ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

OBJECTIVE: To analyze the prevalence and burden of headache disorders in China and its provinces from 1990 to 2021. METHODS: Using data from the Global Burden of Disease Study (GBD) 2021, the number of prevalent cases, prevalence rate, disability-adjusted life years (DALYs), and age-standardized DALY rates were analyzed by sex, age group, and province for headache disorders and their subtypes (migraine and tension-type headache [TTH]) between 1990 and 2021. Percentage changes during this period were also estimated. RESULTS: In 2021, approximately 426 million individuals in China were affected by headache disorders, with an age-standardized prevalence rate of 27,582.61/100,000. The age-standardized DALY rate for all headache disorders was 487.15/100,000. Between 1990 and 2021, the number of prevalent cases increased by 37.78%, while the prevalence of all headache disorders, migraine, and TTH increased by 6.92%, 7.57%, and 7.86%, respectively. The highest prevalence was observed in the 30-34 age group (39,520.60/100,000). Migraine accounted for a larger proportion of DALYs attributable to headache disorders, whereas TTH has a greater impact on its prevalence. In 2021, the highest age-standardized DALY rates for headache disorders were observed in Heilongjiang (617.85/100,000) and Shanghai (542.86/100,000). CONCLUSION The prevalence of headache disorders is increasing in China. Effective health education, improve diagnosis and treatment are essential, particularly for middle-aged working populations and women of childbearing age.
Humans ; China/epidemiology* ; Female ; Male ; Adult ; Middle Aged ; Prevalence ; Young Adult ; Adolescent ; Aged ; Child ; Headache Disorders/epidemiology* ; Disability-Adjusted Life Years ; Child, Preschool ; Cost of Illness ; Infant ; Aged, 80 and over

To further investigate the molecular genetic characteristics of enzomatic nasal tumor vi-rus of goats(ENTV-2)in Yunnan Province,this study measured and analyzed the entire genome of ENTV-2 in Yunnan Province.The results showed that the complete genome sequence of the EN-TV-2 YN2023 strain(GenBank accession number:PP682590.1)was successfully obtained.The YN2023 strain has a total length of 7 307 bp and a typical structure of 5'-M5-gag-pro-pol-env-M3-3'.Whole genome sequence homology analysis showed that the nucleotide homology between YN2023 strain and 41 reference strains ranges from 85.3％to 95.5％.The whole genome evolution-ary tree indicates that the YN2023 strain is closely related to the prevalent strains in China,with certain genetic diversity and geographical clustering.The analysis of the gag gene evolutionary tree shows that the gag gene cluster of YN2023 strain is on a branch of the ENTV-2 gag gene,and YN2023 is clustered on the same small branch as enENTV-FJ1 and GDQY2017 strains,with the closest genetic relationship.The env gene evolutionary tree shows that YN2023 is on the same branch as GDQY2017,GDZJ2022,ENTV-2CHN1-6,ENTV-FJ1,and ENTV-FJ3,and is also on the same branch as GDQY2017,indicating a close genetic relationship.Recombination analysis showed that the YN2023 strain underwent a potential recombination event between breakpoint positions 6378-7478 bp,with the Chinese Chongqing strain enENTV-CQ1(OR669623.1)as the primary parent and the Chinese Sichuan strain BH(MT254062.1)as the secondary parent.This study enriches the genomic information of the ENTV-2 strain in Yunnan Province and provides data sup-port for the genetic variation of ENTV-2 in Yunnan Province.

Objective To investigate internal arsenic exposure levels and influencing factors in infants and young children from low-arsenic regions.Methods A total of 390 urine samples from 130 children aged 0-7 years in Wuhan(central China)and Shenzhen(southern China)were analyzed using high performance liquid chromatography-inductively coupled plasma mass spec-trometry.A linear mixed model was applied to assess factors influencing arsenic exposure levels,and risk evaluation was conduc-ted based on biomonitoring equivalents.Results The average urinary total arsenic level in children was 15.6 μg/L.The concen-trations of these species increased with age,except for arsenate(AsⅤ).Children in Shenzhen had higher level of arsenobetaine(AsB)than in Wuhan(P＜0.05).The urinary levels of monomethyl arsenic acid(MMA)and dimethyl arsenic acid(DMA)were significantly higher in winter than in autumn(P＜0.05).Total urinary arsenic levels in 72％of the children exceeded the bio-monitoring equivalent.Conclusion Arsenic exposure among children shows an increasing trend with age,and there are regional and seasonal differences.More than half of the children may suffer potential health risks of As exposure,highlighting the urgent need for improved monitoring and preventive measures.

To further investigate the molecular genetic characteristics of enzomatic nasal tumor vi-rus of goats(ENTV-2)in Yunnan Province,this study measured and analyzed the entire genome of ENTV-2 in Yunnan Province.The results showed that the complete genome sequence of the EN-TV-2 YN2023 strain(GenBank accession number:PP682590.1)was successfully obtained.The YN2023 strain has a total length of 7 307 bp and a typical structure of 5'-M5-gag-pro-pol-env-M3-3'.Whole genome sequence homology analysis showed that the nucleotide homology between YN2023 strain and 41 reference strains ranges from 85.3％to 95.5％.The whole genome evolution-ary tree indicates that the YN2023 strain is closely related to the prevalent strains in China,with certain genetic diversity and geographical clustering.The analysis of the gag gene evolutionary tree shows that the gag gene cluster of YN2023 strain is on a branch of the ENTV-2 gag gene,and YN2023 is clustered on the same small branch as enENTV-FJ1 and GDQY2017 strains,with the closest genetic relationship.The env gene evolutionary tree shows that YN2023 is on the same branch as GDQY2017,GDZJ2022,ENTV-2CHN1-6,ENTV-FJ1,and ENTV-FJ3,and is also on the same branch as GDQY2017,indicating a close genetic relationship.Recombination analysis showed that the YN2023 strain underwent a potential recombination event between breakpoint positions 6378-7478 bp,with the Chinese Chongqing strain enENTV-CQ1(OR669623.1)as the primary parent and the Chinese Sichuan strain BH(MT254062.1)as the secondary parent.This study enriches the genomic information of the ENTV-2 strain in Yunnan Province and provides data sup-port for the genetic variation of ENTV-2 in Yunnan Province.

Objective To investigate internal arsenic exposure levels and influencing factors in infants and young children from low-arsenic regions.Methods A total of 390 urine samples from 130 children aged 0-7 years in Wuhan(central China)and Shenzhen(southern China)were analyzed using high performance liquid chromatography-inductively coupled plasma mass spec-trometry.A linear mixed model was applied to assess factors influencing arsenic exposure levels,and risk evaluation was conduc-ted based on biomonitoring equivalents.Results The average urinary total arsenic level in children was 15.6 μg/L.The concen-trations of these species increased with age,except for arsenate(AsⅤ).Children in Shenzhen had higher level of arsenobetaine(AsB)than in Wuhan(P＜0.05).The urinary levels of monomethyl arsenic acid(MMA)and dimethyl arsenic acid(DMA)were significantly higher in winter than in autumn(P＜0.05).Total urinary arsenic levels in 72％of the children exceeded the bio-monitoring equivalent.Conclusion Arsenic exposure among children shows an increasing trend with age,and there are regional and seasonal differences.More than half of the children may suffer potential health risks of As exposure,highlighting the urgent need for improved monitoring and preventive measures.

Objective To evaluate the value of a machine learning-based biparametric magnetic resonance imaging(bpMRI)radiomics model in predicting clinically significant prostate cancer(csPCa)in the transitional zone.Methods A retrospective analysis was con-ducted on 507 cases in two medical centers.All patients underwent prostate MRI examinations before surgery,with complete patho-logical data.The case distribution was as follows:256 cases of csPCa,97 cases of clinically insignificant prostate cancer(ciPCa),and 154 cases of benign prostatic hyperplasia(BPH).Using the R language,the data from Center One was randomly divided into training and test groups at a ratio of 7∶3,and the data from Center Two as an independent external validation group.The image features from T2 WI and diffusion weighted imaging(DWI)were extracted,and the least absolute shrinkage and selection operator(LASSO)was used to reduce dimensionality and filter features.Two datasets were constructed based on T2 WI features alone and combined T2 WI and DWI features.Six prediction models were established using random forest(RF),logistic regression(LR),and support vector machine(SVM).The efficacy of six models of T2 WI features and combined T2 WI and DWI features in the diagnosis of prostate dis-eases through receiver operating characteristic(ROC)curve,area under the curve(AUC),and decision curve analysis(DCA)were compared and evaluated.Results In the training group,feature screening identified 7 and 8 features from the T2WI single sequence and the T2WI with DWI dual sequence for csPCa prediction in the transitional zone.The results showed that the T2WI with DWI dual sequence RF model had the highest AUC performance.The AUC of the training,test,and validation groups were 0.950,0.866,and 0.818,respectively.The test group accuracy was 0.805,sensitivity was 0.690,and specificity was 0.920;the validation group accu-racy was 0.726,sensitivity was 0.661,and specificity was 0.793.DCA showed that within a wide probability threshold range,the T2 WI with DWI dual sequence RF model had the greatest net benefit.Conclusion Based on the bpMRI radiomics model,non-invasive prediction of csPCa in the transitional zone can be achieved before surgery,which helps to make clinical diagnosis and treatment decisions.

Background Children and adolescents drink sugar-sweetened beverages (SSBs) frequently. Research has confirmed that SSBs associate with weight gain and overweight or obesity. However, it is unclear whether high SSBs intake associates with abnormal changes in physical growth and glucolipid metabolism before causing adverse health outcomes such as overweight and obesity. Early identification of associated health risks of overconsumption of SSBs have important public health implications. Objective To investigate the differences in physical growth and glucolipid metabolism between different SSBs intake frequency groups in normal weight children and adolescents aged 6-17 years, and to evaluate the early effects of SSBs intake on physical growth and glycolipid metabolism before causing overweight and obesity, aiming to provide a scientific basis for the prevention and control of childhood overweight and obesity and related chronic diseases, and for the formulation of policies on the control of SSBs consumption. Methods Data were from the Shanghai Diet and Health Survey (SDHS) among primary and secondary school students. The participants were normal weight children and adolescents aged 6-17 years. Propensity scores were calculated according to energy intake and physical activity factors, after stratifying by age and gender. Participants were 1:1 matched with the closest propensity scores in the high-frequency (≥1 time·d⁻¹) and the low-frequency (≤1 time·week⁻¹) SSBs intake groups. The outcome indicators were physical measurements such as height, weight, percent of body fat, and waist circumference, and metabolic indicators such as fasting blood glucose, total triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Body mass index (BMI) was calculated. Food frequency questionnaire was used to collect SSBs consumption in the past three months through face-to-face interview. A paired t-test was used to compare the differences in physical and glycolipid metabolic indicators between the high-frequency intake group and the low-frequency intake group of SSBs. Results A total of 431 pairs were obtained. For children and adolescents in grades 6-9, overall height (difference=2.92 cm, P=0.002), weight (difference=2.53 kg, P=0.003), and waist circumference (difference=1.34 cm, P=0.035) were higher in those who consumed SSBs ≥1 time·d⁻¹ than in those who consumed ≤1 time·week⁻¹. For children and adolescents in grades 10-12, overall weight (difference=2.27 kg, P=0.041) was higher in those who consumed SSBs ≥1 time·d⁻¹ than in those who consumed ≤1 time·week⁻¹. Over 95% of the study subjects reported blood glucose and lipid test results within the normal range; but girls in grades 1-5 who consumed SSBs ≥1 time·d⁻¹ had a higher total cholesterol (difference=0.20 mmol·L⁻¹, P=0.027) and low-density lipoprotein cholesterol (difference=0.19 mmol·L⁻¹, P=0.010) than those who consumed ≤1 time·week⁻¹; boys in grades 6-9 who consumed SSBs ≥1 time·d⁻¹ had a lower high-density lipoprotein cholesterol (difference=-0.10 mmol·L⁻¹, P=0.039) than those who consumed ≤1 time·week⁻¹. Conclusion High-frequency intake of SSBs may be associated with higher total cholesterol and low-density lipoprotein cholesterol in normal weight children and adolescents in grades 1-5, and higher weight in normal weight children and adolescents in grades 6-12. There is an urgent need to educate children and adolescents about nutritional health, enhance their ability to make healthy food and beverage choices, and take early interventions to control the intake of SSBs in children.

Objective To measure and compare the lateral posterior tibial slope (LPTS) , medial posterior tibial slope ( MPTS) and tibial torsion angle ( TTA) between the patients of recuiTent patellar dislocation and the heathy people, and to analyze the correlation between LPTS, MPTS and TTA and the risk factors of recuiTent patellar dislocation. Methods A total of 33 patients (44 knees) with recuiTent patellar dislocation in our hospital from July 2019 to June 2021 were selected and listed as the stud)' group. Twenty-three subjects (46 knees) who were suspected iliac vascular and lower limb vascular diseases during the same period were selected and listed as the control group. All the enrolled researchers had fulllength CT scans date of the lower limbs. Three-dimensional models were reconstructed using Mimics 21. 0 software and then imported into 3-matic software. The LPTS, MPTS and TTA were measured and compared between the two groups. Results In the study group, the LPTS, MPTS and TTA were (7. 69} 1. 42) ° , ( 10. 06} 1. 71) ° , ( 36. 42}8. 13 ) ° , respectively while the control group, the LPTS, MPTS and TTA were ( 8. 42 } 1. 65 ) ° , ( 10. 44 } 0. 86 ) ° , ( 25. 77} 3. 90 ) ° , respectively. There were no signiiicant differences in the LPTS, MPTS and TTA between different genders and sides both in the stud)' group and the control group ( P > 0. 0 5 ) . Compared with the control group, the LPTS in the stud)' group was smaller, and the difference was statistically significant (P<0. 0 5 ) . There was no statistically significant difference between the stud)' group and the control group in the MPTS (P>0. 05). Compared with the control group, the TTA in the stud)' group was higher, and the difference was statistically significant (P< 0. 0 5 ) . Compared with the control group, the LPTS and MPTS in the study group were significant asymmetry, and the difference was statistically significant ( P < 0 . 0 5 ). Conclusion The lateral posterior tibial slope of patients with recurrent patellar dislocation is significantly smaller than that in the healthy people, while there is no significant difference in the medial posterior tibial slope; The tibial torsion angle of patients with recurrent patellar dislocation is significantly larger than in the healthy people; The lateral posterior tibial slope and tibial torsion angle have certain correlation with recurrent patellar dislocation, which can conduct the diagnosis of recurrent patellar dislocation.

OBJECTIVE: To develop a few-shot learning (FSL) approach for classifying optical coherence tomography (OCT) images in patients with inherited retinal disorders (IRDs). METHODS: In this study, an FSL model based on a student-teacher learning framework was designed to classify images. 2,317 images from 189 participants were included. Of these, 1,126 images revealed IRDs, 533 were normal samples, and 658 were control samples. RESULTS: The FSL model achieved a total accuracy of 0.974-0.983, total sensitivity of 0.934-0.957, total specificity of 0.984-0.990, and total F1 score of 0.935-0.957, which were superior to the total accuracy of the baseline model of 0.943-0.954, total sensitivity of 0.866-0.886, total specificity of 0.962-0.971, and total F1 score of 0.859-0.885. The performance of most subclassifications also exhibited advantages. Moreover, the FSL model had a higher area under curves (AUC) of the receiver operating characteristic (ROC) curves in most subclassifications. CONCLUSION This study demonstrates the effective use of the FSL model for the classification of OCT images from patients with IRDs, normal, and control participants with a smaller volume of data. The general principle and similar network architectures can also be applied to other retinal diseases with a low prevalence.
Humans ; Tomography, Optical Coherence ; Deep Learning ; Retinal Diseases/diagnostic imaging* ; Retina/diagnostic imaging* ; ROC Curve