OBJECTIVETo summarize the clinical characteristics and long-term prognosis of herpes simplex virus encephalitis (HSE) in childhood and to analyze genotype of UNC93B1 and TLR3.

METHODData of a total of 30 HSE patients admitted to Beijing Children's Hospital from January 2008 to September 2013 were retrospectively analyzed, the data included clinical manifestations, physical sign, auxiliary examination, therapy and long-term clinical prognosis. The family history obtained during follow-up visit was also analyzed for genetic predisposition. With parents' agreement, the blood specimens of patients were collected in EDTA anticoagulant tubes, the first 2 genetic etiologies UNC93B1 and TLR3 were sequenced, and the genetic susceptibility to HSE in childhood was summarized.

RESULT(1) All the 30 patients (100%) had fever, 28 (93%) had seizure, 25 (83%) had altered state of consciousness, only 11 (37%) had personality changes, and in 8 (73%) appeared at or after 2 weeks of onset . (2) During the long-term follow up, 2 (7%) patients died after discharge, 23 patients (82%) had neurological sequelae, 13 patients (57%) had moderate, severe disability and vegetative state. (3) After sequencing of UNC93B1, and TLR3, one patient was found homozygous for a single-nucleotide substitution at position C.414C>G in exon 4 of UNC93B1 which affected the expression of UNC93B1, and may block or decrease the production of interferon. (4) Six single nucleotide polymorphisms (SNPs) were found in this study, their genotype frequency and gene frequency of Chinese were respectively searched in Genomes Project in NCBI and defined 1 000 genomes group. The genotype frequency of UNC93B1 rs7149 between 1 000 genomes group and HSE group was significantly different (χ² = 55.37, P<0.05). The frequency of CC type and C type was higher in HSE group, both of them had significant difference (χ² = 93.90, P<0.05, OR=61.563; χ² = 134.40, P<0.05, OR=12.491).

CONCLUSIONHSE lacks specific clinical manifestations, the long-term prognosis is poor. One HSE patient carrying a heterozygous mutation in UNC93B1 which may lead to the susceptibility to HSE and had harmful effect on long-term prognosis. The SNP UNC93B1 rs7149 may also have relationship with susceptibility to HSE and the children carrying CC genotype or C gene in this gene site maybe more susceptible to HSE.

Child ; Encephalitis, Herpes Simplex ; diagnosis ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Membrane Transport Proteins ; genetics ; Mutation ; Polymorphism, Single Nucleotide ; Prognosis ; Retrospective Studies ; Toll-Like Receptor 3 ; genetics

OBJECTIVE: To investigate the clinical characteristics and treatment strategies of anomalous origin of the cor⁃onary artery accompanied with myocardial damage,so as to improve the level of clinicians' diagnosis and treatment of this disease. METHODS: The clinical data of 72 cases of anomalous origin of the coronary artery accompanied with myo⁃cardial damage admitted in Department of Cardiology,Beijing Children's Hospital,Capital Medical University from2015 to 2017 were analyzed retrospectively. The clinical characteristics,diagnosis and treatment methods were analyzed.RESULTS: In 42 cases(58.3%),chest pain,chest tightness and palpitation were the main clinical symptoms. ECG abnor⁃malities were mainly ST-T changes(62.5%). Echocardiography showed 13 cases(18.1%)of cardiac enlargement,4 cas⁃es(5.6%)of left ventricular systolic dysfunction. Coronary artery CT angiography(CTA)showed that the anomalous ori⁃gin of the left coronary artery was the most frequent(73.6%),followed by the anomalous origin of bilateral coronary arter⁃ies(13.9%),and the anomalous origin of the right coronary artery was the least frequent(12.5%). The whole group was successfully treated with no death. CONCLUSION: There might be a correlation between the anomalous origin of coronary artery and ischemic myocardial damage. In the examination of patients,pediatricians should pay more attention to the judgments of the position and movement of the coronary artery by CTA,and attach importance to the differential diagno⁃sis between ischemic myocardial damage and myocarditis.

OBJECTIVETo observe the efficacy and safety of atomoxetine hydrochloride in children with narcolepsy.

METHODTotally 66 patients with narcolepsy who were conformed international classification of sleep disturbances (ICSD-2) diagnostic criteria treated with atomoxetine hydrochloride seen from November 2010 to December 2014 were enrolled into this study, 42 of them were male and 24 female, mean age of onset was 7.5 years (3.75-13.00 years), mean duration before diagnosis was 1.75 years (0.25-5.00 years). Complete blood count, liver and kidney function, multiple sleep latency test (MSLT), polysomnography (PGS), neuroimaging and electroencephalography (EEG) were performed for each patient. For some of the children HLA-DR2 gene and serum markers of infection were tested. The 66 cases were followed up from 2 to 49 months (average 18 months) to observe the clinical efficacy and adverse reactions.

RESULTSIn 62 cases excessive daytime sleepiness was improved, in 11 cases (16.7%) it was controlled (16.7%), in 29 cases (43.9%) the treatment was obviously effective and in 22 (33.3%) it was effective; cataplexy occurred in 54 cases, in 18 (33.3%) it was controlled, in 19 (35.2%) the treatment was obviously effective and in 10 (18.5%) effective; night sleep disorders existed in 55 cases, in 47 cases it was improved, in 14 (25.5%) it was controlled, in 20 (36.4%) the treatment was obviously effective and in 13 (23.6%) effective; hypnagogic or hypnopompic hallucination was present in 13 cases, in only 4 these symptoms were controlled. Sleep paralysis existed in 4 cases, it was controlled in only 1 case. In 18 cases attention and learning efficiency improved.Anorexia occurred in 18 cases, mood disorder in 5 cases, depression in 2 cases, nocturia, muscle tremors, involuntary tongue movement each occurred in 1 case. P-R interval prolongation and atrial premature contraction were found in 1 case.

CONCLUSIONAtomoxetine hydrochloride showed good effects in patients with narcolepsy on excessive daytime sleepiness, cataplexy and night sleep disorders, the effects on hallucinations and sleep paralysis were not significant. Adverse reactions were slight, anorexia and mood disorder were common. As a non-central nervous system stimulant, atomoxetine hydrochloride does not induce drug dependence and has no prescription limits; it has good tolerability, safety and effectiveness, it can be a good alternative in treatment of children with narcolepsy.

Adolescent ; Atomoxetine Hydrochloride ; adverse effects ; therapeutic use ; Cataplexy ; drug therapy ; Child ; Child, Preschool ; Electroencephalography ; Female ; Humans ; Male ; Narcolepsy ; drug therapy ; Neuroimaging ; Polysomnography

OBJECTIVETo study the clinicopathological and immunohistochemical features, histogenesis and prognosis of pleuropulmonary blastoma (PPB) in children.

METHODSPPB specimens from 16 pediatric cases with an age ranging from 1 year and 7 months to 5 years and 3 months (mean age of 3 years) were retrieved and analyzed by routine histological, immunohistochemical and electron methods.

RESULTSAmong 16 patients, there were 2 type I, 7 type II and 7 type III PPB cases. Type I PPB as multilocular cystic structure, consisted of thin fibrous wall lining the respiratory epithelium, subepithelial primitive blastema or immature mesenchymal cells, with or without rhabdomyoblastic differentiation or cartilage; Type II PPB as cystic-solid tumor, comparing with type I, consisted of intracystic components with appearance of anaplastic tumor cells. Type III PPB consisted of completely solid mass, the same as the solid region of type II, had mixed pattern including blastema, undifferentiated spindle-cell proliferations and sarcomas. In addition, anaplastic tumor cells and intra-and extra- cytoplasmic eosinophilic globules were also commonly present. Epithelial components in PPB were benign. Immunohistochemical study showed primitive mesenchymal differentiation of tumors. All cases were positive for vimentin, desmin, myogenin and SMA in tumors with skeletal muscle differentiation, S-100 was positive in tumors with cartilage differentiation. All tumors were negative for synaptophysin, CD99, and CD117. Benign epithelial components were positive for AE1/AE3 and EMA. In 12 cases, electron microscopy revealed few organelles in the primitive mesenchymal cells and rich heterochromatin in mesenchymal cells, the latter also demonstrating cytoplasmic myofilament dysplasia. Nine cases had clinical follow-up ranging from 5 to 48 months, of which 4 patients died.

CONCLUSIONSPPB is a rare lung neoplasm of children under the age of 6 years, with distinct pathological morphology. PPB may arise from lung or pleura mesenchymal cells and has a poor clinical outcome.

Child, Preschool ; Cysts ; pathology ; Desmin ; analysis ; Female ; Humans ; Infant ; Lung Neoplasms ; chemistry ; pathology ; Male ; Microscopy, Electron ; Myogenin ; analysis ; Prognosis ; Pulmonary Blastoma ; chemistry ; pathology ; Sarcoma ; pathology ; Vimentin ; analysis

OBJECTIVE: To summarize the experience in the application of muscle relaxants in the perioperative period in neonates with congenital esophageal atresia-tracheoesophageal fistula (EA-TEF). METHODS: A retrospective analysis was performed on the medical data of 58 previously untreated neonates with EA-TEF who were treated in the Neonatal Center of Beijing Children's Hospital, Capital Medical University from 2017 to 2019. The incidence rate of anastomotic leak was compared between the neonates receiving muscle relaxants for different durations after surgery (≤ 5 days and > 5 days). The correlation between the duration of postoperative use of muscle relaxants and the duration of mechanical ventilation was evaluated. RESULTS: Among the 58 neonates with EA-TEF, 44 underwent surgery, among whom 35 with type III EA-TEF underwent thoracoscopic surgery. Among these 35 neonates, 30 (86%) received muscle relaxants after surgery, with a median duration of 4.75 days, and 6 (18%) experienced anastomotic leak. There was no significant difference in the incidence rate of anastomosis leak between the ≤ 5 days and > 5 days groups ( CONCLUSIONS Prolonged use of muscle relaxants after surgery cannot significantly reduce the incidence of anastomotic leak, but can prolong the duration of invasive mechanical ventilation in neonates with EA-TEF. Therefore, prolonged use of muscle relaxants is not recommended after surgery.
Child ; Esophageal Atresia/surgery* ; Humans ; Infant, Newborn ; Muscles ; Postoperative Complications/etiology* ; Prognosis ; Retrospective Studies ; Tracheoesophageal Fistula/surgery* ; Treatment Outcome

BACKGROUNDThe treatment of the patient with pelvic fracture urethral disruption defects (PFUDD) remains controversial especially in pediatric urology. Debate continues in regarding the advisability of immediate repair versus delayed repair. The aim of this study was to analyze our experience in the outcomes of immediate and delayed repair of pelvic fracture urethral distraction defects in young boys.

METHODSWe retrospectively reviewed the records of 210 boys with posterior urethral disruption after pelvic injury between 1992 and 2012. Exclude partial urethral injury, a total of 177 cases acquired follow-up. All patients were evaluated by plain radiography, ultrasonography, or a computed tomography scan to assess the conditions of the upper urinary tract and to exclude other severe injuries. Data on 35 patients who underwent immediate repair were compared to those on 142 treated with delayed urethroplasty. After the diagnosis of a complete urethral injury, the immediate repair group underwent urethroplasty via the perineal approach if the patient's condition was stable, and serious complications were treated. The delayed repair group patients with the delayed urethroplasty average 6 months after injury. All patients were evaluated postoperatively for urethral strictures, incontinence and impotence. The patients were assessed by uroflowmetry and renal ultrasonography with evaluation of the postmictional residue every 3 months during the first year of follow-up. We assessed incontinence and erectile function by questioning the parents or the children themselves. Statistical analysis with the chi-square test was performed using SPSS software.

RESULTSOne hundred and seventy-seven patients were followed up with an average 58 months (range 6 to 192 months). Strictures developed in 3 (9%) patients in immediate repair group; two required direct visual internal urethrotomy (DVIU), the other patient required dilatation. Strictures developed in 11.9% of the delayed repair group, 17 patients need visual internal urethrotomy or urethroplasty. Incontinence (11.4%) and impotence (8.6%) seem less frequent in the immediate repair group than in the delayed reconstruction group (17.7% and 21.8%, respectively). However, the results showed that there was no statistical difference between the two groups in strictures after first surgery, incontinence and impotence. Patients with delayed reconstruction underwent an average of 2.6 procedures compared with an average of 1.1 in the immediate repair group.

CONCLUSIONSImmediate repair of urethral disruption is possible when the patient's condition was stable. It may decrease the requirement for subsequent urethral surgeries. Immediate repair does not appear to increase the rate of impotence or incontinence. The strictures after immediate repair also may be easier to treat. Although immediate repair could be inconvenient in the massively injured patient, it is still a worthwhile maneuver in dealing with PFUDD.

Adolescent ; Anastomosis, Surgical ; methods ; Child ; Child, Preschool ; Fractures, Bone ; surgery ; Humans ; Male ; Pelvic Bones ; injuries ; surgery ; Retrospective Studies ; Urologic Surgical Procedures ; methods

OBJECTIVE： To investigate the labelling problems of pediatric medication in the package inserts of skin external drugs in our hospital， and to put forward the suggestions. METHODS： A total of 46 package inserts for skin external medicine were collected from outpatient pharmacy of our hospital during Jan.-Dec. in 2018. Information on pediatric medication， precautions for pediatric medication， pediatric usage and dosage， and pediatric pharmacokinetic labelling in those package inserts was analyzed and summarized according to the types of domestic， imported and joint enterprises， classification of western medicine and Chinese patent medicine and labelling clarity， etc. RESULTS： Among 46 package inserts， 37 western medicines and 9 Chinese patent medicines were included； 31 domestic enterprises， 9 import enterprises and 6 joint ventures were involved. The ratio of pediatric medication， precautions （for pediatric medication）， pediatric usage and dosage， and pediatric pharmacokinetics labelling were 38.7％， 58.1％，  29.0％ and 0 for domestic drugs； 88.9％， 55.6％， 44.4％ and 33.3％ for imported drugs； 33.3％， 83.3％， 16.7％ and 0 for joint venture drugs； 59.5％， 62.2％， 32.4％ and 8.1％ for western medicine； 0， 55.6％， 22.2％ and 0 for Chinese patent medicine. 5 （10.9％） drug package inserts clearly indicated the usage and dosage of children； 12 （26.1％） drug package inserts were clearly labeled for the usage and dosage involving children； 12 （26.1％） drug package inserts were clearly marked to remind children to use under the supervision of doctors and adults； 11 （23.9％） drug package inserts clearly indicated that pediatric medication was not clear and the safety of pediatric medication was not yet established； 1 （2.2％） package insert clearly indicated that children should be cautious and forbidden； 3 （6.5％） package inserts did not involve package insert for pediatric medication； 2 （4.3％） package inserts clearly indicated that the drugs were stored in places not accessible to children. CONCLUSIONS： There are some problems in the package inserts of skin external drugs in our hospital， such as the marked rate of pediatric medication is quite different； the contents of the labels of pediatric medication are ambiguous and pharmacokinetic data is absent； the contents of the package inserts are inconsistent and the patients are not easy to understand professional terms. The standardization， strictness and guidance of drug package inserts for children can be improved by strengthening the supervision and management of drug package inserts by drug regulatory authorities， increasing the research and development of children’s special drugs， increasing the attention of pharmaceutical enterprises to pediatric medication， paying the attention to the revision of standard package inserts， advancing the clinical trials of children， and raising the awareness of safe drug use of patients and users.

Hypertrophic cardiomyopathy(HCM)is mainly hereditary heart disease caused by gene mutation encoding cardiac sarcomere protein. HCM is the main cause of sudden cardiac death in athletes and adolescents. The clinical manifestations of HCM in children are complex and varied,including being asymptomatic,exercise intolerance,syncope,and sudden death,etc. Labor dyspnea and chest pain are the most common symptoms in older children. The diagnosis of HCM in children is mainly based on imaging examination,which can be divided clinically into three types:obstructive,non-obstructive and occult obstructive. Risk factors were assessed according to the patient's age,clinical symptoms,imaging findings and family history to guide further treatment,management and prognosis.Drug therapy mainly includes beta blockers,non-dihydropyridine calcium antagonists and other anti-arrhythmic drugs,as well as anticoagulants,diuretics and other applications. For those who are not satisfied with the effect of drug treatment,implantable cardioverter defibrillator(ICD)or surgical treatment can be used. In recent years,with the development of gene detection,the diagnosis of HCM in children is more refined and the treatment is accurate.

Cardiovascular disease(cardiomyopathy, myocardial infarction, heart failure)seriously endanger child health.Although the incidence in children is not very high, the prognosis is usually poor due to limited treatment options.With the rapid development of stem cell technology and regenerative medicine in recent years, stem cell transplantation has been proved to be able to promote cardiomyocyte regeneration, improve myocardial remodeling and left ventricular ejection fraction(LVEF), so as to alleviate cardiovascular diseases fundamentally.Mesenchymal stem cells(MSCs), a kind of pluripotent adult stem cell with profound self-renewal capacity and multi-directional differentiation potential, have been gradually applied in the treatment of children′s cardiovascular diseases, such as cardiomyopathy, myocardial infarction and end-stage heart failure, and initial success has now been achieved.This review is to summarize the advance of MSCs in the treatment of cardiovascular diseases in children.

OBJECTIVELeukemia is the most common pediatric malignancy and a major cause of morbidity and mortality in children. Among all subtypes, a lack of consensus exists regarding the diagnosis and treatment of acute myeloid leukemia (AML). Patient survival rates have remained modest for the past three decades in AML. Recently, targeted therapy has emerged as a promising treatment.

DATA SOURCESWe searched the PubMed database for recently published research papers on diagnostic development, target therapy, and other novel therapies of AML. Clinical trial information was obtained from ClinicalTrials.gov. For the major purpose of this review that is to outline the latest therapeutic development of AML, we only listed the ongoing clinical trials for reference. However, the published results of complete clinical trials were also mentioned.

STUDY SELECTIONThis article reviewed the latest developments related to the diagnosis and treatment of AML. In the first portion, we provided some novel insights on the molecular basis of AML, as well as provided an update on the classification of AML. In the second portion, we summarized the results of research on potential molecular therapeutic agents including monoclonal antibodies, tyrosine kinase/Fms-like tyrosine kinase 3 (FLT3) inhibitors, epigenetic/demethylating agents, and cellular therapeutic agents. We will also highlight ongoing research and clinical trials in pediatric AML.

RESULTSWe described clonal evolution and how it changes our view on leukemogenesis, treatment responses, and disease relapse. Pediatric-specific genomic mapping was discussed with a novel diagnostic method highlighted. In the later portion of this review, we summarized the researches on potential molecular therapeutic agents including monoclonal antibodies, tyrosine kinase/FLT3 inhibitors, epigenetic/demethylating agents, and cellular therapeutic agents.

CONCLUSIONGene sequencing techniques should set the basis for next-generation diagnostic methods of AML, and target therapy should be the focus of future clinical research in the exploration of therapeutic possibilities.

Antibodies, Monoclonal ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; Protein Kinase Inhibitors ; therapeutic use ; fms-Like Tyrosine Kinase 3 ; antagonists & inhibitors