Objective:To investigate the clinical characteristics and genetic etiology of a child with Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) and epilepsy due to a TUBG1 gene variant. Methods:A child diagnosed with CDCBM4 and epilepsy at the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in May 2024 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral venous blood samples were collected from the child and her parents for genomic DNA extraction. Trio-based whole-exome sequencing (WES) was performed, and candidate variants were validated by Sanger sequencing. According to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG), candidate variants were classified for pathogenicity. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Ethics No.: PJ2021-097).Results:The child, a 4-month-old female infant, had no special facial features, normal limb muscle strength, and increased muscle tone of infantile onset, with generalized tonic-clonic seizures as the main manifestation. During seizures, she exhibited head retroflexion, tightly closed eyes, and tonic convulsions of the limbs, occurring approximately 2-3 times per day. Electroencephalogram suggested bilateral anterior predominant medium-to-high amplitude 7-8 Hz mixed rhythm discharges. Head MRI revealed ventricular system dilatation and pachygyria. Trio-WES results indicated that the child has harbored a TUBG1 gene variant of c. 776C>T (p.Ser259Leu). Sanger sequencing verification showed that neither of her parents had carried the same variant, confirming it as de novo in origin. According to the ACMG guidelines, the variant was rated as pathogenic (PS2+ PS3+ PM2_Supporting+ PP3). Combining the child′s clinical phenotype, the child was diagnosed as CDCBM4 with epilepsy. Conclusion:Children with CDCBM4 and epilepsy due to TUBG1 gene variants may show pachygyria or agyria and commonly present with intellectual and motor developmental delays and seizure disorders of variable severity. The heterozygous TUBG1 c. 776C>T (p.Ser259Leu) variant is likely the genetic etiology underlying this disorder. The results of this study has expanded the mutational spectrum of the TUBG1 gene associated with CDCBM4 and epilepsy.

OBJECTIVE: To investigate the clinical characteristics and genetic etiology of a child with Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) and epilepsy due to a TUBG1 gene variant. METHODS: A child diagnosed with CDCBM4 and epilepsy at the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in May 2024 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral venous blood samples were collected from the child and her parents for genomic DNA extraction. Trio-based whole-exome sequencing (WES) was performed, and candidate variants were validated by Sanger sequencing. According to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG), candidate variants were classified for pathogenicity. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Ethics No.: PJ2021-097). RESULTS: The child, a 4-month-old female infant, had no special facial features, normal limb muscle strength, and increased muscle tone of infantile onset, with generalized tonic-clonic seizures as the main manifestation. During seizures, she exhibited head retroflexion, tightly closed eyes, and tonic convulsions of the limbs, occurring approximately 2-3 times per day. Electroencephalogram suggested bilateral anterior predominant medium-to-high amplitude 7-8 Hz mixed rhythm discharges. Head MRI revealed ventricular system dilatation and pachygyria. Trio-WES results indicated that the child has harbored a TUBG1 gene variant of c.776C>T (p.Ser259Leu). Sanger sequencing verification showed that neither of her parents had carried the same variant, confirming it as de novo in origin. According to the ACMG guidelines, the variant was rated as pathogenic (PS2+PS3+PM2_Supporting+PP3). Combining the child's clinical phenotype, the child was diagnosed as CDCBM4 with epilepsy. CONCLUSION Children with CDCBM4 and epilepsy due to TUBG1 gene variants may show pachygyria or agyria and commonly present with intellectual and motor developmental delays and seizure disorders of variable severity. The heterozygous TUBG1 c.776C>T (p.Ser259Leu) variant is likely the genetic etiology underlying this disorder. The results of this study has expanded the mutational spectrum of the TUBG1 gene associated with CDCBM4 and epilepsy.
Humans ; Female ; Epilepsy/genetics* ; Malformations of Cortical Development/genetics* ; Infant ; Phenotype ; Exome Sequencing ; Microtubule-Associated Proteins/genetics*

Objective To investigate the serum amino acid levels in patients with acute schizophrenia(SCZ)and their predictive effect on the improvement of cognitive function after treatment,so as to provide new insights into the clinical intervention of cognitive impairment in SCZ patients.Methods A total of 66 patients with acute SCZ were enrolled(case group-baseline period).Among them,36 cases completed the follow-up after 3 months of standardized treatment(case group-follow-up period);52 healthy controls(HCs)were included.The MATRICS Consensus Cognitive Battery(MCCB)was used to assess the cognitive function of all the participants.Liquid chromatography-tandem mass spectrometry(LC-MS)was employed to detect the concentrations of 18 amino acids in fasting serum of the case group-baseline period and the control group.Independent samples t-test was used to compare serum amino acid levels and cognitive function between the case group-baseline period and the control group.Paired t-test was used to compare the differences in cognitive function between the baseline period and the follow-up period of the case group.Spearman correlation analysis and multivariate linear regression model were used to investigate the correlation between serum amino acid levels at baseline in the case group and the improvement of cognitive function after 3 months of treatment.Results Compared with the control group,the cognitive function of SCZ patients in multiple dimensions at baseline was significantly reduced(P＜0.05).After treatment,the scores of Trail Making Test(TMT),Brief Assessment of Cognition in Schizophrenia:Symbol Coding(BACS),Wechsler Memory Scale-Ⅲ(WMS),and Brief Visuospatial Memory Test-Revised(BVMT)in patients were significantly improved(all P＜0.05).In addition,the levels of proline,methionine,histidine,phenylalanine,arginine,tyrosine,aspartic acid,tryptophan,lysine,and glutamic acid were significantly lower in the case group at baseline than in the control group(all P＜0.05).Among them,the baseline tyrosine level had a significant predictive value for the improvement of TMT(R2=0.136,P=0.029),Neuropsychological Assessment Battery(NAB)(R2=0.339,P＜0.001),and Mayer-Salovey-Caruso Emotional Intelligence Test(MSCEIT)test(R2=0.165,P=0.015).The baseline arginine level had a significant predictive value for the improvement rate of Fluency test(R2=0.113,P=0.048).Conclusion There is a decrease in various amino acid levels in patients with SCZ,and some amino acids can effectively predict the improvement of cognitive function after treatment.

Objective To investigate the serum amino acid levels in patients with acute schizophrenia(SCZ)and their predictive effect on the improvement of cognitive function after treatment,so as to provide new insights into the clinical intervention of cognitive impairment in SCZ patients.Methods A total of 66 patients with acute SCZ were enrolled(case group-baseline period).Among them,36 cases completed the follow-up after 3 months of standardized treatment(case group-follow-up period);52 healthy controls(HCs)were included.The MATRICS Consensus Cognitive Battery(MCCB)was used to assess the cognitive function of all the participants.Liquid chromatography-tandem mass spectrometry(LC-MS)was employed to detect the concentrations of 18 amino acids in fasting serum of the case group-baseline period and the control group.Independent samples t-test was used to compare serum amino acid levels and cognitive function between the case group-baseline period and the control group.Paired t-test was used to compare the differences in cognitive function between the baseline period and the follow-up period of the case group.Spearman correlation analysis and multivariate linear regression model were used to investigate the correlation between serum amino acid levels at baseline in the case group and the improvement of cognitive function after 3 months of treatment.Results Compared with the control group,the cognitive function of SCZ patients in multiple dimensions at baseline was significantly reduced(P＜0.05).After treatment,the scores of Trail Making Test(TMT),Brief Assessment of Cognition in Schizophrenia:Symbol Coding(BACS),Wechsler Memory Scale-Ⅲ(WMS),and Brief Visuospatial Memory Test-Revised(BVMT)in patients were significantly improved(all P＜0.05).In addition,the levels of proline,methionine,histidine,phenylalanine,arginine,tyrosine,aspartic acid,tryptophan,lysine,and glutamic acid were significantly lower in the case group at baseline than in the control group(all P＜0.05).Among them,the baseline tyrosine level had a significant predictive value for the improvement of TMT(R2=0.136,P=0.029),Neuropsychological Assessment Battery(NAB)(R2=0.339,P＜0.001),and Mayer-Salovey-Caruso Emotional Intelligence Test(MSCEIT)test(R2=0.165,P=0.015).The baseline arginine level had a significant predictive value for the improvement rate of Fluency test(R2=0.113,P=0.048).Conclusion There is a decrease in various amino acid levels in patients with SCZ,and some amino acids can effectively predict the improvement of cognitive function after treatment.

Objective:To investigate the clinical characteristics and genetic etiology of a child with Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) and epilepsy due to a TUBG1 gene variant. Methods:A child diagnosed with CDCBM4 and epilepsy at the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in May 2024 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral venous blood samples were collected from the child and her parents for genomic DNA extraction. Trio-based whole-exome sequencing (WES) was performed, and candidate variants were validated by Sanger sequencing. According to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG), candidate variants were classified for pathogenicity. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Ethics No.: PJ2021-097).Results:The child, a 4-month-old female infant, had no special facial features, normal limb muscle strength, and increased muscle tone of infantile onset, with generalized tonic-clonic seizures as the main manifestation. During seizures, she exhibited head retroflexion, tightly closed eyes, and tonic convulsions of the limbs, occurring approximately 2-3 times per day. Electroencephalogram suggested bilateral anterior predominant medium-to-high amplitude 7-8 Hz mixed rhythm discharges. Head MRI revealed ventricular system dilatation and pachygyria. Trio-WES results indicated that the child has harbored a TUBG1 gene variant of c. 776C>T (p.Ser259Leu). Sanger sequencing verification showed that neither of her parents had carried the same variant, confirming it as de novo in origin. According to the ACMG guidelines, the variant was rated as pathogenic (PS2+ PS3+ PM2_Supporting+ PP3). Combining the child′s clinical phenotype, the child was diagnosed as CDCBM4 with epilepsy. Conclusion:Children with CDCBM4 and epilepsy due to TUBG1 gene variants may show pachygyria or agyria and commonly present with intellectual and motor developmental delays and seizure disorders of variable severity. The heterozygous TUBG1 c. 776C>T (p.Ser259Leu) variant is likely the genetic etiology underlying this disorder. The results of this study has expanded the mutational spectrum of the TUBG1 gene associated with CDCBM4 and epilepsy.

Objective To investigate the unmet needs for assistive technology for people with physical disabilities in Chengdu,and analyze the related factors. Methods From November,2023 to March,2024,the persons with physical disabilities in Chengdu were selected from Sichuan Individuation service platform,and investigated using World Health Organization rapid Assistive Tech-nology Assessment. Results A total of 558 questionnaires were set up,and 527 effective questionnaires retured.26.8%of them reported un-met needs for aids,with the highest need for mobility aids(66.0%).Lack of support(54.9%),high price(26.3%)and lack of knowledge about aids(20.3%)were the main reasons for not obtaining the aids they needed.Loss of spouse(OR=3.615),serious mobility impairment(OR＞2.926)and serious self-care impairment(OR＞2.781)were the risks of unmet needs for aids. Conclusion It is important to popularize policies and products of aids,pay attention to personal adaptation for people with different barriers,and strengthen the service system,to meet the needs of people with disabilities.

ObjectiveTo analyze the current situation and frontier trends of the research on intelligent rehabilitation in China. MethodsLiteratures with the theme of intelligent rehabilitation were retrieved from CNKI, Wanfang database and VIP database from 2014 to 2024, and visual analysis was carried out using CiteSpace 6.2.R4. ResultsA total of 1 861 Chinese literatures were included. The annual number of publications in the field of intelligent rehabilitation in China showed an upward trend, reaching the highest value of 659 in 2023. The institution that has published the largest number of Chinese literature is Shanghai University of Science and Technology. The high-frequency Chinese keywords included stroke, rehabilitation training, robot, etc., and the bursting keywords included early intervention, newborn, cerebral palsy, etc. ConclusionThe annual number of publications in the field of intelligent rehabilitation is on the rise. Artificial intelligence, stroke and intellectual development are the key research areas. In-depth research on the application of technologies such as artificial intelligence and robots in the field of rehabilitation and focusing on the rehabilitation needs of special populations may be the research trends in the future.

Objective:To explore the clinical phenotype and genetic etiology of a child with Developmental epileptic encephalopathy type 104 (DEE 104).Methods:A child who had presented at the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in February 2021 for recurrent seizures over 1 month was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The child, a five-month-old male, had presented with frequent focal seizures with severe developmental retardation from infancy. Physical examination showed emaciation, microcephaly, oblique palpebral fissures, Stahl′s ears, and hypotonia in the limbs. Electroencephalogram revealed multi-focal sharp waves, slow waves and slow spinal waves. Cranial magnetic resonance imaging revealed enlargement of bilateral lateral ventricles and the third ventricle, along with widening of brain sulci, fissure and cisterna. WES revealed that he had harbored a heterozygous c. 2401C>T (p.His801Tyr) missense variant of the ATP6V0A1 gene. Sanger sequencing showed that both of his parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS2+ PM2_Supporting+ PP3). The proband was diagnosed with DEE 104. Early treatment with sodium valproate has failed, but the child had become seizure free after the addition of levetiracetam and topiramate. He still had abnormal EEG discharges and severe psychomotor retardation. Combining our case and a review of literature, DEE104 is mainly caused by de novo heterozygous variants of the ATP6V0A1 gene with an autosomal dominant inheritance. The patients may show refractory epilepsy and severe global developmental delay from infancy. Conclusion:The c. 2401C>T (p.His801Tyr) variant probably underlay the DEE104 in this child.

OBJECTIVE: To construct polyhydroxyalkanoate (PHA) microspheres loaded with bone morphogenetic protein 2 (BMP-2) and human β-defensin 3 (HBD3), and evaluate the antibacterial activity of microspheres and the effect of promoting osteogenic differentiation, aiming to provide a new option of material for bone tissue engineering. METHODS: The soybean lecithin (SL)-BMP-2 and SL-HBD3 were prepared by SL-mediated introduction of growth factors into polyesters technology, and the functional microsphere (f-PMS) containing BMP-2 and HBD3 were prepared by microfluidic technology, while pure microsphere (p-PMS) was prepared by the same method as the control. The morphology of microspheres was observed by scanning electron microscopy and the water absorption was detected; the release curves of BMP-2 and HBD3 in f-PMS were detected by ELISA kit. The antibacterial effect of microspheres in Staphylococcus aureus and Escherichia coli was tested with the LIVE/DEAD^TM BacLight^TM bacterial staining kit; the biocompatibility of microspheres was tested using Transwell and cell counting kit 8 (CCK-8). The effect of microspheres on osteogenic differentiation was determined by collagen type Ⅰ (COL-1) immunofluorescence staining and alkaline phosphatase (ALP) concentration. RESULTS: In this experiment, the f-PMS and p-PMS were successfully constructed. Morphological characteristics showed that p-PMS surface was rough and distributed with micropores of 1-3 μm, while f-PMS surface was smooth and existed white granular material. There was no significant difference in water absorption between the two groups (P>0.05). The release curves of BMP-2 and HBD3 in the f-PMS and p-PMS were basically the same, showing both early sudden release and late slow release. The antibacterial activity of f-PMS was significantly higher than that of p-PMS in the test that against Staphylococcus aureus and Escherichia coli (P<0.05), but there was no significant difference in biocompatibility between the two groups (P>0.05). The results of osteogenic differentiation of human BMSCs showed that the fluorescence intensity of osteogenic specific protein COL-1 of f-PMS was significantly higher than that in p-PMS, and the activity of ALP in f-PMS was also significantly higher than that in p-PMS (P<0.05). CONCLUSION The p-PHA have good antibacterial activity and biocompatibility, and can effectively promote the osteogenic differentiation of human BMSCs, which is expected to be applied to bone tissue engineering in the future.
Humans ; Osteogenesis ; Polyhydroxyalkanoates ; Microspheres ; Alkaline Phosphatase ; Anti-Bacterial Agents/pharmacology* ; Coloring Agents ; Escherichia coli

Neurodegenerative diseases(NDs)are closely related to the central nervous system and characterized by morphological abnormalities and progressive loss of function in specific neuron groups.The main NDs include Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,multiple sclerosis and Huntington's disease.However,no direct therapies for NDs exist.In recent years,single cell RNA-sequencing(scRNA-seq)has been widely used in various NDs.The pathogenesis of NDs is closely related to morphology of immune cells,and the pathogenesis mainly involves mitochondrial function,glucose metabolism,inflammation,and synaptic transmission.Induced pluripotent stem cells are a potential therapy for NDs.Ultimately,we review the application of scRNA-seq to various NDs and provide a reference for prevention and treatment of NDs.