Objective:To investigate the clinical manifestations of medically refractory hereditary movement disorders in children and the efficacy of deep brain stimulation (DBS).Methods:A case series study.The clinical and follow-up data of 20 children with medically refractory hereditary movement disorders who underwent DBS treatment at the Neurology and Functional Neurosurgery Departments of Beijing Children′s Hospital, Capital Medical University, from July 2018 to April 2024, were retrospectively analyzed.The severity of movement disorder symptoms and surgical effects were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale Movement(BFMDRS-M) or the Unified Parkinson′s Disease Rating Scale Ⅲ(UPDRS Ⅲ).Results:There were 12 males and 8 females among the 20 children, with an onset age ranging from 4 months to 12 years and 5 months.Fourteen patients had hereditary dystonia, which is related to KMT2B in 11 patients, TOR1A in 2 patients and SGCE in 1 patient.Two patients had choreoathetosis, which is related to ADCY5-related familial movement disorders.Two patients had early-onset Parkinson′s disease, which is related to ATP6AP2 in 1 patient and VPS13C in 1 patient.Two patients had neurodevelopmental disorders with involuntary movements, which is related to GNAO1 in 1 patient, and the other patient was idiopathic.All the children were given oral Levodopa, Benzhexol, Baclofen, Tiapride Hydrochloride, Clonazepam alone or in combination.Three children showed obvious dyskinesia after Levodopa treatment.The symptoms of movement disorders in all children exhibited little to no improvement.Levetiracetam and Zonisamide had unstable effects in the treatment of myoclonia.DBS surgery was performed on all the patients aged from 3 to 16 years.Electrodes were successfully inserted into bilateral globus pallidus internus in 14 cases and bilateral subthalamic nuclei in 4 cases.The target was unknown in 2 cases.No surgery-related complications were observed.The patients were followed up for 3 months to 6 years, and the last follow-up age of the patients ranged from 5 years and 7 months to 22 years and 1 month.The rate of improvement in BFMDRS-M score was 37%-100% in 16 patients and >70% in 7 patients with hereditary dystonia.The rate of improvement in UPDRS Ⅲ score was 23% in 1 patient with VPS13C-related early-onset Parkinson′s disease. Conclusions:Childhood medically refractory hereditary movement disorders are a case series that exhibits significant phenotypic and genotypic heterogeneity.DBS surgery demonstrates significant efficacy for KMT2B-, TOR1A-, and SGCE-related hereditary movement disorders.

Objective To establish a dexamethasone(Dex)-induced zebrafish model of glucocorticoid-induced osteoporosis(GIOP)combined with glucocorticoid-induced hypertension(GIHT),and to validate the model by the systematic evaluation of both the phenotypic manifestations and molecular mechanisms.Methods Zebrafish larvae at 3 or 4 d post-fertilization(dpf)were divided randomly into a control group(0.1％dimethyl sulfoxide)and a model group(10 μmol/L Dex).Osteogenic parameters and vessel diameter were assessed at 0,48,and 96 h post-administration(n=10).Bone mineralization and density were determined by the total area and sum brightness after Alizarin red staining.Vessel diameter was measured by detecting blood flow in the dorsal aorta.After confirming the optimal administration time,expression levels of bone-formation-related proteins(protein kinase B(Akt),glycogen synthase kinase(GSK)-3β,β-catenin)and angiogenesis-related proteins(AMP-activated protein kinase(AMPK),nuclear factor(NF)-κB)were detected by Western Blot to verify the molecular effectiveness of the model.Results Exposure to Dex for 96 h reduced bone mineralization and density in zebrafish larvae compared with the control group,and statistical analysis identified 4 dpf zebrafish and Dex administration for 96 h as the optimal modeling times for the GIOP model.Blood vessel diameter was significantly decreased in the model group compared with the control group(P＜0.05),and the difference became more pronounced with longer administration time and was particularly evident at 4 dpf and treatment for 96 h.Western Blot analysis showed that Dex significantly decreased protein expression levels of Akt,β-catenin,and NF-κB(P＜0.05)and significantly increased the expression of GSK-3β and AMPK(P＜0.05),suggesting that Dex effectively inhibited bone formation and angiogenesis after 96 hours treatment in 4 dpf zebrafish.Conclusions Treatment of 4 dpf zebrafish larvae with 10 μmol/L Dex rapidly established a reliable zebrafish model of GIOP combined with GIHT,providing an ideal animal model for further studies of the common mechanisms of the two diseases and for screening new drugs.

Objective To establish a dexamethasone(Dex)-induced zebrafish model of glucocorticoid-induced osteoporosis(GIOP)combined with glucocorticoid-induced hypertension(GIHT),and to validate the model by the systematic evaluation of both the phenotypic manifestations and molecular mechanisms.Methods Zebrafish larvae at 3 or 4 d post-fertilization(dpf)were divided randomly into a control group(0.1％dimethyl sulfoxide)and a model group(10 μmol/L Dex).Osteogenic parameters and vessel diameter were assessed at 0,48,and 96 h post-administration(n=10).Bone mineralization and density were determined by the total area and sum brightness after Alizarin red staining.Vessel diameter was measured by detecting blood flow in the dorsal aorta.After confirming the optimal administration time,expression levels of bone-formation-related proteins(protein kinase B(Akt),glycogen synthase kinase(GSK)-3β,β-catenin)and angiogenesis-related proteins(AMP-activated protein kinase(AMPK),nuclear factor(NF)-κB)were detected by Western Blot to verify the molecular effectiveness of the model.Results Exposure to Dex for 96 h reduced bone mineralization and density in zebrafish larvae compared with the control group,and statistical analysis identified 4 dpf zebrafish and Dex administration for 96 h as the optimal modeling times for the GIOP model.Blood vessel diameter was significantly decreased in the model group compared with the control group(P＜0.05),and the difference became more pronounced with longer administration time and was particularly evident at 4 dpf and treatment for 96 h.Western Blot analysis showed that Dex significantly decreased protein expression levels of Akt,β-catenin,and NF-κB(P＜0.05)and significantly increased the expression of GSK-3β and AMPK(P＜0.05),suggesting that Dex effectively inhibited bone formation and angiogenesis after 96 hours treatment in 4 dpf zebrafish.Conclusions Treatment of 4 dpf zebrafish larvae with 10 μmol/L Dex rapidly established a reliable zebrafish model of GIOP combined with GIHT,providing an ideal animal model for further studies of the common mechanisms of the two diseases and for screening new drugs.

Objective:To investigate the clinical manifestations of medically refractory hereditary movement disorders in children and the efficacy of deep brain stimulation (DBS).Methods:A case series study.The clinical and follow-up data of 20 children with medically refractory hereditary movement disorders who underwent DBS treatment at the Neurology and Functional Neurosurgery Departments of Beijing Children′s Hospital, Capital Medical University, from July 2018 to April 2024, were retrospectively analyzed.The severity of movement disorder symptoms and surgical effects were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale Movement(BFMDRS-M) or the Unified Parkinson′s Disease Rating Scale Ⅲ(UPDRS Ⅲ).Results:There were 12 males and 8 females among the 20 children, with an onset age ranging from 4 months to 12 years and 5 months.Fourteen patients had hereditary dystonia, which is related to KMT2B in 11 patients, TOR1A in 2 patients and SGCE in 1 patient.Two patients had choreoathetosis, which is related to ADCY5-related familial movement disorders.Two patients had early-onset Parkinson′s disease, which is related to ATP6AP2 in 1 patient and VPS13C in 1 patient.Two patients had neurodevelopmental disorders with involuntary movements, which is related to GNAO1 in 1 patient, and the other patient was idiopathic.All the children were given oral Levodopa, Benzhexol, Baclofen, Tiapride Hydrochloride, Clonazepam alone or in combination.Three children showed obvious dyskinesia after Levodopa treatment.The symptoms of movement disorders in all children exhibited little to no improvement.Levetiracetam and Zonisamide had unstable effects in the treatment of myoclonia.DBS surgery was performed on all the patients aged from 3 to 16 years.Electrodes were successfully inserted into bilateral globus pallidus internus in 14 cases and bilateral subthalamic nuclei in 4 cases.The target was unknown in 2 cases.No surgery-related complications were observed.The patients were followed up for 3 months to 6 years, and the last follow-up age of the patients ranged from 5 years and 7 months to 22 years and 1 month.The rate of improvement in BFMDRS-M score was 37%-100% in 16 patients and >70% in 7 patients with hereditary dystonia.The rate of improvement in UPDRS Ⅲ score was 23% in 1 patient with VPS13C-related early-onset Parkinson′s disease. Conclusions:Childhood medically refractory hereditary movement disorders are a case series that exhibits significant phenotypic and genotypic heterogeneity.DBS surgery demonstrates significant efficacy for KMT2B-, TOR1A-, and SGCE-related hereditary movement disorders.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Humans ; Huntington Disease/diagnostic imaging* ; Brain/diagnostic imaging* ; Brain Mapping ; Magnetic Resonance Imaging

OBJECTIVETo analyze the opioid binding protein/cell adhesion molecule-like (OPCML) methylation status at different stages of malignant transformation of human bronchial epithelial (16HBE) cells induced by Glycidyl Methacrylate (GMA) and to explore the effect of OPCML methylation in the process of malignant transformation.

METHODSCells were harvested at different stages (the 10th generation, the 20th generation and the 30th generation). To verify the Methylation chip result of OPCML methylation status in the process of malignant transformation, we detected it by methylation-specific-PCR (MSP); Real-time fluorescence Quantitative PCR (qPCR) were applied to measure the gene expression levels of OPCML at different transformed stage, and compared with the control groups (treated with DMSO).

RESULTSBased on the result of methylation chip, the gene of OPCML methylation occurred in all stages, which was consistent to the result of MSP; qPCR showed that the levels of gene expression decreased in the 20th generation and 30th generation.

CONCLUSIONMethylation status of OPCML gene promoter could be considered as a stable and specific biomarker in the transformation process.

Cell Adhesion Molecules ; metabolism ; Cell Transformation, Neoplastic ; chemically induced ; Cells, Cultured ; DNA Methylation ; Epithelial Cells ; cytology ; drug effects ; Epoxy Compounds ; adverse effects ; GPI-Linked Proteins ; metabolism ; Genes, Tumor Suppressor ; Humans ; Methacrylates ; adverse effects ; Promoter Regions, Genetic