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 induding, 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.

Objective:To explore the clinical efficacy of modified Chaihu Jia Longgu Muli Decoction in patients with liver and kidney Yin deficiency syndrome of Parkinson's disease (PD) and the effects on phosphatase and tensin homolog-induced putative kinase 1 (PINK1) /E3 ubiquitin ligase (Parkin) signaling pathway.Methods:A randomized controlled trial study was conducted. A total of 120 PD patients from the Department of Encephalopathy of Xi'an Hospital of Traditional Chinese Medicine from May 2020 to May 2024 were selected as the observation objects and divided into 2 groups through random number table method, with 60 cases in each group. The control group took dopashydrazine tablets orally, while the combined group took Chaihu Jia Longgu Muli Decoction on the basis of the control group. Two groups were treated continuously for 2 months. The levels of glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and basic fibroblast growth factor 2 (FGF2) were detected by ELISA. The expression levels of PINK1, Parkin and chelate 1 (SQSTM1) mRNA were detected by real-time fluorescence quantitative PCR. The adverse reactions during the treatment were observed and recorded to evaluate the clinical efficacy.Results:The total effective rate was 95.00% (57/60) in the combined group and 83.33% (50/60) in the control group, with statistical significance ( χ2=4.23, P=0.040). After treatment, the levels of serum GDNF [(510.78±31.57) ng/L vs. (431.89±30.45) ng/L, t=13.93], BDNF [(36.47±3.72) ng/L vs. (27.84±3.55) ng/L, t=13.00], NGF [(57.24±4.17) ng/L vs. (50.72±4.11) ng/L, t=8.63] and FGF2 [(26.21±3.71) ng/L vs. (21.63±3.54) ng/L, t=6.92] in the combined group were higher than those in the control group ( P<0.001). After treatment, the mRNA expression levels of PINK1 (2.38±0.07 vs. 2.19±0.05, t=17.11), Parkin (1.89±0.03 vs. 1.74±0.05, t=19.93), and SQSTM1 (1.82±0.07 vs. 1.61±0.05, t=18.91) in the combined group were higher than those in the control group ( P<0.001). During the treatment period, the incidence of adverse reactions was 6.67% (4/60) in the combined group and 10.00% (6/60) in the control group, without statistical significance ( χ2=0.44, P=0.509). Conclusion:Modified Chaihu Jia Longgu Muli Decoction can increase the levels of neurotrophic factors in patients with PD of liver and kidney yin deficiency syndrome, regulate the PINK1/Parkin pathway, protect neurons, improve mitochondrial autophagy function, and enhance clinical efficacy.

This article systematically summarizes the clinical experience of Professor Yang Jun,a nationally renowned traditional Chinese medicine(TCM)physician,in applying refined direct moxibustion(applying a moxibustion pen made by Chinese medical extract)to treat functional dyspepsia(FD)of the stuffiness-fullness type.Based on decades of clinical practice,Professor Yang innovatively established a moxibustion therapy system for FD,which centers on TCM syndrome differentiation and treatment.The system emphasizes the refined identification of epigastric stuffiness and fullness syndrome,particularly focusing on the relative significance of abdominal distension and poor appetite.Its therapeutic features lie in establishing the principle of"prioritizing mind regulation while holistically harmonizing body and spirit",combined with personalized moxibustion dosage control and a unique refined direct moxibustion technique.By optimizing the configuration of each step in moxibustion therapy,the system maximizes therapeutic efficacy,providing novel theoretical foundations and clinical strategies for moxibustion treatment of stuffiness-fullness type of FD.

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

The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.

Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.

ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹-¹ and Hcy>15 μmol·L⁻¹ was 1.532 times (95%CI: 1.017‒2.309 times, P=0.041) and 1.738 times (95%CI: 1.119‒2.699 times, P=0.014) higher respectively, compared to T2DM patients with Hcy≤10 μmol·L⁻¹. T2DM patients with TyG>9.074 had 1.396 times higher risk of stroke (95%CI: 1.091‒1.787, P=0.008) compared to those with TyG≤9.074. The study found that urea and α1-antitrypsin (α1-AT) were independent risk factors for the incidence of stroke in T2DM patients. For every unit increase in urea andα1-AT, the risk of stroke in T2DM patients increased by 233.6% (HR=3.336, 95%CI: 1.588‒7.009, P=0.001) and 11.3% (HR=1.113, 95%CI: 1.028‒1.205, P=0.008), respectively. Cumulative risk curves showed that Hcy>10 μmol·L⁻¹ and TyG>9.074 accelerated the time to stroke occurrence in T2DM patients. ConclusionElevated levels of Hcy>10 μmol·L⁻¹ and a higher TyG index are risk factors for stroke in T2DM patients. Effective interventions for Hcy and TyG should be conducted for diabetic patients to reduce the incidence of stroke.

Objective To study the dynamic changes in the secretion of neurotransmitters glutamic acid(Glu)and γ-aminobutyric acid(GABA)in the central auditory brain area,in order to explore the effects of sodium salicy-late on different locations of the auditory pathway.Methods A total of 126 SD rats were injected intraperitoneally with salicylate,and were divided into 10 groups including injection groups for 1,2,4,8,and 24 hours,chronic in-jection groups for 3,7,and 14 days,and chronic recovery groups for 21 and 28 days with 6 rats in each group,as well as their corresponding blank control groups.Rats in each group were anesthetized and materials were collected for further use.High-performance liquid chromatography(HPLC)was performed to detect and compare the dynam-ic changes in the levels of Glu and GABA in the auditory cortex,inferior colliculus,cochlear nucleus,and hippocam-pus of the auditory center of rats in each group at different time points.Results Compared with the control group,within 24 hours of acute injection of salicylate,the Glu content in the auditory cortex reached the peak in 1 hour,and the hippocampus reached the peak at the 4th hour after injection,and then decreased slowly.The GABA con-tent in the four brain regions showed a slow upward trend in the chronic injection period,reached the peak on the 7th day,decreased and approached normal level on the 14th day,and basically returned to the normal level in the re-covery period.Conclusion These findings indicate that salicylate has a certain short-term excitatory and stimulating effect on the central auditory system.Under the mechanism of central plasticity,after long-term injection of salicy-late,the release of neurotransmitters reaches a new excitation/inhibition balance in the central area.Glu and GABA may each play a different role that may ultimately lead to the development of tinnitus.

Objective To study the dynamic changes in the secretion of neurotransmitters glutamic acid(Glu)and γ-aminobutyric acid(GABA)in the central auditory brain area,in order to explore the effects of sodium salicy-late on different locations of the auditory pathway.Methods A total of 126 SD rats were injected intraperitoneally with salicylate,and were divided into 10 groups including injection groups for 1,2,4,8,and 24 hours,chronic in-jection groups for 3,7,and 14 days,and chronic recovery groups for 21 and 28 days with 6 rats in each group,as well as their corresponding blank control groups.Rats in each group were anesthetized and materials were collected for further use.High-performance liquid chromatography(HPLC)was performed to detect and compare the dynam-ic changes in the levels of Glu and GABA in the auditory cortex,inferior colliculus,cochlear nucleus,and hippocam-pus of the auditory center of rats in each group at different time points.Results Compared with the control group,within 24 hours of acute injection of salicylate,the Glu content in the auditory cortex reached the peak in 1 hour,and the hippocampus reached the peak at the 4th hour after injection,and then decreased slowly.The GABA con-tent in the four brain regions showed a slow upward trend in the chronic injection period,reached the peak on the 7th day,decreased and approached normal level on the 14th day,and basically returned to the normal level in the re-covery period.Conclusion These findings indicate that salicylate has a certain short-term excitatory and stimulating effect on the central auditory system.Under the mechanism of central plasticity,after long-term injection of salicy-late,the release of neurotransmitters reaches a new excitation/inhibition balance in the central area.Glu and GABA may each play a different role that may ultimately lead to the development of tinnitus.