Analysis of OTC gene variants in four children with delayed onset Ornithine transcarbamylase deficiency / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical manifestation and genetic basis for four children with delayed onset Ornithine transcarbamylase deficiency (OTCD).@*METHODS@#Clinical data of four children with OTCD admitted to the Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2020 to April 2021 were reviewed. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Bioinformatic analysis and Sanger sequencing verification were carried out to verify the candidate variants. Impact of the candidate variants on the protein structure was also predicted.@*RESULTS@#The clinical manifestations of the four children included vomiting, convulsion and disturbance of consciousness. WES revealed that the child 1 was heterozygous for a c.421C>T (p.R141X) variant in exon 5, children 2 and 3 were hemizygous for a c.119G>A (p.R40H) variant in exon 2, and child 4 was hemizygous for a c.607T>A (p.S203T) variant in exon 5 of the OTC gene. Among these, the c.607T>A variant was unreported previously and predicted to be pathogenic (PM1+PM2_Supporting+PP3+PP4). Bioinformatic analysis has predicted that the variant may result in breakage of hydrogen bonds and alter the protein structure and function. Sanger sequencing confirmed that the variants in children 2 to 4 have derived from their mothers.@*CONCLUSION@#The pathogenic variants of the OTC gene probably underlay the delayed OTCD in 4 children. The discovery of the c.607T>A variant has enriched the mutational spectrum of the OTC gene.

Clinical and genetic analysis of a child with mental retardation autosomal dominant 7 / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical and genetic characteristics of a child with clinical manifestations of hypoplasia, epilepsy and abnormal face.@*METHODS@#The clinical data of the child were collected. The peripheral blood samples of the patient and his parents were extracted for high-throughput sequencing, and Sanger sequencing verification and bioinformatics analysis were performed to detect suspected pathogenic variants.@*RESULTS@#The clinical manifestations of the child were overall developmental backwardness, seizures, autism, and special facial appearance. High throughput sequencing showed that there was a heterozygous mutation of exon 11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) of the DYRK1A gene. The same variant was found in neither of her parents, suggesting that it has a denovo origin.@*CONCLUSION@#The exon11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) mutation in DYRK1A gene was the genetic etiology of the case, which enriches the pathogenic gene spectrum of DYRK1A and provides the basis for clinical diagnosis and genetic counseling.

Interpretation of European Academy of Allergy and Clinical Immunology guideline: Anaphylaxis (2021 update) / 中国小儿急救医学

Anaphylaxis is a clinical emergency that could be fatal.Pediatricians in China have insufficient understanding of pediatric anaphylaxis and lack of comprehending of diagnosis and treatment protocols or guidelines.As a regional guideline in 2021, the European Academy of Allergy and Clinical Immunology Anaphylaxis guideline updated, which focused on the initial management of anaphylaxis in the community, emphasized the importance of adrenaline autoinjectors and training for healthcare professionals, and provided evidence-based advices for clinical diagnosis and long-term management, complementing the World Allergy Organization anaphylaxis guidance 2020.

Differential expression of microRNAs profile in the peripheral blood of children with drug-resistant epilepsy / 中华实用儿科临床杂志

Objective:To study the profile of microRNAs (miRNAs) in the peripheral blood of children with drug-resistant epilepsy, and to find diagnostic biomarkers for early identification of drug-resistant epilepsy in children.Methods:Retrospective study.Five peripheral blood samples were collected from children in drug-resistant epilepsy group (group R), drug-responsive epilepsy group (group F) composed of the children with epilepsy in pediatric neurology clinic of the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2019 and healthy control group (group J) composed of healthy children who underwent physical examination in the children′s health care clinic at the same time for analyzing miRNA profiles by high-throughput sequencing.In addition, peripheral blood samples were collected from children in R′ group (5 cases), F′ group (7 cases) and J′ group (6 cases) similarly for validating expression levels of 11 candidate miRNAs by quantificational real-time polymerase chain reaction (qPCR). Receiver operating characteristic curves (ROC) were plotted to analyze the diagnostic potential of 7 targeted miRNAs in distinguishing children with drug-resistant epilepsy from drug-responsive epilepsy.Target genes of the 7 validated miRNAs were predicted using online databases, which were then analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO). Kruskal-Wallis rank sum test was used for comparison among the three groups.Results:High-throughput sequencing found that compared with group F, there were 68 differentially expressed miRNAs in group R, involving 22 up-regulated and 46 down-regulated miRNAs.qPCR results showed that, expression trends of 7 miRNAs (let-7f, miR-99a-5p, miR-99b-5p, and miR-125a-5p, miR-125b-5p, miR-142-5p, miR-100) were consistent with high-throughput sequencing results among the 11 selected miRNAs.ROC analysis found that when the cut-off values of miR-99a-5p, miR-99b-5p, miR-125a-5p, miR-125b-5p, miR-142-5p and miR-100 were greater than 0.56, 1.00, 3.17, 2.24, 2.09 and 0.59, respectively, their area under curve (AUC) (≥0.871), sensitivity (≥80.0%) and specificity (≥85.7%) were relatively high, which were expected to be diagnostic marker for drug-resistant epilepsy in children.Among them, the diagnostic potential of miR-125b-5p was the best.Bioinformatics analysis found that miR-125b-5p was enriched in the regulation of hypoxia inducible factor-1 signaling pathway, insulin signaling pathway, pluripotent stem cell signaling pathway, mitogen-activated protein kinase signaling pathway, sphingomyelin signaling pathway, neurotrophic protein signaling pathway and mammalian target of rapamycin signaling pathway.Conclusions:The miRNA profile in the whole blood of children with drug-resistant epilepsy is significantly different from that in children with drug-responsive epilepsy.miR-125b-5p is expected to be a potential biomarker of drug-resistant epilepsy in children.

Three cases of febrile infection-related epilepsy syndrome / 中华实用儿科临床杂志

Objective:To investigate the clinical features, diagnosis and treatment of febrile infection-related epilepsy syndrome.Methods:The data of 3 children with febrile infection-related epilepsy syndrome admitted to the First Affiliated Hospital of Zhengzhou University from May to June 2019 were collected retrospectively, and their clinical characteristics, diagnosis, treatments and prognosis were summarized in combination with relevant literature.Results:The age of onset was 6-9 years old.The time interval from fever to first convulsion was 4-7 days, and they progressed to status epilepticus within 24 hours.The seizures were mainly multifocal seizures.Cerebrospinal fluid laboratory examination was normal.Electrocardiogram shows diffuse slow wave activity as the background, and epileptic waves dominated by the temporal area.Cranial magnetic resonance imaging showed signs of edema in 2 cases during the acute phase.All patients were resistant to multiple (4-5) anti-epileptic drugs, but high-dose anesthetic drugs can effectively terminate status epilepticus.All cases developed into refractory epilepsy, 2 cases had cognitive impairment and 1 case had movement impairment after 1 year.Conclusion:Febrile infection-related epilepsy syndrome often occurs in school-age children who have been physically healthy, which was included by fever.The seizures are explosive and refractory in febrile infection-related epilepsy syndrome, and it lacked specific laboratory indicators.High-dose anesthetics can effectively terminate status epilepticus, but it always has a poor prognosis.

Case report of 16p11.2 microdeletion only manifested as paroxysmal kinesigenic dyskinesia / 中华实用儿科临床杂志

The clinical data of a child with paroxysmal kinesigenic dyskinesia (PKD) and being diagnosed and treated in the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University in October 2018 were analyzed retrospectively.The male patient was 13 years old.The clinical manifestation was the change of body position, and the temporary movement cannot appear.The manifestations included the turning of head to one side, the falling back of neck, head shaking, swinging, the tightly hugging of hands in front of the chest, the touching of two tiptoes to the ground, numb sole, and ache.Gene detection: chromosome 16p11.2 (chr16: 29594293-30189789) had about 595.5 kb heterozygosity deletion.A total of 8 cases of 16p11.2 microdeletion in children with PKD were reported in details.16p11.2 microdeletion is another form of gene expression that causes PKD.16p11.2 microdeletion should be screened for genetic evaluation in patients with PKD.

Gut microbiome and sepsis-associated encephalopathy / 国际儿科学杂志

Sepsis-associated encephalopathy(SAE)is a common complication with high mortality in patients with sepsis, but its pathogenesis is not clear, and there is no recognized diagnostic criteria and specific treatment.Intestinal tract plays an engine-like role in the occurrence and development of sepsis.The destruction of intestinal barrier and the disorder of intestinal microorganisms can affect the outcome of sepsis, in which gut microbiome affect the pathophysiology of intestine and brain through " the microbiome-gut-brain axis" (MGBA), and "gut microbiome-mitochondrial crosstalk" explains its role at the organelle level.The gut microbiome disorder exists in SAE animal model, while fecal bacteria transplantation can improve the symptoms and prognosis, suggesting that the exploration of gut microbiome may be of certain significance to understand the mechanism of SAE and explore its treatment.Here we review from three aspects: the gut microbiome, MGBA and the role of gut microbiome in SAE.

Erythema multiforme caused by Mycoplasma pneumoniae infection in 3 children / 中华实用儿科临床杂志

Objective:To summarize the clinical features, diagnosis and treatment of erythema multiforme caused by Mycoplasma pneumoniae infection.Methods:The data of clinical features, treatment and prognosis of children diagnosed with erythema multiforme caused by Mycoplasma pneumoniae infection and treated in the First Affiliated Hospital of Zhengzhou University from Jane 2016 to December 2019 were retrospectively analyzed, and related literature was summarized.Results:All the 3 patients suffered from fever, cutaneous and mucous membrane lesions.Cutaneous lesions were manifested as exudative erythema multiforme, and the mucous membranes involved included oral mucosa, ocular conjunctiva and genital mucosa.The symptoms in all 3 cases were alleviated after the treatment with glucocor-ticoid, high doses of gamma globulin, anti-Mycoplasma pneumoniae and symptomatic support.Two children suffered secondary infection during treatment and improved with anti-infection.Neither patients had sequelae during the follow-up.Conclusions:Mycoplasma pneumoniae can cause erythema multiforme in children, but it is always misdiagnosed due to its clinical rarity.The mechanism of erythema multiforme caused by Mycoplasma pneumoniae infection is not clear.Early administration of glucocorticoid and high doses of gamma globulin, anti-Mycoplasma pneumoniae and symptomatic support often lead to a good prognosis.

Case report of X-linked intellectual disability caused by DDX3X gene mutation and literature review / 中华实用儿科临床杂志

Retrospective analysis of the clinical data of a child with type 102 mental retardation caused by DDX3X gene mutation in the pediatric diagnosis of the First Affiliated Hospital of Zhengzhou University in April 2019.A 2 years and 3 months old girl with " delay for more than 1 year" , using second-generation sequencing technology for full exon detection, and the result is DDX3X gene 13 th exon c. 1463G>A hybridization mutation, this is a new mutation.There are no Chinese cases reported with DDX3X gene mutations, and there are 8 related cases were reported in foreign literature, all children have different degrees of intellectual disability.So patients with unexplained intellectual disability(especially female patients) need to be wary of the possibility of DDX3X gene mutation.

Influencing factors of postencephalitic epilepsy in children with viral encephalitis at acute symptomatic seizure / 中华实用儿科临床杂志

Objective:To discuss the incidence rate and influencing factors of postencephalitic epilepsy (PE) in children with viral encephalitis at acute symptomatic seizure(ASS).Methods:The data of 132 children with ASS in the First Affiliated Hospital of Zhengzhou University from September 2013 to July 2018 were retrospectively analyzed, and the patients were divided into PE group (62 cases) and non-PE group (70 cases) according to whether they had PE at final follow-up.The risk factors of PE in children with ASS were analyzed using the multivariate Logistic regre-ssion methods. Results:The incidence of PE in children with ASS was 46.97% (62/132 cases). There were statistically significant differences in terms of psychological and behavioral abnormalities[19.4%(12/62 cases) vs.2.9%(2/70 cases)], repetitive seizures (more than 5 seizures) [67.7%(42/62 cases) vs.17.1%(12/70 cases)], status epilepticus (SE) [30.6%(19/62 cases) vs.11.4%(8/70 cases)], generalized seizures [72.6%(45/62 cases) vs.88.6%(62/70 cases)], endotracheal intubation [21.0%(13/62 cases) vs.2.9%(2/70 cases)], the duration of fever [5.5(3.0, 11.0) d vs.3.0(2.0, 6.0) d], the duration in the intensive care unit (ICU) [13(5, 21) d vs.6(3, 8) d], electroencephalography epileptiform discharges [49.1%(27/55 cases) vs.6.8%(4/59 cases)], presence of subcortical involvement on neuroimaging [37.3%(22/55 cases) vs.20.3%(14/59 cases)] in children with ASS between the PE group and the non-PE group(all P<0.05). The multivariate Logistic regression analysis showed that repetitive seizures (more than 5 seizures) ( OR=5.256, 95% CI: 1.538-17.961, P=0.008), SE( OR=6.003, 95% CI: 1.411-25.539, P=0.015), electroencephalography epileptiform discharges ( OR=36.693, 95% CI: 7.031-191.485, P<0.01) and the duration in ICU ( OR=1.170, 95% CI: 1.058-1.298, P=0.002) were the risk factors for PE in children with ASS. Conclusions:The incidence rate of PE in children with ASS is high.Children with ASS are more likely to develop into PE if they have repetitive seizures (more than 5 seizures), SE, electroencephalography epileptiform discharges, and the longer duration in ICU.

Changes and significance of serum intestinal fatty acid binding protein in children with traumatic brain injury complicated with gastrointestinal dysfunction / 中国小儿急救医学

Objective To study the changes and significance of serum intestinal fatty acid binding protein (IFABP) in children with traumatic brain injury(TBI) complicaled with acute gastrointestinal injury (AGI). Methods A total of 95 children suffering from TBI hospitalized in the PICU of the First Affiliated Hospital of Zhengzhou University from January 2017 to March 2018 were enrolled in the study. According to the modified Glasgow coma score combined with clinical classification criteria for acute closed head injury, the cases were devided into mild(43 cases),moderate (23 cases),and severe(29 cases). Children were gra-ded according to AGI (AGI Ⅰ42 cases,AGI Ⅱ 30 cases,AGI Ⅲ 13 cases,and AGI Ⅳ 10 cases). Thirty healthy children who underwent physical examination at outpatient service were enrolled as the control group. Blood samples were collected at the time of admission and on the 3rd day after admission. Serum IFABP was detected by ELISA,and the differences of serum IFABP concentrations were compared among groups. The correlations between IFABP with TBI classification and AGI grade were analyzed. The receiver operating characteristic (ROC) curve was drawn,and the predictive values of IFABP for the diagnosis of children with TBI complicated with AGI were evaluated. Results On the day of admission,the serum levels of IFABP in mild,moderate and severe brain injury group were significantly higher than that in control group (all P <0. 01). And serum IFABP concentration gradually increased with the increase of brain injury (all P < 0. 01).Serum IFABP levels in children with AGI grade Ⅰto Ⅳ were significantly higher than those in control group (all P < 0. 01). The levels of serum IFABP also increased with the increase of AGI level (all P < 0. 01). The concentration of serum IFABP was positively correlated with the grade of TBI and AGI (rs = 0. 82,P < 0. 01;rs = 0. 70,P < 0. 01). In each group,the levels of serum IFABP on the 3rd day after admission were lower than those on admission (all P < 0. 01). The ROC curve analysis showed that serum IFABP was of high diag-nostic value in children with TBI complicated with AGI,and the area under the ROC curve was 0. 88. When the cutoff value of IFABP was 431. 36 ng/ L,the sensitivity and specificity were 71. 61％ and 90. 00％ ,re-spectively. Conclusion Serum IFABP can be used as a sensitive indicator for the early diagnosis and disease assessment in children with TBI complicated with gastrointestinal dysfunction.

Clinical characteristics and risk factors of post-traumatic seizures in children / 中华实用儿科临床杂志

Objective To analyze the clinical characteristics and risk factors for post-traumatic seizures (PTS) in children,so as to provide a theoretical evidence for clinicians to prevent PTS.Methods From January 2010 to November 2016,the clinical data and auxiliary examination of 388 post-traumatic patients hospitalized at the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively.According to the presence of epileptic seizure,these patients were divided into PTS group and non post-traumatic seizures (nPTS)group.The risk factors associated PTS were investigated by univariate analysis.Results Among the 388 post-traumatic children,72 cases had seizures,which occurred almost predominantly less than 1 year.Fifty-six point nine percent (41/72 cases) were immediately PTS,and 31.9％ (23/72 cases) were early PTS,and 11.1％ (8/72 cases) were late PTS.Among the seizures types,generalized seizures accounted for 51.4％ (37/72 cases),and tonic-clonic seizures were in common;focal seizures accounted for 36.1％ (26/72 cases);focal combined generalized seizures accounted for 2.8％ (2/72 cases),and the remaining 9.7％ (7/72 cases) were ominous.Electroencephalogram showed the slow wave and spike wave most common.There were significant differences in factors statistically,included age,Glasgow Coma Scale (GCS) score,the severity of traumatic brain injury,cerebral contusion,subdural hematoma,therapy method between the patients with seizures group and the patients without seizures group (Z =4.717,x2 =13.079,17.852,5.664,17.457,5.496,all P ＜ 0.05).In single factor analysis and multi-factor regression analysis,age,GCS score,the severity of traumatic brain injury,subdural hematoma,therapy method were associated with the incidence of PTS (all P ＜ 0.05).Conclusions PTS is a severe complication of brain trauma in children.Small age,GCS ≤8 scores,severe brain injury,subdural hematoma,surgery are the risk factors of PTS.

Identification of pathogenic mutation in a Chinese pedigree affected with split hand/split foot malformation / 中华医学遗传学杂志

OBJECTIVE@#To detect potential mutation in a Chinese pedigree affected with split hand/split foot malformation (SHFM).@*METHODS@#The patients were screened for genome-wide copy number variations with single nucleotide polymorphism (SNP) microarray. Copy number variations were verified by real-time fluorescence quantitative PCR.@*RESULTS@#There were 3 SHFM patients from three generations, which conformed to an autosomal dominant inheritance. SNP microarray assay revealed that all patients have carried a 0.34 Mb duplication in 10q24.31-q24.32 (102 993 649-103 333 271) encompassing the BTRC and DPCD genes. The result was verified by real-time fluorescence quantitative PCR, confirming that the duplication has co-segregated with the SHFM phenotype in the pedigree.@*CONCLUSION@#The 10q24.31-q24.32 duplication probably underlies the pathogenesis of SHFM in this pedigree. Tiny copy number variations can result in diseases featuring autosomal dominant inheritance.

Study on glycyrrhizin in reducing neuronal damage by inhibiting high mobility group protein 1 in immature rats with epilepsy / 中华实用儿科临床杂志

Objective To study the effect of glycyrrhizin(GL) on the gene expression of high mobility group protein 1 (HMGB1) in hippocampus and serum.To evaluate the effect on the expression of neuron-specific nuclear-binding protein (Neu-N) in the hippocampus CA1,CA3 regions in the chronic stage of an immature rat epilepsy model.Methods Fifty-two 21 day-old SD rats were randomly divided into control group,model group Ⅰ and model group Ⅱ according to the random table method.Model group Ⅰ was induced epilepsy by kainic acid (KA),and the model group Ⅱ was pretreated with GL by intraperitoneal injection at 30 min before KA injection.According to the different observation time points,each group was divided into 4 subgroups:3 h,12 h,24 h and 7 d.Model group Ⅱ was divided into 3 subgroups:10 mg/kg,50 mg/kg,100 mg/kg,according to the different doses of GL.There were 3 animals in each subgroup.Score was performed according to the Racine score,and quantitative real-time polymerase chain reaction and Western blot were applied to detect the mRNA and protein expression of HMGB1 in the acute phase.Enzyme-linked immunosorbent assay(ELISA) was applied to measure the expression of HMGB1 in blood;immunohistochemical was applied to measure the expression of Neu-N in hippocampus in the chronic phase(7 d).Results Compared with model group Ⅰ,seizure onset time was obviously prolonged in model group Ⅱ [(24.08 ± 1.98) min vs.(33.39 ± 2.66) min],and the difference was statistically significant (t =9.231,P ＜0.05);Comparing KA model group Ⅰ with control group,the gene expression of HMGB1 significantly increased,and reached a peak at the time of 12 h (H =10.532,P ＜ 0.05),but the protein expression of HMGB1 was changed obviously and there was no significant difference (H =5.227,P ＞0.05).The expression of HMGB1 in the serum also significantly increased,especially at 12 h (H =6.897,P ＜0.05).At the time of 12 h after KA injection,the gene expression of HMGB1 in the hippocampus was significantly decreased in model group Ⅱ compared with model group Ⅰ (H =10.721,P ＜0.05) (especially in the 100 mg/kg model group).Also,the expression of HMGB1 in the scrum was obviously decreased (H =6.967,P ＜ 0.05) (especially in the 100 mg/kg model group).At the time of 7 d after KA injection,hippocampal neuron loss in model group.Ⅰ was significantly reduced compared with control group (P ＜ 0.05),and hippocampal neuron loss in model group Ⅱ was evidently decreased compared with model group Ⅰ (P ＜ 0.05),(especially in the 100 mg/kg model group in CA1,50 mg/kg model group in CA3).Conclusions In the immature rat temporal lobe epilepsy model,GL may have neuroprotective by inhibiting the synthesis and release of HMGB1,inhibiting inflammation further to restrain the loss of neurons in the chronic phase.

Value of apparent diffusion coefficient of magnetic resonance diffusion-weighted imaging for differential diagnosis of common pediatric posterior fossa tumors / 中华实用儿科临床杂志

Objective To investigate the value of apparent diffusion coefficient (ADC) of magnetic resonance diffusion-weighted imaging(DWI) for differential diagnosis of common pediatric posterior fossa tumors.Methods Forty-five children with posterior fossa tumors confirmed by surgery and pathology,who were hospitalized at the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2013 to December 2015 were analyzed by using retrospective case-control study,including 24 cases of medulloblastomas,12 cases of pilocytic astrocytomas,and 9 cases of ependymomas.All the children were examined by preoperative magnetic resonance imaging(MRI) plain scan,enhanced scan and DWI.The minimum ADC (ADCmin) values of different tumors were measured,and the receiver operating characteristic (ROC) curve was delineated.The threshold value of ADCmin,sensitivity,specificity and the accuracy for differential diagnosis of 3 tumors were obtained.Results The ADCmin value of medulloblastoma was the lowest [(0.482±0.290)×10-3 mm2/s],and the ADCmin value of pilocytic astrocytoma was the highest [(1.592±0.320)×10-3 mm2/s],while that of ependymoma was in the middle [(0.826±0.390)×10-3mm2/s].There was a significant difference in ADCmin value among 3 tumors(F=48.415,P=0.000).The threshold value of ADCmin to distinguish medulloblastoma from ependymoma was 0.672×10-3 mm2/s,the sensitivity was 97.0%,the specificity was 100.0%,and the diagnostic accuracy rate was 97.8%.The threshold value ADCmin to distinguish ependymoma from pilocytic astrocytoma was 1.058×10-3 mm2/s,the sensitivity was 95.7%,the specificity was 97.9%,and the diagnostic accuracy rate was 94.7%.Conclusions The minimum ADC value can be used as a supplementary means for conventional MRI,which is helpful for the differential diagnosis of pediatric posterior fossa tumors.

The management of antiepileptic drugs in women during lactation / 中华实用儿科临床杂志

Epilepsy is one of the most common chronic diseases of the central nervous system,many epilepsy patients need lifelong medication.Epidemiological studies have shown that 3‰-5‰ neonates born by women suffering from epilepsy.Treatment become more challenging because not only the patients themselves but also the breastfed in fants should be taken into consideration.This paper reviewed how to choose lactation antiepileptic drug.In short,choosing drugs which transport less to milk and have less side effects to infants,using the lowest effective dose and avoiding combination if possible can ensure the safety of breastfeeding.

Mutational analysis of PHEX,FGF - 23,and DMP - I genes in 4 families patients with familial hypophos-phatemic vitamin D resistant rickets / 中华实用儿科临床杂志

Objective To evaluate the frequency of mutations that occur in PHEX,FGF - 23 and DMP - I genes associated with familial hypophosphatemic vitamin D resistant rickets among 6 patients from 4 families in China. Methods The peripheral blood samples from 4 families were collected and other 10 persons from different families were selected as normal controls,and then the total gene DNA was extracted from the whole blood. Using polymerase chain reaction(PCR)amplication,sequences of the exons and flanking zones in PHEX,FGF - 23 and DMP - I genes were sequenced by direct DNA sequencing and TA cloning,and then the mutations found were analyzed. Results In exon 6 of DMP - I gene,c1218 C ﹥ T and c1230 G ﹥ A mutations were detected in lineage 1,as same sense mutation (propositus and its sister:homozygous mutation;mother:heterozygous mutation);c1333 - 1334 GC ﹥ TT mutation,as missense mutation,was found in exon 12 of PHEX gene on the propositus of lineage 2,determined as heterozygous muta-tion,but the same mutation was not found from their parents. In exon 3 of FGF - 23 gene,c716 C ﹥ T,p. T239M hetero-zygous mutation was found on the propositus and its mother. In exon 6 of the DMP - I gene,c205 A ﹥ T homozygous mutation was detected in lineage 3. In lineage 3,c716 C ﹥ T mutation of the FGF - 23 gene was detected,and the pro-positus and their father had the same mutation. No disease causing mutations of the PHEX,FGF - 23 and DMP - I genes were detected in the family members of lineage 1,3 and 4. Conclusions The mutation c1333 - 1334 GC ﹥ TT detected in exon 12 of PHEX gene might be the cause of disease for the propositus of lineage 2,as missense mutation, which needs further verification;c716 C ﹥ T,p. T239M mutation of the FGF - 23 gene detected in lineage 2 and 3 might not be the causes of the hypophosphatemic rickets and abnormal phenotype.

Change and significance of the soluble triggering receptor expressed of myeloid cells-1 and soluble urokinase plasminogen activator receptor expression in children with sepsis / 中华实用儿科临床杂志

Objective To investigate the change and clinical significance of soluble triggering receptor expression of myeloid cells-1 (sTREM-1) and soluble urokinase plasminogen activator receptor (suPAR) expression in children with sepsis.Methods There were 80 systemic inflammatory response syndrome (SIRS)patients who were included in the study,60 cases in the sepsis group,20 cases in the non-infectious SIRS group and 30 cases in the healthy control group.By using the enzyme-linked immunosorbent assay (ELISA)to dynamically monitor the levels of serum sTREM-1,suPAR in children with sepsis,the differences of sTREM-1,suPAR levels between children with sepsis and non-sepsis were observed,the correlation with the pediatric critical illness score(PCIS) was analyzed,and the sensitivity and specificity of sTREM-1,suPAR,C-reactive protein (CRP)and procalcitonin (PCT)and other biochemical markers were compared,and the value of sTREM-1,suPAR,CRP,PCT in the early determination and prognosis of sepsis were investigated.Results Serum sTREM-1,suPAR,PCT levels in sepsis group were significantly higher than non-infectious SIRS group and the healthy control group,and the difference was statistically significant (P ＜ 0.05),but the differences of serum CRP levels in non-infectious SIRS group and sepsis group were not statistically significant(P ＞ 0.05).In sepsis subgroup,serum sTREM-1,suPAR,PCT levels between the three groups were of statistically significant difference (P ＜ 0.05).Through dynamic monitoring of sepsis group,serum sTREM-1,suPAR,CRP,PCT levels had a gradual downward trend in 1,4,7 day,at each time point difference was statistically significant (P ＜ 0.05).Serum sTREM-1,suPAR levels in sepsis group had significant negative correlation with PCIS (r =-0.322,-0.333,P ＜ 0.05).The sensitivity and specificity of sTREM-1,suPAR,CRP,PCT on diagnosing sepsis were in a descending order,and sTREM-1 combined with suPAR has the highest sensitivity and specificity.Conclusions sTREM-1 and suPAR all can serve as indicators of infection and inflammation,as their expression level can reflect the severity of sepsis.sTREM-1 combined with suPAR diagnostic sensitivity and specificity of sepsis was significantly better than a single indicator of sTREM-1,suPAR,CRP,PCT.Combining multiple indicators can improve the accuracy of diagnosis.

The comparison and analysis of risk factors and outcomes of arterial ischemic stroke and hemorrhagic stroke in children / 临床儿科杂志

ObjectivesTo study the clinical characteristics, the risk factors and outcomes of arterial ischemic stroke (AIS) and hemorrhagic stroke (HS) in children.MethodsThe clinical data from 142 children with AIS or HS were retrospectively re-viewed and compared from Nov. 2010 to May 2014.ResultsIn these children, 92 cases (64.8%) was diagnosed of AIS, amont whom there were 60 males and 32 females and the onset age of stroke was 4.6±3.6 years (1 months to 16 years old), and 50 cases (35.2%) was diagnosed of HS, among whom there were 34 males and 16 females and the onset age of stroke was 2.6±3.7 years (1 months to 13 years old). The difference in age between two groups was statistically signiifcant (P=0.007). The most common presentation of AIS were focal neurological dysfunction including paralysis (73 cases, 79.3%), central facial palsy (30 cases, 32.6%) and speech impairment (19 cases, 20.7%). The most common presentation of HS were diffuse neurological dysfunction including dizziness (29 cases, 58.0%), nausea/vomiting (22 cases, 44.0%) and headache (14 cases, 28.0%). The major risk factors of AIS were arteriopathy (49 cases, 53.3%), infection (47 cases, 51.1%) and minor head injury (16 cases, 17.4%). The major risk factors of HS were vitamin K deifciency (22 cases, 44.0%), intracranial vascular anomalies (8 cases, 16.0%) and haematological disorders (6 cases, 12.0%). Five cases (6.4%) were died, 48 cases (61.5%) became disabled and 9 cases (11.5%) were relapsed in children with AIS while 15 cases (34.1%) were died, 19 cases (43.2%) became disabled in children with HS. The mortality was signiifcantly higher in children with HS than that in children with AIS (P<0.01).ConclusionsIn childhood stroke, HS occurs more frequently than is commonly appreciated and it has a poorer prognosis than AIS.