OBJECTIVE: To develop a user-friendly visualization application for the automatic annotation of Human Phenotype Ontology (HPO) terms based on large language models and retrieval-augmented generation (RAG) technology, and to validate its performance in an authoritative case dataset. METHODS: By integrating the domestic open-source large language model DeepSeek-V3 with RAG technology, an interactive web application was deployed on the Streamlit cloud platform. Using only the latest official HPO dataset as the data source, the lightweight sentence-embedding model BAAI/bge-small-en-v1.5 was employed to construct a FAISS vector index. During the online phase, a four-step closed-loop process is automatically completed: multilingual translation, phenotype phrase extraction, RAG candidate retrieval, term mapping, and official database validation. 121 English case reports publicly released by BMJ Case Reports and Oxford Medical Case Reports (with a gold-standard HPO set of 1 794 terms) were selected for application validation. Precision, recall, and F1 score were calculated and compared horizontally with traditional dictionary tools, standalone large language models, and the similar application "RAG-HPO". Finally, replace the model with the more advanced ChatGPT-5 and evaluate its performance on the newly extracted dataset. RESULTS: An HPO term automatic annotation visualization application named PhenoRAG, based on large language models and RAG technology, was successfully developed. Users can access it directly via a web link. Across the 112 cases, a total of 2 150 HPO terms were generated; 2,064 (96.0%) were fully validated by the official database, with a hallucination rate of 1.3% and an HPO ID-name mismatch rate of 2.7%. After deduplication, 1,906 terms remained for testing. The overall precision was 63.65%, recall was 67.34%, and F1 was 65.44%, significantly outperforming traditional annotation tools (F1: 0.45-0.49, P < 0.001). Although PhenoRAG's F1 was lower than that of RAG-HPO (F1 = 0.78, P < 0.001), which relies on a manually constructed synonym database of 54 000 entries plus the HPO dataset, it requires no additional dictionary maintenance and can be used without any background in computer programming. Moreover, after switching to the GPT-5 model, PhenoRAG exhibited no hallucination rate on the new dataset, and its F1 score significantly increased (P = 0.038). CONCLUSION Without constructing a synonym database, the PhenoRAG achieved high-accuracy automatic mapping from clinical text to standard HPO terms. It features a low usage threshold, free access, and a Chinese-language interface, and can directly serve rare disease diagnosis, genetic counseling, and research scenarios in China and worldwide, warranting further clinical promotion and multicenter validation.
Humans ; Phenotype ; Biological Ontologies ; Language ; Software ; Large Language Models

Chaihu Longgu Muli Decoction can be used to treat perimenopausal insomnia (PMI). It can be used either alone with modification or in combination with Western medicine or acupuncture and moxibustion and other external TCM treatment methods, which has achieved good efficacy, and can improve the symptoms of patients with difficulty falling asleep and decreased sleep quality, with good safety. The treatment of Chaihu Longgu Muli Decoction for PMI may exert its effects through multiple pathways, such as inhibiting HPA axis hyperactivity, regulating hormone and neurotransmitter levels, inhibiting oxidative stress and inflammatory responses. However, existing clinical studies suffer from issues such as small sample sizes, inconsistent research protocols, and inconsistent efficacy evaluation criteria, which require further improvement and deeper exploration of relevant mechanisms.

Objective To detect the expression of lactate dehydrogenase A(LDHA),FoxP3,and CD4 in hepatocellular carcinoma(HCC)and to analyze the effect of bufalin on LDHA as well as on the differentiation and function of regulatory T(Treg)cells in the tumor microenvironment of HCC mice.Methods Immunohistochemical staining was performed to detect the difference in the expression of LDHA,FoxP3(Treg cell marker),and CD4 between the tumor and adjacent tissues from 91 HCC patients.Hepl-6 subcutaneous tumor-bearing mouse model was established.The mice were randomly divided into control,bufalin+pyruvic acid,oxalate,and bufalin groups(n=5 each group).The mass and volume of subcutaneous tumors were compared.Immunohistochemical staining was performed to detect the expression of LDHA,FoxP3,and CD4 in tumors of mice in each group.ELISA was used to detect the levels of transforming growth factor β(TGF-β)and interleukin-10(IL-10)in the serum of mice in each group to evaluate the immune function of Treg cells.Results Compared with adjacent tissues,HCC tissues exhibited significantly higher LDHA and FoxP3 expression and lower CD4 expression(P＜0.001).The results of the correlation analysis showed that LDHA was positively correlated with FoxP3 expression and negatively correlated with CD4 expression(P＜0.05).The experimental results of Hep1-6 subcutaneous tumor-bearing mice showed that the tumor volume was significantly smaller in the bufalin and oxalate groups than in the control group and was significantly larger in the bufalin+pyruvic acid group than in the bufalin group(P＜0.001).The results of immunohistochemical staining showed that the expression levels of LDHA and the percentage of FoxP3+cells in the bufalin and oxalate groups were significantly lower than those in the control group,and the percentage of CD4+cells in the bufalin group was significantly higher than that in the control group(P＜0.001).The expres-sion level of LDHA and the percentage of FoxP3+cells in the bufalin+pyruvic acid group were significantly higher than those in the bufalin group,while the percentage of CD4+cells was significantly lower than that in the bufalin group(P＜0.001).The results of ELISA showed that the levels of TGF-β and IL-10 in the bufalin and oxalate groups were significantly lower than those in the control group(P＜0.001).Conclusion Bufalin inhibits cell growth,downregulates LDHA expression,and suppresses the differentiation and proliferation of Treg cells in HCC mice.

Objective:To analyze the relationship between the social network characteristics and mental health of elderly people in rural areas.Methods:A total of 274 elderly individuals aged 60 and above from rural communi-ties were selected.A self-designed structured interview questionnaire on social network structure was used to collect social network data,and Brief Version of the Mental Health Inventory for the Elderly(MHIE)was used to assess mental health levels.Based on the social escort model,the elderly people's social relationships were represented u-sing a three-tier concentric circle structure,indicating different levels of social relationship closeness.The structure of the social network included the size,frequency of contact,and intimacy of the relationships.The network size was represented by the number of nominators,and heterogeneity refers to the different types of relationships.Results:The concentric circle structure of the social network of rural elderly people consists of core family relationships,ex-tended family relationships,and friendships,from inner to outer circles.Regression analysis results showed that the heterogeneity of the social network was positively correlated with the MHIE scores(β=2.58).The intimacy of ex-tended family members and friends was positively correlated with the MHIE scores(β=1.07,0.87).The size of the extended family members was negatively correlated with the MHIE scores(β=-5.52).Conclusion:The het-erogeneity of the social network and intimacy play a positive role in the mental health of rural elderly people,while a large extended family network may impose psychological burdens.

Kinesiophobia is prevalent among school-aged children with asthma,and severe kinesiophobia can hinder their participation in physical activities and disease control,adversely affecting their physical and mental health.This paper reviews the concept,development,assessment tools,influencing factors,and intervention strategies of kinesiophobia in school-aged children with asthma,analyzes existing challenges,and proposes directions for future research.It aims to provide insights for developing scientific and personalized intervention plans to enhance children's exercise levels and improve their quality of life.

Antibody-drug conjugates (ADCs) are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker. Currently, 15 ADCs have been clinically approved worldwide. More than 100 clinical trials at different phases are underway to investigate the newly developed ADCs. ADCs represent one of the fastest growing classes of targeted antitumor drugs in oncology drug development. It takes advantage of the specific targeting of tumor-specific antigen by antibodies to deliver cytotoxic chemotherapeutic drugs precisely to tumor cells, thereby producing promising antitumor efficacy and favorable adverse effect profiles. However, emergence of drug resistance has severely hindered the clinical efficacy of ADCs. In this review, we introduce the structure and mechanism of ADCs, describe the development of ADCs, summarized the latest research about the mechanisms of ADC resistance, discussed the strategies to overcome ADCs resistance, and predicted biomarkers for treatment response to ADC, aiming to contribute to the development of ADCs in the future.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Objective:To analysis the possible behavior of coders in the reform of Diagnosis Related Groups(DRG)payment mode.Methods:To collect through questionnaires the possible coders'behaviors,and extract the common factors of possible behaviors according to factor analysis,and cluster the coders by the K-means clustering method.Results:Classify the possible coders'behaviors into positive behaviors such as following coding norms and standards,and negative behaviors such as directly coding without detailed reading of medical records.Less than 25 years old were more inclined to adopt negative behaviors,and associate senior titles and higher cognitive level of DRG were more inclined to adopt positive behaviors.The coders are divided into"positive group"who tend to take positive behaviors and"negative group"who take negative behaviors.Conclusion:Coders are more likely to adopt positive behavior,and we should be pay attention to the impact of different demographic characteristics on coders.To adopt different management strategies for different categories of coders,and strengthen training through hierarchical classification,and enhance coders'cognitive of DRG are more conducive to the selection of positive behaviors.

To investigate the pathogenicity of Sheep-origin Proteus mirabilis and the immunity effect of its inactivated vaccine.In this study,autopsy were performed on sick and dead sheep with severe diarrhea,collected liver,spleen and other diseased organs.And identified the isolated strains by morphology,Gram staining microscopy,biochemical test,molecular biology and 16S rRNA se-quencing;Drug resistance and pathogenicity were studied by drug sensitivity test,pathogenicity test in mouse and pathological histological observation;The isolated strains were inactivated by formaldehyde and mixed with alum adjuvant containing aluminum hydroxide to prepare the inacti-vated vaccine;mice were immunized after safety testing to test antibodies,cytokines and evaluate the immunological effects.Results showed that the isolate was Gram-negative short bacillus with blunt rounded ends after purification staining.Combined with biochemical tests,PCR amplified fragments and 16S rRNA sequencing results showed that the strain was Proteus mirabilis;The re-sults of drug sensitivity test showed that the isolate was highly sensitive to four antibiotics,including amikacin and piperacillin(S),the rest of the strain was moderately or poorly sensitive,or even resistant;The isolate was highly sensitive to the four antibiotics,such as amikacin and pip-eracillin(S).The lethal concentration of the isolated strain was 1.6 × 105 CFU/mL and it could cause different degrees of congestion and bruising and inflammatory cell infiltration in the liver,spleen and other major organs;The formaldehyde inactivated vaccine did not cause adverse reac-tions in mice,and the serum levels of antibodies to IgG,IgG1 and IgG2a,and the levels of antibod-ies to IL-4 and IFN-γ were higher than that of the PBS group,and the vaccine immunoprotection rate was 90％in the attacking bacterial test.In the present experiment,Proteus mirabilis was suc-cessfully isolated from the organs of sick and dead sheep.The inactivated vaccine prepared by form-aldehyde inactivation method can mediate humoral immunity to play a preventive role against the infection of S.chimaera,which can provide a new method for the prevention of bacterial diseases in sheep breeding.

Mesenchymal stem cells(MSCs)are multipotent stromal cells that possess the capacity for self-renewal and differentiation into multiple cell lineages.Due to the ease of procurement,robust expansion in vitro,the multipotency,they are recognized as a vital source of stem cells in the field of regenerative medicine.MSCs can be isolated from various tissues,including bone marrow,adipose tissue,and umbilical cord.Research indicates that Human umbilical cord mesenchymal stem cells(hUCMSCs)play an effective role in wound healing and tissue regeneration,and can be utilized for the repair of skin wounds.They are also considered to be the most promising seed cells for skin tissue engineering.This review aims to provide an overview of the biological characteristics of hUCMSCs,the mechanisms in promoting skin wound healing,and their clinical applications.