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 identify the components of Prunus mume f. viridicalyx based on ultra performance liquid chromatography-QE-Orbitrap mass spectrometry (UPLC-QE-Orbitrap-MS); To predict and analyze its substances and mechanisms to exert anti-depression effects combined with network pharmacology.Methods:UPLC-QE Orbitrap MS technology was used to analyze the chemical components of Prunus mume f. viridicalyx. Based on ChemSpider, mzCloud online platform, orbitrap TCM library and existing literature research, the secondary mass spectra of target compounds were compared and confirmed to identify the chemical composition of Prunus mume f. viridicalyx. The active components of the Prunus mume f. viridicalyx were screened. The Swiss Target Prediction database was used to predict targets with high correlation to active components in Prunus mume f. viridicalyx, and obtaining depression related disease targets from GeneCards and DisGeNET databases. The intersection targets of constituents and diseases were obtained using Venny platform. Protein-protein interaction network (PPI) was constructed by using String database, and the core targets were screened. Gene ontology function and Kyoto encyclopedia of genes and genomes pathway enrichment analysis of potential core targets were performed by using David database, and "active component-core target-signal pathway" network was constructed. PyMOL software was used to perform molecular docking between active components and key targets.Results:A total of 54 components, including organic acids, flavonoids and their glycosides, alkaloid, amino acids and other compounds were identified from Prunus mume f. viridicalyx. A total of 22 active components were screened and 92 active components and disease intersection targets were identified. A total of 13 core targets were screened through PPI network, including tumor necrosis factor, albumin, amyloid beta-protein precursor, AKT serine/threonine kinase 1 and so on. Enrichment analysis showed that Prunus mume f. viridicalyx mainly participated in transcription from RNA polymerase Ⅱ promoter, gene expression, protein binding and other functions, and presented the effects of anti-depression through MAPK, Toll-like receptor signaling pathway and other pathways. 12 key targets and 7 key active components were further obtained through the analysis of the "active component-core target-signal pathway" network, three of them were confirmed as kaempferol, quercetin, and isorhamnetin by reference substance. Molecular docking showed that 3 compounds could bind to the target proteins of depression well.Conclusion:Prunus mume f. viridicalyx exerts antidepressant effects through multiple components, targets, and pathways, mainly through the MAPK signaling pathway.

Objective:To analyze and summarize clinical phenotypic characteristics and genetic variations in patients with intellectual disability and pathogenic variations of the DYNC1H1 gene across 4 generations within a single family. Methods:Retrospective case analysis.Clinical data of a child with epilepsy and intellectual disability and her family members were collected from the Children′s Medical Center, Peking University First Hospital on December 2019.The child was followed up regularly.DNA was extracted from the peripheral blood of the child′s family members.Then whole-exome sequencing and Sanger sequencing were performed to identify the genetic variation type in the proband and her family members.The relationship between genotype and phenotype was further analyzed.Results:A total of 13 patients across 4 generations in the family had intellectual disability, and the proband also had drug-resistant epilepsy.The variation c. 13556C> A (p.A4519E) of the DYNC1H1 gene was confirmed by gene testing in 8 patients (no blood samples were obtained from the remaining patients). Conclusions:DYNC1H1 gene-related intellectual disability in most previously reported cases are caused by novel variations of this gene.In this study, a large family of 13 intellectual disability patients across 4 generations caused by a pathogenic mutation in the DYNC1H1 gene was summarized.The findings make precise genetic counseling possible for this family and provide a basis for further studies on the relationship between the genotype and phenotype of the DYNC1H1 gene.

The clinical and genetic characteristics of a male child diagnosed with autosomal recessive cerebellar ataxia caused by compound heterozygous variants in VPS41, who was admitted to the Department of Neurology, Children′s Medical Center, Peking University First Hospital in July 2023, was retrospectively analyzed with a comprehensive literature review.The 10-year-old patient exhibited motor delay since infancy, achieving independent sitting at age 1 and independent walking at age 2, yet manifested unsteady gait with frequent falls.Motor skills progressed slowly, alongside academic underperformance.Physical examination revealed impaired ocular pursuit, nystagmus, and signs of ataxia.Brain magnetic resonance imaging (MRI) demonstrated mild cerebellar atrophy.Trio-based whole-exome sequencing identified compound heterozygous VPS41 variants (c.1247G>A, p.R416H and c. 1175dup, p.H392Qfs*2), segregating from each parent.This represents the first reported Chinese case of autosomal recessive cerebellar ataxia associated with VPS41 variants.Globally, only 13 patients with VPS41-related hereditary ataxia have been documented, involving 7 distinct variants.Both variants detected in this case are novel, expanding the disease′s mutational spectrum.

Objective:To analyze and summarize clinical phenotypic characteristics and genetic variations in patients with intellectual disability and pathogenic variations of the DYNC1H1 gene across 4 generations within a single family. Methods:Retrospective case analysis.Clinical data of a child with epilepsy and intellectual disability and her family members were collected from the Children′s Medical Center, Peking University First Hospital on December 2019.The child was followed up regularly.DNA was extracted from the peripheral blood of the child′s family members.Then whole-exome sequencing and Sanger sequencing were performed to identify the genetic variation type in the proband and her family members.The relationship between genotype and phenotype was further analyzed.Results:A total of 13 patients across 4 generations in the family had intellectual disability, and the proband also had drug-resistant epilepsy.The variation c. 13556C> A (p.A4519E) of the DYNC1H1 gene was confirmed by gene testing in 8 patients (no blood samples were obtained from the remaining patients). Conclusions:DYNC1H1 gene-related intellectual disability in most previously reported cases are caused by novel variations of this gene.In this study, a large family of 13 intellectual disability patients across 4 generations caused by a pathogenic mutation in the DYNC1H1 gene was summarized.The findings make precise genetic counseling possible for this family and provide a basis for further studies on the relationship between the genotype and phenotype of the DYNC1H1 gene.

The clinical and genetic characteristics of a male child diagnosed with autosomal recessive cerebellar ataxia caused by compound heterozygous variants in VPS41, who was admitted to the Department of Neurology, Children′s Medical Center, Peking University First Hospital in July 2023, was retrospectively analyzed with a comprehensive literature review.The 10-year-old patient exhibited motor delay since infancy, achieving independent sitting at age 1 and independent walking at age 2, yet manifested unsteady gait with frequent falls.Motor skills progressed slowly, alongside academic underperformance.Physical examination revealed impaired ocular pursuit, nystagmus, and signs of ataxia.Brain magnetic resonance imaging (MRI) demonstrated mild cerebellar atrophy.Trio-based whole-exome sequencing identified compound heterozygous VPS41 variants (c.1247G>A, p.R416H and c. 1175dup, p.H392Qfs*2), segregating from each parent.This represents the first reported Chinese case of autosomal recessive cerebellar ataxia associated with VPS41 variants.Globally, only 13 patients with VPS41-related hereditary ataxia have been documented, involving 7 distinct variants.Both variants detected in this case are novel, expanding the disease′s mutational spectrum.

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 establish an ultra-high performance liquid chromatography(UPLC)fingerprint and multi-index content determination method of Siraitiae fructus standard decoction.Methods 15 batches of Siraitiae fructus from different producing areas were collected,Siraitiae fructus standard decoction was prepared according to Technical Requirements for Quality Control and Standardization of Traditional Chinese Medicine Formula Granules,and the extract rate was calculated.UPLC was used to establish the fingerprint of 15 batches of Siraitiae fructus standard decoction and determine the contents of 11-O-mogroside V,kaempferitrin and mogroside V,which were the main effective components.The chemometrics analysis was used to evaluate the quality of Siraitiae fructus standard decoction and find possible quality markers.Results The extraction rate of 15 batches Siraitiae fructus standard decoction ranged from 24.79％to 34.95％.There were 16 common peaks in the fingerprint,and 4 components were identified.The Siraitiae fructus standard decoction was divided into 2 categories by chemometrics analysis,among which samples from Liuzhou,Guangxi were in one category and samples from Guilin,Guangxi were in another category.Seven differential markers were screened out under the condition of variable importance projection value,and the order was as follows:peak 8＞peak 7＞peak 5＞peak 12(kaempferitrin)＞peak 1＞peak 13＞peak 4.The contents of kaempferitrin,11-O-mogroside V and mogroside V in samples from Guilin,Guangxi were slightly higher than those in samples from Liuzhou,Guangxi.Conclusion The UPLC fingerprint and content determination method established in this study are feasible,which can provide a basis for the quality evaluation of Siraitiae fructus.The results of principal component analysis show that kaempferol is likely to become a quality marker of Siraitiae fructus.

Objective:To establish HPLC fingerprints of Aristolochia contorta and honey-processed Aristolochia contorta; To analyze the changes of chemical components before and after honey processing with multivariate statistics; To provide a reference for the study on the toxicity reduction of Aristolochia contorta.Methods:The fingerprints of 11 batches of Aristolochia contorta and honey-processed Aristolochia contorta were established through HPLC. Clustering analysis (HCA), principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA) and independent sample t-test were used to compare the changes of chemical components of Aristolochia contorta before and after honey processing.Results:The results showed that there were 14 common peaks in the fingerprints of Aristolochia contorta and Aristolochia contorta. 7 common peaks were identified. Both HCA and PCA could clearly distinguish the samples of Aristolochia contorta before and after honey processing. OPLS-DA found and screened 7 differential markers, and the order of difference significance was peak 3 > peak 7 (7-hydroxy aristolochic acid A) > peak 5 (aristolochic acid C)> peak 8 (aristolochic acid D) > peak 6 > peak 2 (Magnolia alkaloid) > peak 14 (aristolochic acid Ⅰ). After honey processing, the content of chemical components represented by peaks 2, 3, 5, 6, 7, 8 and 14 decreased ( P<0.05). Conclusion:This method is simple and specific, which can be used for the fingerprint analysis of Aristolochia contorta and honey-processed Aristolochia contorta, and can effectively distinguish Aristolochia contorta and honey-processed Aristolochia contorta, and provide a reference for the processing research of toxicity reduction of Aristolochia contorta honey processing.

Objective:To establish the ultra-high performance liquid chromatography (UPLC) fingerprint and high performance liquid chromatography (HPLC) content determination method of Curcumae Radix standard decoction; To predict the quality markers of Curcumae Radix standard decoction combined with network pharmacology.Methods:UPLC method was used to establish the fingerprint of Curcumae Radix standard decoction, and the common peaks were determined. Combined with chemical pattern recognition techniques such as similarity analysis and clustering analysis, Curcumae Radix standard decoction from different producing areas was studied, and curcumol was used as an index to determine the content of 24 batches of Curcumae Radix standard decoction. At the same time, network pharmacology was used to predict potential of curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one.Results:A total of 24 batches of Curcumae Radix standard decoction from different habitats were compared and analyzed, and 10 common peaks were calibrated. The similarity of 24 batches of samples ranged from 0.982 to 0.999. Clustering analysis and principal component analysis divided them into three categories. Heat map analysis showed that peak 8 (curcumol) and peak 9 ((1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one) were the main components. The content of curcumol in 24 batches of Curcumae Radix standard decoction was 0.69-1.87 mg/g; curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β- (3-oxobutyl) bicyclo [4.1.0] heptan-3-one may regulate the neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation by regulating neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation. It was preliminarily predicted that curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one were potential quality markers of Curcumae Radix.Conclusion:Curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one are potential quality markers of Curcumae Radix standard decoction, and the established fingerprint can be used for the quality control of Curcumae Radix standard decoction.