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Newborn screening for remethylation disorders and vitamin deficiency-evaluation of new strategies in cohorts from Qatar and Germany

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World Journal of pediatrics 2017年第2期13卷 136-143页

作者： Gwendolyn Gramer Ghassan Abdoh Tawfeg Ben-Omran Noora Shahbeck Rehab Ali Laila Mahmoud Junmin Fang-Hoffmann Georg F.Hoffmann Hilal Al Rifai Jürgen G.Okun university hospital Heidelberg Center for Pediatric and Adolescent MedicineDivision of Neuropediatrics and Metabolic MedicineHeidelbergGermany department of pediatrics Hamad Medical CorporationDohaQatar

Background:Newborn screening is a precondition for early diagnosis and successful treatment of remethylation disorders and classical homocystinuria (cystathionine-β-synthase deficiency).Newborn screening for classical homocystinuria using total homocysteine measurement in dried blood spots has been very successfully performed for many years for newborns from ***:A new optimized newborn screening strategy for remethylation disorders and homocystinuria was developed and evaluated for newborns from Qatar using total homocysteine measurement as first-tier and methionine,methionine-phenylalanine-ratio and propionylcarnitine as *** cnt-offs were also retrospectively evaluated in newborn screening samples of 12 patients with remethylation disorders and vitamin B12 deficiency from Qatar and ***:Over a 12 months period,the proposed strategy led to a decrease in the recall rate in homocysteine screening for Qatar from 1.09% to 0.68%,while allowing for additional systematic inclusion of remethylation disorders and vitamin B12 deficiency into the screening panel for *** the evaluated period the applied strategy would have detected all patients with classical homocystinuria identified by the previous strategy and in addition 5 children with maternal nutritional vitamin B12 deficiency and one patient with an isolated remethylation *** retrospective evaluation of newborn screening samples of 12 patients from Germany and Qatar with remethlyation disorders or vitamin B12 deficiency showed that all of these patients would have been detected by the cutoffs used in the proposed new *** addition,an adapted strategy for Germany using methionine,methionine-phenylalanine-ratio and propionylcarnitine as first-tier,and homocysteine as a second-tier test was also positively evaluated ***:The proposed strategy for samples from Qatar allows inclusion of remethylation disorders and vitamin B12 deficiency

关键词： classical homocystinuria newborn screening remethylation disorders second-tier vitamin B12 deficiency

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The role of pineal microRNA-325 in regulating circadian rhythms after neonatal hypoxic-ischemic brain damage

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Neural Regeneration Research 2021年第10期16卷 2071-2077页

作者： Ning Sha Hua-Wei Wang Bin Sun Min Gong Po Miao Xiao-Lu Jiang Xiao-Feng Yang Mei Li Li-Xiao Xu Chen-Xi Feng Yuan-Yuan Yang Jie Zhang Wen-Jing Zhu Yuan-Yuan Gao Xing Feng Xin Ding Soochow Key Laboratory of Prevention and Treatment of Child Brain injury Children’s Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina department of pediatrics Affiliated Huai’an Hospital of Xuzhou Medical UniversityHuai’anJiangsu ProvinceChina pediatrics Research Institute Children’s Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina department of pediatrics The First Affiliated Hospital of Soochow University(Dushuhu Branch)SuzhouJiangsu ProvinceChina Cambridge-SU Genomic Resource center Soochow UniversitySuzhouJiangsu ProvinceChina Clinical Laboratory Children’s Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina

Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely *** previously showed that,in a rat model of HIBD,up-regulation of microRNA-325(miR-325)in the pineal gland is responsible for the suppression of Aanat,a key enzyme involved in melatonin synthesis and circadian rhythm *** better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD,we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated hospital of Soochow university(Dushuhu Branch)in *** found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with ***,a luciferase reporter gene assay revealed that LIM homeobox 3(LHX3)is a novel downstream target of *** addition,in miR-325 knock-down mice,the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal *** established a neonatal mouse model of HIBD by performing doublelayer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 ***3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same ***,we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and *** together,our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal *** clinical trial was approved by Institutional Review Board of Children’s hospital of Soochow university(approval No.2015028)on July 20,*** experiments were approved by An

关键词： brain injury circadian rhythm hypoxic-ischemic brain damage miRNA neonate pineal gland sleep transcription factor

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IFN-a production by human mononuclear cells infected with varicella-zoster virus through TLR9-dependent and-independent pathways

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Cellular & Molecular Immunology 2011年第2期8卷 181-188页

作者： Hong-Ren Yu Hsin-Chun Huang Ho-Chang Kuo Jiunn-Ming Sheen Chia-Yo Ou Te-Yao Hsu Kuender D Yang department of pediatrics Chang Gung Memorial Hospital-Kaohsiung Medical CenterGraduate Institute of Clinical Medical ScienceChang Gung University College of MedicineTaiwan department of Obstetrics Chang Gung Memorial Hospital-Kaohsiung Medical CenterGraduate Institute of Clinical Medical ScienceChang Gung University College of MedicineTaiwan

Understanding the defense mechanisms of the host of an organism is important for infection *** previous studies,we demonstrated that interferon-a(IFN-a),but not IL-12,was produced by human peripheral blood mononuclear cells infected with varicella-zoster virus(VZV).Here,we investigated what kind of cell(s)and which signal molecule(s)are involved in IFN-a *** cell isolation and ELISA,we found that plasmacytoid dendritic cells(pDCs)were responsible for IFN-a production during VZV *** also found that Toll-like receptor 9(TLR9)was involved in VZV-induced IFN-a production because inhibitory CpG oligodeoxynucleotide inhibited IFN-a ***-inactivated VZV-induced IFN-a production was lower than that of active VZV,indicating another TLR9-independent *** studies demonstrated that double-stranded RNA-dependent protein kinase,but not DNA-dependent protein kinase was involved in VZV-induced IFN-a ***,these results suggest that pDCs play an important role in IFN-a production during VZV infection through TLR9-dependent and-independent pathways.

关键词： IFN-a mononuclear cells plasmacytoid dendritic cell TLR9 varicella-zoster virus

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Epidemiological and Diagnostic Features of Non-Traumatic Gonalgia in Adults in bouake (Ivory Coast): About 140 Patients

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Open Journal of Rheumatology and Autoimmune Diseases 2023年第4期13卷 78-87页

作者： Kouakou Ehaulier Soh Christian Louis Sougué Charles Yao Konan Joe Clauvis Traore Aissata Koffi Joseph Kan Enock Goua Jean Jacques Same Bebey Francine Goupille Phillipe Daboiko Jean Claude Felix Rheumatology department University Hospital Center Bouaké Bouaké C&#244te d’Ivoire Internal Medicine department University Hospital Center Sour&#244 Sanou Bobo Dioulasso Burkina Faso Rheumatology department Laquintinie Hospital Douala Cameroon Rheumatology department University Hospital Center Tours France

Background: Non traumatic gonalgia is the second most common reason for rheumatology consultations and accounted for 15.6% of rheumatological disorders in Abidjan. Objective: The aim of this work was to study the epidemiological and diagnostic features of non-traumatic gonalgia (NTG) in a black adult population from sub-Saharan Africa. Patients and Methods: This was a five-year retrospective descriptive study (January 2014 to December 2018) of black sub-Saharan African adult patients with non traumatic gonalgia seen in the rheumatology department of the bouake university hospital in Côte d’Ivoire. Results: Of 2198 patients seen for rheumatological conditions, 140 had non traumatic gonalgia (6.4%). The mean age of patients was 56.13 ± 13.3 years (extremes 20 and 87 years), and the sex ratio was 0.43 (42 men and 98 women). Gonalgia without swelling was observed in 33.6% of cases. Symptoms were predominantly progressive (97.1%), chronic (82.1%) and bilateral (50%). The causes of TNM were gonarthrosis (85%), septic arthritis (7.1%), reactive arthritis (2.9%), gout (2.9%), rheumatoid arthritis (1.4%) and chondrocalcinosis (0.7%). Gonarthrosis (119/140) was bilateral in 65 patients, bi- or tri-compartmental in 83, radiographic stage (Kellgren and Lawrence) III in 80 and IV in 15. A germ was isolated in two cases of septic arthritis (methicillin-sensitive Staphylococcus aureus and Streptococcus pneumoniae). Conclusion: GNT is common in rheumatology practice in bouake, and mainly affects women in their fifties. It is most often a chronic bilateral gonalgia, with gonarthrosis as the main etiology.

关键词： Non-Traumatic Gonalgia Gonarthrosis bouake

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High Prevalence of Genetic Alterations in Infantile-Onset Cardiomyopathy

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Congenital Heart Disease 2021年第4期16卷 397-410页

作者： Junsung Park Go Hun Seo Yena Lee Yunha Choi Minji Kang Hyo-Sang Do Young-Hwue Kim Jeong Jin Yu Ellen Ai-Rhan Kim Euiseok Jung Byong Sop Lee Jae Suk Baek Beom Hee Lee department of pediatrics Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea billion Inc.SeoulKorea Genome Research center for Birth Defects and Genetic Diseases Asan Institute for Life SciencesAsan Medical CenterSeoulKorea Division of Cardiology Department of PediatricsAsan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea Division of Neonatology Department of PediatricsAsan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea Medical Genetics center Asan Medical Center Children’s HospitalUniversity of Ulsan College of MedicineSeoulKorea

Background and Method:The genetic cause of infantile-onset cardiomyopathy is rarely ***,we conducted whole exome sequencing(WES)and mitochondrial DNA(mtDNA)sequencing in eight patients with infantile-onset cardiomyopathy to identify genetic ***:Among these patients,two(25%)had dilated cardiomyopathy(DCMP),two(25%)had left ventricular non-compaction(LVNC),and four(50%)had hypertrophic cardiomyopathy(HCMP).Except four patients identified prenatally,the remaining patients presented at a median age of 85.5 *** identified genetic variants in a total of seven(87.5%)patients and mtDNA sequencing in the other ***1 and MYH7 variants were identified in the two patients with DCMP;MYH11 and MYLK2 variants in the two patients with LVNC;HRAS,BRAF,and MYH7 variants in three patients with HCMP;and MT-ND1 variant in one patient with HCMP having high blood lactic acid *** the eight variants,four were classified as pathogenic or likely-pathogenic according to the American College of Medical Genetics(ACMG)guidelines,and the remaining were identified as variants of unknown significance(VUSs).Three pathogenic mutations were de novo,whereas four(likely-pathogenic or VUSs)were inherited from a respective parent,excluding one variant where parental testing was unavailable,questioning whether these inherited variants are *** patients died before 3 months of ***:Genomic studies,such as WES with additional mtDNA sequencing,can identify a genetic variant in high proportions of patients with infantile-onset *** clinical implication of the parentally inherited variant needs to be assessed in a larger patient and family cohort with a longitudinal follow-up.

关键词： Cardiomyopathy whole exome sequencing infantile-onset

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Factors Affecting the Genetic Diagnostic Rate in Congenital Heart Disease

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Congenital Heart Disease 2022年第6期17卷 653-673页

作者： Jun Sung Park Go Hun Seo Yunha Choi Soojin Hwang Minji Kang Hyo-Sang Do Young-Hwue Kim Jeong Jin Yu Ellen Ai-Rhan Kim Euiseok Jung Byong Sop Lee Jae Suk Baek Beom Hee Lee department of pediatrics Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea 3 Billion Inc.SeoulKorea Genome Research center for Birth Defects and Genetic Diseases Asan Institute for Life SciencesAsan Medical CenterSeoulKorea Division of Cardiology Department of PediatricsAsan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea Division of Neonatology Department of PediatricsAsan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea Medical Genetics center Asan Medical Center Children’s HospitalUniversity of Ulsan College of MedicineSeoulKorea

Background: Over 400 genes contribute to the development of congenital heart disease (CHD). Additionally,multisystemic manifestations accompanying syndromic CHD pose a higher risk of genetic diseases. This studyinvestigated the diagnostic yield of whole-exome sequencing (WES) in patients with sporadic syndromic CHDand the phenotypic factors affecting the genetic diagnostic rate. Methods: Sixty-four patients with sporadic syndromicCHD aged center,and the association between genetic testing data and extracardiac phenotypes was analyzed. Results: Extracardiacphenotypes were measured as 3.66 ± 3.05 (standard deviation, interquartile range: 2–5) items per patient. WESdetected diagnostic variants in 19 (29.7%) patients: seven (36.8%), seven (36.8%), and five (26.3%) with pathogenicvariants, likely pathogenic variants, and variants of unknown significance, respectively. Post-diagnosis surveillanceidentified the extracardiac phenotype in 54.5% (6/11) of patients. De novo variants accounted for 76.2%(15/19) of variants and autosomal dominant inheritance for 94.7% (18/19). Most diseases were ultra-rare. No significantdifferences were noted in cardiac and extracardiac phenotypes, single or combined (all P > 0.05), betweenthe groups with and without a diagnostic variant. However, patients with ≥3 extracardiac phenotypes had a significantlyhigher likelihood of having a diagnostic variant than those with ≤2 (38.3% vs. 5.9%, odds ratio = 9.93,95% confidence interval = 1.21–81.44, P = 0.013). Conclusions: The number of extracardiac phenotypes is importantin predicting the possibility of genetic diagnosis. Physicians will be able to select patients with a high probabilityof genetic diagnosis and provide appropriate genetic counseling based on the results of this study.

关键词： Heart defects congenital whole-exome sequencing genetic testing phenotype

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Primary gastric teratoma on the cardiac orifice in an adult

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World Journal of Gastroenterology 2009年第14期15卷 1782-1785页

作者： Liu Liu Wen Zhuang Zhong Chen Yong Zhou Xiao-Ran Huang department of Gastrointestinal Surgery West China Hospital/West China Medical Center Sichuan University Chengdu 610041 Sichuan Province China department of pediatrics The 2nd West China Hospital of Sichuan University Chengdu 610041 Sichuan Province China department of Pathology West China Hospital/West China Medical Center Sichuan University Chengdu 610041 Sichuan Province China

Gastric teratoma (GT) is a seldom seen congenital abnormality. GT always occurs in children. The greater curvature and posterior wall of the stomach are the most common sites involving GT. We diagnosed a case of GT located on the inferior wall of the cardiac orifice in a 20-year-old man. To the best of our knowledge, this is the first case of GT located on the wall of the cardiac orifice in an adult in the English literature. We report this unusual case as an addition to this rare disease usually found in children. Computed tomography combined with endoscopic ultrasonography can be selected to diagnose GT.

关键词： Adult Cardiac orifice Endoscopic ultrasonography Stomach Teratoma

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Treatment of pediatric mild persistent asthma with low-dose budesonide inhalation suspension *** in China

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World Journal of pediatrics 2021年第6期17卷 619-625页

作者： Zhi-Min Chen De-Yu Zhao Li Xiang Jian-Guo Hong department of Respiratory Diseases Children's HospitalZhejiang University School of MedicineHangzhou 310006China department of Respiratory Diseases Children's Hospital of Nanjing Medical UniversityNanjing 210029China department of Allergy Beijing Children's HospitalCapital Medical UniversityNational Children's Hospital CenterBeijing 100045China department of pediatrics Shanghai General HospitalShanghai Jiaotong UniversityNo.100Haining RoadHongkou DistrictShanghai 200080China

Background There are limited studies comparing budesonide inhalation suspension(BIS)with montelukast in real-world settings where treatment adherence and persistency may be *** real-world study aims to investigate the control effectiveness of montelukast or BIS as a monotherapy in Chinese children with mild *** Data were derived from a retrospective questionnaire-based analysis of 2-14-year-old children with mild persistent asthma,who received either 500 pg of BIS(n=153)or 4-5 mg of montelukast(n=240)once *** indicators of asthma control,the Asthma Control Test(ACT)/Childhood ACT(C-ACT)score,and the asthma-related medical costs were *** differences between the two groups were compared using an unpaired-t-test(normally distributed).Mann-Whitney U test(non-normally distributed)or chi-squared test(categorical variables).Results Medication compliance in the past 3-month period was better in the montelukast group than in the BIS group(P=0.042).The montelukast group exhibited better asthma control in the past 4-week period,including lower percentages of asthmatic children with symptoms more than twice a week(P=0.021),had night waking or night coughing(P=0.022),or required reliever medication more than twice a week(P<0.001).The montelukast group had a lower percentage of children with an ACT/C-ACT score≤19(P=0.015).Caregivers reported a significantly better exercise tolerance in the children who received montelukast *** in the past 12 months(P<0.001).Significantly higher medical expenditures attributable to asthma in the past 12 months were observed in the BIS group *** group(P<0.001).Conclusion Both treatments provided acceptable overall asthma control in children with mild persistent asthma;however,more reliever medication and more medical expenditures attributable to asthma were needed for BIS *** in real-world settings,where factors such as compliance were also taken into account.

关键词： Allergic rhinitis Asthma Budesonide Child Montelukast

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Comparison of Clinical and Epidemiological Characteristics of Asymptomatic and Symptomatic SARS-CoV-2 Infection in Children

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Virologica Sinica 2020年第6期35卷 803-810页

作者： Jiehao Cai Xiangshi Wang Jun Zhao Yanling Ge Jin Xu He Tian Hailing Chang Aimei Xia Jiali Wang Jinqiang Zhang Zhongqiu Wei Jingjing Li Chuning Wang Jianshe Wang Qirong Zhu Xiaowen Zhai Mei Zeng department of Infectious Diseases Children’s Hospital of Fudan UniversityShanghai 201102China department of pediatrics Shanghai Public Health Clinical Center of Fudan UniversityShanghai 201102China department of Clinical Laboratory Children’s Hospital of Fudan UniversityShanghai 201102China department of Infectious Diseases Xiamen Children’s HospitalChildren’s Hospital of Fudan University Xiamen BranchShanghai 201102China department of Hematology Children’s Hospital of Fudan UniversityShanghai 201102China

To understand the epidemiological and clinical features of the symptomatic and asymptomatic pediatric cases of COVID-19,we carried out a prospective study in Shanghai during the period of January 19 to April 30,2020.A total of 49 children(mean age 11.5±5.12 years)confirmed with SARS-CoV-2 infection were enrolled in the study,including 11(22.4%)domestic cases and 38(77.6%)imported ***(81.8%)local cases and 12(31.6%)imported cases had a definitive epidemiological ***-eight(57.1%)were symptomatic and 21(42.9%)were *** asymptomatic nor symptomatic cases progressed to severe *** mean duration of viral shedding for SARS-CoV-2 in upper respiratory tract was 14.1±6.4 days in asymptomatic cases and 14.8±8.4 days in symptomatic cases(P>0.05).Forty-five(91.8%)cases had viral RNA detected in *** mean duration of viral shedding in stool was 28.1±13.3 days in asymptomatic cases and 30.8±18.6 days in symptomatic participants(P>0.05).Children<7 years shed viral RNA in stool for a longer duration than school-aged children(P<0.05).Forty-three(87.8%)cases had seropositivity for antibodies against SARS-CoV-2 within 1–3 weeks after confirmation with *** conclusion,asymptomatic SARS-CoV-2 infection may be common in children in the community during the COVID-19 pandemic *** cases shed viral RNA in a similar pattern as symptomatic cases *** is of particular concern that asymptomatic individuals are potentially seed transmission of SARS-CoV-2 and pose a challenge to disease control.

关键词： SARS-CoV-2 infection Children Epidemiology Viral shedding Seropositivity

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Interventricular Septal Hematoma after Congenital Cardiac Defects Repair at a Single Institution

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Congenital Heart Disease 2022年第6期17卷 687-695页

作者： Yuan Hu Xiaohui Yang Jie Dong Peng Huang Jinwen Luo Guangxian Yang James D.StLouis Xicheng Deng department of Echocardiography and Ultrasound Hunan Children’s HospitalChangshaChina Heart center Hunan Children’s HospitalChangshaChina pediatrics Research Institute of Hunan Province Hunan Children’s HospitalChangshaChina departments of Surgery and pediatrics Children’s Hospital of GeorgiaAugusta UniversityAugustaGeorgiaUSA

Background: Interventricular septal hematoma is a rare complication after congenital cardiac repair. The managementvaries according to the literature. We present our experience with this rare complication. Methods:Echocardiography database were reviewed with the term ‘‘hematoma’’ or “hypoechoic mass” for patients whounderwent congenital heart surgery from January 2018 to December 2021 at our institution to identify potentialinterventricular septal hematoma cases. Relevant data of the patients identified were collected. Focus was put onthe presentation, management, outcomes according to patent medical charts and serial echocardiographic reportdata. Results: In total, there were 5 patients included. The mean age and weight at surgery were 5.5 ± 3.6 monthsand 5.5 ± 1.4 kg, respectively. Four patients were diagnosed with ventricular septal defect and the other one beingdouble outlet of the right ventricle. While all patients had intraoperative transesophageal echocardiography, 80%(4 of 5) of Interventricular septal hematoma were revealed intraoperatively. Only one patient received hematomadrainage intraoperatively while the other 3 identified in the operating room were only closely observed. One afterventricular septal defect repair presented continuous dysfunction of the left ventricle at the last follow-up, whilethe others were doing well. All hematomas resolved completely with a mean time to interventricular septal hematomaresolution of 35.8 ± 16.9 days. Conclusion: Infants seem to be at a higher risk for Interventricular septalhematoma following congenital heart surgery. While the majority of interventricular septal hematoma has abenign postoperative course, some may result in ventricular dysfunction. Management strategies may be chosenon a case-by-case basis.

关键词： Interventricular septal hematoma ventricular septal defect double outlet right ventricle transesophageal echocardiography high-pressure waterjet

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