Objective:To summarize the clinical phenotypes, genotypes, and treatment outcomes of NPRL2-related epilepsy. Methods:This was a case summary.Clinical data of patients with NRPL2 variants admitted to the Department of Pediatrics, Peking University People′s Hospital between October 1, 2013 and October 31, 2023 were retrospectively analyzed.Previous reports of patients with the same disease were reviewed. Results:Six cases of NPRL2-related epilepsy were collected, and 37 cases were reported in the previous literatures.The age of onset ranged from 3 days to 18 years with the median age of 24 months.There were 15 patients with onset in infancy.Among the 41 patients diagnosed with epilepsy, 73.1% (30/41) had focal seizures, 34.1% (14/41) had frontal lobe epilepsy, and 17.1% (7/41) had epileptic spasms.Among the patients with known cranial imaging, 58.6% (17/29) had cortical malformations. NPRL2 variants involved 11 nonsense mutations, 10 splice site mutations, 7 frameshift mutations, 1 large fragment deletion, and 14 missense mutations; among them, 39 mutations were pathogenic or likely pathogenic, while the rest 4 mutations had unclear pathogenicity.Among the 27 patients with known outcomes, 11 (40.7%) had no seizures after administration of 1 or 2 types of drugs, and 16 (59.2%) had drug-resistant epilepsy.Among the 16 patients, 1 had no seizures after treatment with 3 types of anti seizure medications, and 7 had no seizures after surgery.Most patients had varying degrees of delay in intellectual and motor development. Conclusions:Patients with NPRL2 variants usually present with frequent focal seizures and epileptic spasms, and the age of onset varies greatly.About half of the patients have drug-resistant epilepsy, half of whom have cortical malformations.For those with drug-resistant epilepsy and abnormal cranial imaging, surgery may be considered.

Objective:To summarize the phenotype and genotype of leukoencephalopathy with calcifications and cysts(LCC).Methods:A case summary.Clinical, imaging, and genetic data of 2 patients with early-onset LCC admitted to the Department of Pediatrics, Peking University People′s Hospital between December 2023 and August 2024 were retrospectively summarized.A review of the literature was also conducted.Results:Case 1: a 19-month-old female infant presented with febrile seizures in infancy and mild developmental delay.Trio whole-exome sequencing (trio-WES) identified compound heterozygous pathogenic variants in the SNORD118 gene: n.92C>T (paternally inherited) and n. 72A>G (maternally inherited). Case 2: an 11-year-and-4-month-old girl had non-specific encephalopathy in the neonatal period, developmental delay with regression, and seizures since early childhood.Trio-WES revealed compound heterozygous pathogenic variants in SNORD118: n.3C>T (paternally inherited) and n. 57G>C (maternally inherited). Both cases showed typical imaging findings of leukoencephalopathy, intracranial calcifications, and cysts.Case 2 has been treated with Bevacizumab for 3 months and remains under follow-up.Combining this 2 cases with previously reported genetically confirmed cases, a total of 97 LCC patients with identified SNORD118 variants were analyzed.The median age of onset was 5 years.Seventy-one cases had childhood onset, including 31 cases with onset at ≤1 year.The inaugural symptoms were: seizures in 40 patients (41.2%), motor disorders in 25 patients (25.8%), developmental delay or cognitive impairment in 19 patients (19.6%) and headaches or increased intracranial pressure in 13 patients (13.4%). Neurological dysfunctions progress during the course.All patients had typical leukoencephalopathy, intracranial calcifications and cysts, with varied imaging progress.A total of 61 variants of SNORD118 were reported and most were compound heterozygous variants.Treatment is primarily symptomatic.Three out of the 4 patients treated with Bevacizumab showed improvement. Conclusions:LCC is a rare autosomal recessive inherited cerebral microangiopathy, characterized by progressive neurological dysfunction and radiological triad of diffuse and asymmetric leukoencephalopathy, intracranial calcifications and cysts.Patients with pathogenic SNORD118 variants should definitely be diagnosed.Symptomatic treatment is the mainstay therapy and Bevacizumab may slow down the progression.

Objective:To summarize the phenotype and genotype of leukoencephalopathy with calcifications and cysts(LCC).Methods:A case summary.Clinical, imaging, and genetic data of 2 patients with early-onset LCC admitted to the Department of Pediatrics, Peking University People′s Hospital between December 2023 and August 2024 were retrospectively summarized.A review of the literature was also conducted.Results:Case 1: a 19-month-old female infant presented with febrile seizures in infancy and mild developmental delay.Trio whole-exome sequencing (trio-WES) identified compound heterozygous pathogenic variants in the SNORD118 gene: n.92C>T (paternally inherited) and n. 72A>G (maternally inherited). Case 2: an 11-year-and-4-month-old girl had non-specific encephalopathy in the neonatal period, developmental delay with regression, and seizures since early childhood.Trio-WES revealed compound heterozygous pathogenic variants in SNORD118: n.3C>T (paternally inherited) and n. 57G>C (maternally inherited). Both cases showed typical imaging findings of leukoencephalopathy, intracranial calcifications, and cysts.Case 2 has been treated with Bevacizumab for 3 months and remains under follow-up.Combining this 2 cases with previously reported genetically confirmed cases, a total of 97 LCC patients with identified SNORD118 variants were analyzed.The median age of onset was 5 years.Seventy-one cases had childhood onset, including 31 cases with onset at ≤1 year.The inaugural symptoms were: seizures in 40 patients (41.2%), motor disorders in 25 patients (25.8%), developmental delay or cognitive impairment in 19 patients (19.6%) and headaches or increased intracranial pressure in 13 patients (13.4%). Neurological dysfunctions progress during the course.All patients had typical leukoencephalopathy, intracranial calcifications and cysts, with varied imaging progress.A total of 61 variants of SNORD118 were reported and most were compound heterozygous variants.Treatment is primarily symptomatic.Three out of the 4 patients treated with Bevacizumab showed improvement. Conclusions:LCC is a rare autosomal recessive inherited cerebral microangiopathy, characterized by progressive neurological dysfunction and radiological triad of diffuse and asymmetric leukoencephalopathy, intracranial calcifications and cysts.Patients with pathogenic SNORD118 variants should definitely be diagnosed.Symptomatic treatment is the mainstay therapy and Bevacizumab may slow down the progression.

Oocyte maturation disorders and fertilization failures are caused by a variety of factors, including complex factors such as chromosomal abnormalities and poor oocyte quality. With the widespread use of high-throughput sequencing technology, more and more genetic mutations have been found to be associated with oocyte maturation and fertilization process in infertile patients. This paper summarizes and discusses 11 key genes ( TRIP13, TBPL2, LHX8, PATL2, TUBB8, CDC20, WEE2, ZP, ASTL, JUNO and CD9) related to oocyte maturation and fertilization-related disorders in females, providing a basis for research on the prevention of diseases associated with oocyte maturation blockage and fertilization failure and the development of targeted therapies.

Purpose To investigate the feasibility of a deep learning framework to automatically analyze echocardiographic color Doppler videos in detecting valvular regurgitation.Materials and Methods This study retrospectively collected echocardiographic images of 1 109 patients with valvular regurgitation in the Fourth Medical Center of PLA General Hospital,from June 2015 to September 2019 as the training and validation sets.A prospective continuous collection of 1 562 echocardiography images was used as the test set in the Fourth Medical Center of PLA General Hospital from May 13 to June 13,2023,including 378 cases of mitral regurgitation and 223 cases of aortic regurgitation.This study developed deep learning networks to establish view classification model and valvular regurgitation recognition model,including the efficiency of section classification of deep learning models.Results The deep learning view classification model in this study could automatically identify two views for diagnosing mitral regurgitation and aortic regurgitation.The recognition accuracy for the parasternal long axis color Doppler view and the apical four chamber mitral color Doppler view was 1.00 and 0.93,respectively.The sensitivity,specificity,accuracy and area under the curve of the deep learning model for diagnosing mitral regurgitation were 0.847,0.852,0.849 and 0.930,respectively.The sensitivity,specificity,accuracy and area under the curve of the deep learning model in diagnosing aortic regurgitation were 0.857,0.861,0.859 and 0.940,respectively.Conclusion Deep learning algorithms can automatically identify valvular regurgitation and have the potential to become a screening tool for valvular heart disease.

OBJECTIVE: To elucidate the clinical and genetic characteristics of familial cases with Glucose transporter type 1 deficiency syndrome (Glut1DS). METHODS: A survey of family history was conducted on children (proband) with Glut1DS who had visited Peking University First Hospital between November 2008 and April 2024 by focusing on the clinical manifestations of family members. Peripheral venous blood (2 mL) was collected from the pediatric patients and their parents. Genomic DNA was extracted and sequenced subsequently. Sanger sequencing was performed to validate the identified variant sites of the SLC2A1 gene in the probands and their family members. The pathogenicity of suspected variants was analyzed according to the 2015 American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants. The clinical features, auxiliary examinations, and mutational characteristics of family members with SLC2A1 variants were analyzed. This study has been approved by the Clinical Research Ethics Committee of Peking University First Hospital (Ethics No. 2021 Research 332). RESULTS: Among 87 cases with Glut1DS, 10 families with autosomal dominate inherited cases were identified, accounting for 11.0% of the cases. Of the 11 children, 8 were boys and 3 were girls. The onset of the disease had ranged from 3 months to 120 months (median 6 months), with 4 cases of early-onset classic type, 2 cases of late-onset classic type, and 5 cases of non-classic type. Six children had seizures, and 7 exhibited movement disorders. Seven children underwent developmental assessment, of which 3 had mild developmental delay, 2 were borderline, and 2 were normal. Nine children underwent lumbar puncture. The cerebrospinal fluid glucose levels ranged from 1.45 to 2.25 mmol/L (median 1.86 mmol/L), and the cerebrospinal fluid to blood glucose ratios ranged from 0.29 to 0.44 (median 0.35). Among the 8 fathers with SLC2A1 gene variants, 4 were asymptomatic, 2 developed paroxysmal exercise-induced movement disorders (PED) in childhood and adulthood, respectively. 1 had poor memory since childhood, 1 developed migraines during adolescence, and his sister was an asymptomatic carrier. The father with childhood-onset PED had a cerebrospinal fluid test with CSF glucose of 1.85 mmol/L. Of the 3 mothers with SLC2A1 gene mutations, 1 was an asymptomatic carrier; 2 developed PED in childhood and after the age of 20, respectively. The mother who developed PED in childhood also had psychomotor developmental delay. Genetic testing results revealed that among 10 families, 8 carried missense variants, 1 carried a nonsense variant, and 1 carried a small fragment insertion leading to a frameshift variant. Among the 11 cases, SLC2A1 gene variants in 8 children were inherited from their fathers, while in 3 cases, the variants were inherited from their mothers. The pathogenicity of the genetic variants was evaluated according to the Standards and Guidelines for the Interpretation of Sequence Variants published by the ACMG. Among the 8 variants identified in the 10 families, 4 were classified as pathogenic variants, 1 as likely pathogenic, and 3 as variants of uncertain significance (VUS). Four variant sites, including c.204_205insTCTC (p.V69fs), c.412G>C (p.G138R), c.431T>G (p.V144G), and c.875A>G (p.Y292C), were not previously reported in the literature. Among these, the latter three were categorized as VUS. CONCLUSION Familial Glut1DS account for 11.0% of the cases in China, with the majority of SLC2A1 gene variants inherited from the fathers, predominantly missense mutations, and with an autosomal dominant inheritance pattern. Probands tend to have earlier onset and more severe symptoms than their parents, who often present with mild or no symptoms.
Humans ; Male ; Female ; Glucose Transporter Type 1/deficiency* ; Monosaccharide Transport Proteins/deficiency* ; Child ; Child, Preschool ; Carbohydrate Metabolism, Inborn Errors/genetics* ; Mutation ; Infant ; Pedigree ; Adolescent ; Adult

BACKGROUND: Inflammation plays a critical role in severe cerebral venous thrombosis (CVT) pathogenesis, but the benefits of anti-inflammatory therapies remain unclear. This study aimed to investigate the association between steroid therapy combined with anticoagulation and the prognosis of acute/subacute severe CVT patients. METHODS: A prospective cohort study enrolled patients with acute/subacute severe CVT at Xuanwu Hospital (July 2020-January 2024). Patients were allocated into steroid and non-steroid groups based on the treatment they received. Functional outcomes (modified Rankin scale [mRS]) were evaluated at admission, discharge, and 6 months after discharge. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), cerebrospinal fluid (CSF) IL-6, and intracranial pressure were measured at admission and discharge in the steroid group. Fundoscopic Frisén grades were assessed at admission and 6 months after discharge. Univariate and multivariate logistic regression were used to evaluat associations between steroid use and favorable outcomes (mRS ≤2) at the 6-month follow-up. Paired tests assessed changes in hs-CRP and other variables before and after treatment, and Spearman's correlations were used to analyze relationships between these changes and functional improvements. RESULTS: A total of 107 and 58 patients in the steroid and non-steroid groups, respectively, were included in the analysis. Compared with the non-steroid group, the steroid group had a higher likelihood of achieving an mRS score of 0-2 (93.5% vs . 82.5%, odds ratio [OR] = 2.98, P  = 0.037) at the 6-month follow-up. After adjusting for confounding factors, the result remained consistent. Pulsed steroid therapy did not increase mortality during hospitalization or follow-up, nor did it lead to severe steroid-related complications (all P  >0.05). Patients in the steroid group showed a significant reduction in serum hs-CRP, IL-6, CSF IL-6, and intracranial pressure at discharge compared to at admission, as well as a significant reduction in the fundoscopic Frisén grade at the 6-month follow-up compare to at admission (all P  <0.001). A reduction in serum inflammatory marker levels during hospitalization positively correlated with improvements in functional outcomes ( P  <0.05). CONCLUSION: Short-term steroid use may be an effective and safe adjuvant therapy for acute/subacute severe CVT when used alongside standard anticoagulant treatments, which are likely due to suppression of the inflammatory response. However, these findings require further validation in randomized controlled trials. TRAIL REGISTRATION ClinicalTrials.gov , NCT05990894.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Anticoagulants/therapeutic use* ; C-Reactive Protein/metabolism* ; Interleukin-6/metabolism* ; Intracranial Thrombosis/drug therapy* ; Prospective Studies ; Steroids/therapeutic use* ; Venous Thrombosis/drug therapy*

With the emergence of deep learning techniques based on convolutional neural networks, artificial intelligence (AI) has driven transformative developments in the field of medical image analysis. Recently, large language models (LLMs) such as ChatGPT have also started to achieve distinction in this domain. Increasing research shows the undeniable role of AI in reshaping various aspects of medical image analysis, including processes such as image enhancement, segmentation, detection in image preprocessing, and postprocessing related to medical diagnosis and prognosis in clinical settings. However, despite the significant progress in AI research, studies investigating the recent advances in AI technology in the aforementioned aspects, the changes in research hotspot trajectories, and the performance of studies in addressing key clinical challenges in this field are limited. This article provides an overview of recent advances in AI for medical image analysis and discusses the methodological profiles, advantages, disadvantages, and future trends of AI technologies.
Artificial Intelligence ; Humans ; Image Processing, Computer-Assisted/methods* ; Neural Networks, Computer ; Deep Learning ; Diagnostic Imaging/methods*

Microglial functions are linked to Ca²⁺ signaling, with endoplasmic reticulum (ER) calcium stores playing a crucial role. Microglial abnormality is a hallmark of Alzheimer's disease (AD), but how ER Ca²⁺ receptors regulate microglial functions under physiological and AD conditions remains unclear. We found reduced ryanodine receptor 2 (Ryr2) expression in microglia from an AD mouse model. Modulation of RyR2 using S107, a RyR-Calstabin stabilizer, blunted spontaneous Ca²⁺ transients in controls and normalized Ca²⁺ transients in AD mice. S107 enhanced ATP-induced migration and phagocytosis while reducing ramification in control microglia; however, these effects were absent in AD microglia. Our findings indicate that RyR2 stabilization promotes an activation state shift in control microglia, a mechanism impaired in AD. These results highlight the role of ER Ca²⁺ receptors in both homeostatic and AD microglia, providing insights into microglial Ca²⁺ malfunctions in AD.
Animals ; Microglia/pathology* ; Alzheimer Disease/pathology* ; Phagocytosis/drug effects* ; Ryanodine Receptor Calcium Release Channel/metabolism* ; Disease Models, Animal ; Mice ; Cell Movement/drug effects* ; Mice, Transgenic ; Calcium Signaling/physiology* ; Calcium/metabolism* ; Mice, Inbred C57BL ; Male ; Endoplasmic Reticulum/metabolism*