ObjectiveTo address the challenges of unstructured classical Chinese expressions， nested entity relationships， and limited annotated data in famous traditional Chinese medicine（TCM） case records， this study proposes a joint relation extraction framework that integrates data augmentation and entity mapping， aiming to support the construction of TCM diagnostic knowledge graphs and clinical pattern mining. MethodsWe developed an annotation structure for entities and their relationships in TCM case texts and applied a data augmentation strategy by incorporating multiple ancient texts to expand the relation extraction dataset. A cascade binary tagging framework for relation triple extraction（CasRel） model for TCM semantics was designed， integrating a pre-trained bidirectional encoder representations from transformers（BERT） layer for classical TCM texts to enhance semantic representation， and using a head entity-relation-tail entity mapping mechanism to address entity nesting and relation overlapping issues. ResultsExperimental results showed that the CasRel model， combining data augmentation and entity mapping， outperformed the pipeline-based Bert-Radical-Lexicon（BRL）-bidirectional long short-term memory（BiLSTM）-Attention model. The overall precision， recall， and F₁-score across 12 relation types reached 65.73%， 64.03%， and 64.87%， which represent improvements of 14.26%， 7.98%， and 11.21% compared to the BRL-BiLSTM-Attention model， respectively. Notably， the F₁-score for tongue syndrome relations increased by 22.68%（69.32%）， and the prescription-syndrome relations performed the best with the F₁-score of 70.10%. ConclusionThe proposed framework significantly improves the semantic representation and complex dependencies in TCM texts， offering a reusable technical framework for structured mining of TCM case records. The constructed knowledge graph can support clinical syndrome differentiation， prescription optimization， and drug compatibility， providing a methodological reference for TCM artificial intelligence research.

Objective: To develop a prediction model for mild cognitive impairment (MCI) risk among the elderly, so as to provide a tool for MCI early screening. Methods : From July 2022 to September 2024, a multi-stage stratified random cluster sampling method was used to recruit permanent residents aged ≥65 years from the Xinjiang Uygur Autonomous Region as study participants. Data on sociodemographic characteristics, nutritional status, body composition indices, bone mineral density, and handgrip strength were collected through questionnaires and physical examinations. Sarcopenia was defined based on appendicular skeletal muscle index and handgrip strength. MCI was assessed using the Mini-Mental State Examination, with adjustments for educational level. Participants were randomly divided into a training set and a validation set in a 7∶3 ratio. LASSO regression and multivariable logistic regression models were employed to screen for predictors and construct an MCI risk prediction model. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: A total of 1 641 participants were surveyed, including 755 males (46.01%) and 886 females (53.99%). The majority of participants were aged 65-<75 years, comprising 1 154 individuals (70.32%). MCI was detected in 517 participants, corresponding to a detection rate of 31.51%. Resultsfrom LASSO regression and multivariate logistic regression analysis showed that residence (rural, OR = 2.323, 95% CI: 1.682-3.210), age (75-<85 years, OR = 1.405, 95% CI: 1.019-1.937; ≥85 years, OR = 3.655, 95% CI: 1.696-7.875), educational level (primary school, OR = 0.341, 95% CI: 0.247-0.472; junior high school, OR = 0.255, 95% CI: 0.160-0.408; high school, OR = 0.286, 95% CI: 0.154-0.531; bachelor's degree or above, OR = 0.120, 95% CI: 0.041-0.351), history of alcohol consumption (yes, OR = 3.216, 95% CI: 2.164-4.779), risk of malnutrition (yes, OR = 1.464, 95% CI: 1.064-2.014), sarcopenia (yes, OR = 3.197, 95% CI: 2.332-4.385), and waist-to-hip ratio (abnormal, OR = 1.540, 95% CI: 1.159-2.048) were identified as predictive factors for MCI among the elderly. In the training set, the area under the ROC curve, sensitivity, and specificity were 0.788, 0.719, and 0.712, respectively. In the validation set, the corresponding values were 0.784, 0.913, and 0.542, respectively. DCA demonstrated that the model provided a higher clinical net benefit for predicting MCI risk when the risk threshold probability ranged from 0.124 to 0.764. Conclusion The prediction model developed in this study demonstrates good discriminative ability and clinical utility, indicating its substantial value for predicting the MCI risk among the elderly.

Objective: To explore the effect of a computer assisted audiovisual combined intervention model on the core symptoms of children with autism spectrum disorder (ASD), in order to provide references for enriching intervention and treatment methods for ASD children. Methods: From December 2023 to March 2024, 36 ASD children aged 4-8 years were recruited from Tianjin Disabled Persons Rehabilitation Center and Xinxinyu Children s Rehabilitation Center, and were divided into a training group (22 cases) and a control group (14 cases). The training group completed a 12 week audiovisual training course (visual sessions:twice a week, for 50-60 minutes each session; auditory sessions:three times a week, for 15 minutes each time), while the control group received only conventional treatment interventions. Before and after the intervention, the core symptoms of ASD children were assessed using the Short Sensory Profile (SSP), Social Responsiveness Scale (SRS), and Repetitive Behavior Questionnaire-2 ( RBQ- 2). Eye tracking experiments were used to test preferences for social attention. Results: Before the intervention, there were no statistically significant differences in the total scores and factor scores of the SSP and RBQ-2 scales between the two groups ( t =-1.63, 0.38, both P >0.05). The SRS total score, social communication, and restricted interests and repetitive behavior factor scores of the training group (90.68±25.83, 33.36±11.80, 15.64±7.00) were significantly higher than those of the control group (72.29±19.84, 24.93±7.85, 10.21±5.67) ( t =2.27, 2.36, 2.43, all P <0.05). Children in the training group with higher social communication factor scores before the intervention scored lower than the control group at the post intervention test (simple slope=-14.17, t =-2.48, P = 0.02), while there was no statistically significant difference in post intervention scores between children with lower social communication factor scores before the intervention and the control group (simple slope=2.31, t =0.57, P >0.05). Eye tracking experiments showed that the total fixation time on geometric images decreased significantly more in the training group [ -4.56 (-11.42, 1.21)] compared to the control group [6.55 (-0.32, 16.53)] after the intervention ( Z=2.48, P <0.05). Conclusions The computer assisted audiovisual intervention model can effectively improve the core symptoms of ASD children with poorer social communication levels. The promotion of the intervention model needs to consider individual differences in ASD.

[摘 要] 目的：探讨从小分子化合物库中筛选获得的小分子化合物 WAY-312对胶质母细胞瘤干细胞（GSC）增殖与自我更新能力的抑制作用及分子机制。方法：通过肿瘤球形成实验与细胞活力检测技术，对小分子化合物库开展系统性化合物筛选；以筛选得到的小分子抑制剂WAY-302386（按化合物序号将其命名为WAY-312）为研究对象，采用CCK-8法、WB法、流式细胞术及Caspase-Glo 3/7活性检测法，检测WAY-312在不同浓度下对GSC增殖能力、干性标志物表达、细胞周期分布及凋亡水平的影响，明确WAY-312对GSC干性维持、自我更新能力的调控效应，进一步阐明WAY-312对GSC细胞周期进程和细胞凋亡的作用机制。结果：WAY-312可有效抑制GSC存活（P < 0.05）；WAY-312显著抑制GSC肿瘤球形成数目和大小（P < 0.05），WAY-312处理细胞后降低干性标志物SOX2、OLIG2、BMI1的表达水平；WAY-312可有效抑制GSC的自我更新能力（P < 0.05）；WAY-312通过调控细胞周期相关蛋白Cyclin B1、CDK4、CDK6的表达，诱导GSC细胞周期阻滞于G2/M期（P < 0.05）；WAY-312诱导GSC凋亡，增加凋亡相关蛋白cleaved-PARP、BAX的表达，降低BCL2的表达，经WAY-312处理后增强GSC的Caspase-3/7活性。结论：WAY-312可呈浓度依赖性抑制GSC增殖、干性维持及自我更新能力，诱导GSC周期阻滞于G2/M期并促进细胞凋亡。

Recurrent spontaneous abortion （RSA） is a common gynecological disease during pregnancy， clinically characterized by repeated spontaneous abortions， yet its pathological mechanism remains incompletely understood. Traditional Chinese medicine attributes the pathogenesis of RSA to the deficiency of Chong Ren and the lack of fetal solidity. It has amassed experience in treating RSA， with Shoutaiwan being widely utilized for addressing miscarriage symptoms such as habitual abortion due to kidney deficiency， bleeding during pregnancy， and fetal movement. In recent years， there has been a gradual increase in experimental studies on the application of Shoutaiwan in treating RSA and on related experiments. These studies have demonstrated that Shoutaiwan preserves the fetus mainly by modulating hormone balance， alleviating immune inflammation， and enhancing blood coagulation equilibrium during pregnancy. Besides， through the modulation of key signaling pathways such as nuclear factor， erythroid 2 like 2 （Nrf2）/heme oxygenase-1 （HO-1） and Janus kinase 1 （JAK1）/signal transducer and activator of transcription （STAT）， as well as mitogen-activated protein kinase （MAPK）， Shoutaiwan has improved cellular antioxidant capacity， adjusted the phenotype of trophoblast and metaphase cells， and inhibited immune rejection， thus improving the pregnancy success rate. These findings not only elucidate the diverse biological foundations underlying Shoutaiwan's efficacy in treating RSA but also offer a scientific rationale for its clinical application and further mechanism research. Nonetheless， there remains a dearth of systematic reviews on RSA treatment with Shoutaiwan. Therefore， this review summarizes and synthesizes existing research findings to systematically analyze existing literature and studies， delving deeply into the principal pharmacological effects and associated signaling pathways of Shoutaiwan in regulating RSA. It aims to establish crucial reference points for its clinical application in RSA treatment and future experiments and research.

Objective:To express,purify,prepare antibodies,and analyze the subcellular localization of Toxoplasma gondii thioredoxin 20(Trx20),and to provide the reference for the development of Toxoplasma gondii vaccine.Methods:Bioinformatics-related websites and software were used to perform bioinformatics analysis of the Trx20 protein;specific primers were designed to amplify the target fragment and construct the prokaryotic expression vector;the protein was expressed in vitro and purified;experimental animals were immunized to prepare antibodies;enzyme-linked immunosorbent assay(ELISA)method was used to detect the titer of the polyclonal antibodies;Western blotting method was used to verify the specificity and sensitivity of the antibodies and to determine the natural expression of the protein;immunofluorescence assay(IFA)was used to analyze the subcellular localization of the protein.Results:The bioinformatics analysis results showed that Trx20 protein was a relatively stable hydrophilic protein with a molecular formula of C2172H3412N548O616S20,containing 424 amino acids,a predicted relative molecular mass of 47 700,and a theoretical isoelectric point of 8.55;it was predicted that the protein had one signal peptide,no transmembrane region,contained one domain named"Thioredoxin like Superfamily",and had 35 phosphorylation sites,one N-glycosylation site,and 17 antigenic determinants;in the secondary structure,alpha-helices accounted for 41.51％of the total amino acids,and random coils accounted for 39.86％;the recombinant plasmids pET-28a-Trx20 and pGEX-4T-1-Trx20 were successfully constructed,and the soluble recombinant protein was expressed and purified;polyclonal antibodies were successfully prepared with a titer as high as 1:64 000,and they specifically recognized the endogenous Trx20 protein in Toxoplasma gondii;the subcellular localization results showed that Trx20 protein was widely distributed in the cytoplasm of the parasite.Conclusion:Toxoplasma gondii Trx20 protein is a secretory protein containing phosphorylation/glycosylation modification sites and a thioredoxin domain,and it is localized in the cytoplasm of the parasite.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

OBJECTIVES: To analyze the differential expression and biological functions of circRNAs in the anterior lens capsules of high myopic patients with cataract and their pathogenic roles in the development of this condition. METHODS: Anterior lens capsule specimens were collected intraoperatively from 36 patients with age-related cataract (ARC) and 36 high myopic patients with cataract. Among these, 18 specimens from each group were selected for whole transcriptome sequencing and biological analysis, and the remaining 36 specimens were used for validation of circPDGFRA, circFOXJ3, hsa_circ_0004767, hsa_circ_0007528, ciCRIM1, circMAN1A2, circSLC5A3, and circPTK2 expressions using RT-qPCR. hsa_circ_0007528 was selected for cell experiments to examine its effects on proliferation, migration, and apoptosis of lens epithelial cells (LECs). RESULTS: A total of 16 192 circRNAs were detected in the specimens from both groups, among which 62 circRNAs were differentially expressed (29 upregulated and 33 downregulated). GO and KEGG analyses revealed that the differentially expressed circRNAs were primarily localized in the cytoplasm, nucleoplasm, and endoplasmic reticulum, and were involved in signaling pathways associated with Gap junction and the PI3K-Akt, NF-κB, Jak-STAT, HIF-1, and MAPK signaling pathways. The ceRNA network predicted multiple target genes. RT-qPCR validation results were consistent with the sequencing data. In the LECs, upregulation of hsa_circ_0007528 significantly inhibited cell proliferation and migration and obviously promoted cell apoptosis. CONCLUSIONS The expression profile of circRNAs in the anterior lens capsule of high myopic patients with cataract differs from that of ARC patients. Upregulation of hsa_circ_0007528 inhibits LEC proliferation and migration and promotes cell apoptosis.
Humans ; Cataract/complications* ; RNA, Circular ; Myopia/genetics* ; Apoptosis ; Cell Proliferation ; Epithelial Cells ; Cell Movement ; Anterior Capsule of the Lens/metabolism* ; Male ; Female

To investigate the prevalence of influenza D virus(IDV)in cattle and swine populations in Jilin Province,China,277 nasopharyngeal swabs were collected from livestock exhibiting influ-enza-like symptoms for IDV detection.Virus isolation was performed using swine testicular(ST)cells for PCR-positive samples,followed by comprehensive analyses including whole-genome se-quencing,phylogenetic analysis,electron microscopic observation of viral morphology,and glycosy-lation site prediction.Two IDV strains were successfully isolated from bovine samples,designated as D/bovine/China/JL22/2024(JL22)and D/bovine/China/JL34/2024(JL34).These strains were demonstrated to have specific hemagglutination activity against turkey red blood cells,while no he-magglutination to chicken,rabbit,or guinea pig erythrocytes.Virus-inoculated ST cells exhibited distinct cytopathic effects(CPE)within 48 h,with a hemagglutination titer of 4 log2 in the culture supernatant.Phylogenetic analysis of the hemagglutinin-esterase-fusion(HEF)gene indicated that these strains were most closely related to the Japanese isolate D/Yamagata2019,belonging to the YAMA2019 lineage.Genomic sequence analysis showed the absence of genetic reassortment in these isolates.In this study,two IDV strains were successfully isolated and characterized,which provides preliminary insights into their genomic sequences and biological properties.The findings confirm the presence of IDV in bovine populations in Jilin Province and provide the fundamental data for future epidemiological surveillance and control strategies of IDV.

Objective To explore TCM syndrome distribution law in patients with overlapping non-erosive reflux disease(NERD)and epigastric pain syndrome(EPS)gastrointestinal symptoms.Methods A multi-center,cross-sectional study was conducted to investigate the general information of 800 patients with overlapping NERD and EPS gastrointestinal symptoms in four hospitals,such as gender,age,body mass index(BMI)and four diagnostic information of TCM.Descriptive frequency analysis,factor analysis and clustering analysis were used to summarize the TCM syndrome types and distribution characteristics.Results The average age of 800 patients with overlapping NERD and EPS gastrointestinal symptoms was(44.50±14.43)years old,the average BMI was(23.17±4.80)kg/m2,and the male to female ratio was 3:5.Frequency of 95 TCM symptoms/signs≥20%.18 common factor variables were obtained based on factor analysis,and the cumulative contribution rate was 67.11%.The first three syndrome elements of disease location were liver,stomach and spleen,and the disease nature syndrome elements were qi stagnation,qi deficiency and yin deficiency.Based on the clustering analysis of 18 common factor variables,combined with expert discussion,four main TCM syndrome types were obtained,which were liver-stomach stagnation heat syndrome(213 cases,26.63%),spleen-stomach damp heat syndrome(209 cases,26.13%),spleen-stomach deficiency and cold qi stagnation syndrome(190 cases,23.75%)and qi-phlegm stagnation syndrome(188 cases,23.50%).There was no significant difference in the distribution of TCM syndrome types among patients with different genders,ages and BMI values(P>0.05).Patients with a course of disease≥2 years and those residing long-term north of the Qinling-Huaihe Line showed a significantly higher prevalence of spleen-stomach dampness-heat syndrome(P<0.05).Conclusion The syndrome elements of disease location of overlapping NERD and EPS gastrointestinal symptoms are mainly liver,stomach and spleen.The TCM syndrome types are liver-stomach stagnation heat syndrome,spleen-stomach damp heat syndrome,spleen-stomach deficiency cold qi stagnation syndrome and qi-phlegm stagnation syndrome.The course of disease and the regional differences between north and south may be the influencing factors of the distribution of syndrome types.