Novel pathogenic variants in an Indian cohort with epidermolysis bullosa: Expanding the genotypic spectrum

BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases.     

小儿腹股沟斜疝日间手术与专科住院手术的卫生经济学评价

目的对小儿日间手术模式和专科住院手术模式的卫生经济学进行评价,为小儿腹股沟斜疝手术的优选和决策提供参照依据。方法收集2016年6月至2017年7月间所有在重庆医科大学附属儿童医院治疗且符合纳入标准的单侧腹股沟斜疝患儿的临床资料,其中日间手术患儿324例(日间组),专科住院手术患儿65例(专科组)。比较两种手术模式下的患儿一般资料、治疗指标、容错情况、术后需要留院处理的并发症发生率、复发率、院内的感染等卫生效果指标;比较两种模式的HCAHPS优化星表满意度、住院时间、住院费用等卫生经济学指标。统计分析两种模式的成本-效果:治疗效果权重W、治疗效果指数(EI)、成本-效果比(CER)。结果日间外科组和专科组在性别、区域方面的差异无统计学意义,专科组年龄分布更广。日间组与专科组占用床位时间分别为(23.17±0.49)h和(112.06±19.75)h,差异具有统计学意义(P<0.01);两组的医疗费用分别为(3372±430)元和(6063±2104)元,差异具有统计学意义(P<0.01)。两组麻醉分级ASA比例的差异具有统计学意义,两组术后并发症发生率的差异无统计学意义(P>0.05)。日间组与专科组治疗EI分别为0.98和1.02,CER分别为3305和6184,日间组经济学效益较大。结论日间手术的成本-效果优于专科住院手术模式,患儿满意度和术后复发率与专科住院模式的差异无统计学意义,推荐符合日间手术指征的患儿采用该模式。     

Curcumin attenuates spatial memory impairment by anti-oxidative,anti-apoptosis,and anti-inflammatory mechanism against methamphetamine neurotoxicity in male Wistar rats: Histological and biochemical changes

ObjectiveMethamphetamine is used extensively around the world as a psychostimulant. The complications related to methamphetamine include methamphetamine-induced neurotoxicity, mainly involving intraneuronal processes, such as oxidative stress and excitotoxicity. Curcumin is effective against neuronal injury due to its antioxidant, anti-inflammatory effects. In this study, we examined the protective effects of curcumin against methamphetamine neurotoxicity.MethodsSixty male Wistar rats were divided into the following groups: control (n = 12), DMSO (n = 12), methamphetamine (n = 12), and methamphetamine + curcumin (100 and 200 mg/kg, respectively, intraperitoneal [IP]; n = 12). Neurotoxicity was induced by 40 mg/kg of methamphetamine administrated through 4 injections (4 × 10 mg/kg, q2h, IP). Curcumin (100 and 200 mg/kg) was administered at 7 days after the last methamphetamine injection. By using a Morris water maze task, the hippocampus-dependent memory and spatial learning were evaluated 1 day after the last curcumin injection. Then, the animal brains were isolated for biochemical measurements, as well as glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1(Iba-1) and caspase-3 immunohistochemical staining.ResultsThe current study demonstrated that administration of curcumin significantly attenuates spatial memory impairment (P < 0.01) following methamphetamine neurotoxicity. Curcumin caused a significant increase in the levels of superoxide dismutase and glutathione peroxidase (P < 0.05). However, it decreased tumor necrosis factor (TNF-α) (P < 0.05) and malondialdehyde (P < 0.01) levels as compared to the methamphetamine group. Also, curcumin significantly reduced Iba-1 (P < 0. 01), GFAP and caspase-3 positive cells in the hippocampus (P < 0.001).ConclusionCurcumin exerted neuroprotective effects on methamphetamine neurotoxicity because of its antioxidant and anti-inflammatory effect.     

STAT3 couples with 14-3-3σ to regulate BCR signaling,B-cell differentiation,and IgE production

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Allele-specific PCR and Next-generation sequencing based genetic screening for Congenital Adrenal Hyperplasia in India

Genetic screening of Congenital Adrenal Hyperplasia (CAH) is known to be challenging due to the complexities in CYP21A2 genotyping and has not been the first-tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating its utility in screening extended panel of genes implicated in CAH. In this study, we have established and utilized an Allele-Specific Polymerase Chain Reaction (ASPCR) based approach for screening eight common mutations in CYP21A2 gene followed by targeted Next Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes in 72 clinically diagnosed CAH subjects from India. Through these investigations, 88.7% of the subjects with 21 hydroxylase deficiency were positive for eight CYP21A2 mutations with ASPCR. The targeted NGS assay was sensitive to pick up all the mutations identified by ASPCR. Utilizing NGS in subjects negative for ASPCR, five study subjects were homozygous positive for other CYP21A2 variants: one with a novel c.1274G>T, three with c.1451G>C and one with c.143A>G variant. One subject was compound heterozygous for c.955C>T and c.1042G>A variants identified using ASPCR and NGS. One subject suspected for a Simple Virilizing (SV) 21 hydroxylase deficiency was positive for a CYP19A1:c.1142A>T variant. CYP11B1 variants (c.1201-1G>A, c.1200+1del, c.412C>T, c.1024C>T, c.1012dup, c.623G>A) were identified in all six subjects suspected for 11 beta-hydroxylase deficiency. The overall mutation positivity was 97.2%. Our results suggest that ASPCR followed by targeted NGS is a cost-effective and comprehensive strategy for screening common CYP21A2 mutations and the CAH panel of genes in a clinical setting.     

孤独症谱系障碍儿童发育倒退的影响因素

孤独症谱系障碍(ASD)是一组以不同临床表现为主要特征的神经发育性障碍。近年来,ASD儿童的发育倒退(DR)受到越来越多的关注,并被认为可能是ASD的一种特殊亚型。目前关于ASD儿童DR的影响因素尚不清楚,综合文献分析主要是由遗传、环境及其交互作用共同引起。本文拟从遗传和环境两方面对目前报道的ASD儿童DR影响因素进行总结,为该部分ASD患儿的临床早期识别和干预提供参考。     

早期预测食物过敏高风险儿童方法探讨

目的探讨联合多种危险因素获得的过敏风险评分预测食物过敏高风险儿童的价值。方法采用问卷调查方式获得≤3岁婴幼儿的过敏危险因素信息,以多元logistic逐步回归分析婴幼儿食物过敏危险因素,计算各危险因素对食物过敏的阳性预测值,依据回归方程计算过敏风险评分,通过ROC曲线评价过敏风险评分在筛查食物过敏高风险儿童中的价值。结果获得78例确诊为食物过敏及156例非过敏性疾病的≤3岁婴幼儿的回顾性调查信息。其中过敏性疾病家族史、剖宫产、孕期使用抗生素或解热镇痛药、孕期吸烟或接触吸烟环境、孕期接触杀虫剂或驱蚊剂、家中饲养宠物均是婴幼儿发生食物过敏的危险因素(P0.05)。过敏家族史预测食物过敏的阳性预测值为63.2%,ROC曲线下面积(AUC)为0.696(95%CI:0.620～0.771)。当联合多因素获得的过敏风险评分≥2.85时,其预测食物过敏的AUC为0.804(95%CI:0.746～0.863),灵敏度为0.526,特异度为0.910,尤登指数为0.436。结论多危险因素联合指标筛查食物过敏高风险儿童的预测价值高于过敏家族史。     

粪便自诱导分子-2在新生儿坏死性小肠结肠炎临床病情监测中的价值

目的初步探讨粪便自诱导分子-2(AI-2)监测新生儿坏死性小肠结肠炎(NEC)病情变化的价值。方法以2017年10月至2018年4月收治的12例NEC患儿为研究对象,并按照胎龄、日龄、生产方式、喂养方式、抗生素使用等选择12例与NEC组患儿匹配的非NEC新生儿为对照组。NEC诊断时定为急性期,再次开奶3天后定为恢复期。采集NEC急性期、恢复期和对照组的粪便标本,以BB170生物荧光检测法检测粪便AI-2浓度,采用16s rDNA高通量测序分析粪便菌群。结果在菌门水平,拟杆菌门比例在NEC组急性期、恢复期和对照组之间差异有统计学意义(P0.05),其中NEC恢复期比例最低。在菌属水平,肠球菌属、拟杆菌属比例在三组之间差异均有统计学意义(P0.05),其中NEC急性期肠球菌属比例最低,恢复期拟杆菌属比例最低。三组粪便AI-2浓度差异有统计学意义(P0.05),以NEC急性期为最低。结论 AI-2在监测NEC病情变化方面具有潜在临床应用价值。