Urinary β2‐microglobulin and bronchopulmonary dysplasia: Trends in preterm infants

Background

The developmental process of bronchopulmonary dysplasia (BPD) is not identical between very preterm infants born small for gestational age (SGA) and those born appropriate for gestational age (AGA). In this study, we compared the pattern of the inflammatory response in infants of each group, by measuring urinary β2‐microglobulin (Uβ2M) as an alternative, concise, and less‐invasive biomarker.

Methods

Uβ2M and clinical details were examined at birth and at 4 weeks of age in 146 very preterm infants.

Results

Of the 57 infants diagnosed with BPD, 18 were SGA, and 39 were AGA. Uβ2M at birth was significantly lower in SGA BPD infants than in AGA BPD infants, but it increased with time. The prevalence of chorioamnionitis (CAM) was significantly lower in SGA BPD infants than in AGA BPD infants, while that of pregnancy‐induced hypertension was the opposite.

Conclusions

Exposure to prenatal factors other than CAM may sensitize fetal lungs to become vulnerable to postnatal inflammation in very preterm SGA infants with BPD.     

30 417例儿童地中海贫血基因类型分析

目的了解广西地区儿童地中海贫血基因类型及其分布。方法2011年1月至2019年12月对广西壮族自治区妇幼保健院30 417例地中海贫血筛查阳性患儿采用单管多重PCR后经琼脂糖凝胶电泳和反向点杂交技术进行常见α、β地中海贫血基因检测。对2 703例疑似罕见地中海贫血患儿进行跨越断裂点PCR检测和/或基因序列分析。结果30 417例地中海贫血筛查阳性患儿中，确诊地中海贫血23 214例（76.32%），其中α、β及α合并β地中海贫血检出率分别为47.77%、23.75%和4.80%。检出13种α地中海贫血等位基因共计18 480个，以--^SEA为主（54.98%），包括7种罕见等位基因：--^THAI（0.43%）、HKαα（0.02%）、-α³⁰（0.01%）、-α^1.0（0.01%）、-α^2.4（0.01%）、-α^21.9（0.01%）和HBA₂:C272-279 del（0.01%）；检出17种β地中海贫血等位基因共计9 168个，主要为CD41-42（47.79%），其次是CD17（25.53%），包括3种罕见等位基因：IVS-Ⅱ-5（0.02%）、IVS-I-2（0.01%）和^Gγ(^Aγδβ)⁰（0.01%）。14 531例α地中海贫血患儿中检出37种基因类型，6种主要类型为--^SEA/αα（52.20%）、-α^3.7/αα（13.24%）、α^CSα/αα（7.52%）、-α^4.2/αα（6.06%）、--^SEA/-α^3.7（5.91%）和α^WSα/αα（3.41%），共占88.34%。7 223例β地中海贫血患儿中检出49种基因类型，6种主要类型为CD41-42/β^N（45.81%）、CD17/β^N（24.30%）、IVS-Ⅱ-654/β^N（7.49%）、-28/β^N（5.62%）、CD71-72/β^N（4.42%）和CD26/β^N（3.94%），共占91.13%。1 460例α合并β地中海贫血患儿中检出137种基因类型，主要为--^SEA/αα合并CD41-42/β^N（14.17%）、CD17/β^N（8.35%）。HbH病（α⁰/α⁺）2 050例，包括合并β地中海贫血杂合子134例；巴氏水肿胎（--^SEA/--^SEA）12例；β地中海贫双重杂合子355例、纯合子128例，包括合并α地中海贫血93例。结论广西地区儿童地中海贫血基因突变多样，基因类型丰富；以α地中海贫血为主，--^SEA/αα是主要基因类型；α合并β地中海贫血比例较高，β地中海贫血双重杂合子和纯合子（中重型）患儿出生较多。     

糖尿病母亲婴儿的神经发育结局

随着孕前糖尿病及妊娠糖尿病发生率的增高，糖尿病母亲婴儿（infants of diabetic mothers，IDMs）也呈逐年增多的趋势，IDMs易发生不良围生期结局，并可能对IDMs神经发育造成负面影响，但目前关于IDMs神经发育结局的研究还相对较少。该文查阅相关文献，从感知觉、运动、语言、智力发育、神经精神疾病、神经学检查和药物影响等方面，对IDMs的神经发育结局予以总结，为临床工作提供参考。 引用格式:     

应用近红外光谱技术监测脓毒症患儿胃肠功能障碍的前瞻性研究

目的探讨脓毒症患儿胃肠功能障碍的发生率、病死率，应用近红外光谱技术（near-infrared spectroscopy，NIRS）监测肠系膜局部组织血氧饱和度（regional oxygen saturation，rSO₂），观察胃肠功能障碍患儿rSO₂差异。方法前瞻性选择2021年1~12月儿科重症监护病房79例脓毒症患儿（脓毒症组）及儿童保健科40例健康体检儿童（健康对照组）为研究对象，收集患儿入院及出院基本情况、在院治疗情况和实验室检查指标，应用NIRS测定肠系膜rSO₂，根据有无胃肠功能障碍发生进行组间对比。结果79例脓毒症患儿胃肠功能障碍发生率为49%（39/79），胃肠功能障碍患儿28 d病死率为26%（10/39）。胃肠功能障碍患儿机械通气时间更长、28 d病死率更高（P<0.05）。胃肠功能障碍患儿肠系膜rSO₂（64%）低于无胃肠功能障碍患儿（72%）及健康对照组（78%）（P<0.05）。结论脓毒症患儿胃肠功能障碍发生率及病死率较高，影响患儿预后。肠系膜rSO₂的降低与胃肠功能障碍发生相关。     

阵发性睡眠性血红蛋白尿克隆在儿童重型再生障碍性贫血免疫抑制治疗中的意义

目的探究儿童重型再生障碍性贫血（severe aplastic anemia，SAA）中阵发性睡眠性血红蛋白尿（paroxysmal nocturnal hemoglobinuria，PNH）克隆与免疫抑制治疗（immunosuppressive therapy，IST）之间的关系。方法回顾性分析2012年1月至2020年5月收治且行IST的151例SAA患儿的临床资料，根据治疗前PNH克隆状态分为PNH克隆阴性组（135例）和PNH克隆阳性组（16例）。采用倾向性评分匹配控制混杂因素，分析PNH克隆对IST疗效的影响。结果PNH克隆阳性患儿占10.6%（16/151），中位粒细胞克隆大小为1.8%。PNH克隆阳性组患儿初诊年龄偏大，初诊网织红细胞绝对值偏高（P<0.05）；倾向性评分匹配后，PNH克隆阴性组和PNH克隆阳性组患儿的基线特征差异均无统计学意义（P>0.05）。PNH克隆阳性组IST后6、12、24个月的总有效率均低于PNH克隆阴性组（P<0.05）。IST后PNH克隆演变存在一定异质性，伴PNH克隆者再生障碍性贫血-阵发性睡眠性血红蛋白尿综合征的3年累积发病率增加（P<0.05）。结论初诊时PNH克隆阳性的SAA患儿对IST的反应较差，且更易进展为再生障碍性贫血-阵发性睡眠性血红蛋白尿综合征。     

Lipin基因表达与宫内发育迟缓大鼠肝脏脂肪含量的相关性研究

目的探讨宫内发育迟缓（intrauterine growth retardation，IUGR）大鼠肝脏Lipin2基因和内脏脂肪组织Lipin1基因的表达与肝脏脂肪含量的相关性。方法使用母孕期低蛋白（10%蛋白）饮食法喂养孕鼠制造IUGR仔鼠模型，对照组孕鼠在孕期使用正常蛋白饲料喂养（蛋白含量21%）。分别在两组仔鼠生后1 d、1周、3周、8周和12周时称体重并留取仔鼠的肝脏组织，在生后3周、8周和12周留取两组仔鼠的内脏脂肪组织。采用3.0T氢质子磁共振波谱法检测两组大鼠生后3周、8周、12周时肝脏脂肪含量；采用Real-time PCR法检测两组大鼠各时间点肝脏组织Lipin2、内脏脂肪组织Lipin1基因的mRNA表达水平；采用Western blot法检测两组大鼠肝脏组织Lipin2、内脏脂肪组织Lipin1蛋白表达水平。采用Pearson相关分析Lipin mRNA及其蛋白表达与肝脏脂肪含量的相关性。结果生后3周、8周、12周时，IUGR组仔鼠内脏脂肪组织Lipin1 mRNA及其蛋白表达水平均高于对照组（P<0.05）。生后1 d时IUGR组肝脏组织Lipin2 mRNA及其蛋白表达水平低于对照组（P<0.05），而生后1周、3周、8周、12周时Lipin2 mRNA及其蛋白表达水平均高于对照组（P<0.05）。生后3周时IUGR仔鼠和对照组肝脏脂肪含量比较差异无统计意义（P>0.05），生后8周、12周时IUGR组仔鼠肝脏脂肪含量显著高于对照组（P<0.05）。Lipin1蛋白和mRNA表达与肝脏脂肪含量呈正相关（分别r=0.628、0.521，P<0.05），Lipin2蛋白和mRNA表达与脂肪含量呈正相关（分别r=0.601、0.524，P<0.05）。结论IUGR大鼠内脏脂肪组织Lipin1和肝脏组织Lipin2 mRNA及其蛋白表达上调可引起肝脏脂肪含量增加，可能与导致IUGR大鼠成年期肥胖有关。     

Neurocognitive function in patients with β‐thalassemia major

Background: Children with β‐thalassemia major (β‐TM) have multiple risk factors for developing cognitive impairment. The aim of the present study was to evaluate cognitive function in patients with β‐TM. Methods: Twenty children with β‐TM were enrolled into the study and were compared with a control group consisting of 21 healthy children. All participants were evaluated with neuropsychological tests and event‐related potentials (ERP). Results: All of the participants had normal IQ scores, but the patient group had significantly lower full‐scale, performance, and verbal IQs compared with the control group (P < 0.05). The number of children with visuomotor dysfunction was higher in the patient group compared with the control group (P < 0.05). In the P300 test, the patient group had significantly prolonged N1, P2 and N2 latencies at the FZ, and a prolonged N1 latency at the Cz compared with the control group (P < 0.05). The patient group also had lower N1 and P3N4 amplitudes at the Fz, and lower N1, N1P2 and P3N4 amplitudes at the Cz when compared with the control group (P < 0.05). Mismatch negativity latency and duration were longer in the patient group (P < 0.05). Conclusions: Neuropsychological tests are safe, and reliable for the diagnosis of cognitive impairment in β‐TM patients, and the use of ERP may facilitate early diagnosis. The number of β‐TM patients in the present study was limited, however, and larger numbers of patients are required in further studies.     

A 5‐HT2A/2C receptor agonist, 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane,mitigates developmental neurotoxicity of ethanol to serotonergic neurons

Prenatal ethanol exposure causes the reduction of serotonergic (5‐HTergic) neurons in the midbrain raphe nuclei. In the present study, we examined whether an activation of signaling via 5‐HT_2A and 5‐HT_2C receptors during the fetal period is able to prevent the reduction of 5‐HTergic neurons induced by prenatal ethanol exposure. Pregnant Sprague–Dawley rats were given a liquid diet containing 2.5 to 5.0% (w/v) ethanol on gestational days (GDs) 10 to 20 (Et). As a pair‐fed control, other pregnant rats were fed the same liquid diet except that the ethanol was replaced by isocaloric sucrose (Pf). Each Et and Pf group was subdivided into two groups; one of the groups was treated with 1 mg/kg (i.p.) of 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI), an agonist for 5‐HT_2A/2C receptors, during GDs 13 to 19 (Et‐DOI or Pf‐DOI), and another was injected with saline vehicle only (Et‐Sal or Pf‐Sal). Their fetuses were removed by cesarean section on GD 19 or 20, and fetal brains were collected. An immunohistological examination of 5‐HTergic neurons in the fetuses on embryonic day 20 using an antibody against tryptophan hydroxylase revealed that the number of 5‐HTergic neurons in the midbrain raphe nuclei was significantly reduced in the Et‐Sal fetuses compared to that of the Pf‐Sal and Pf‐DOI fetuses, whereas there were no significant differences between Et‐DOI and each Pf control. Thus, we concluded that the reduction of 5‐HTergic neurons that resulted in prenatal ethanol exposure could be alleviated by the enhancement of signaling via 5‐HT_2A/2C receptors during the fetal period.     

Impaired β‐cell sensitivity to glucose and maximal insulin secretory capacity in adolescents with type 2 diabetes

Elder DA, Woo JG, D’Alessio DA. Impaired β‐cell sensitivity to glucose and maximal insulin secretory capacity in adolescents with type 2 diabetes. Background: Adults with type 2 diabetes mellitus (T2DM) have broad impairments in β‐cell function, including severe attenuation of the first‐phase insulin response to glucose, and reduced β‐cell mass. In adolescents with T2DM, there is some evidence that β‐cell dysfunction may be less severe. Our objective was to determine β‐cell sensitivity to glucose and maximal insulin secretory capacity (AIR_max) in teenagers with T2DM. Methods: Fifteen adolescents with T2DM [11 F/4 M, age 18.4 ± 0.3 yr, body mass index (BMI) 39.8 ± 2.2 kg/m²] and 10 non‐diabetic control subjects (7 F/3 M, age 17.4 ± 0.5 yr, BMI 41.5 ± 2.2 kg/m²) were studied. T2DM subjects had a mean duration of diabetes of 48.8 ± 6.4 months, were treated with conventional therapies, and had good metabolic control [hemoglobin A1c (HbA1c) 6.7 ± 1.2%]. Insulin and C‐peptide were determined before and after a graded glucose infusion and after intravenous arginine at a whole blood glucose level of ≥22 mM. Results: The insulin response to increasing plasma glucose concentrations was blunted in the diabetic compared with control subjects (34.8 ± 11.9 vs. 280.5 ± 57.8 pmol/mmol; p < 0.0001), and AIR_max was also significantly reduced in the diabetic group (1868 ± 330 vs. 4445 ± 606; p = 0.0005). Conclusion: Even adolescents with well‐controlled T2DM have severe impairments of insulin secretion. These data support β‐cell dysfunction as central in the pathogenesis of T2DM in young people, and indicate that these abnormalities can develop over a period of just several years.     

亲子合作式音乐疗法对孤独症谱系障碍儿童及其母亲影响的前瞻性随机对照研究

目的探讨亲子合作式音乐疗法对孤独症谱系障碍（autism spectrum disorder，ASD）儿童的核心症状及其母亲的影响。方法前瞻性采用随机数字表法将112例ASD儿童及其母亲分为音乐疗法组和应用行为分析法（applied behavior analysis，ABA）组，每组各56例。ABA组采用ABA进行干预，音乐疗法组在ABA组基础上采用亲子合作式音乐疗法。2组干预时长均为8周。采用儿童孤独症评估量表（Childhood Autism Rating Scale，CARS）、儿童孤独症家长评定量表（Autism Behavior Checklist，ABC）、亲职压力简表（Parenting Stress Index-Short Form，PSI-SF）、家庭关怀度指数量表（Family APGAR Index，APGAR）和Herth希望量表（Herth Hope Index，HHI），评估干预前和干预后ASD儿童的核心症状及其母亲的亲职压力、家庭关怀度和希望水平。结果共100对母子参与了全程研究（每组各50对）。干预后音乐疗法组ASD儿童ABC量表总分、感觉维度、社交维度、躯体运动维度得分，以及CARS量表总分低于ABA组（P<0.05）。干预后音乐疗法组母亲的PSI-SF总分、亲子互动失调维度得分，HHI量表总分和各维度得分，以及APGAR量表总分、合作度和亲密度得分均高于ABA组（P<0.05）。结论在ABA的基础上，加用亲子合作式音乐疗法可改善ASD儿童的核心症状，减轻母亲的亲职压力，提升其家庭关怀度指数和希望水平。     

不同液体负荷状态对持续肾替代治疗脓毒症相关急性肾损伤患儿预后的影响

目的评估不同液体负荷（fluid load，FL）对使用持续肾替代治疗（continuous renal replacement therapy，CRRT）的脓毒症相关急性肾损伤（acute kidney injury，AKI）患儿预后的影响。方法回顾性选取2018年8月至2021年3月因脓毒症相关AKI行CRRT的患儿121例为研究对象，根据患儿从入院或病情变化开始至行CRRT前的不同FL分为低液体负荷组（n=35，FL<5%）、高液体负荷组（n=35，5%≤FL<10%）和液体超负荷组（n=51，FL≥10%）。收集各组患儿CRRT治疗前的基线资料和临床生化资料进行比较分析。采用Kaplan-Meier生存曲线分析各组间的28 d生存情况。采用多因素logistic回归分析影响不同FL状态患儿预后的危险因素。结果生存分析结果提示液体超负荷组患儿28 d病死率高于低液体负荷组和高液体负荷组（P<0.05）；多因素logistic回归分析结果提示正超液体量增加为导致液体超负荷组患儿28 d病死率增高的危险因素，而CRRT开始时间提前为其保护因素（P<0.05）。结论CRRT开始前液体超负荷会增加脓毒症相关AKI患儿的病死率，对该类患儿应尽早行CRRT治疗。     

Effect of recombinant human fibroblast growth factor‐2 on bone formation in rabbit mandibular distraction models using β‐tricalcium phosphate

This study was designed to evaluate the effect of recombinant human fibroblast growth factor‐2 (rhFGF‐2) on the amount and period of new bone formation in rabbit mandibular distraction models using β‐tricalcium phosphate (β‐TCP) as a bone graft substitute. Sixteen male Japanese White rabbits were divided into the following four experimental groups: 1, distraction alone; 2, distraction with β‐TCP granules; 3, distraction with rhFGF‐2 (25 µg/50 µL) injected into β‐TCP granules; and 4, distraction with rhFGF‐2 (100 µg/50 µL) injected into β‐TCP granules. The bones were harvested at 4 weeks after the operation and examined using soft radiography, micro‐computed tomography (micro‐CT), and peripheral quantitative computed tomography (pQCT). The dissected mandibles were stained using the Villanueva bone staining method, and the amount of new bone formed, bioresorption of β‐TCP, and new blood vessel formation were morphometrically calculated using bone histomorphometry. Radiopaque areas were observed more frequently in the distracted area of groups 3 and 4. Micro‐CT analysis revealed partial new bone formation in the central region of the distracted area in groups 3 and 4. pQCT analysis revealed increased bone mineral density in groups 3 and 4. Histomorphometric analysis revealed increased newly formed bone and blood vessel areas in groups 3 and 4. In group 4, the number of osteoclasts around the β‐TCP granules had significantly increased. The present findings suggested that the combined use of rhFGF‐2 and β‐TCP reduced the treatment period for distraction osteogenesis and accelerated the formation of a new high‐quality bone.     

β–HCG Elevation in Wilms Tumor: An Uncommon Presentation

Wilms tumor (nephroblastoma) is a readily diagnosed common abdominal tumor in children. Rarely, it may present with factors that may confound the diagnosis. We report a 6‐year‐old female child who presented with a rapidly growing and invasive abdominal mass with the histopathologic features of Wilms tumor associated with an elevated serum beta human chorionic gonadotropin, which has not been previously reported in this condition.     

中国11市93 720例胎龄24~42周单胎儿出生体重曲线及其地区差异特征

目的研制胎龄24~42周单胎新生儿出生体重曲线，并探讨其地区差异特征。方法在中国11市（海口、广州、深圳、柳州、桂林、泉州、重庆、成都、长沙、宁波、连云港）选择年分娩量7 000例以上的11家妇幼保健院，纳入其2017年1月1日至2020年12月31日分娩的全部活产单胎新生儿进行出生体重曲线研制。结果纳入了11市合计93 720例胎龄24~42周单胎新生儿进行研究。建立了中国11市合计及各市单胎儿出生体重3rd~97th百分位数参考值，并绘制了出生体重百分位曲线图。深圳市和泉州市单胎儿出生体重曲线水平与中国11市合计单胎儿水平基本相同；海口市、广州市、桂林市、柳州市单胎儿出生体重曲线水平略低于中国11市合计单胎儿水平；重庆市、成都市、长沙市单胎儿出生体重曲线水平略高于中国11市合计单胎儿水平；宁波市和连云港市单胎儿出生体重曲线高于中国11市合计单胎儿水平。中国11市合计单胎儿出生体重曲线与中国协作网2011~2014年单胎儿出生体重曲线非常接近。结论制定了中国11市合计及各市单胎新生儿出生体重3rd~97th百分位数参考值，可作为该区域新生儿宫内生长评价的参考标准。部分地区新生儿宫内生长水平与全国水平有差异。     

儿童肺炎支原体肺炎合并腺病毒感染的临床观察

目的探讨儿童肺炎支原体肺炎（Mycoplasma pneumoniae pneumonia，MPP）合并腺病毒（adenovirus，ADV）感染的临床特征，为临床诊断和治疗提供依据。方法回顾性收集单纯MPP患儿228例，MPP合并ADV患儿28例的病例资料，比较两组患儿临床特征、实验室检查结果及治疗转归的差异。结果与单纯MPP组相比，MPP合并ADV组的热程和住院时间均较长，支气管镜下气道黏膜严重病变（糜烂、剥脱）比例、临床肺部感染评分及需要氧疗比例均较高（P<0.05）。两组白细胞计数、C-反应蛋白、支气管肺泡灌洗液肺炎支原体DNA复制倍数，以及胸腔积液、肺外并发症比例，差异无统计学意义（P>0.05）。结论MPP合并ADV感染儿童临床表现及气道黏膜病变程度比单纯MPP患儿更严重，更易需要氧疗，但实验室指标大多无明显特异性。