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

OBJECTIVE To study the interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes. METHODS In vitro ferroptosis model was established in pancreatic β cells of mice by using high glucose. The effects of low-dose and high-dose 1，8-cineole （0.25， 0.5 μmol/L） on the level of Fe2+ in pancreatic β cells were investigated. The effects of 1，8-cineole （0.5 μmol/L） combined with ferroptosis inducer Erastin （20 μmol/L） and ferroptosis inhibitor Ferrostatin-1 （20 μmol/L） on the protein expressions of glutathione peroxidase-4 （GPX4） and cyclooxygenase-2 （COX2） were also detected. The type 2 diabetes model mice were established by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The effects of low-dose and high-dose 1，8-cineole （50， 200 mg/kg） on the pathological morphology of pancreatic tissue， the content of iron as well as the protein expressions of GPX4 and COX2 were investigated. RESULTS The results of the cell experiment showed that compared with the model group， pretreatment with 1，8-cineole significantly reduced intracellular Fe2+ levels and upregulated GPX4 protein expression， while downregulated COX2 protein expression in pancreatic β cells （P＜0.05）. After combining with Ferrostatin-1， the expression trends of the above two proteins were the same， while there was no statistically significant difference after combining with Erastin. The results of animal experiments showed that compared with the model group， after intervention with 1，8-cineole， the structure of the pancreatic islets in mice recovered intact and their morphology improved； the iron content of pancreatic tissue and protein expression of COX2 were decreased significantly （P＜0.05）， while protein expression of GPX4 was increased significantly （P＜0.05）. CONCLUSIONS 1，8-cineole could ameliorate pancreatic β cell injury induced by diabetes， the mechanism of which may be related to reducing intracellular iron deposition and regulating ferroptosis-related proteins.

Objective:To summarize the therapeutic effect of deep brain stimulation (DBS) for dystonia.Methods:Detailed clinical information and peripheral blood of children with dystonia at Peking University First Hospital from April 2017 to July 2020 were collected.The motor scores of Burke-Fahn-Marsden Dystonia Rating Scale were recorded of the dystonia before and after the treatment of DBS.Whole-exome sequencing was performed on children with dystonia.Then the effect of DBS was evaluated.Results:A total of 32 cases of patients with dystonia treated with DBS were enrolled, including 16 males and 16 females.Twelve cases were treated with globus pallidus internus DBS, and 20 cases were treated with subthalamic nucleus DBS.Twenty cases (62.5%) with pathogenic gene mutations were detected.Pathogenic variants in PANK2 (9 cases), KMT2B(3 cases), GNAO1 (2 cases), GCDH (2 cases), PINK1(1 case), NDUFAF6(1 case), DYT27(1 case) and ADCY5(1 case) were found.The follow-up period was 1 month to 3 years and 8 months.Only 1 case had local infection due to improper home care.The postoperative improvement was 5.66%-95.92%. Conclusions:All patients have a certain degree of relief after DBS without obvious adverse reactions.DBS is an effective treatment for pediatric dystonia.

In the past 30 years, with the advancement of functional neurosurgery, neuroelectrophysiology and neuroimaging, deep brain stimulation (DBS), as a new tool for the treatment of dyskinesia, has been considered to have underwent the fastest development in this field.Many patients with dyskinesias have significantly improved their main clinical symptoms after treatment with DBS, some of the improvement are even dramatic.Due to its minimally invasive characteristics, reversibility and adjustability, DBS therapy has been increasingly used in the treatment of dystonia in children.Hereditary dystonia is the most common type of dyskinesia in children, and there is no effective treatment yet.Recently, some dyskinesia at home and abroad centers have carried out DBS treatment for pediatric hereditary dystonia and achieved some encouraging results.Now, the effect of DBS in the treatment of hereditary dystonia in children and the main process of DBS treatment were mainly discussed, and shared the experience based on the clinical practices of Multidisciplinary Collaborative Diagnosis and Treatment Center for Children′s Motor Disorders, Peking University First Hospital.

Objective: To study the mutational characteristics of KCNT1 and its clinical features in children with early-onset epileptic encephalopathy. Methods: Retrospective analysis of clinical data of 175 children with early onset epilepsy from the Department of Pediatrics at Peking University First Hospital from January 2012 to December 2017. Gene-based analysis was performed on children with targeted capture second-generation sequencing and the source of mutations was verified by PCR-Sanger. The clinical features of children with KCNT1 mutation were summarized. Results: In 175 infants with early-onset epileptic encephalopathy, 6 children were found to have KCNT1 mutations, all of which were new mutations with an overall mutation rate of 3.4% (6/175). All the mutations were missense mutations. The age of onset was from 2 days to 32 days. Five children were diagnosed with epilepsy of infancy with migrating focal seizure, one case was diagnosed with epilepsy, focal seizures, focal seizures with generalization. A total of 6 children were treated with multi-antiepileptic drugs. The disease in 4 patients were partially controlled, while in 2 patients, the disease was not significantly alleviated. One patient died of "severe pneumonia" at one year and 4 months of age. Then, four cases were treated with quinidine. The seizure frequency had no change in 3 cases, the frequency decreased and then relapsed in 1 case. The case once ketogenic diet and failed. Ketogenic diet treatment was applied to 5 cases, no significant effect was achieved. All the 6 patients had severe developmental delay. They could not sit alone, follow the light and objects and had no language. Conclusions The mutation of KCNT1 gene is mainly de novo. The onset of the disease was early, and mostly occurs in neonate and early infancy. The main seizure type was epilepsy of infancy with migrating focal seizure. Patients usually had severe psychomotor developmental delay. Antiepileptic drugs are ineffective. The efficacy of quinidine was not significant. Though, it still need studies on a large sample.

Obstructive sleep apnea syndrome (OSAS) increases the risk of post-surgery complications. This study uses Berlin Questionnaire (BQ) to identify Chinese adult surgical patients who are at a high risk of OSAS and to determine if the BQ could be used to detect potential high risk of adverse respiratory events in the post anesthesia care unit (PACU). Results indicated that only 11.4% of the patients were considered at a high risk of OSAS. Age and body mass index are the key factors for the risk of OSAS prevalence in China and also gender specific. Furthermore, the incidence of adverse respiratory events in the PACU was higher in patients with high risk of OSAS than others (6.8% vs. 0.9%, P < 0.001). They also stayed longer than others in the PACU (95 ± 28 min vs. 62 ± 19 min, P < 0.001). Age, high risk for OSAS, and smoking were independent risk factors for the occurrence of adverse respiratory events in the PACU. The BQ may be adopted as a screening tool for anesthesiologists in China to identify patients who are at high risk of OSAS and determine the potential risk of developing postoperative respiratory complications in the PACU.
Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Anesthesia Recovery Period ; Berlin ; Body Mass Index ; China ; epidemiology ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Postoperative Complications ; epidemiology ; Risk Assessment ; Risk Factors ; Severity of Illness Index ; Sex Distribution ; Sleep Apnea, Obstructive ; epidemiology ; Surgical Procedures, Operative ; adverse effects ; Surveys and Questionnaires ; Young Adult

Objective To investigate the incidence and risk factors of chronic post-surgical pain (CPSP) and its effects on the quality of life in a large sample prospective study.Methods A total of 1098 patients of either sex,aged 18-70 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,undergoing elective surgery,were enrolled in the study.Data regarding patient age,gender,body mass index,educational level,marital status,living situations,occupation,pre-surgical pain in the site of surgery,complications,type of surgery,surgery time and anesthesia method were recorded.The highest numeric rating scale scores within 3 days after surgery were also recorded.The patients were followed up at 3,6 and 12 months after surgery to record the development of CPSP.The patients were divided into CPSP group and non-CPSP group according to whether or not CPSP developed.Multivariable logistic regression analysis was performed to identify the risk factors for CPSP,and the quality of life was scored.Results A total of 981 patients completed the 1 year follow-up after surgery,the incidence of CPSP was 35.7％,and the constituent ratio of the distribution of the course was as follows:3 months ≤ postsurgical course ＜ 6 months was 33.1％;6 months ≤ postsurgical course ＜ 12 months was 16.8％;postsurgical course ≥ 12 months was 50.1％.Female,no diabetes mellitus and pre-surgical pain in the site of surgery were the independent risk factors for CPSP (P＜ 0.05).Compared with non-CPSP group,the physiological function score,professional function score,body pain score,vitality score,social function score,mental health score and general health score were significantly decreased (P＜0.01),and no significant change was found in the emotional function score in CPSP group (P＞0.05).Conclusion The probability of development of CPSP is high and the course is long,and the quality of life score is decreased;female,no diabetes mellitus and pre-surgical pain in the site of surgery are the independent risk factors for CPSP.

Objective Toinvestigate the related risk factors of newly diagnosed diabetes among residents aged over 40 years in Nanjing City , and to provide evidence for diabetes prevention. Methods The clinical data were collected from the diabetes epidemiologic investigation among residents aged 40 -79 years from 6 communities in Nanjing City. Univariate and multiple logistic regression analyses were performed to analyze the potential risk factors for newly diagnosed diabetes. Results The prevalence rate of new diagnosed diabetes from 8039 subjects was 10.87%. A higher prevalence rate of new diagnosed diabetes was found in male than that in female (13.15% vs. 9.74%, P < 0.01). Multiple logistic regression analyses revealed that the main risk factors for newly diagnosed diabetes were male, age, family history, body mass index (BMI) and less physical activity after adjusting other factors (adjusted OR 1.339-1.862, P < 0.05). Conclusions Male, age, family history, body mass index (BMI) and less physical activity may be the main risk factors for diabetes among residents in Nanjing City.

BACKGROUND:Cytological studies show that bone marrow mesenchymal stem cel s play an important role in postmenopausal osteoporosis mechanism.
OBJECTIVE:To study the osteogenic differentiation in vitro of bone marrow mesenchymal stem cel s from ovariectomied osteoporotic rats.
METHODS:The osteoporotic animal model was established by performing ovariectomy in the 6-month-old female Sprague-Dawley rats. There were four groups:bone marrow mesenchymal stem cel s control group, bone marrow mesenchymal stem cel s osteoporosis group, bone marrow mesenchymal stem cel s osteogenic induction group and oseogenesis induction group. Bone marrow mesenchymal stem cel s were isolated from the rats of control group and oseogenesis induction group by means of the whole bone marrow adherence method and cultured to the 3rd generation. Then the bone marrow mesenchymal stem cel s were used in al the experiments. Cel morphology was observed under the inverted phase contrast microscope, cel cycle and proliferation index of bone marrow mesenchymal stem cel s were detected by flow cytometry. After osteogenic induction, the expression level of alkaline phosphatase was detected, and the fornation of calcium nodes of bone marrow mesenchymal stem cel s were marked by alizarin red staining.
RESULTS AND CONCLUSION:The cel s in the osteogenic induction group and oseogenesis induction group had the morphology of osteobalsts, and the change of morphology of the cel s in the oseogenesis induction group was relatively tardiness. The proliferation index in the control group was higher than that in the osteoporosis group (P<0.05);expression level of alkaline phosphatase in the osteogenic induction group was significantly higher than that in the oseogenesis induction group (P<0. 05), and the control group was significantly higher than the oseogenesis group (P<0.05). The alizarin red staining of the cel s in the osteogenic induction group was positive, while negative in the control group and the oseogenesis group;the staining in the osteogenic induction group was stronger than that in the oseogenesis induction group. These findings indicate that both the proliferative potential and the osteogenic potential of bone marrow mesenchymal stem cel s from the ovariectomized osteoporotic rats are decreased, which may be related with the ostoeporosis pathogensis of ovariectomied rats.

Objective:This study aims to analyze the epidemiological data of 2 829 cases of head and neck cancer, as well as pro-vide guidance and basis for the prevention and treatment of head and neck cancer among the inhabitants of Xinjiang. Methods:Data on head and neck cancers diagnosed at the First Affiliated Hospital of Xinjiang Medical University between January 2002 and December 2011 were collected, and constituent ratios were analyzed. Results:The sample consisted of 1 657 (58.57%) males and 1 172 (41.43%) females, with a male-to-female ratio of 1.4:1. Median age was 55 years, mainly distributed in the range of 40 years to 69 years. Patients within this age group constituted 63.38% of the total patients. Ethnic groups comprising the samples were as follows: Han, 59.5%;Uygur, 27.7%;Kazakh, 6.3%;Hui, 3.1%;and Mongol, 1.6%. Other ethnic groups constituted 1.6%of the sample. The five cancers with the highest constituent ratios were oral cancer, thyroid carcinoma, laryngeal cancer, nasopharyngeal cancer, and nasal sinus cancer. The five most common cancers diagnosed in males were oral cancer, laryngeal cancer, nasopharyngeal cancer, nasal sinus cancer, and thy-roid carcinoma;those in women were thyroid carcinoma, oral cancer, nasal sinus cancer, nasopharyngeal carcinoma, and facial skin can-cer. The five most common cancers by ethnic groups were identified as follows:thyroid carcinoma, oral cancer, laryngeal cancer, naso-pharyngeal cancer, and nasal sinus cancer in Han patients;oral cancer, nasopharyngeal cancer, nasal sinus cancer, thyroid carcinoma, and laryngeal cancer in Uygur patients;and oral cancer, thyroid cancer, nasal sinus cancer, laryngeal cancer, and oropharyngeal and hy-popharyngeal cancer in Kazakh patients. Conclusion:Efforts toward cancer prevention should be focused on oral and thyroid cancers. Sufficient attention is needed for the prevention and treatment of laryngeal, nasopharyngeal, and nasal sinus cancer in the Xinjiang area.