ObjectiveTo observe the clinical efficacy of electroacupuncture in treatment of simple obesity patients and its effects on the metabolism-inflammation network. MethodsSeventy-two patients with simple obesity were randomly divided into a electroacupuncture group and a sham electroacupuncture group， with 36 patients in each group. In the electroacupuncture group， conventional acupuncture was applied at Zhongwan （CV 12）， bilateral Tianshu （ST 25）， bilateral Daheng （SP15）， Qihai （CV 6）， Guanyuan （CV 4）， bilateral Zusanli （ST 36） and Fenglong （ST 40）. The sham electroacupuncture group used placebo needle at same acupoints as the electroacupuncture group. Both groups were given sparse-dense waves with a frequency of 2/10 Hz， 30 minutes per session， 3 times a week， for a total of 8 weeks of treatment. The changes of human body parameters including body weight， body mass index （BMI）， waist circumference， and body fat percentage （BFP）， metabolic factors including serum fasting blood glucose （FBG）， triglyceride （TG）， total cholesterol （TC）， high density lipoprotein （HDL）， low density lipoprotein （LDL）， leptin， and ghrelin， and inflammatory factors including interleukin-6 （IL-6） and tumor necrosis factor α （TNF-α） were compared before and after treatment. Correlations between changes in leptin， ghrelin and inflammatory factors were further analyzed. ResultsWaist circumference was significantly reduced after treatment in both groups compared with baseline （P＜0.05）， and the post-treatment waist circumference was lower in the electroacupuncture group than in the sham electroacupuncture group （P＜0.05）； body weight， BMI and BFP decreased significantly after treatment compared to pretreatment levels in the electroacupuncture group （P＜0.05）. Serum leptin， IL-6 and TNF-α declined significantly after treatment in both groups versus baseline （P＜0.05）； the electroacupuncture group had lower post-treatment levels of leptin， IL-6 and TNF-α as well as larger pre-post changes than the sham group （P＜0.05）； ghrelin increased markedly after treatment in both groups （P＜0.05）， with higher post-treatment ghrelin and greater pre-post variation observed in the electroacupuncture group （P＜0.05）. In the electroacupuncture group， changes in ghrelin were negatively correlated with IL-6 and positively correlated with TNF-α （P＜0.01）； in the sham electroacupuncture group， ghrelin changes were negatively correlated with both IL-6 and TNF-α， whereas leptin changes were positively correlated with the two inflammatory markers （P＜0.01）. ConclusionElectroacupuncture can effectively improve clinical manifestations， as well as regulate serum metabolic and pro-inflammatory factors in patients with simple obesity， and discrepant correlation patterns of metabolism-inflammation are observed between the two groups.

To develop a method for determining the antibody-dependent cell-mediated phagocytosis (ADCP) activity of human epidermal growth factor receptor 2 (HER2)-targeted antibody drug conjugate (ADC) based on the reporter gene assay, we established an ADCP activity assay with Jurkat/NFAT/FcγRIIa cells as the effector cells and BT474 as the target cells. Then, the target cell density, the ratio of effector to target cells, the target cell adhesion time, the incubation time for drug administration, and the induction time after adding effector cells were optimized by the method of design of experiment (DOE). The method showed a significant dose-response relationship, which was complied with the four-parameter equation: y=(A-D)/[1+(x/C)^B]+D. The durability ranges of the target cell density, the ratio of effector to target cells, the target cell adhesion time, the incubation time for drug administration, and the induction time after adding effector cells were (2.5-4.0)×10⁵ cells/mL, 3-5, 1.0-2.0 h, 0 h, and 5.0-6.0 h, respectively. The results of the methodological validation showed that the linear equation was y=1.106 8x-0.011 6, r=0.969 2. The established method showed the relative accuracy ranging from -6.59% to 2.98% and the geometric coefficient of variation less than 11% in the intermediate precision test. Furthermore, the method was target-specific. The method was then applied to the determination of ADCP activity of HER2-targeted ADC, demonstrating the result of (103.5±5.7)%. We developed a reporter gene assay for determining the ADCP activity of HER2-targeted ADC and the assay demonstrated high accuracy and good reproducibility, which proposes a highly efficient and approache for evaluating ADCP effect of this HER2-targeted ADC, and also provides a referable technique for characterizing the Fc effector functions of ADCs with diverse targets.
Humans ; Receptor, ErbB-2/immunology* ; Phagocytosis/drug effects* ; Immunoconjugates/immunology* ; Genes, Reporter ; Antibody-Dependent Cell Cytotoxicity ; Jurkat Cells

Prolactin, a peptide hormone primarily synthesized and secreted by lactotrophs in the anterior pituitary gland, plays key roles in lactation, reproduction, and immune regulation. Recent research has highlighted its critical involvement in maintaining metabolic homeostasis, with both elevated and deficient levels disrupting metabolic functions such as glucose and lipid metabolism, as well as energy regulation. This study reviews recent advancements in prolactin and its receptors′ role in metabolic regulation, emphasizing its pivotal contribution to metabolic homeostasis.

Objective Chronic atrophic gastritis(CAG)is often accompanied by intestinal flora disorder and intestinal symptoms,forming the phenomenon of"stomach disease involving intestine".This study explored the dynamic correlation between intestinal symptoms and qi-stagnation degree in patients with CAG qi-stagnation syndrome and analyzed the characteristics of gut microbiota from the perspective of"spleen-stomach system serving as the pivotal hub of qi movement"in TCM.Methods According to the syndrome element differentiation method,410 patients with CAG were divided into four groups:non-qi-stagnation group,mild qi-stagnation group,moderate qi-stagnation group and severe qi-stagnation group.Correlation analysis and 16S intestinal flora sequencing technology were used to analyze the correlation and differential flora between the degree of CAG qi-stagnation and intestinal symptoms.Results Patients with CAG qi-stagnation syndrome were often accompanied by intestinal symptoms such as frequent flatulence,poor defecation and alternating loose-constipated stools.The frequency of cases was significantly positively correlated with the degree of qi-stagnation"non-mild-moderate-severe"(P<0.05).There was a difference in the abundance of gut microbiota between the four groups of CAG qi-stagnation none,mild,moderate and severe.The relative abundance of Streptococcus,Subdoligranulum,Eubacterium_coprostanoligenes_group and Haemophilus was positively correlated with the degree of qi-stagnation.The relative abundance of Ruminococcus_torques_group and Butyricicoccus showed a negative correlation,and Haemophilus was statistically significant among the four groups(P<0.05).Conclusion This study can provide clinical evidence and micro-mechanism for the connotation of"gastrointestinal co-morbidities"and"different diseases with the same syndrome",which may open up new ideas for clinical diagnosis and treatment.

OBJECTIVE: To investigate the clinical phenotypes and genetic variant characteristics in children with epilepsy. METHODS: A total of 91 children with epilepsy admitted to the Women's and Children's Hospital Affiliated to Ningbo University from July 2021 to October 2022 were selected as the study subjects. Peripheral blood samples were collected from the children for whole exome sequencing. Candidate genetic variants were validated by Sanger sequencing and copy number variation sequencing (CNV-seq). The clinical phenotypes and treatment outcomes of the children with epilepsy were followed up, and an analysis of the relationship between genotype and phenotype was conducted. This study was approved by the Women's and Children's Hospital Affiliated to Ningbo University (Ethics No.: EC2020-048). RESULTS: Among the 91 children with epilepsy, 21 cases (23.08%, 21/91) were found to carry pathogenic or likely pathogenic variants. Of these, 18 cases had involved single base variant or insertional deletion, while 3 cases involved copy number variations. The gene with the highest detection rate was PRRT2 (38.10%, 8/21). Among the children with genetic variants, 47.62% (10/21) had onset during infancy, with 8 diagnosed with Benign familial infantile epilepsy (BFIE), 8 with Developmental epileptic encephalopathy (DEE), and 3 with Epileptic encephalopathy (EE). One case of Dravet syndrome (DS) and one case of Infantile spasms (IS) were also noted. The clinical manifestations of children were diverse and primarily included generalized tonic-clonic seizures and focal seizures. Among them, 52.38% (11/21) had exhibited cluster seizures, 23.81% (5/21) showed fever sensitivity, and 14.29% (3/21) experienced status epilepticus. After pharmacological treatment, 42.86% (9/21) of children had achieved complete seizure control, while 61.90% (13/21) had intellectual disability and 19.05% (4/21) had co-morbid autism spectrum disorder. CONCLUSION Pathogenic or likely pathogenic variants were identified in 23.08% of the pediatric epilepsy cases, with the PRRT2 gene being the most frequently involved. Among children carrying genetic variants, 47.62% had seizure onset during infancy. Genetic factors are an important cause of epilepsy, and early genetic testing may facilitate precise diagnosis, treatment, and prognostic evaluation.
Humans ; Female ; Male ; Epilepsy/genetics* ; Child, Preschool ; Child ; Phenotype ; Genotype ; DNA Copy Number Variations/genetics* ; Infant ; Membrane Proteins/genetics* ; Nerve Tissue Proteins/genetics* ; Adolescent ; Exome Sequencing

Objective:To investigate the clinical phenotypes and genetic variant characteristics in children with epilepsy.Methods:A total of 91 children with epilepsy admitted to the Women′s and Children′s Hospital Affiliated to Ningbo University from July 2021 to October 2022 were selected as the study subjects. Peripheral blood samples were collected from the children for whole exome sequencing. Candidate genetic variants were validated by Sanger sequencing and copy number variation sequencing (CNV-seq). The clinical phenotypes and treatment outcomes of the children with epilepsy were followed up, and an analysis of the relationship between genotype and phenotype was conducted. This study was approved by the Women′s and Children′s Hospital Affiliated to Ningbo University (Ethics No.: EC2020-048).Results:Among the 91 children with epilepsy, 21 cases (23.08%, 21/91) were found to carry pathogenic or likely pathogenic variants. Of these, 18 cases had involved single base variant or insertional deletion, while 3 cases involved copy number variations. The gene with the highest detection rate was PRRT2 (38.10%, 8/21). Among the children with genetic variants, 47.62% (10/21) had onset during infancy, with 8 diagnosed with Benign familial infantile epilepsy (BFIE), 8 with Developmental epileptic encephalopathy (DEE), and 3 with Epileptic encephalopathy (EE). One case of Dravet syndrome (DS) and one case of Infantile spasms (IS) were also noted. The clinical manifestations of children were diverse and primarily included generalized tonic-clonic seizures and focal seizures. Among them, 52.38% (11/21) had exhibited cluster seizures, 23.81% (5/21) showed fever sensitivity, and 14.29% (3/21) experienced status epilepticus. After pharmacological treatment, 42.86% (9/21) of children had achieved complete seizure control, while 61.90% (13/21) had intellectual disability and 19.05% (4/21) had co-morbid autism spectrum disorder. Conclusion:Pathogenic or likely pathogenic variants were identified in 23.08% of the pediatric epilepsy cases, with the PRRT2 gene being the most frequently involved. Among children carrying genetic variants, 47.62% had seizure onset during infancy. Genetic factors are an important cause of epilepsy, and early genetic testing may facilitate precise diagnosis, treatment, and prognostic evaluation.

The liver is the largest visceral organ in the human body, responsible for multiple important functions such as metabolism, detoxification, nutrient storage, and immune regulation. Hepatocytes located along the portal-central vein axis have heterogeneity in gene expression and function, which led to the concept of liver zonation. Cells in different regions play different roles in metabolic processes, and the coordination and cooperation between these cells are crucial for maintaining normal liver function. In recent years, the advancements in single-cell genomics and spatial transcriptomics technologies have significantly improved our understanding of liver zonation. This article summarizes the important role of metabolic zonation in maintaining liver function and its relationship with disease and aging, providing a theoretical basis for further research and therapeutic strategies.

Objective:To analyze the trend of infertility disease burden from 1990 to 2019 and predict the age-standardized prevalence rate (ASPR) and age-standardized disability-adjusted life-year (DALY) rate of male and female infertility for 2020—2029, providing a certain reference for the prevention and treatment of infertility diseases.Methods:Based on the Global Burden of Disease 2019, prevalence, ASPR, DALY rate, and age-standardized DALY rate were used to evaluate the global burden of infertility comprehensively. The estimated annual percentage change was used to describe trends in the disease burden of infertility in 21 regions worldwide. The Bayesian age period cohort model was used to predict the ASPR and age-standardized DALY rate for male and female infertility in 204 countries and regions from 2020 to 2029. Sensitivity analysis was performed using the autoregressive integrated moving average model.Results:The prevalence, DALY rate, ASPR and age-standardized DALY rate of global male infertility increased from 319.52 per 100 000,1.82 per 100 000, 2 856.53 per 100 000, and 16.19 per 100 000 in 1990 to 565.30 per 100 000, 3.22 per 100 000, 3 398.53 per 100 000, and 19.36 per 100 000 in 2019, respectively. The prevalence, DALY rate, ASPR, and age-standardized DALY rate of global female infertility increased from 656.67 per 100 000, 3.53 per 100 000, 6 036.36 per 100 000, and 32.27 per 100 000 in 1990 to 1 223.78 per 100 000, 6.59 per 10 000, 7 483.12 per 100 000, and 40.33 per 100 000 in 2019, respectively. The burden of infertility disease was the highest in men and women aged 30-34 years, and the ASPR and age-standardized DALY rates were 4 407.47 per 100 000, 25.08 per 100 000, 10 270.55 per 100 000 and 55.65 per 100 000, respectively. Only in 45-49 years of age, the prevalence of infertility (11.31 per 100 000) and DALY rate (0.06 per 100 000) in women were lower than those in men (15.68 per 100 000 and 0.08 per 100 000). In addition, the burden of infertility was the lowest in high socio-demographic index regions. Cameroon had the highest ASPR (7 652.40 per 100 000) and age-standardized DALY rate (43.94 per 100 000) for male infertility. Chinese women had the highest ASPR (20 402.30 per 100 000) and age-standardized DALY rate (106.16 per 100 000) of infertility. The forecast results show that the burden of male and female infertility diseases will increase in 204 countries and regions from 2020 to 2029.Conclusion:The burden of infertility diseases in men and women increased in 204 countries and regions from 1990 to 2019, and it is predicted that the global burden of infertility diseases will continue to rise in 2020—2029. Preliminary screening of infertility should be carried out as soon as possible, health education should be strengthened and effective prevention and treatment strategies should be formulated.

Objective:To analyze the trend of infertility disease burden from 1990 to 2019 and predict the age-standardized prevalence rate (ASPR) and age-standardized disability-adjusted life-year (DALY) rate of male and female infertility for 2020—2029, providing a certain reference for the prevention and treatment of infertility diseases.Methods:Based on the Global Burden of Disease 2019, prevalence, ASPR, DALY rate, and age-standardized DALY rate were used to evaluate the global burden of infertility comprehensively. The estimated annual percentage change was used to describe trends in the disease burden of infertility in 21 regions worldwide. The Bayesian age period cohort model was used to predict the ASPR and age-standardized DALY rate for male and female infertility in 204 countries and regions from 2020 to 2029. Sensitivity analysis was performed using the autoregressive integrated moving average model.Results:The prevalence, DALY rate, ASPR and age-standardized DALY rate of global male infertility increased from 319.52 per 100 000,1.82 per 100 000, 2 856.53 per 100 000, and 16.19 per 100 000 in 1990 to 565.30 per 100 000, 3.22 per 100 000, 3 398.53 per 100 000, and 19.36 per 100 000 in 2019, respectively. The prevalence, DALY rate, ASPR, and age-standardized DALY rate of global female infertility increased from 656.67 per 100 000, 3.53 per 100 000, 6 036.36 per 100 000, and 32.27 per 100 000 in 1990 to 1 223.78 per 100 000, 6.59 per 10 000, 7 483.12 per 100 000, and 40.33 per 100 000 in 2019, respectively. The burden of infertility disease was the highest in men and women aged 30-34 years, and the ASPR and age-standardized DALY rates were 4 407.47 per 100 000, 25.08 per 100 000, 10 270.55 per 100 000 and 55.65 per 100 000, respectively. Only in 45-49 years of age, the prevalence of infertility (11.31 per 100 000) and DALY rate (0.06 per 100 000) in women were lower than those in men (15.68 per 100 000 and 0.08 per 100 000). In addition, the burden of infertility was the lowest in high socio-demographic index regions. Cameroon had the highest ASPR (7 652.40 per 100 000) and age-standardized DALY rate (43.94 per 100 000) for male infertility. Chinese women had the highest ASPR (20 402.30 per 100 000) and age-standardized DALY rate (106.16 per 100 000) of infertility. The forecast results show that the burden of male and female infertility diseases will increase in 204 countries and regions from 2020 to 2029.Conclusion:The burden of infertility diseases in men and women increased in 204 countries and regions from 1990 to 2019, and it is predicted that the global burden of infertility diseases will continue to rise in 2020—2029. Preliminary screening of infertility should be carried out as soon as possible, health education should be strengthened and effective prevention and treatment strategies should be formulated.

Objective:To investigate ferroptosis-related genes in pterygium tissue by using bioinformatic analysis.Methods:The pterygium gene expression profile dataset GSE2513 was downloaded from the Gene Expression Omnibus Database to identify differentially expressed genes (DEGs) related to ferroptosis.Functional annotation and enrichment analysis of the DEGs were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).Hub genes were identified from the DEGs using LASSO logistic regression analysis and a support vector machine recursive feature elimination (SVM-REF).Single-gene GSEA analysis was performed on hub genes and a competitive endogenous RNA interaction network was constructed to determine the RNA regulatory relationships of the hub genes.Pterygium tissue samples from 9 patients (9 eyes) undergoing pterygium surgery and conjunctival tissue samples from 9 patients (9 eyes) undergoing strabismus surgery who visited the First Affiliated Hospital of Zhengzhou University were collected from 2022 to 2023 during surgery, and the expression of hub genes and ferroptosis-related marker genes was detected by fluorescence quantitative PCR.This study followed the Declaration of Helsinki, and the study protocol was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No.2022-KY-0006-001).Results:In the dataset, there were 37 ferroptosis-related genes with significant expression differences, including 16 upregulated genes and 21 downregulated genes.GO analysis revealed significant enrichment in responses to external stimuli, responses to nutritional levels, responses to extracellular stimuli, responses to oxidative stress and starvation, transcription regulatory complexes, and RNA polymerase Ⅱ transcription regulatory complexes, RNA polymerase Ⅱ-specific transcription, and DNA-binding transcription.KEGG analysis showed that the DEGs were primarily enriched in ferroptosis and NOD-like receptor signaling pathways.LASSO regression analysis identified DUOX2, ATF3, NDRG1, EGR1, and ALDH3A2 as hub genes, and SVM-REF analysis identified NDRG1, NF2, IDH2, DUOX2, CHP1, ATF3, and SREBF1 as hub genes. DUOX2, ATF3, and NDRG1 were identified as the intersection hub genes.Single-gene GSEA analysis revealed that DUOX2 was enriched in the cell adhesion molecule CAMs pathway, the heparan sulfate glycosaminoglycan biosynthesis pathway, and the glycosaminoglycan biosynthesis ganglioside series pathway. ATF3 and NDRG1 were enriched in the PPAR signaling pathway and other pathways.Compared with normal conjunctival tissue, the relative expression levels of the ferroptosis markers PTGS2 and TFRC mRNA were increased in pterygium tissue, while the relative expression levels of FTH1, GPX4, SLC40A1, HSPB1, and NFE2L2 mRNA were decreased, with statistically significant differences ( t=12.220, 16.580, 5.664, 6.455, 8.691, 9.883, 17.590; all P<0.01). Conclusions:Ferroptosis may play an important role in the pathogenesis of pterygium. DUOX2, ATF3, and NDRG1 may be the hub genes affecting this complicated process.