Objective:To investigate the long-term prognosis and related factors in children with multiphasic myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).Methods:A bidirectional cohort study was conducted. This study included 41 children with MOGAD who were treated at the Children′s Medical Center of Peking University First Hospital between January 2013 and December 2024, with a disease duration of ≥5 years. Demographic characteristics, clinical episodes, therapy, and prognostic indicators (including the expanded disability status scale (EDSS) and modified Rankin scale (mRS)) were collected. Children were stratified into relapse and non-relapse groups based on the presence or absence of relapse within 5 years of the last follow-up. χ2 test or Mann-Whitney U test was used to analyze factors associated with relapse. The Log-rank test was used to compare relapse-free rates between children with disease onset 0-<5 years and those with onset at 5-10 years. Results:A total of 41 children were enrolled, including 20 boys and 21 girls. The age at onset was 5.3 (3.8, 8.5) years, the age at last follow-up was 16.1 (13.2, 17.5) years, and the disease duration was 9.4 (8.1, 10.9) years. The annualized relapse rate (ARR) during follow-up was 0.34 (0.19, 0.56) times/year. The duration to first relapse was 0.8 (0.4, 1.5) years. At the last follow-up, the EDSS score was 0.0 (0.0, 0.0) score, and the mRS score was 0 (0, 0) score. A total of 40 children (98%) experienced relapses within the first 5 years after onset, while only 1 child (2%) relapsed at 6.7 years. The relapse rate between 5-10 years was lower than that between 0-<5 years ( HR=0.27, 95% CI 0.16-0.47, P<0.001). A total of 25 children (61.0%) exhibited clustered relapses during the disease course. There were 20 children (49%) in non-relapse groups, who were aged 16.6 (14.8, 17.6) years, disease duration 9.8 (9.3, 10.8) years at the last follow-up. Among those 20 children, 15 children (75%) had discontinued corticosteroids and immunosuppressants. The relapse group had higher clinical event rates and ARR compared to the relapse-free group (both P<0.01), the age at last follow-up was yonger ( P<0.05), while no significant differences were observed in age at onset, disease duration, or timing of immunosuppressant use (all P>0.05). Conclusions:Pediatric multiphasic MOGAD generally has a favorable prognosis, about half of patients remain relapse-free for ≥5 years at last follow-up. Relapses predominantly occur early in the disease course (mostly within 5 years of onset) and often exhibit a clustered pattern.

Objective:To investigate the long-term prognosis and related factors in children with multiphasic myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).Methods:A bidirectional cohort study was conducted. This study included 41 children with MOGAD who were treated at the Children′s Medical Center of Peking University First Hospital between January 2013 and December 2024, with a disease duration of ≥5 years. Demographic characteristics, clinical episodes, therapy, and prognostic indicators (including the expanded disability status scale (EDSS) and modified Rankin scale (mRS)) were collected. Children were stratified into relapse and non-relapse groups based on the presence or absence of relapse within 5 years of the last follow-up. χ2 test or Mann-Whitney U test was used to analyze factors associated with relapse. The Log-rank test was used to compare relapse-free rates between children with disease onset 0-<5 years and those with onset at 5-10 years. Results:A total of 41 children were enrolled, including 20 boys and 21 girls. The age at onset was 5.3 (3.8, 8.5) years, the age at last follow-up was 16.1 (13.2, 17.5) years, and the disease duration was 9.4 (8.1, 10.9) years. The annualized relapse rate (ARR) during follow-up was 0.34 (0.19, 0.56) times/year. The duration to first relapse was 0.8 (0.4, 1.5) years. At the last follow-up, the EDSS score was 0.0 (0.0, 0.0) score, and the mRS score was 0 (0, 0) score. A total of 40 children (98%) experienced relapses within the first 5 years after onset, while only 1 child (2%) relapsed at 6.7 years. The relapse rate between 5-10 years was lower than that between 0-<5 years ( HR=0.27, 95% CI 0.16-0.47, P<0.001). A total of 25 children (61.0%) exhibited clustered relapses during the disease course. There were 20 children (49%) in non-relapse groups, who were aged 16.6 (14.8, 17.6) years, disease duration 9.8 (9.3, 10.8) years at the last follow-up. Among those 20 children, 15 children (75%) had discontinued corticosteroids and immunosuppressants. The relapse group had higher clinical event rates and ARR compared to the relapse-free group (both P<0.01), the age at last follow-up was yonger ( P<0.05), while no significant differences were observed in age at onset, disease duration, or timing of immunosuppressant use (all P>0.05). Conclusions:Pediatric multiphasic MOGAD generally has a favorable prognosis, about half of patients remain relapse-free for ≥5 years at last follow-up. Relapses predominantly occur early in the disease course (mostly within 5 years of onset) and often exhibit a clustered pattern.

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.

Objective:To investigate the risk factors of acute symptomatic seizures (ASS) and epilepsy in children with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).Methods:A ambispective cohort study was used including 74 children with MOGAD who were admitted to the Department of Pediatrics of Peking University First Hospital from January 2013 to June 2023 and were followed up. Demographic information, clinical information, treatment status, ASS and epilepsy status were collected. The clinical phenotypes were classified. According to the presence or absence of ASS in the course of disease, the children and the course of disease were divided into groups with and without ASS. Chi-square test, Fisher exact test and Mann Whitney U test were used to analyze the correlation between symptoms and auxiliary examination characteristics and the occurrence of ASS in the two groups of children. Multivariate Logistic regression analysis was used for multivariate analysis. Results:The onset age of the 74 children with MOGAD was 6.58 (3.80, 9.67) years, including 38 females (51.4%) and 36 males (48.6%). The duration of the final follow-up was 2.67 (1.10, 4.12) years, with a total of 239 times acute clinical episodes. ASS occurred in 39.2% (29/74) children during the course of disease and in 29.3% (70/239) of attacks. The common phenotypes were ADEM (67 times (28.0%)), optic neuritis (37 times (15.4%)) and cerebral cortical encephalitis (31 times (13.0%)) in 239 times acute clinical episodes. The incidence of ASS in ADEM and cerebral cortical encephalitis phenotype was 28.4%(19/67) and 100.0% (31/31), respectively. Multivariate analysis showed that cortical involvement on magnetic resonance imaging during clinical attacks was an independent risk factor for ASS ( β=-1.49, OR=0.23) after excluding attacks involving only optic nerve or spinal cord (49 episodes). During the follow-up, 5 children (6.8%) had epilepsy, and all children with epilepsy had multiple clinical attacks of MOGAD and previous ASS. Conclusions:Cortical involvement on magnetic resonance imaging during clinical episodes is an independent risk factor for ASS in children with MOGAD. All MOGAD children with epilepsy had ASS and multiple MOGAD clinical episodes in the past.

Objective To investigate the effect of phenformin combined with hexokinase inhibitor 2-deoxyglucose (2-DG) on the treatment of triple-negative breast cancer cell lines 4T1 and MDA-MB-231. Methods Following treatment with phenformin, 2-DG or phenformin combined with 2-DG on 4T1 and MDA-MB-231 cells for 48 h, the cell proliferation in each group was detected by SRB and the apoptosis of cells was detected by flow cytometry. The concentration of glucose and lactic acid in cell culture supernatant was detected by ELISA. The activity of mitochondrial respiratory chain complex Ⅰ was detected by FlexStation3 and the mitochondrial oxygen consumption (OCR) was assayed with the Seahorse X Fe Analyzer. Results The hexokinase expression (4.6±0.17,3.73±0.21), glucose consumption (356±31，397±42) μg/10⁵ cells , Lactic acid concentration (5.59±0.52, 7.83±0.78) μmol/L in the supernatant of 4T1 and MDA-MB-231 cells in Phenformin group were higher than that in control group ( 1±0.15，1±0.12 ) , ( 289±25，301±32) μg/10⁵cells , ( 2.37±0.18，4.01±0.45) μmol/L (P < 0.01). Even if the dose was reduced by 90%, the cell viability of phenformin combined with 2-DG group (64.63±2.28, 51.97±2.29) % was still higher than that of phenformin group (86.70±1.83, 85.53±1.46) % (P<0.001). The combination of the two drugs significantly promoted the apoptosis of 4T1 and MDA-MB-231. In addition, compared with the phenformin group (5.59±0.52, 7.83±0.78) μmol/L, the phenformin combined with 2-DG group (3.46±0.37, 5.18±0.62) μmol/L cell lactic acid production also greatly reduced (P<0.01). Compared with the phenformin or 2-DG single-drug group, the phenformin combined with 2-DG group can significantly inhibit the growth rate of tumors in tumor-bearing mice (P<0.01). The median survival time of tumor-bearing mice in the phenformin combined with 2-DG group was 72.5 d, which was higher than that in the phenformin group 57 d and 2-DG group 55.5 d (P<0.01). Conclusion Hexokinase inhibitor 2-DG significantly enhances the therapeutic effects of phenformin on triple-negative breast cancer cells.

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.

Objective:To analyze the clinical features and genotypes of mitochondrial complex Ⅰ deficiency due to NDUFAF5 gene mutations.Methods:Clinical data of 2 cases with mitochondrial complex Ⅰ deficiency due to NDUFAF5 gene mutations admitted in the Department of Pediatrics, Peking University First Hospital from February 2015 to July 2018 were retrospectively reviewed and followed up.Reported cases of mitochondrial complex Ⅰ deficiency due to NDUFAF5 gene mutations were searched in online databases, including the PubMed, Wanfang, Chinese Journal Full-Text Database and VIP database from January 1975 to February 2020 with " NDUFAF5" as the key word.Through literature review, clinical features and genotypes of mitochondrial complex Ⅰ deficiency due to NDUFAF5 gene mutations were summarized.Results:Case 1 showed mentor and mental regression after infection at the age of 1 year and 4 months.The condition of case 1 remained stable at the age of 5 year and 6 months at the last follow-up.Brain magnetic resonance imaging (MRI) showed multiple lesions in the white matter of the frontal and parieto-occipital lobes, basal ganglia, thalamus, cerebellum, brain stem and corpus callosum.Case 2 showed rapidly bilateral visual impairment at the age of 7 years and 4 months.The patient′s vision moderately recovered at the age of 8 years and 8 months.Brain MRI showed midbrain, periaqueductal gray, medulla oblongata and putamen lesions.Spinal MRI showed continuous lesions in the cervical cord 1-4.Genetic test showed NDUFAF5 gene c. 764C>T (p.Ala255Val) and c. 508C>T (p.Arg170Trp), homozygous c. 836T>G (p.Met279Arg) mutations in case 1 and case 2 respectively.Through online searching, 6 reports involving 14 cases were retrieved.The most common clinical phenotype was Leigh syndrome.Two cases had disease onset during the neonatal period, and their disease progressed rapidly and died within 1 year old.Eleven cases had onset during the infantile period, and 72.7% (8/11 cases) of them had a normal development.The common initial symptoms were mental or motor regression, feeding difficulty and dystonia.Seventy-two point seven percent (8/11 cases) had acute/subacute onset after infection, showing paroxysmal deterioration, and died in infancy or childhood.One patient developed dystonia in childhood and visual impairment in adulthood.Conclusions:The onset age ranged from neonatal period to childhood in patients with NDUFAF5 gene mutations, and their clinical phenotypes vary a lot.The main clinical phenotype is Leigh syndrome.Disease onset during the infantile period is frequent, and mostly presents paroxysmal deterioration after infection, while disease onset in childhood is rare.

Objective: To explore the methods for generating evidence on health outcomes in children with rare diseases. Methods: The data from 30 clinical trials on rare neurological diseases in children from January 2008 to December 2018 were collected and analyzed.Statistical analysis was conducted on the relationship between the study sponsor and the study center, the number of participants and the prevalence rate. Results: Thirty studies involved 6 types of diseases, including 14 kinds of diseases.(1) All global multicenter studies (14 items) were initiated by pharmaceutical companies, whereas most of single-center studies (6/7 kinds, 86%) and multiple centers within one country(7/9 kinds, 78%) were initiated by investigators.There was a significant correlation between the research center and the research sponsor(P<0.001). (2) Most of the drugs studied were selected based on previous clinical trials (9/30 items) and animal experiments (9/30 items). (3) The median number of participants included 39 cases (10-215 cases), and 60%(18/30 items) of the studies was fewer than 50 cases.(4) Study design: 53%(16/30 items) of studies were randomized controlled studies, 33%(10/30 items) studies were open-label single-arm studies, and 14% (4/30 items) were randomized cross-over trials.Seventy-five percent(12/16 items)of randomized controlled studies were initiated by pharmaceutical companies, 50%(5/10 items) open-label single-arm studies and all randomized cross-over trials were initiated by investigators.There was a statistical correlation between the study sponsors and the study design method (χ²=7.602, P=0.022). (5) Outcome index: Scale score was used as the primary outcome in half of studies.Other studies used symptom improvement or pathological changes. Conclusions Clinical trials in rare diseases enrolled fewer participants than that in non-rare diseases, and the study design method was relatively simple.Therefore, it is necessary to further improve the level of evidence of clinical research of rare diseases through global and multi-center recruitment, initiation of pharmaceutical companies and improving the study design method.

Objective　To compare the endocytic routes of exogenous antigen between murine dendritic cells (DCs) and macrophages (Mφs). Methods　Murine bone marrow-derived DCs and peritoneal Mφs were pulsed with horseradish peroxidase (HRP)-5 nm colloidal gold for 10 minutes, then grouped and chased for 0-120 minutes in culture medium. Intracellular distribution of 5 nm colloidal gold was explored by means of the cellular enzymatic-chemistry of acid phosphatase and MHC Ⅱ immuno-cytochemistry under electron microscope. Results　After 10 minutes of pulse with HRP-5 nm colloidal gold and 30 minutes of chase, most HRP-5 nm gold particles internalized by DCs entered into MHC class Ⅱ compartments (MⅡCs), and a small portion entered into acid phosphatase-positive lysosomes. In contrast to DCs, most Mφs lysosomes were accessed by HRP-5 nm gold particles, and a small portion of HRP-5 nm gold particles entered into MⅡCs. After 60 minutes of chase, 5 nm gold particles could hardly be seen within Mφs, whereas most 5 nm gold particles were still retained in DCs. Conclusions　The endocytic route of exogenous antigen in DCs seems to be different from that in Mφs. Antigens taken by Mφs mainly enter into lysosomes within 30 minutes. In the case of DCs, most internalized antigens enter into MⅡCs, which may be related to their unique antigen-presenting function . In addition, Mφs seem to have more powerful capacity to scavenge exogenous antigen than DCs.

Objective:To evaluate the biological characters of C57-TgN(HBV adr2.0)SMMU transgenic mice. Methods: Integration,expression,replication and histology change of hepatitis B virus gene in F6 transgenic mice were estimated by ge-nomic DNA PCR,Western blotting,ELISA,immunohistochemistry,serum DNA PCR,transmission electron microscopy and H-E staining. Results: Hepatitis B virus gene was integrated into F6 C57-TgN(HBV adr2. 0)SMMU transgenic mice and expressed HBsAg,HBcAg and X protein in liver tissue. HBsAg and HBeAg were expressed in serum of 19. 54% and 3. 39% F6 transgenic mice. Hepatitis B virus were replicated in serum and liver tissue of transgenic mice. Long-term integration,expression and replication of hepatitis B virus gene induced pathological lesion of transgenic mice liver and lung. Conclusion: C57-TgNCHBV adr2. 0)SMMU transgenic mice line has the biological characters including integration of hepatitis B virus gene into genomic DNA,expression and replication of hepatitis B virus gene in serum and liver, and histological change in liver and lung. It is a valuable animal system to study pathogenesis, treatment and prevention of hepatitis B virus.