Glyceryl phenylbutyrate in the treatment of argininosuccinate synthetase deficiency: a case report / 中华实用儿科临床杂志

Clinical data of a child with high blood ammonia and suspected argininosuccinate synthetase deficiency (ASSD) in Hunan Children′s Hospital were retrospectively analyzed, including data of mass spectra for blood amino acids and acyl carnitine, urine organic acid analysis and whole exome sequencing.After the exact diagnosis of ASSD and being approved by the Administrative Regulation for Import Medical Devices Urgently Needed in Boao Lecheng International Medical Tourism Pilot Zone of Hainan Free Trade Port, the patient was medicated with Glyceryl phenylbutyrate (GPB) and followed up.The patient was a boy aged 7 years and 8 months, who presented at the Neurology Department of Hunan Children′s Hospital for sleepiness, abnormal mental behavior and personality change for 1 week on December 2, 2021.Before GPB treatment, the highest blood ammonia, alanine aminotransferase and aspartate transaminase were 325.2 μmol/L, 465.7 IU/L and 277.3 IU/L, respectively.Genetic metabolism assay of blood and urine showed a significantly increased citrulline at 697.42 μmol/L; urine organic acid analysis showed increased urinary orotic acid at 144.2 μmol/L, and increased uracil at 65.1 μmol/L.A pure heterozygous variant of the ASS1 gene (c.1087C>T, p.R363W) was detected.After GPB treatment, the blood ammonia levels were 21.3 μmol/L, 54.6 μmol/L and 62.4 μmol/L on the 41 st, 90 th and 146 th days, respectively.Until July 20, 2022 follow-up visit, the patient recovered well without adverse events.This was the first ASSD child in China who was treated with GPB.This case report provided therapeutic experience of ASSD in our country.ASSD has a high mortality rate and unexplained abnormal mental behavior.It is necessary to timely measure blood ammonia, and a series of urea cycle disorders should be well concerned.The diagnosis and management of ASSD rely on the data of metabolism examination and genetic testing.

Analysis of clinical phenotype and genetic variants in a child with mitochondrial F-S disease due to variants of FDXR gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic variants of a child suspected for mitochondrial F-S disease.@*METHODS@#A child with mitochondrial F-S disease who visited Department of Neurology, Hunan Provincial children's Hospital on November 5, 2020 was selected as research subject of this study. Clinical data of the child was collected. The child was subjected to whole exome sequencing (WES). Bioinformatics tools were used to analyze the pathogenic variants. Candidate variants were verified by Sanger sequencing of the child and her parents.@*RESULTS@#WES revealed that the child has harbored compound heterozygous variants of the FDXR gene, namely c.310C>T (p.R104C) and c.235C>T (p.R79C), which were inherited from her father and mother, respectively. Neither variant has been reported in HGMD, PubMed, 1000 Genomes, and dbSNP databases. Both of the variants have been suggested as deleterious according to the prediction results from different bioinformatics analysis software.@*CONCLUSION@#Mitochondrial diseases should be suspected for patients with multiple system involvement. The compound heterozygous variants of the FDXR gene probably underlay the disease in this child. Above finding has enriched the spectrum of FDXR gene mutations underlying mitochondrial F-S disease. WES can facilitate the diagnosis of mitochondrial F-S disease at the molecular level.

Genetic analysis of a child with early onset neurodevelopmental disorder with involuntary movement and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical phenotype and genetic basis of a child with early onset neurodevelopmental disorder with involuntary movement (NEDIM).@*METHODS@#A child who presented at Department of Neurology of Hunan Children's Hospital on October 8, 2020 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Whole exome sequencing (WES) was carried out for the child. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Relevant literature was searched from the CNKI, PubMed and Google Scholar databases to summarize the clinical phenotypes and genetic variants of the patients.@*RESULTS@#This child was a 3-year-and-3-month boy with involuntary trembling of limbs and motor and language delay. WES revealed that the child has harbored a c.626G>A (p.Arg209His) variant of the GNAO1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. The variant had been reported in HGMD and ClinVar databases, but not in the dbSNP, ExAC and 1000 Genomes databases. Prediction with SIFT, PolyPhen-2, and Mutation Taster online software suggested that the variant may be deleterious to the protein function. By UniProt database analysis, the encode amino acid is highly conserved among various species. Prediction with Modeller and PyMOL software indicated that the variant may affect the function of GαO protein. Based on the guideline of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic.@*CONCLUSION@#The GNAO1 gene c.626G>A (p.Arg209His) variant probably underlay the NEDIM in this child. Above finding has expanded the phenotypic spectrum of GNAO1 gene c.626G>A (p.Arg209His) variant and provided a reference for clinical diagnosis and genetic counseling.

The clinical efficacy and follow-up study of ketogenic diet adding treatment for refractor epilepsy in children / 中国医师杂志

Objective To study the clinical efficacy and follow-up study of ketogenic diet adding treatment for refractor epilepsy in children.Methods Cluster sampling method was employed to select children in children's hospital from January 2015 to June 2017,a total of 25 cases were diagnosed refractor epilepsy and adding ketogenic diet.Engel grade was used to evaluate the efficiency,the side effects,electroencephalogram (EEG) changes and intellectual development at 3 months,3-6 months,and more than 6 months.Results The effective rate of epileptic seizure control was 0,66.7％ and 87.5％ at 3 months,3 -6 months and ＞ 6 months respectively.The improvement rate of EEG discharge index was 33.3％,50％ and 81.3％ respectively.The improvement of intelligence development was 33.3％,50％ and 68.8％ respectively.Gastrointestinal disturbances were the main side effects.Severe side effect occurred in two cases--they had severe food refusal and were stopped the ketogenic diet adding treament.Conclusions The ketogenic diet is effective,safe,few side effects and tolerable in infants and children with refractory epilepsy.The ketogenic diet may improve cognition and behavior in addition to reducing seizure frequency,the interical epileptiform discharges (IED) index and improve the quality of life of epileptic children.However,the acceptance of ketogenic diet therapy for children is not satisfactory.The sample size is small and needs further promotion.While large samples and long-term observations are still desired to better recipes,and to provide possibly effective altemative to other therapies for refractor epilepsy.

Study on the Quality Standard of Fresh Gastrodia elata Lyophilized Powder / 中国药房

OBJECTIVE:To provide reference for the establishment of quality standard for Fresh Gastrodia elata lyophilized powder. METHODS:TLC was conducted for the qualitative identification of G. elata in preparation,and HPLC was conducted for the content determination of gastrodin in preparation. The column was Diamonsil C18 with mobile phase of acetonitrile-0.05% phos-phoric acid(3∶97,V/V)at a flow rate of 1.0 ml/min,detection wavelength was 220 nm,column temperature was 25 ℃ and vol-ume injection was 10 μl. RESULTS:TLC pots of Fresh G. elata lyophilized powder were clear and well-separated. The linear of gastrodin was 2.9-14.5 μg/ml(r=0.999 9);RSDs of precision,stability and reproducibility tests were no more than 1.00%;recov-ery was 98.07%-102.70%(RSD=1.74%,n=6). CONCLUSIONS:The method is simple,accurate and reproducible,and suitable for the quality control of Fresh G. elata lyophilized powder.

Study on the Quality Standard of Anti-virus Chewable Tablet / 中国药房

OBJECTIVE:To establish the quality standard for Anti-virus chewable tablet. METHODS:TLC was used for the qualitative identification of Forsythia suspensa,Anemarrhena asphodeloides and Pogostemon cablin in Anti-virus chewable tablet, and HPLC was conducted to determine the content of forsythin in F. suspensa. The column was Diamonsil C18 with mobile phase of acetonitrile- water (20∶80,V/V) at the flow rate of 1.0 ml/min,the detection wavelength was 230 nm,column temperature was 25℃,and injection volume was 10μl. RESULTS:The test sample and the reference sample displayed same color spots on the cor-responding position in TLC diagram. The linear range of forsythin was 0.053 5-2.675 μg(r=0.999 9);RSDs of precision,stabili-ty and reproducibility tests were no more than 1.74%;average recovery was 98.94%(RSD=1.84%,n=6). CONCLUSIONS:The method is simple,rapid,accurate,reliable and reproducible,and can be used for quality control of Anti-virus chewable tablet.

Study on the Quality Standards for Gastrodia elata Horey-fired Tablet / 中国药房

OBJECTIVE:To establish the quality standard for Gastrodia elata hency-fired tablet. METHODS:TLC was used to identify the gastrodin and benzyl alcohol and determine the content of moisture,ash and extract;HPLC was used to determine the content of gastrodin and benzyl alcohol. Column was Diamonsil C18 with mobile phase of acetonitrile-0.05% phosphate(3:97,V/V) at flow rate of 1.0 ml/min,detection wavelength was 220 nm,column temperature was 25 ℃ and volume injection was 10 μl. RE-SULTS:The TLC of gastrodin and benzyl alcohol showed clear spots and good separation. The moisture content40.0%. Linear range of gastrodin was 25.2-126.0,12.7-63.5 μg/ml(r=0.999 9),respectively;RSDs of precision,reproducibility and stability tests were lower than 2.0%;recovery was 99.49%-102.40%(RSD=1.09%,n=6), 98.75-102.63%(RSD=1.53,n=6),respectively. CONCLUSIONS:The method is simple and good reproducibility,and can be used for the quality control of Gastrodia elata hency-fired tablet.

Study on Quality Control of Polygonum Capitatum from GAP Planting Base by HPLC Characteristic Spectrum / 中国中医药信息杂志

Objective To establish HPLC characteristic spectrum of Polygonum Capitatum from GAP planting base, and provide reference for the overall quality control of Polygonum Capitatum. Methods HPLC analysis was performed on a DiamonsiL C18 chromatographic column (250 mm× 4.6 mm, 5μm) with the eluting system of gradient consisted of methanol and 0.2% H3PO4. The flow rate was 1.0 mL/min. The column temperature was maintained at 25℃ and the detection wavelength was at 254 nm.Results HPLC characteristic spectrum of Polygonum Capitatum samples from 10 different areas was established, which contained 11 common peaks, and the similarities of comparative results were over 90%.Conclusion The established method can be used to determine the characteristic spectrum of Polygonum Capitatum and can provide a basis for the overall quality control and quality standards of Polygonum Capitatum.

Changes of Caveolin-1, IL-1β, VEGF in cerebrospinal fluid of children with viral encephalitis and their clinical significance / 国际儿科学杂志

Objective To detect the disparity of three biological molecules Caveolin-1,IL-1β,VEGF in cerebrospinal fluid of children with viral encephalitis at the different stages; to explore the role of Caveolin-1,IL-1β,VEGF in the pathogenesis of viral encephalitis;and to evaluate their clinical significance in assessing the severity and prognosis of viral encephalitis.Methods We recruited 65 inpatients children with viral encephalitis in the Second Neurology Department of Hunan Children's Hospital from July 2011 to July 2012.Subjects were divided into 2 groups:54 cases of acute phase and 11 cases of recovery phase.According to the clinical manifestations,they were re-divided into 40 patients with mild viral encephalitis and 25 cases of severe viral encephalitis.Twenty healthy age matched controls (10 cases of epilepsy and 10 cases of congenital abnormality) were also taken for the study.Cerebrospinal fluid exam,EEG,head MRI and other tests were performed in all patients.Caveolin-1,IL-1β and VEGF levels in cerebrospinal fluid of 65 children with viral encephalitis and 20 age-matched controls were measured using ELISA.Results Cerebrospinal fluid Caveolin-1,IL-1β,VEGF levels in the acute phase of viral encephalitis were (49.209 ± 22.320) pg/ml,(16.923 ± 6.823) ng/ml,(44.342 ± 19.264) ng/ml respectively,and (33.253 ± 20.349)pg/ml,(11.724 ± 3.009)ng/ml,(30.312 ± 18.147) ng/ml in recovery phase,which were significantly higher than those of controls (P ＜0.01).The difference was statistically significant between acute phase and recovery phase (P ＜ 0.05).Acute viral encephalitis patients had higher Caveolin-l,IL-1β,VEGF levels than the epilepsy group,and the difference was statistically significant (P ＜ 0.05).In viral encephalitis group,children with cerebrospinal fluid protein content (0.5 ～ 1.0 g / L) had higher of Caveolin-1,IL-1β and VEGF levels as compared with those with cerebrospinal fluid protein content ≤ 0.5 g/L,and the difference was statistically significant (P ＜ 0.01).Cerebrospinal fluid Caveolin-1,IL-1 β and VEGF showed no significant difference among children with different severity of encephalitis,different levels of frequent seizures,different degrees EEG changes (P ＞ 0.05).But in the patients with severe head MRI changes,cerebrospinal fluid Caveolin-1,IL-1β,VEGF levels increased significantly (P ＜ 0.05).Conclusions Caveolin-1,IL-1β and VEGF may participate in the pathogenesis of viral encephalitis.Detection of these parameters may be helpful to the evaluation of the severity and prognosis of viral encephalitis.

Factors predicting the risk of seizure relapse after antiepilepsy drug withdrawal in childhood epilepsy / 中华实用儿科临床杂志

Objective To investigate the factors associated with seizure relapse after antiepilepsy drug (AED) withdrawal in childhood epilepsy.Methods A retrospective analysis was conducted in epileptic children of Hunan Children's Hospital from Jan.2003 to Jan.2011.Among those with anti-epileptic therapy for seizure-free period over 2 years,the patients who relapsed after withdrawal were followed up through outpatient clinic visits and/or by telephone interviews for at least 2 years.Results Of the 127 cases of children enrolled in this study,28 patients(22.05％) relapsed [male:12/59 cases (20.34％) and female:16/68 cases (23.53％)].Cumulative relapse rates were 18.18％ (8/44 cases) in infancy,15.79％ (6/38 cases) in toddlers,23.53％ (8/34 cases) in preschool children,and 54.55％ (6/11 cases)in school age group.Of the patients who relapsed,generalized seizure occurred in 12/87 cases (13.79％),partial seizure in 16/40 cases(40.00％).According to seizure frequency between the first seizure and AED administration,3 cases(6.25％) relapsed among 48 cases of seizure frequency ＜ 5 times,13 cases(24.07％) relapsed among 54 cases of seizure frequency 5 to 10 times,and 12 cases(48.00％) relapsed among 25 cases of seizure frequency more than 10 times.Relapse occurred in 9 cases of monotherapy(9/91 cases,9.89％) and in 19 cases of polytherapy (19/36 cases,52.78％).According to the seizure control period (period between the beginning of antiepileptic treatment and AED withdrawal),14 cases relapsed among 37 cases with the seizure control period of 2 to 3 years (37.84％),8 cases relapsed among 51 cases with the period of 3 to 4 years (15.69％),and 6 cases relapsed among 39 cases with the period of 4 to 5 years(15.38％).According to AED tapering off period,10 cases relapsed among 24 cases with the period of 3 months (41.67％),9 cases relapsed among 36 cases with the period of 3-6 mc ths (25.00％),and 9 cases relapsed among 67 cases with the period of over 6 months(13.43％).Factors associated with an increased risk of relapse were age of epilepsy onset,seizure type,route of administration,timing of antiepileptic trug withdrawal,tapering speed,which were had statistical significance (x =8.051,6.780,16.896,27.607,7.576,8.451,all P ＜0.05).Gender difference was not associated with the risk of relapse(x2 =0.187,P ＞ 0.05).Conclusions Factors associated with an increased risk of relapse are age of epilepsy onset,seizure type,route of administration,timing of antiepileptic drug withdrawal,tapering speed.Standard therapies of early treatment,adherence to medication for at least 3 years,taper period for more than 6 months are associated with a decreased probability for relapse.

Clinical analysis of purulent meningitis caused by streptococcus pneumoniae in 12 children / 中国小儿急救医学

Objective To investigate the clinical characteristics of purulent meningitis caused by streptococcus pneumoniae.Methods We studied clinical features of 12 children with purulent meningitis caused by streptococcus pneumoniae who were hospitalized from Jan 2007 to Oct 2011 in our hospital.Results Twelve children were penicillin-resistant streptococcus pneumoniae.The ages ranged from 2 months to 10 years.Nine cases(75％) were aged less than 5 years,and 5 cases(41.6％) were aged less than 2 years.All cases were with fever,and with the nervous system symptoms involvement.All cases were with complications:9 cases(75％) with septicemia,8 cases (66.7％) with pneumonia.The white blood cells,blood C-reactive protein,peripheral blood procalcitonin,erythrocyte sedimentation rate,white cells and protein in cerebrospinal fluid were mostly significantly high,sugar in cerebrospinal fluid were low significantly.Eleven cases were eventually treatmented by vancomycin plus 3rd to 4rd generations of cephalosporins antibiotics or other antibiotics.Eight cases were cured,2 cases with serious sequela,and 2 cases died.Conclusion We should attach importance to the meningitis caused by streptococcus pneumoniae.For clinical suspects pneumonia streptococcus meningitis,to given the powerful therapy by vancomycin plus the other antibiotics,as early as possible.

Determination of quercitrin in Polygonum capitatum and relinqing granules by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To establish an HPLC method for determination the contents of quercitrin in Polygonum capitatum and Relinqing granules.</p><p><b>METHOD</b>The samples were analyzed on a Diamonsil C18 colunm (4.6 mm x 250 mm, 5 microm) eluted with the mobile phase consisted of methanol-1% HAc-THF. The flow rate was 1.0 mL x min-m. The detection wavelength was set at 258 nm and the column temperature was 25 degrees C.</p><p><b>RESULT</b>The calibration curve was linear in the range of 0. 081 64-0.4084 microg (r = 0.99997). The average recovery rate of quercitrin in P. capitatum was 102.3% (RSD 0.99%), and was 102.7% (RSD 2.2%) in Relinqing granules.</p><p><b>CONCLUSION</b>The method is reliable and specific with good repeatability, and can be used for the quality control of P. capitatum and Relinqing granules. It can provide a science bases for the planting of polygonum capitatum.</p>

Vascular Stimulating Effect of Sodium Ozagrel for Injection:An Empirical Study / 中国药房

OBJECTIVE:To observe the stimulating effect of instilled sodium ozagrel for injection on rabbits'auricular vein.METHODS:Rabbits'auricular veins were assigned to receive sodium ozagrel for injection(19.0 mL?kg~(-1))or 5% glucose injection(19.0 mL?kg~(-1))q.d for 7 days by instillation.The rabbits were executed at 24 h and 72 h respectively after the last infusion,with rabbits'auricular blood vessel samples taken at the distance of 1 cm and 5 cm distal from injection site for histopathologic examination.RESULTS:Histopathologically,the rabbits treated by sodium ozagrel for injection(19.0 mL?kg~(-1))or 5%glucose injection showed similar changes in the skin and veins of the injection sites,and there were no abnormalities such as congestion,edema,induration and necrosis in both groups.CONCLUSION:No obvious stimulating effect on rabbits'auricular vein blood vessel was noted for sodium ozagrel for injection.

Quality standard for Kangmailing Capsule / 中成药

AIM: To establish the quality standard for Kangmailing Capsule(Ginkgo Biloba extract, Rhizoma Gastrodiae, Rhizoma Chuanxiong). METHODS: The flavone glycoside content in Kangmailing Capsule was determined by HPLC. Waters ? bondapak C 18(3.9 mm?300 mm, 5 ?m) column was used. The mobile phase was metanol-0.4%H 3PO 4(50∶50), and UV detection wavelength was at 360 nm. Rhizoma Gastrodiae, Rhizoma Chuanxiong, Ginkgo Lactone and Ginkgolic acid in Capsules were identified by TLC. RESULTS: The calibration curves of Quercetin, Kaempferol and Isorhamnetin were linear at the range of 0.150 ?g-1.50 ?g, 0.142 ?g- 1.42 ?g and 0. 096 ?g-0.96 ?g, respectively. The average recovery was all 98.9%, and RSD was 0.98%, 1.15% and 1.57% (n=5). The TLC sports developed were fairly clear, and the blank test showed no interference, the quantitative limitation of Ginkgolic acid was controlled under 5 mg?kg -1. CONCLUSIONS: The established method is accurate,reliable and specific. The results are stable with good reproducibility. The quality of the capsules can be controlled by the method.