The value of combined detection of serum neurogranin and hypoxia-inducible factor-1α on the prognosis in patients with severe craniocerebral trauma / 中国医师进修杂志

Objective:To investigate the value of combined detection of serum neurogranin (NG) and hypoxia-inducible factor-1α (HIF-1α) in patients with severe craniocerebral trauma.Methods:Ninety-seven patients with severe craniocerebral trauma from June 2018 to March 2020 in Jinshan Branch of Shanghai Sixth People′s Hospital were selected. According to the Glasgow outcome score (GOS), 97 patients were divided into good prognosis group (GOS>3 scores, 46 cases) and poor prognosis group (GOS ≤ 3 scores, 51 cases). The NG, HIF-1α, Glasgow coma score (GCS), acute physiology and chronic health status score Ⅱ (APACHE Ⅱ) were compared between 2 groups. The independent risk factors of prognosis in patients with severe craniocerebral trauma were analyzed by multivariate Logistic regression analysis. The diagnostic efficacy of NG and HIF-1α on poor prognosis in patients with severe craniocerebral trauma was analyzed by receiver operating characteristic (ROC) curve. The correlation between serum NG, HIF-1α and APACHE Ⅱ in patients with severe craniocerebral trauma was analyzed by Pearson analysis.Results:The GCS in good prognosis group was significantly higher than that in poor prognosis group: (6.50 ± 1.74) scores vs. (4.76 ± 0.78) scores, the NG, HIF-1α and APACHE Ⅱwere significantly lower than those in poor prognosis group: (696.98 ± 158.96) ng/L vs. (875.92 ± 188.52) ng/L, (34.72 ± 13.98) μg/L vs. (51.29 ± 14.17) μg/L and (15.69 ± 3.45) scores vs. (22.58 ± 6.45) scores, and there were statistical differences ( P<0.01). Multivariate Logistic regression analysis result showed that the NG, HIF-1α, APACHEⅡ, GCS and type of craniocerebral trauma were independent risk factors on the prognosis in patients with severe craniocerebral trauma ( P<0.05 or<0.01). ROC curve analysis result showed that the AUC of NG and HIF-1αNG and HIF-1α combined detection to assess the poor prognosis in patients with severe craniocerebral trauma was significantly higher than NG and HIF-1α alone detection (0.873 vs. 0.772 and 0.821, Z = 2.276 and 1.949, P<0.05). Pearson correlation analysis result showed that APACHE Ⅱ was positive correlation with serum NG and HIF-1α in severe craniocerebral trauma patients with poor or good prognosis ( r = 0.852 and 0.889, P<0.01; r = 0.717 and 0.851, P<0.01). Conclusions:The combined detection of serum NG and HIF-1α can be used as an evaluation index for the prognosis in patients with severe craniocerebral trauma, which helps to determine the severity of craniocerebral trauma and has great value for clinical diagnosis and treatment.

Relationship between high mobility group protein A2 gene polymorphisms and the efficacy of recombinant human growth hormone treatment in children with prepubertal idiopathic short stature / 中华实用儿科临床杂志

Objective:To investigate the relationship of single nucleotide polymorphism (SNP) of high mobi-lity group protein A2 ( HMGA2) gene with prepubertal idiopathic short stature (ISS) and the efficacy of recombinant human growth hormone (rhGH) in Han population of Henan Province. Methods:A total of 120 children who were diagnosed with prepubertal ISS and treated with rhGH standards for at least one year from July 2017 to September 2019 at the Children′s Endocrinology Clinic of the Third Affiliated Hospital of Zhengzhou University were enrolled in the ISS group of this study.Meanwhile, 120 healthy children (control group) of the same age and gender whose height was within the normal range were selected as controls.Their peripheral blood was collected, and the polymorphism distributions of SNP loci(rs1042725 and rs7968682)were determined by molecular biology.Analysis was carried out to specify the annual growth rate, height standard deviation score (HtSDS), and insulin-like growth factor-1(IGF-1) of ISS children with different genotypes (before and after treatment )and those in the control group.Results:(1)In both ISS group and control group, children with CC and CT alleles at rs1042725 locus of HMGA2 had higher growth rate than those with TT allele before treatment[(4.33±0.64) cm/year, (3.95±0.45) cm/year; (6.35±0.41) cm/year, (6.12±0.32) cm/year vs.(3.76±0.52) cm/year, (5.96±0.42) cm/ year], therefore the difference were statistically significant (all P<0.05). (2)After treatment with GT genotype at the HMGA2 rs7968682 locus in children with ISS, the growth rate of age and bone HtSDS was higher than that of TT genotype [(0.74±0.30) cm/year vs. (0.63±0.24) cm/year, (0.16±0.05) cm/year vs.(0.14±0.05) cm/year], therefore the differences were statistically significant(all P<0.05). Conclusions:The polymorphism of the HMGA2 SNP locus (rs1042725) in the Han population of Henan province may be related to ISS level, while the polymorphism of the SNP locus (rs7968682) may be related to rhGH efficacy.

Identification of a novel nonsense IQSEC2 variant in a child with X-linked intellectual disability / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child featuring X-linked intellectual disability.@*METHODS@#The 1-year-and-6-month-old child presented with growth retardation, intellectual disability and bilateral alternating squint. With DNA extracted from the child and his parents' peripheral venous blood samples, whole exome sequencing was carried out to identify potential variants that can explain his condition. Suspected variants were validated by Sanger sequencing. The impact of variants was predicted by bioinformatic tools.@*RESULTS@#The child was found to harbor a de novo nonsense c.3163C>T (p.Arg1055*) variant of the IQSEC2 gene. The variant, unreported previously, was predicted to be pathogenic based on MutationTaster, PROVEAN and SIFT. Analysis using a HomoloGene system suggested Arg1055 in IQSEC2 residues to be highly conserved evolutionarily, and that replacement of Arg1055 may cause destroy of the PH domain (AA 951-1085) and serious damage to the function of IQSEC2 protein. Analysis with UCSF chimera software suggested that the c.3163C>T (p.Arg1055*) variant can induce serious damages to the secondary structures of IQSEC2 protein, causing loss of its function.@*CONCLUSION@#The patient's condition may be attributed to the de novo nonsense variant c.3163C>T (p.Arg1055*) of the IQSEC2 gene.

Analysis of ARSA gene variant in an infant with late infantile metachromatic leukodystrophy / 中华医学遗传学杂志

Objective@#To detect pathogenic variant of ARSA gene in an infant with late infantile metachromatic leukodystrophy (MLD).@*Methods@#The male proband had an onset of walking dysfunction and seizure at 28 months. Arylsulfatase A activity of his peripheral blood leucocytes was 26.9 nmol/mg.17h, and cranial MRI showed wild symmetrical demyelination. With genomic DNA extracted from his peripheral blood sample, all coding exons and splicing sites of the ARSA gene were subjected to Sanger sequencing. PubMed Protein BLAST system was employed to analyze cross-species conservation of the mutant amino acid. Ucsf chimera software was used to analyze the impact of candidate variants on the secondary structure of the protein product. Impact of potential variants was also analyzed with software including PolyPhen-2, Mutation Taster, SIFT and PROVEAN. Whole-exome sequencing was carried out to identify additional variants which may explain the patient’s condition.@*Results@#The proband was found to harbor compound heterozygous variants of the ARSA gene [c.467G>A (p.Gly156Asp) and c. 960G>A (p.Trp320*)], neither of which was reported previously. As predicted by Ucsf chimera software, the c. 960G>A (p.Trp320*) variant may demolish important secondary structures including α-helix, β-strand and coil of the ARSA protein, causing serious damage to its structure and loss of function. The c. 467G>A (p.Gly156Asp) variant was predicted to be "probably damaging" by PolyPhen-2, Mutation Taster and SIFT software.@*Conclusion@#The patient’s condition may be attributed to the compound heterozygous c. 467G>A (p.Gly156Asp) and c. 960G>A (p.Trp320*) variants of the ARSA gene. Above results have facilitated genetic counseling and prenatal diagnosis for this family.

Analysis of ARSA gene variant in an infant with late infantile metachromatic leukodystrophy / 中华医学遗传学杂志

OBJECTIVE@#To detect pathogenic variant of ARSA gene in an infant with late infantile metachromatic leukodystrophy (MLD).@*METHODS@#The male proband had an onset of walking dysfunction and seizure at 28 months. Arylsulfatase A activity of his peripheral blood leucocytes was 26.9 nmol/mg.17h, and cranial MRI showed wild symmetrical demyelination. With genomic DNA extracted from his peripheral blood sample, all coding exons and splicing sites of the ARSA gene were subjected to Sanger sequencing. PubMed Protein BLAST system was employed to analyze cross-species conservation of the mutant amino acid. Ucsf chimera software was used to analyze the impact of candidate variants on the secondary structure of the protein product. Impact of potential variants was also analyzed with software including PolyPhen-2, Mutation Taster, SIFT and PROVEAN. Whole-exome sequencing was carried out to identify additional variants which may explain the patient's condition.@*RESULTS@#The proband was found to harbor compound heterozygous variants of the ARSA gene [c.467G>A (p.Gly156Asp) and c.960G>A (p.Trp320*)], neither of which was reported previously. As predicted by Ucsf chimera software, the c.960G>A (p.Trp320*) variant may demolish important secondary structures including α-helix, β-strand and coil of the ARSA protein, causing serious damage to its structure and loss of function. The c.467G>A (p.Gly156Asp) variant was predicted to be "probably damaging" by PolyPhen-2, Mutation Taster and SIFT software.@*CONCLUSION@#The patient's condition may be attributed to the compound heterozygous c.467G>A (p.Gly156Asp) and c.960G>A (p.Trp320*) variants of the ARSA gene. Above results have facilitated genetic counseling and prenatal diagnosis for this family.

Analysis of PMM2 gene variant in an infant with congenital disorders of glycosylation type 1a / 中华医学遗传学杂志

OBJECTIVE@#To identify potential mutation of PMM2 gene in an infant with congenital disorders of glycosylation type 1a (CDG-1a).@*METHODS@#Genomic DNA was extracted from peripheral blood sample of the patient. All coding exons (exons 1-8) and splicing sites of the PMM2 gene were amplified with PCR. Potential variants were detected by direct sequencing of the PCR products and comparing the results against the ESP and SNP human gene databases. A protein BLAST system was employed to analyze cross-species conservation of the variants amino acid. A PubMed BLAST CD-search system was employed to identify functional domains damaged by variants of the PMM2 gene. Impact of potential variants was analyzed using software including PolyPhen-2 SIFT and Mutation Taster. Whole exome sequencing was used to identify additional variants of the PMM2 gene which may explain the condition of the patient.@*RESULTS@#The child was found to carry compound heterozygous variants (c.458_462delTAAGA and c.395T>C) of the PMM2 gene, which were inherited respectively from his father and mother. The c.458_462delTAAGA has not been reported previously and may result in disruption of 10 functional domains within the PMM2 protein. The c.395T>C mutation has been recorded by a SNP database with frequency unknown. Both mutations were predicted as "probably damaging". Whole exome sequencing has identified no additional disease-causing variant which can explain the patient's condition.@*CONCLUSION@#The patient's condition may be attributed to the compound heterozygous variants c.458_462delTAAGA and c.395T>C of the PMM2 gene. Above results has facilitated molecular diagnosis for the patient.

Sensitivity of supplementation of thyroid hormone on treatment of idiopathic short-stature children during therapy with recombinant human growth hormone / 医学前沿

This study aimed to evaluate the effects of thyroid hormone supplementation on growth rate of children with idiopathic short stature (ISS) and low-normal serum free thyroxine FT4 who were receiving growth hormone therapy. We selected 64 prepubertal children with FT4 levels in the lowest third of the normal range as the lower FT4 group, and these children were divided randomly into two subgroups: L-thyroxine (L-T4)-treated subgroup was treated with L-T4 (0.5-3.0 g/(kg·d)) from the beginning of the study, and the non-L-T4-treated subgroup received placebo. We also selected 39 ISS children with FT4 in the upper two-thirds of the normal range as the higher FT4 group. During the first year, the lower FT4 group featured lower FT3, FT4, thyroid stimulating hormone (TSH), and insulin-like growth factor-I standard deviation score (IGF-I SDS) and significantly lower height velocity (HV) compared with the higher FT4 group. However, in the lower FT4 group, the L-T4-treated subgroup presented higher FT4, FT3, TSH, and IGF-I SDS concentrations and significantly higher HV compared with children in the non-L-T4-treated subgroup. In children with ISS, the negative effect of thyroid hormone deficiency on growth rate should be considered when FT4 level lies in the low-normal range prior to recombinant human growth hormone treatment.

Infantile Sandhoff disease:a case report and literature review / 临床儿科杂志

Objective To summarize the clinical manifestations, diagnosis, and treatment of infantile Sandhoff disease. Methods The clinical data of one case with infantile Sandhoff disease were reviewed retrospectively. The related literatures were reviewed. Results The girl aged 1 year and 2 months suffered from psychomotor regression and intractable convulsions. The parents were consanguineous marriage. The fundus microscopy showed fundus erythema. Brain magnetic resonance imaging showed an abnormal signal of long T2WI and identical T1WI at left pons, white matter edema, and diffuse demyelination. No abnormal karyotype was observed. A chromosome microarray suggested multiple large homozygous chromosomes segments. The second generation gene sequencing showed deletion of c.1263_1268delTGAAGT:P. (Glu422_Val423del) deletion in exon 11 and a shear mutation of c.1614_2A>G:P? in intron 13 of HEXB gene which were carried by her parents respectively . The activity of HexA, HexA & HexB were 84 and 112 nmol?mg?1?h?1, respectively. Finally, this girl was diagnosed of infantile Sandhoff's disease. After treatment with valproate, levetiracetam combined with antiepileptic and glucocorticoids, episodes of convulsions were decreased gradually, and the reaction was better than before. In 5 months of follow up, the condition was stable, and no progression and no seizures exist. Her mother got pregnant again and received an amniocentesis on her 21+6 weeks of pregnancy, and results suggest that the fetus had the same mutation as this girl. Conclusions Sandhoff's disease is a type of rare hereditary lysosomal disease, characterized by progressive neurological impairment. Currently there are no effective treatments. Genetic testing is helpful in the diagnosis and prenatal diagnosis.

Analysis of the influence of iron overload in glucose metabolism in thalassemia major patients / 中华儿科杂志

Objective@#This study aimed at determining the characteristics of the glucose homeostasis and its relationship with iron overload of the patients with β-thalassemia major (β-TM).@*Method@#From Sun Yat-sen Memorial Hospital between January 2014 and December 2015, a total of 57 transfusion-dependent β-TM patients with 5-18 years old were enrolled in this study and fasting blood glucose(FBG) and insulin level, serum ferritin (SF), serum iron, transferrin, total iron binding capacity, unsaturated iron binding capacity were determined.Insulin resistance index (IRI), insulin sensitivity index and β-cell function index (BFI) were also estimated. Besides, in 36 patients cardiac T2* and liver T2* were estimated.@*Result@#(1) Four patients(7%) with β-TM were diagnosed diabetes mellitus, and 14(24%) had impaired fasting glucose. (2) The incidence of abnormal glucose metabolism was significantly different according to levels of SF and degrees of the cardiac iron overload(χ2=9.737, P<0.05; χ2=17.027, P<0.05). It rose while the level of SF increased and the degree of cardiac iron overload aggravated. (3) The incidence of abnormal glucose level was not significantly different in cases with different degree of liver iron overload.The severe group of liver iron overload had significantly higher levels of INS, HOMA-βFI, HOMA-ISI, HOMA-βFI than the non-severe group (Z=-2.434, -2.515, F=8.658, all P<0.05), while no differences were found in the level of FBG, HOMA-βFI between two groups. (4) The result of logistic regression analysis indicated that the cardiac T2* was a significant predictor for the incidence of abnormal glucose metabolism in TM patients (P=0.035, OR=1.182%, 95%CI=1.048 to 1.332).@*Conclusion@#The high prevalence of abnormal glucose metabolism in β-TM patients was mainly closely related with the internal iron overload, especially in organs.The cardiac T2* was an independent risk factor for the incidence of abnormal glucose metabolism in TM patients.

Changes of serum sodium and urine sodium of children with febrile seizures and its clinical significance / 中国基层医药

Objective To analyze the changes of the urine sodium and serum sodium in different types and different duration and different temperature in children with febrile seizures,to explore its clinical significance. Methods The children with febrile seizures(n =50)were selected as the group Ⅰ,and the children with fever but without seizure(n =50)were selected as the group Ⅱ,both of them were from pediatric ward.The control group(n =20)without fever or seizure was from Children's Health Section.All the children were checked serum sodium level and urine sodium and urine creatinine level.Results The sodium/creatinine ratio in the groupⅠ[(25.07 ±6.517)] was significantly higher than that in the group Ⅱ[(20.43 ±5.48)]and group Ⅲ[(14.88 ±5.11)](F =33.519, P <0.05),but there was no significant difference of the sodium/creatinine ratio in different ages and different types of the group Ⅰ,and there was negative relevance between the serum sodium and the sodium/creatinine ratio in the groupⅠ(r =-0.517,P <0.05).The mean serum sodium level in the groupⅠ[(133.50 ±3.14)mmol/L]was signifi-cantly lower than that in the group Ⅱ[(137.60 ±2.59)mmol/L]and group Ⅲ[(138.90 ±2.24)mmol/L](F =39.220,P <0.05),but there were no significant differences of the serum sodium in different types and different dura-tion and different temperature of seizure in the group Ⅰ.Conclusion The study shows that serum sodium is lower and the urine sodium is higher in children with febrile seizures,the changes of the urine sodium and serum sodium are not related to the types.The children with febrile seizures should be timely monitoring of serum sodium,urine sodium levels,and according to changes in the level of serum sodium,urine sodium,early appropriate supplement containing sodium liquid and maintaining the blood sodium to normal levels can reduce the recurrence of seizure.

Effect of bone marrow mesenchymal stem cells on inflammatory factors released by LPS-stimulated BV-2 microglia / 实用医学杂志

Objective To explore the effect of bone marrow mesenchymal stem cells (MSCs) on LPS-stimulated BV2 microglia in inflammatory reaction. Methods Mouse MSCs were isolated and purified by adherence screening. The routinely cultured BV2 microglia in vitro were divided into PBS control group (group A),PBS plus MSCs treatment group(group B),LPS stimulation group(group C) and LPS plus MSCs group(group D).MSCs and BV2 microglia were cultured in the transwell co-culture system for 24 hours. We observed BV2 microglia morphological changes under the microscope,detected the concentrations of NO by Griess reaction,and the level of IL-1β,TNF-αby ELISA. Results MSCs can improve the morphology of activated microglia. The concentrations of TNF-a, IL-1βand N0 in culture supernatants were increased significantly (P < 0.05) after microglia activation, however, at the present of MSCs,the concentration of these inflammatory factors declined dramaticly (P<0.05). Conclusions MSCs can significantly inhibit the activation of microglia. It may play a neuroprotective effect by reducing the inflammation of microglia. MSCs showing anti-inflammatory effects through non-direct contact with nicroglial, suggesting that MSCs outside the brain may also inhibit the activation of microglia.

The relationship between cytokines and epilepsy / 中国病理生理杂志

The interaction between the immune system and nervous sytem affcts nervous function.There is a close relationship between the episode of epilepsy and immunity,the molecular basis of which is the network of cytokines.In order to quest new methods of contolling epilepsy by regulating the network of cytokines,the roles of several cytokines in the ocurrence and onset of epilepsy were reviewed in this article.

Changes of the BDNF in the hippocampus of P77PMC during seizures / 中国病理生理杂志

AIM: To quest the relationship bwteen BDNF and seizures. METHODS: BDNF and other correlative proteins in the hippocampus of audioepileptic rat (P77PMC) have been detected by immunohistochemistry at different stages of seizures including quiet stage, preconvulsive stage, convulsive stage and postconvulsive stage. Wistar rats were served as controls. RESULTS: At quiet stage, the BDNF in the hippocampus of P77PMC were less than that of control group and stepped up after stimulation, trkB in the hippocampus of P77PMC were high at every stages, but PY20 were increased only after stimulation. NPY in the hippocampus of P77PMC were in a low level before seizures. CONCLUSION: The endogenetic BDNF may alter the excitement of P77PMC by adjusting the expression of NPY in hippocampus and activating its receptor trkB.

Research progress in neuropeptide Y and epilepsy / 中国病理生理杂志

Neuropeptide Y (NPY) is a pancreatic polypeptide-related peptide, consisting of 36 amino acids. NPY is expressed in the nervous system widely and abundantly, mainly in the hippocampus, regulates the excitability of neurons through its receptors (Y_1, Y_2, Y_5). In recent years the research progress indicated the changes induced by seizures in the level and distribution of NPY, its receptors subtypes and their respective mRNAs in brain. The inhibitory action of NPY on glutamate-mediated neurotransmission and in seizure phenomena, suggests that one of its roles in hippocampal physiology is to modulate neuronal excitability by regu-lating glutamate release.