[Study on risk factors of mycobacterium tuberculosis infection among health workers in medical institutions].

Objective: To understand the infection status of mycobacterium tuberculosis among health workers in tuberculosis designated medical institutions and explore the risk factors of infection. Methods: From September 2021 to June 2022, a questionnaire survey was conducted among health workers in relevant departments of 4 tuberculosis designated medical institutions by cluster stratified sampling, including the implementation of hospital infection control measures in medical institutions and occupational exposure of medical staff to mycobacterium tuberculosis. Peripheral blood interferon gamma release assays (IGRAs) and lung imaging examination were performed to determine the mycobacterium tuberculosis infection. Factors with statistical significance in univariate analysis were included in multivariate logistic regression to analyze the risk factors of mycobacterium tuberculosis infection. Results: A total of 657 people completed the lung imaging examination and questionnaire, of which 654 people had peripheral blood IGRAs detection, and the latent infection rate of tuberculosis was 39.45% (258/654) . Univariate analysis showed that age, sex, marital status, economic income, occupational category, professional title, length of service, and other variables had statistical significances in tuberculosis latent infection (P<0.05) . In terms of personal health status, there were statistically significant differences in the distribution of health workers in terms of their tuberculosis history, tuberculosis history of their immediate family members, previous tuberculin skin test (TST) (P<0.05) . Multivariate analysis showed that there were four risk factors related to tuberculosis, including professional title (X(1)) , years of tuberculosis related works (X(2)) , tuberculosis history (X(3)) and previous TST (X(4)) . The regression equation of the probability of tuberculosis among health workers was y=-1.920+0.246X(1)+0.046X(2)+1.231X(3)+0.478X(4). Conclusion: The latent infection rate of tuberculosis among health workers in tuberculosis designated medical institutions is high. It is necessary to strengthen the management of infection control, carry out regular screening, enhance the self-protection awareness of health workers, and reduce their exposure to mycobacterium tuberculosis and infection risk.

[Clinical analysis of 11 cases multisystem inflammatory syndrome associated with SARS-CoV-2 Omicron variant infection in children].

Objective: To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection. Methods: A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study. Results: The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months. Conclusions: MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

[Mechanical circulatory support combined with immunomodulation treatment for patients with fulminant myocarditis: a single-center real-world study].

Objective: To investigate the relationship between the mechanical circulatory support (MCS) combined with immunomodulation and the prognosis of patients with fulminant myocarditis. Methods: This is a retrospective study. A total of 88 patients with fulminant myocarditis admitted to Dongguan Kanghua hospital from Aug. 2008 to Dec. 2020 were included. Medical histories, results of laboratory tests, treatment regimens and clinical outcomes of these patients during their hospitalization were collected from the medical record system. According to the treatment methods, the patients were divided into MCS+immunomodulation group (38 cases), MCS group (20 cases) and traditional treatment group (30 cases). Patients in the MCS+immunomodulation group received intra-aortic balloon pump (IABP) or IABP combined with extracorporeal membrane oxygenation (ECMO) and immunoglobulin or glucocorticoid. Patients in the MCS group only received mechanical circulatory support. Patients in the traditional treatment group received neither mechanical circulatory support nor immunomodulatory therapy, and only used vasoactive drugs and cardiotonic drugs. The in-hospital mortality and length of stay were compared among the three groups. Results: A total of 88 patients with fulminant myocarditis aged (35.0±10.8) years were included, and there were 46 males (52.3%). The mortality of MCS+immunomodulation group (7.9% (3/38) vs. 56.7% (17/30), P=0.001 2) and MCS group (30.0% (6/20) vs. 56.7% (17/30), P=0.002 8) were lower than that of traditional treatment group. Compared with the MCS group, the in-hospital mortality in the MCS+immunomodulation group was lower (P=0.005 4). The most common cause of death was multiple organ dysfunction syndrome (MODS). The constituent ratios of death in MCS+immunomodulation group, MCS group and traditional treatment group were 3/3, 4/6 and 12/17, respectively. The incidence of MODS in the MCS group (20% (4/20)) and the traditional treatment group (40% (12/30)) was significantly higher than that in the MCS+immunomodulation group (7.9% (3/38)) (both P<0.01). In discharged patients, the hospitalization time of MCS+immunomodulation group was shorter than that of traditional treatment group ((13.4±5.5)d vs. (18.5±7.4)d, P<0.05) and MCS group ((13.4±5.5)d vs. (16.9±8.5)d, P<0.05). Conclusion: MCS combined with immunomodulatory therapy is associated with lower in-hospital mortality and shorter hospital stay in patients with fulminant myocarditis.

[Clinical follow-up study of myelin oligodendrocyte glycoprotein antibody-associated disease in children].

Objective: To summarize the clinical characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and compare the differences in efficacy of different disease-modifying drugs. Methods: An ambispective cohort study was conducted in 42 children diagnosed with MOGAD at Department of Pediatrics, Peking University First Hospital from January 2012 to March 2021 and conducted long-term follow-up to analyze clinical phenotypes and compare the efficacy of different disease-modifying drugs such as rituximab, mycophenolate mofetil and azathioprine. Kruskal-Wallis H test was used to compare the annual relapse rate of disease-modifying drugs at different times, expanded disability status scale (EDSS) score at the last follow-up, and Wilcoxon rank test was used to compare the annual relapse rate before and after modified disease therapy. The Log-rank (Mantel-Cox) survival curve was used to compare the relapse rate of different disease-modifying drugs. Results: Of the 42 cases, 22 were male and 20 were female, with the age at disease onset of 5.96 (2.33-12.90) years. The disease duration was 4.46 (1.25-13.00) years at the last follow-up with 161 clinical acute attacks. Acute disseminated encephalomyelitis (ADEM) was the most common phenotype of first attack and all attacks during disease course ((60% (25/42) for first attack, 38% (61/161) for all attacks). The most common clinical syndrome was neuromyelitis optica spectrum disorders (NMOSD) (50%, 21/42). Of the 42 children, 5 (12%) showed encephalitis and 6 (14%) combined with anti-N-methyl-D-aspartate receptor (NMDAR) antibody overlap syndrome. The most commonly involved areas of brain magnetic resonance imaging (MRI) were subcortical white matter (71%, 88/124), cortex (26%, 32/124) and periventricular white matter (25%, 32/124). Spinal cord MRI was most frequently involved in cervical (70%, 16/23) and thoracic (61%, 14/23) medulla, and 43% (10/23) longitudinally extensive transeverse myelitis. Disease-modifying drugs were used in 34 patients. The annual relapse rate after treatment with rituximab, mycophenolate mofetil and azathioprine decreased (all P<0.05) and there was no statistically significant difference in the annual relapse proportion among the groups (P=0.307). Conclusions: The most common clinical attack of first and all of MOGAD in children is ADEM, and the most common clinical syndrome is NMOSD. Rituximab, mycophenolate mofetil and azathioprine can reduce the annual relapse rate, but it is not clear effect of which treatment is better.

[Effectiveness of influenza vaccination for school-age children in preventing school absenteeism in Shenzhen: an empirical study].

Objective: To assess the impact of vaccination at school and influenza vaccination rates among school-age children on school absenteeism in Shenzhen. Methods: The study subjects were primary school students in Shenzhen. School absenteeism panel database from December 2017 to June 2020 of 286 primary schools in Shenzhen was merged with vaccination rates and organizational patterns (i.e., vaccination at school vs. non-school) data of 9 districts in Shenzhen after influenza vaccination for children. The outcome was the number of school absenteeism. The treatment and control groups were distinguished by organizational patterns and district vaccination rates. Difference-in-Difference (DiD) Poisson regressions were used to analyze the effectiveness of vaccination at school and higher vaccination rates. Besides, a robustness test was performed on the regression results. Results: Poisson regression analysis and robustness test of regression results showed that vaccination at school and higher vaccination rates effectively reduced the risk of school absenteeism, with effectiveness against absenteeism of 32.6% (95%CI: 17.0%-45.3%, P<0.01) and 53.0% (95%CI: 42.1%-61.8%, P<0.01), respectively. Conclusion: A free influenza vaccination program for school-age children in Shenzhen and prioritizing school-based vaccination may be an effective measure to reduce the risk of school absenteeism.

[The screening of potential biological markers of seizure onset zone in focal cortical dysplasia based on bioinformatics analysis].

Three patients diagnosed with focal cortical dysplasia (FCD) in the First Hospital of Peking University from September to November 2020 were recruited in the study. Based on stereotactic electroencephalogram (SEEG) or electrocorticogram (ECoG) analysis to localize the seizure onset zone (SOZ), RNA sequencing (RNA-seq) analysis was performed for the SOZ and para-SOZ tissue obtained from surgery. The differentially expressed genes between SOZ and para-SOZ samples were analyzed by performing Go (Gene ontology) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis."Extracellular matrix"was significantly enriched, which included collagen synthesis genes (e.g., COL1A1)."Ether lipid metabolism"was enriched in the KEGG pathway enrichment analysis. These differences could be the potential biological markers for SOZ localization.

[Consumption of sugar-sweetened beverages and artificially sweetened beverages and risk of cardiovascular disease: a meta-analysis].

Objective: Using Meta-analysis to evaluate the relation of sugar-sweetened beverages (SSBs) intakes and artificially sweetened beverages (ASBs) intakes with risk of incident cardiovascular disease. Methods: "Sugar-sweetened beverages"(SSBs),"artificially sweetened beverages"(ASBs),"coronary heart disease"(CHD),"stroke","cardiovascular disease"(CVD), and related terms (both in English and in Chinese) were searched in Pubmed, EMBASE, Web of Science, Cochrane library, ProQuest, China National Knowledge Infrastructure (CNKI), Wanfang databases, and VIP Chinese Science and Technology Journal. Besides, it searched for additional references in websites including Clinical Tirals.gov and International Clinical Trials Registry Platform. The time was up to May 31st 2020. Stata 13 software was used to calculate pooled RR, perform heterogeneity test, and assess publication bias. Results: A total of 14 articles were included from the 40 804 articles retrieved, including 12 articles from European and American countries and 2 articles from Asian countries. The baseline mean age of the participants ranged from 52 to 69 years, and the mean follow-up time was from 6 to 26 years. Meta-analysis showed that compared with those in the lowest group, the RR (95%CI) for those in the highest group of SSBs consumption was 1.11 (1.04-1.08) for CHD, 1.10 (1.01-1.19) for stroke, and 1.09 (0.96-1.24) for CVD events. The corresponding RR (95%CI) comparing extreme groups of ASBs consumption was 1.10 (0.98-1.23) for CHD, 1.19 (1.09-1.29) for stroke, and 1.32 (1.15-1.52) for CVD events. Further analysis for subtypes of stroke showed that compared with the lowest group, the RR (95%CI) for those in the highest groups of SSBs consumption was 1.10 (0.99-1.22) for ischemic stroke and 0.86 (0.71-1.04) for hemorrhagic stroke. The corresponding RR (95%CI) comparing extreme consumption of ASBs was 1.23 (1.04-1.46) for ischemic stroke and 1.33 (1.03-1.72) for hemorrhagic stroke. Conclusion: Higher consumption of SSBs or ASBs may lead to increased risk of incident CHD and stroke (particularly ischemic stroke).

[Evaluation of fast nucleic acid detection system in severe acute respiratory syndrome coronavirus 2].

Objective: To evaluate the performance and application of a fast nucleic acid detection system for testing severe acute respiratory syndrome virus 2 (SARS-COV-2). Methods: Clinical samples were collected from February to July 2020 from Beijing Center for Diseases Prevention and Control and the Laboratory Department of China-Japan Friendship Hospital, to evaluate the sensitivity, specificity, anti-interference ability, precision and clinical sample coincidence rate of fast nucleic acid detection system for SARS-CoV-2. The analytical sensitivity was determined by a dilution series of 20 replications for each concentration. Analytical specificity study was performed by testing organisms whose infection produces symptoms similar to those observed at the onset of corona virus disease 2019 (COVID-19), and of the normal or pathogenic microflora that may be present in specimens collected. Potential interference substances were evaluated with different concentration in the interference study. Precision study was conducted by estimating intra-and inter-batch variability. Clinical evaluation was performed by testing 230 oropharyngeal swab specimens and 95 sputum specimens in fast nucleic acid detection system, comparing with conventional real-time fluorescent quantitative PCR (RT-qPCR) and clinical diagnostic results. Results: The analytical sensitivity of SARS-CoV-2 using fast nucleic acid detection system was 400 copies/ml. The result is negative for testing with the organisms that may likely in the circulating area or causing similar symptoms with SARS-CoV-2 and human nucleic acid, indicating that no cross reactivity with organisms. The results of precision test showed that the Coefficient of variation of Ct value of high, medium and low concentration samples was 1.90%-3.92%, and all of them were less than 5% in intra-and inter-batch testing. The results of the samples were still positive after adding the potential interfering substances, indicating that the possible interfering substances in the samples had no effect on the results. 98.46% and 97.85% diagnosis results of fast nucleic acid detection system were consistent with RT-qPCR and clinical diagnostic results, respectively. Conclusion: The fast nucleic acid detection system based on molecular parallel reaction can be used as a selection method for SARS-CoV-2 testing.

[Genotypes and clinical features of neonatal-onset genetic epilepsy in 141 patients].

Objective: To summarize the genotypes and clinical features of neonatal-onset genetic epilepsy. Methods: Patients (114 cases) with identified gene variants were collected from May 2013 to May 2019 in Peking University First Hospital, retrospectively. The genotype, clinical, electroencephalographic and neuroimaging characteristics were analyzed. Results: A total of 141 neonatal-onset epilepsy patients with identified gene variants were enrolled, including 76 males and 65 females and involving 33 epilepsy genes. Top five genes were KCNQ2 (56 cases), SCN2A (25 cases), STXBP1 (9 cases), CDKL5 (8 cases) and KCNT1 (6 cases), accounting for 73.8% (104/141). The age of seizure onset was 3(1-28) days of age, 71.6% (101/141) were within 1 week of age. The age of genetic diagnosis was 4 months (1 month to 13 years) of age. A total of 130 patients presented focal seizures; 47 patients presented epileptic spasms. Other seizure types included generalized tonic-clonic seizures, clonic seizures, myoclonic seizures, tonic seizures and absence seizures. Fifty-eight patients experienced multiple seizure types. The results of video-electroencephlogram (VEEG) were abnormal in 127 patients and in 62 patients clinical seizures were captured. Global developmental delay was presented in 122 patients. Epilepsy syndromes were diagnosed in 59 patients. Thirteen patients were diagnosed as Ohtahara syndrome (OS), 9 as epilepsy of infancy with migrating focal seizures (EIMFS), 17 as West syndrome (WS), 4 as OS developed to WS, 9 as benign neonatal epilepsy (BNE), 2 as benign familiar neonatal-infantile epilepsy (BFNIE), 2 as benign infantile epilepsy (BIE) and 3 as benign familial infantile epilepsy (BFIE). Sixty-seven patients were diagnosed as unclassified early infantile epileptic encephalopathy (EIEE), 13 patients could not be diagnosed as any epilepsy syndrome, and 2 patients were diagnosed as pyridoxine-dependent epilepsy. Forty-six patients had abnormal neuroimaging including cortical atrophy, corpus callosum dysplasia and cerebellar atrophy, involving 19 genes. Conclusions: Neonatal-onset epilepsy is related to many different genes. Seizure onset age of most patients is within one week after birth. Focal seizures and epileptic spasms are more common. Some patients show abnormal neuroimaging.

[Genotype and phenotype of children with DEPDC5 gene variants related epilepsy].

Objective: To summarize the clinical characteristics and the features of electroencephalograph (EEG) of children with DEPDC5 gene variants related epilepsy. Methods: The clinical data, gene variation, EEG and head magnetic resonance image (MRI) of 20 epileptic children with DEPDC5 gene variants admitted to Department of Pediatrics, Peking University First Hospital from May 2017 to November 2020 were retrospectively analyzed. Results: Twenty patients with heterozygous DEPDC5 gene variants were enrolled, 8 of 20 patients were nonsense variants, 6 were missense variants, 3 were frame-shift variants, 2 were splicing variants, and 1 was large fragment deletion. Sixteen cases had hereditary variation and 4 had de novo variation. Fifteen of variations were novel. Nine were male, while 11 were female. Their latest follow-up age ranged from 10 months to 13 years and one month.The epilepsy onset age ranged from 3 hours to 11 years and 3 months, the median age was 10.5 months. Twelve (60%) patients had developmental delay. Nineteen patients had focal seizures, 7 had epileptic spasms, 1 had multiple seizure types including tonic, atypical absence, dystonic and myoclonic seizures. Epileptic form discharges were observed in 18 patients during the interictal phase, and 11 were focal discharges, 7 were multifocal discharges. Ten (50%) patients had abnormal brain MRI, including focal cortical dysplasia in 5 patients, undefined malformation of cortical development in 4 patients, hemimegalencephaly in 1 patient. Four patients were diagnosed as West syndrome and one patient was diagnosed as Lennox-Gastaut syndrome. Fourteen (70%) patients were diagnosed as drug-resistant epilepsy. Four patients became seizure-free by treatment with anti-epileptic drugs. Three children were treated with surgery, and 2 of them became seizure-free, 1 had more than 75% reduction in seizures. Conclusions: DEPDC5 gene variant epilepsy is inherited with incomplete penetrance and focal seizure is the major seizure type. However, epileptic spasms, generalized seizures can also be observed. Half of the patients brain malformations. Most of the patients are drug-resistant epilepsy. Patients with clear epileptogenic zones can be treated with surgery. Treatment-resistant patients are more likely to be complicated with developmental delay.

[Investigation on the status of monotherapy for newly diagnosed tic disorders and its comorbidity in children].

Objective: To investigate the status of monotherapy for newly diagnosed tic disorders and its comorbidity in children, so as to provide a reference for clinical medication. Methods: A questionnaire survey was conducted to collect the application experience of monotherapy for newly diagnosed tic disorders and comorbidities in 110 pediatric neurologists and psychiatrists from Chinese Tic Disorders Study Consortium from February to August in 2019. Doctors were asked to rate treatment options based on a rank 5-point scale with "1" least appropriate and "5" most appropriate. The drug evaluation index was based on the comparison of the median score of a single drug with the overall scores of all drugs in this disease (M (Q1, Q3)), single drug M ≥ overall Q3 was recommended as preferred drugs; overall Q1≤ single drug M < overall Q3 was considered as secondary drugs; single drug M < overall Q1 was considered as unsuitable drugs. Results: Among 110 electronic questionnaires, 94 (86%) were availably responded, responding doctors included 37 (39%) males and 57 (61%) females, the age of responding doctors was (48±10) years, and their working year was (17±10) years. In the investigation of the first and second monotherapy for newly diagnosed tic disorders in children without comorbidities, there were no preferred drugs for mild transient tic disorders. The scores of clonidine, aripiprazole and tiapride were 4 (3, 4), 4 (3, 4), 4 (4, 5) scores respectively, and were greater than overall scores (3 (2, 4) scores), so they could be recommended as the preferred drugs for moderate chronic tic disorders, the recommendation for initial mild Tourette syndrome (TS) treatment was the same as preferred drugs for moderate chronic tic disorders. Similarly, clonidine, aripiprazole, tiapride and haloperidol could be recommended as the preferred drugs for other kinds of tic disorders. As for the second monotherapy, the preferred drugs for moderate transient tic disorders, mild chronic tic disorders and severe TS were all aripiprazole, tiapride, haloperidol, sulpiride, clonidine and topiramate. While clonidine, aripiprazole, tiapride could be considered as preferred drugs for severe transient tic disorders, moderate to severe chronic tic disorders and mild to moderate tic disorders. In the investigation of monotherapy for newly diagnosed tic disorders in children with comorbidities, for moderate chronic tic disorders and TS comorbid with obsessive-compulsive disorder, aripiprazole (4 (3, 5) scores) and sertraline (4 (3, 4) scores) were preferred drugs,the median scores of which were all greater than overall scores (3 (3, 4) scores), they were also the preferred treatment for severe transient tic disorders and mild chronic tic disorders. For mild and moderate transient tic disorders, severe chronic tic disorders and TS comorbid with obsessive-compulsive disorder, aripiprazole, fluvoxamine, fluoxetine, haloperidol and sertraline were preferred drugs. When comorbid with attention deficit hyperactivity disorder (ADHD), severe transient tic disorders, moderate chronic tic disorders and TS, tomoxetine and clonidine were recommended as preferred drugs (both 4 (4, 5) scores), and tomoxetine and clonidine were also the preferred treatment for severe TS. For severe chronic tic disorders comorbid with ADHD, clonidine (5(4, 5) scores) was preferred drug, greater than overall scores (4 (3, 5) scores), while for mild and moderate transient tic disorders clonidine, tomoxetine, guanidine and methylphenidate were recommended as preferred drugs. For mild chronic tic disorders and TS comorbid with ADHD tomoxetine was preferred drug. When comorbid with sleep disorders, there were no preferred drugs for mild transient tic disorders; estazolam (3 (2, 3) scores) was the preferred drug for mild chronic tic disorders and TS comorbid with sleep disorders. For othe kind of tic disorders comorbid with sleep disorders, estazolam, melatonin and clonazepam were preferred drugs. When comorbid with anxiety and depressive disorders, for all kinds of tic disorders sertraline was recommended as preferred drugs, the median scores of sertraline were all (4 (3, 5) scores) in severe transient tic disorders, moderate to severe chronic tic disorders and moderate TS, and greater than overall scores (3 (3, 4) scores). While severe chronic tic disorders comorbid with anxiety and depressive disorders, fluvoxamine could also be chosen as preferred drugs. Conclusions: Drug therapy is not recommended for mild transient tic disorders, while tiapride, aripiprazole, clonidine, and haloperidol are mainly preferred drugs for the other kinds of tic disorders. Corresponding drugs should be selected when tic disorders are combined with obsessive-compulsive disorder, ADHD, sleep disorders, anxiety, depression, etc.

[The phenotypes and genotypes in 314 patients with isolated methylmalonic acidemia].

Objectives: To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention. Methods: Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test. Results: Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ(2)=4.261, 6.930, P=0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common (n=211, 93%) cause of this condition. c.729_730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ(2)=3.859, P=0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ(2)=13.729, P=0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ(2)=4.789, 7.705, P=0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions: The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects.

[Percutaneous full-endoscopic removalof lumbar dumbbell tumors viatransforaminal approach].

Objective: To investigate the novel application and effectof Percutaneous Full-Endoscopic transforaminal approach for lumbar dumbbell tumors. Methods: A retrospective analysis of 12 cases of lumbar dumbbell tumors was conducted by Percutaneous full-endoscopic transforaminal approach in the Department of Neurosurgery, Fujian Medical University Union Hospital from Feb, 2018 to Jul, 2019. According to Eden classification, 5 cases in type Ⅲ and 7 cases in type Ⅳ. The Japanese Orthopaedic Association (JOA) score and Pain Visual analogue Scale (VAS) were used to compare the recovery of neurological function before and after surgery. Results: All the 12 tumors were completely removed in one stage. The pathological reports were all schwannomas (WHO grade Ⅰ). The VAS scores were significantly decreased compared with preoperative ones (P<0.001). The JOA scores were significantly improved without obvious complications and spinal instability. Median length of follow-up was 14 months with a range of 4 months to 20 months, there is no tumor recurrence and spinal instability. Conclusion: In the treatment of lumbar dumbbell spinal tumor, the full endoscopic transforaminal approach is a novel, safe and effective surgical procedure which removes the tumors intra-foramen and extra-foramen with less damage of spine, smaller possibility of instability and faster recovery.

[Electroclinical characteristics of epilepsy children with midline epileptiform discharges related epileptic negative myoclonus as the first symptom].

Objective: To investigate the electroclinical findings in epilepsy children with epileptic negative myoclonus (ENM) restricted to the lower limb as the first seizure type. Methods: Each retrieved electroencephalogram record performed between March 2011 and March 2018 at the Department of Pediatrics of Peking University First Hospital was searched with "midline" . There were 302 records of 175 patients with "benign" or "functional" midline spikes. A retrospective review of each patient's hospital record was performed. Thirteen patients had ENM restricted to the lower limb as the first seizure type. The clinical and electroencephalogram characteristics of them were analyzed. Results: Thirteen patients manifested ENM restricted to the lower limb as the first seizure type, diagnosed as benign childhood focal epilepsy with vertex spikes (BEVS). Six patients had ENM as the first and only seizure type during the short-time follow-up. Among them, there were 1 male and 5 females. The age at seizure onset was (2.5±0.7) years. One of them had electrical status epilepticus during sleep (ESES) identified on electroencephalogram at theage of 4 years and 8 months. The last follow-up age was (3.8±1.5) years. The remaining 7 patients developed nocturnal focal motor seizures. Among them, there were 4 males and 3 females. The age at seizure onset was (3.5±0.7) years. Two of them were diagnosed as BEVS evolving into benign childhood epilepsy with centrotemporal spikes (BECTS) and 5 were diagnosed as BEVS concurring with BECTS. The age at focal seizures was (4.1±0.6) years. The interval ranged from 1 month to 1 years. Six of 7 patients had electrical ESES with the age of (5.2±1.0) years. All had developmental regression, further diagnosed as atypical benign partial epilepsy (ABPE). The median age at last follow-up was 5.9 years. Five of 13 patients had repeated electroencephalogram records at our apartment, showing that epileptiform discharges in midline regions were significantly reduced either in frequency or amplitude with the improvement of ENM restricted to the lower limb and that independent epileptiform discharges in Rolandic regions from midline regions were noticed with the onset of nocturnal focal seizures. Conclusions: ENM restricted to the lower limb has a close association with vertex (midline) epileptiform discharges. ENM restricted to the lower limb as the first seizure type is a peculiar phenomenon of BEVS. Some patients could evolve into BECTS or overlap with BECTS, and further into ABPE. The age of seizure onset in BEVS with ENM restricted to the lower limb as the first symptom is a little earlier than in BECTS. Ignorance of the close association between midline spikes and ENM restricted to the lower limb may lead to misdiagnosis of these patients.

[Clinical features of 54 cases of leukoencephalopathy with vanishing white matter disease in children].

Objective: To summarize the clinical features of leukoencephalopathy with vanishing white matter disease (VWM) in children. Methods: A retrospective cohort study was performed on 54 genetically diagnosed VWM patients in Peking University First Hospital from January 2007 to March 2019. Paper registration form and electronic medical record system were used to collect the data,and the children were divided into five groups according to the age of disease onset:<1 year, 1-<2 years, 2-<4 years, 4-<8 years and 8-<18 years respectively. The progression of motor function, episodic aggravation, epileptic seizures, survival time, brain magnetic resonance imaging (MRI) and genotype features were analyzed and compared. Non-parametric test, χ(2) test or Fisher's exact test were used for comparison among groups; Kaplan-Meier survival curve was adopted to delineate the survival status of the children. Results: Fifty-four VWM patients were included in the study, including 34 males and 20 females.The age of disease onset was 2 years and 8 months (ranged from 6 months to 9 years and 7 months). Onset age was less than 1 year in 5 cases; onset age was 1-<2 years in 12 cases; onset age was 2-<4 years in 25 cases; onset age was 4-<8 years, in 10 cases; onset age was 8-<18 years in 2 cases; 94% (51/54) of patients had complaint of motor regression at the first visit; 87% (47/54) of patients suffered from episodic aggravation. Episodic seizures occurred in 43% (23/54) patients. In survivors with disease durations of 1-3 years, in 38% (9/24) patients the disease was classified as grades Ⅳ-Ⅴ by gross motor function classification system (GMFCS). For the onset age 1-<2 years group, 1 patient was classified as GMFCS Ⅳ among 3 survivors with disease durations of 1-3 years. As for the 2-<4 years group, 6 patients were classified as GMFCS Ⅳ-Ⅴ among 15 patients with disease durations of 1-3 years, whereas 1 patient was classified as GMFCS Ⅳ-Ⅴ among 4 patients with disease durations of 1-3 years in the 4-<8 years group. Lesions, liquefaction and diffusion restriction in brain MRI were compared among different groups, and it was revealed that the earlier the age of disease onset was, the more likely the subcortical white matter (frontal lobe P<0.01,temporal and parieto-occipital lobe both P=0.002), internal capsule (anterior limb P<0.01, posterior limb P=0.00) and brain stem (midbrain P=0.001, pons P<0.01) were to be involved. In addition, internal capsule (anterior limb P=0.002, posterior limb P=0.005) and brain stem (midbrain P=0.001, pons P=0.003) showed more diffuse restricted diffusion. Moreover, the subcortical white matter (frontal and parieto-occipital lobe both P<0.01, temporal lobe P=0.005) showed earlier rarefaction. The 1-year and 2-year survival rates of the overall patients were 81% and 75% respectively, while the 15-year survival rate was 45%. EIF2B5 gene variation was the most common, which accounts for 43% (23/54), followed by EIF2B3 (22%, 12/54). Conclusions: The majority of VWM patients complained of motor regression at the first visit, episodic aggravation and epileptic seizures are common in the course. Earlier age at onset is associated with more rapid clinical progression, shorter survival time as well as more extensive lesions, liquefaction and diffusion restriction in brain MRI. The most common variant gene is EIF2B5, followed by EIF2B3.

[Clinical characteristics of PCDH19-female limited epilepsy].

Objective: To analyze the clinical characteristics of patients with PCDH19-female limited epilepsy (PCDH19-FE). Methods: The clinical data of 60 female epilepsy patients with PCDH19 gene heterozygous variations at the Department of Pediatrics, Peking University First Hospital from October 2007 to December 2018 were collected and analyzed retrospectively, their clinical manifestations, accessory examination and follow-up treatment were summarized. Results: Data of a total of 60 cases of PCDH19-FE were collected. The seizure onset occurred between 4 and 42 months of age (median: 11 months of age). Focal seizures occurred in 47 patients (78%), generalized tonic-clonic seizures (GTCS) occurred in 30 patients (50%), and other rare types of seizures included atypical absence, myoclonic, clonic, tonic, and atonic seizures. Two or more seizures types existed in 24 patients (40%), and seven patients (12%) had attacks of status epilepticus. Sensitivity to fever was observed in 47 out of them (78%) and clustering of seizures as found in all patients. During the interictal phase, focal discharges were monitored in 22 cases (22/45, 49%), multifocal discharges in 12 cases (12/45, 27%), widely discharging in 2 cases (4%), and both focal and widely discharging in 9 cases (20%). Clinical seizures were detected in 30 patients during the electroencephalogram (EEG) recording, including focal seizures in 22 cases, GTCS seizures in 8 cases, tonic seizure in three cases, myoclonic seizure followed by GTCS in one case, and two types of seizures in four cases. Before seizure onset, 57 patients had normal development and three patients had delayed language development. After seizure onset, varied degrees of intelligence disability were present in 38 cases (63%), language delay in 36 cases (60%), and gait instability in 10 cases (17%). Autistic features occurred in 17 cases (28%); and other behavioral problems like learning difficulties, personality, or emotional disorders existed in 33 cases (55%). Age at last follow-up ranged from one year and 3 months to 22 years and 3 months of age, 17 patients (28%) were seizure-free for more than 2 years (5 to 22 years at the last follow-up). The efficiency of antiepileptic drugs were 65% (33/51) in sodium valproate, 63% (27/43) in levetiracetam and 59% (20/34) in topiramate. Conclusions: The clinical features of PCDH19-FE are characterized by clustering of seizures, focal seizures in most cases, sensitivity to fever mostly, focal discharges principally in EEG, varied degrees of intellectual disability or movement disorder, combined with autism spectrum disorders in partial and high efficiency in sodium valproate or levetiracetam treatment.