结果与正常对照组比较,1型糖尿病患者血浆ET-1和vWF、HbA1c明显增高,尤其是微量白蛋白尿组升高更明显(均P<0·01),血浆ET-1和vWF与UAER、HbA1c均呈正相关。结论1型糖尿病患儿在出现白蛋白尿前已存在血管内皮功能异常,其白蛋白排泄与血管内皮功能障碍程度有一定相关性。血浆ET-1、vWF检测可作为早期筛查糖尿病肾病的可靠指标。     

关注甲型H1N1流感

2009年3月在墨西哥出现一种新型流感病毒,因这种新型流感病毒与北美猪流感病毒基因节段极其相似,曾被称为"猪流感",后由世界卫生组织、联合国粮农组织和世界动物卫生组织将其更名为2009 A(H1N1)流感,我国相应命名为甲型H1N1流感.这次疫情可谓"来势汹汹",在不到1个月的时间内迅速蔓延到全球,其传播速度之快前所未有.     

甲型H1N1流感的研究进展

甲型H1N1流感病毒是人流感病毒基因、禽流感病毒基因和猪流感病毒基因混合的重配株,其造成的疫情来势凶猛,引起世界各国的广泛关注.为了早发现、早诊断、早治疗及有效地预防甲型H1N1流感,本文综述了甲型H1N1流感病毒的特点、流行病学、致人发病的机制、甲型H1N1流感患者的临床表现、实验室检查及有效的治疗和预防措施.     

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??Objective??To describe the clinical characteristics of neurologic complications associated with 2009 influenza A ??H1N1?? infection in children. Methods??A prospective study of 150 children confirmed 2009 influenza A ??H1N1?? infection in Shenzhen Children Hospital from November 4, 2009, to January 19, 2010 was conducted. The clinical features and outcome of the patients with neurologic complications were analyzed. Results??The incidence rate of neurologic complications associated with 2009 influenza A ??H1N1?? infection was 14% of the hospitalized patients. 18??85.7%?? patients were diagnosed as encephalopathy??2??9.5%?? patients were diagnosed as seizures??1??4.7%?? patient was diagnosed as encephalitis. 14 were male, 7 were female?? the median age was 5 years. 12??57%?? patients were admitted to an ICU, 6??28.5%?? required mechanical ntilation. 17??80.9%?? patients were fully recovered and discharged, three ??14%?? died from severe encephalopathy. Conclusion??The incidence rate of neurologic complications associated with 2009 influenza was high, severe encephalopathy canlead to death. This result should attract a great deal of attention as 2009 influenza A ??H1N1?? pandemic continues.     

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目的探讨甲型H1N1流感患儿的临床特点及治疗。方法对2009-11-04—2009-12-24桂林市人民医院收治的12例甲型H1N1流感重症患儿的临床资料进行回顾性分析。结果12例患儿均有发热,其中10例以呼吸道症状起病,如咽痛、咳嗽、咳痰等流感样症状;1例以消化系统症状(腹泻)起病;1例以神经系统症状起病;2例伴明显喘憋、呼吸困难;3例双肺闻及痰鸣音、湿啰音,2例闻及喘鸣音。12例患儿白细胞计数增高4例,降低3例;中性粒细胞比例增高4例,降低4例;淋巴细胞比例增高4例,降低2例;血小板计数降低1例,增高1例。6例丙氨酸转移酶(ALT)增高,7例天冬氨酸转移酶(AST)增高,7例乳酸脱氢酶(LDH)增高,7例肌酸激酶(CK)增高,3例肌酸激酶同工酶(CK-MB)增高。随着患儿病情好转,白细胞、肝功、心肌酶恢复正常。结论甲型H1N1流感重症患儿多以呼吸道症状发病,主要靶器官是肺,常合并细菌、支原体感染,出现各种并发症累及多脏器功能。以神经系统症状起病患儿进展迅速、病情凶险。     

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目的通过观察3例儿童2009年新型甲型H1N1流感病毒急性坏死性脑病(ANE)脑组织病理性改变,探讨ANE脑组织可能的免疫病理反应。方法对2009年11月至2010年1月深圳儿童医院3例因ANE死亡患儿脑组织行HE染色形态学观察、髓鞘染色、小胶质细胞石蜡切片染色及免疫组织化学EliVision法检测分析。结果 ANE患儿脑组织小胶质细胞棘突消失变为圆形,髓鞘染色证实脑实质神经纤维呈脱髓鞘改变,经Naomenke及Feigin染色法证实小胶质细胞处于激活状态,免疫组化发现ANE患儿小胶质细胞产生TNF-α和IFN-α,脑组织未见淋巴细胞、中性粒细胞浸润。结论小胶质细胞异常增生可能是导致ANE发病的原因之一。     

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目的探讨葡萄糖醛酸转移酶1A1(UGT1A1)基因G71R突变、葡萄糖-6-磷酸脱氢酶(G6PD)缺陷对新生儿生后前3d胆红素浓度的影响.方法测定81例新生儿脐血的G6PD活性及G71R基因型,分组比较生后前3d光疗前胆红素值的组间差异.用等位基因特异性寡核苷酸探针点杂交法(ASO)确定G71R基因型.结果在G71R野生型新生儿中,G6PD缺乏组与G6PD正常组相比,生后前3d胆红素值间无统计学差异.G6PD正常新生儿中,G71R突变纯合子或杂合子的新生儿生后前3d胆红素浓度与G71R正常野生型新生儿相比无统计学差异.G6PD缺陷新生儿中,同时合并有G71R突变纯合子或杂合子的新生儿组生后第2天、第3天胆红素浓度高于G71R正常野生型新生儿组.结论G6PD缺乏与G71R基因突变并存加重新生儿黄疸程度.     

儿童甲型H1N1流感临床特点

<正>甲型H1N1流感是由流感病毒H1N1亚型引起的急性呼吸道传染病。其临床特点与流感病毒的亚型及其变异有关,也与人体的免疫状况和当时的流行情况有关。2009年3月北美发生猪流感,世界卫生组织于2009-04-30宣布不再使用猪流感一词,开始使用甲型H1N1流感。它具有起病急、传染性强、流行广泛、传播迅速的特点。儿童感     

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目的探讨甲型H1N1流感患儿感染后细胞免疫功能的变化。方法回顾性分析2009年10月至2010年1月苏州大学附属儿童医院收治的86例甲型H1N1流感确诊病例(分成危重组和重症组)的临床资料;采用流式细胞仪检测患儿外周血T淋巴细胞、B淋巴细胞和NK细胞亚群比例。以23例外科住院患儿的淋巴细胞亚群作为对照组来观察甲型H1N1流感患儿的细胞免疫功能变化特征。结果 (1)CD3+、CD3+CD4+、CD3+CD8+亚群百分比:重症组和危重组较对照组明显降低,而该两组之间差异无统计学意义;(2)CD3-CD19+、CD19+CD23+亚群百分比统计结果示危重组>重症组>对照组,各组间比较有统计学意义(P<0.05);(3)CD3-CD16+CD56+亚群百分比在重症患儿和对照组之间差异无统计学意义,危重组较其他两组均有显著下降;(4)CD4+/CD8+比值在各组之间差异无统计学意义。结论甲型H1N1流感患儿感染后细胞免疫功能存在明显紊乱:T淋巴细胞受到全面抑制,B淋巴细胞激活参与病毒的清除,NK细胞比例的降低与危重患儿的病情相关。     

广西黑衣壮族高胆红素血症新生儿UGT1A1基因突变分析

目的 探讨广西黑衣壮族高胆红素血症新生儿尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）基因的突变分布特点及其与高胆红素血症的关系。方法 提取黑衣壮族高胆红素血症新生儿（病例组）及对照组新生儿血液基因组DNA各100例,对UGT1A1 启动子TATA盒及所有外显子进行PCR扩增及直接测序。结果 检测到UGT1A1 启动子TATA盒（TA）7插入突变、第1外显子G71R错义突变及第5外显子中4个SNP位点（rs199539868、rs114982090、rs1042640、rs8330）。病例组的G71R等位基因频率显著高于对照组（PP>0.05）。Logistic回归分析显示UGT1A1 TATA盒、G71R、rs1042640及rs8330对新生儿高胆红素血症发生的OR值（95%CI）分别为0.846（0.440,1629）、3.932（1.745,8.858）、0.899（0.364,2.222）。结论 UGT1A1基因（TA）7插入突变与G71R错义突变是广西黑衣壮族高胆红素血症新生儿的常见突变类型,4个SNP 位点（rs199539868、rs114982090、rs1042640、rs8330）为国内首次报道。UGT1A1 G71R错义突变是广西黑衣壮族新生儿高胆红素血症的危险因素。     

新生儿高未结合胆红素血症遗传因素的研究

目的：探讨尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）Gly71Arg、TATA盒基因突变和葡萄糖-6-磷酸脱氢酶（G6PD）基因突变与新生儿高未结合胆红素血症的关系。方法：UGT1A1 TATA盒、外显子1、外显子5和G6PD基因外显子12经PCR扩增和测序,构建突变样本的克隆,对其进行验证。分析病例组及对照组UGT1A1 Gly71Arg和TATA盒基因多态性频率的差异,应用logistic回归分析基因突变对新生儿高未结合胆红素血症发生的影响。结果：病例组UGT1A1 Gly71Arg基因多态性的基因型分布与对照组比较差异有统计学意义（P0.05）。Logistic回归分析显示UGT1A1 Gly71Arg、TATA盒基因和G6PD基因突变对新生儿高未结合胆红素血症发生的OR值（95％CI）分别为5.468（2.274,12.818）、0.688（0.266,1.778）和5.081（1.070,24.133）。结论：UGT1A1 Gly71Arg和G6PD基因突变可能是新生儿高未结合胆红素血症发生的原因。     

广西三江县侗族新生儿UGT1A1基因变异分析北大核心CSCD

目的探讨广西柳州三江县侗族新生儿UGT1A1基因变异特点及其与侗族新生儿高胆红素血症发生的关系。方法前瞻性选取2021年1月至2022年1月于三江县人民医院新生儿科诊断不明原因高胆红素血症的新生儿84例为研究对象;另选取同期健康新生儿60例纳入健康对照组。提取两组新生儿外周血基因组DNA,对UGT1A1启动子区TATA盒和外显子1进行PCR扩增并进行基因测序。结果病例组检测出33例G71R错义突变,突变率为39%,A等位基因频率(21%)显著高于健康对照组(10%)(P<0.05)。携带G71R错义突变基因型的侗族新生儿发生高胆红素血症的风险是携带野生型的健康新生儿的2.588倍(P<0.05)。Hardy-Weinberg遗传平衡检验结果提示两组新生儿UGT1A1 G71R位点基因型符合遗传平衡(P>0.05)。结论UGT1A1 G71R突变是三江县侗族新生儿高频基因变异类型,且G71R错义突变与侗族新生儿发生高胆红素血症相关。     

胆红素-尿苷二磷酸葡萄糖醛酸基转移酶G71R基因型对广西地区新生儿黄疸程度的影响

目的 探讨胆红素-尿苷二磷酸葡萄糖醛酸基转移酶1A1(UGT 1A1)基因突变对广西新生儿黄疸的影响.方法 收集73例高胆红素血症新生儿及31例健康新生儿外周血,应用突变特异性扩增系统(amplification refractory mutation system,ARMS)法及直接测序法对所有新生儿行UGT1A1基因G71R突变检测,分析胆红素脑病发生率,胆红素峰值及总胆红素(total serum bilirubin,TSB)>20 mg/dl的机会比.结果 (1)本研究人群G71R等位基因频率为0.1915,病例组为0.2329,健康对照组为0.097,病例组的G71R等位基因频率显著高于健康对照组(P<0.05).(2)G71R纯合子的胆红素脑病发病率及72 h的TSB浓度(28.57%,23.12±4.58 mg/dl)均高于野生型组(0%,17.68±2.69 mg/dl),差异有统计学意义(P<0.001).(3)G71R纯合子组中5例的TSB>20 mg/dl,G71R纯合子TSB>20 mg/dl的机会比(odds ratio,OR)为7.955,总体机会比95%可信区间(confidence interval,CI)为(1.349,46.899).结论 G71R突变与本地新生儿黄疸的发病存在相关性.G71R纯合子的胆红素脑病发病率及生后72 h的TSB较对照组及野生型增高.G71R纯合子发生TSB>20 mg/dl的危险性是野生型的7.955倍.     

Frequencies of A(TA)7TAA, G71R, and G493R mutations of the UGT1A1 gene in the Malaysian population

BACKGROUND: Gilbert syndrome is caused by defects in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene. These mutations differ among different populations and many of them have been found to be genetic risk factors for the development of neonatal jaundice. OBJECTIVES: The objective was to determine the frequencies of the following mutations in the UGT1A1 gene: A(TA)7TAA (the most common cause of Gilbert syndrome in Caucasians), G71R (more common in the Japanese and Taiwanese population), and G493R (described in a homozygous Malay woman with Crigler-Najjar syndrome type 2) in a group of Malaysian babies with hyperbilirubinemia and a group of normal controls. METHODS: The GeneScan fragment analysis was used to detect the A(TA)7TAA variant. Mutation screening of both G71R and G493R was performed using denaturing high performance liquid chromatography. RESULTS: Fourteen out of fifty-five neonates with hyperbilirubinemia (25%) carried the A(TA)7TAA mutation (10 heterozygous, 4 homozygous). Seven out of fifty controls (14%) carried this mutation (6 heterozygous, 1 homozygous). The allelic frequencies for hyperbilirubinemia and control patients were 16 and 8%, respectively (p=0.20). Heterozygosity for the G71R mutation was almost equal among both groups (5.5% for hyperbilirubinemia patients and 6.0% for controls; p=0.61). One subject (1.8%) in the hyperbilirubinemia group and none of the controls were heterozygous for the G493R mutation (p=0.476). CONCLUSIONS: The A(TA)7TAA seems more common than the G71R and G493R mutations in the Malaysian population.     

Chemotherapy-induced unconjugated hyperbilirubinemia caused by a mutation of the bilirubin uridine-5'-diphosphate-glucuronosyltransferase gene

Chemotherapy for malignant neoplasms sometimes causes unconjugated hyperbilirubinemia in the absence of liver dysfunction. We analyzed the association of chemotherapy-induced hyperbilirubinemia with mutations of the bilirubin uridine-5'-diphosphate (UDP)-glucuronosyltransferase gene (UGT1A1) from two leukemic patients in whom chemotherapy resulted in a hyperbilirubinemic response. We isolated genomic DNA from peripheral blood samples and amplified UGT1A1 by polymerase chain reaction. The amplified DNA fragments were analyzed by direct sequencing. The genes of the two patients revealed an identical heterozygous missense mutation in exon 1 (211G-->A: G71R). This UGT1A1 mutation may be the basis of chemotherapy-induced unconjugated hyperbilirubinemia.     

UGT1A1基因G71R突变与新生儿不明原因严重高胆红素血症相关

目的探讨尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)基因G71R突变与新生儿严重高胆红素血症的相关性。方法采用病例对照研究的方法,病例组为复旦大学附属儿科医院(我院)收治的不明原因严重高胆红素血症(血清总胆红素水平≥342μmol·L-1)新生儿,采用PCR对外周血UGT1A1基因进行检测。对照组为我院新生儿出生缺陷生物样本数据库中血清总胆红素水平221μmol·L-1病例。病例组及对照组新生儿均要求胎龄≥35周,出生体重≥2 500 g。结果病例组和对照组各65例。UGT1A1 G71R是病例组中最常见的突变类型(73.8%,48/65)。对照组UGT1A1 G71R突变位点与既往Meta分析中提取的中国健康新生儿对比,在基因型分布及等位基因频率上差异均无统计学意义(P0.05)。病例组和对照组UGT1A1基因G71R突变中A等位基因频率分别为0.5和0.15,差异有统计学意义(P0.001),把握度为0.993。与携带G/G基因型新生儿相比,UGT1A1 G71R突变(A/A+G/A基因)可增加新生儿严重高胆红素血症的发病风险(OR=7.373,95%CI:3.395~16.008),把握度为1.0。结论 UGT1A1基因G71R突变与新生儿不明原因严重高胆红素血症相关。     

Relationship between bilirubin UDP-glucuronosyl transferase 1A1 gene and neonatal hyperbilirubinemia

The variation rate within the coding region of UDP-glucuronosyl transferase 1A1 (UGT1A1) gene in Taiwan Chinese was found to be 29.3%. This study sought to determine whether that high variation rate of UGT1A1 gene is a risk factor for neonatal hyperbilirubinemia. The study subjects consisted of 123 newborn infants suffering from unconjugated hyperbilirubinemia who had no known risk factors for hyperbilirubinemia and 218 healthy control neonates. The promoter area, exons 1 to 4, coding region of exon 5, and the flanking intronic regions in UGT1A1 gene were determined by the PCR in all subjects. Wild UGT1A1 gene, variation in the promoter, variation at nucleotide 211, variation at nucleotide 1091, and compound heterozygous variation of UGT1A1 gene were found. The percentage of neonates with wild UGT1A1 gene and the percentage of neonates with variation at nucleotide 211 were significantly different between the study subjects and controls. The percentages with bilirubin >or=342 micro M (20.0 mg/dL) and with persistent hyperbilirubinemia in the subjects carrying homozygous variation at nucleotide 211 (Gly71Arg) were significantly higher than the neonates carrying wild type or other genotypes. In conclusion, this study has demonstrated that variation at nucleotide 211 of the UGT1A1 gene is a risk factor for the development of neonatal hyperbilirubinemia. Pediatricians should closely follow hyperbilirubinemic newborn infants who carry homozygous 211 G to A variation in UGT1A1 gene.     

Neonatal hyperbilirubinemia and the bilirubin uridine diphosphate-glucuronosyltransferase gene: The common −3263T > G mutation of phenobarbital response enhancer module is not associated with the neonatal hyperbilirubinemia in Japanese

BACKGROUND: Neonatal hyperbilirubinemia is frequent and severe in Japanese newborns. Previously, it has been reported that half of the Japanese neonates with severe hyperbilirubinemia carried the 211G > A (p.G71R) mutation of the bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1) gene causing Gilbert syndrome. Recently, it was reported that the -3263T > G mutation in the phenobarbital response enhancer module in UGT1A1 was associated with the majority of cases of Gilbert syndrome. The gene frequency of the -3263T > G mutation was determined and the relation with neonatal hyperbilirubinemia in Japanese was studied. METHODS: UGT1A1 in 119 neonates born at Yamagata University Hospital, Yamagata, Japan, and 26 subjects who had undergone phototherapy due to severe hyperbilirubinemia at four other hospitals were studied. The gene frequency of -3263T > G mutation in Japanese, Korean, Chinese and German healthy adult controls was also determined. Hyperbilirubinemia was assessed with a Jaundice Meter and UGT1A1 was analyzed by sequence determination or restriction enzyme method. RESULTS: The gene frequency of the -3263T > G mutation was 0.26 in Japanese subjects and was similar to the prevalence in Korean, Chinese and German populations. However, there was no significant increase in the gene frequency of the mutation in the neonates who required phototherapy for hyperbilirubinemia compared to that in the neonates without severe hyperbilirubinemia. In addition, neonates with or without the mutation did not show a significant change in the level of bilirubin and the mutation also did not show a synergic effect with the 211G > A mutation on the level of bilirubin. CONCLUSION: The -3263T > G mutation is not likely to be associated with the neonatal hyperbilirubinemia in Japanese.     

遗传因素在广西新生儿高胆红素血症中的作用

目的探讨UGT1A1 G71R突变、OATP2A388G突变和G-6-PD缺乏对在广西新生儿高胆红素血症发病的作用。方法用四氮唑蓝定量法（NBT法）测定G-6-PD酶活性。聚合酶链反应-等位基因特异性寡核苷酸探针点杂交（PCR-ASO）法确定G71R基因型。限制性片段长度多态性分析（RFLP）检测A388G基因型。测定109例新生儿脐血的G-6-PD活性及G71R基因型,其中101例同时检测了A388G基因型。据G-6-PD活性及G71R或A388G基因型分组,分析UGT1A1G71R突变、OATP2A388G突变和G-6-PD缺乏与足月新生儿高胆红素血症之间关系。结果G71R等位基因频率在G-6-PD缺乏组为22．03％,在G-6-PD正常组为28．00％。G-6-PD缺乏共存有G71R突变纯合子或杂合子的新生儿高胆红素血症发生率（95．50％）高于G-6-PD正常且G71R为野生型的新生儿（53．90％）,x^2=10．45,P=0．0012,前者发生高胆红素血症的机会比（95％可信区间）[OR（95％CI）]为18．00（2．12,152．9）。A388G等位基因频率在G-6-PD缺乏组为20．O％,在G-6-PD正常组为18．5％。G-6-PD缺乏共存有A388G突变新生儿的高胆红素血症发生率（90．0％）高于G-6-PD正常且A388G为野生型的新生）L（44．80％）,X2=10．39,P=0．0013,前者发生高胆红素血症的伽（95％CT）为11．08（2．15,56．48）。结论G71R突变与G-6-PD缺乏共存或A388G突变与G-6-PD缺乏共存对广西足月新生儿高胆红素血症的发生有协同作用。