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

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Osteoarthritis （OA） and stroke are common clinical diseases that reduce patients' quality of life and place a burden on families and society. Ruyi Zhenbaowan， a classic prescription in Tibetan medicine， have the functions of clearing heat， awakening the brain and opening orifices， relaxing tendons and promoting meridian circulation， and eliminating yellow water. Clinically， they are used to treat osteoarthritis， post-stroke sequelae， neuropathic pain， and other related conditions. Modern pharmacological studies have demonstrated their anti-inflammatory， analgesic， and nerve-repairing effects. However， current research remains insufficient regarding the appropriate indications， timing， and efficacy of this medicine in treating relevant diseases. To enhance clinicians' understanding of this medicine and promote its standardized and rational clinical use， a panel of national experts， including clinical specialists， Tibetan medicine practitioners， pharmacologists， and methodologists， formulated this consensus based on clinical experience and evidence-based practice. The Cochrane systematic review framework， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system， and the nominal group method were employed to generate seven graded recommendations and 19 consensus-based suggestions. These recommendations clearly define the key points in the clinical application of Ruyi Zhenbaowan， including therapeutic indications， dosage and administration， treatment duration， and medication safety. The consensus specifically addresses the clinical efficacy， appropriate timing of administration， dosage strategies， treatment cycles， and combination medication strategies for treating osteoarthritis and stroke and provides an overview of safety considerations. The aim is to provide standardized guidance for hospitals and healthcare institutions nationwide to ensure the rational application of Ruyi Zhenbaowan in the treatment of osteoarthritis and stroke， reduce medication-related risks， and further leverage its clinical advantages. This consensus has been approved and issued by the China Association of Chinese Medicine， with the standard number GS/CACM 369-2024.

OBJECTIVE To analyze the correlation of the peak blood concentration （cmax） of compound sulfamethoxazole （TMP/SMZ） and its metabolite N-acetyl sulfamethoxazole （NSMZ） with clinical efficacy and adverse reactions in critically ill patients. METHODS The data of critically ill patients treated with TMP/SMZ in various ICU of Hainan General Hospital from December 2023 to January 2025 were retrospectively collected. The patients were divided into success group and failure group based on the treatment outcome. Simple linear regression and Spearman correlation analysis were used to analyze the correlation of TMP cmax， SMZ cmax， and NSMZ cmax with clinical efficacy and adverse reactions. The receiver operating characteristic curve （ROC） was used to determine the cutoff values of cmax for predicting the occurrence of adverse reactions. RESULTS Among critically ill patients with an acute physiology and chronic health evaluation Ⅱ （APACHE-Ⅱ） ≥15 points 24 h of check-in at ICU， SMZ cmax of success group was significantly higher than failure group （P＜0.05）. The daily total dose of TMP/SMZ was positively correlated with TMP cmax and SMZ cmax（ P＜0.05）. TMP cmax was significantly correlated with hepatotoxicity and nephrotoxicity， SMZ cmax with hepatotoxicity， and NSMZ cmax with nephrotoxicity （P＜0.05）. The cutoff values of TMP cmax for predicting nephrotoxicity and hepatotoxicity were 7.25 μg/mL and 6.63 μg/mL， respectively. The cutoff value of SMZ cmax for predicting hepatotoxicity was 138.00 μg/mL， and that of NSMZ cmax for predicting nephrotoxicity was 60.76 μg/mL. CONCLUSIONS Among critically ill patients with an APACHE-Ⅱ ≥15 points 24 h of check-in at ICU， SMZ cmax is associated with treatment success. Hepatotoxicity risk significantly increases when TMP cmax ≥6.63 μg/mL or SMZ cmax ≥138.00 μg/mL； nephrotoxicity risk significantly increases when TMP cmax ≥7.25 μg/mL or NSMZ cmax ≥60.76 μg/mL.

OBJECTIVE: Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis. METHODS: Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels. RESULTS: In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A. CONCLUSION JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis. Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; 23(6):683-693.
Carcinoma, Hepatocellular/blood supply* ; Humans ; STAT3 Transcription Factor/metabolism* ; Interleukin-8/metabolism* ; Liver Neoplasms/blood supply* ; Aurora Kinase A/metabolism* ; Neovascularization, Pathologic/drug therapy* ; Animals ; Signal Transduction/drug effects* ; Mice ; Drugs, Chinese Herbal/therapeutic use* ; Cell Line, Tumor ; Mice, Inbred BALB C ; Mice, Nude ; Angiogenesis

Uric acid (UA) is the final metabolite of purines in the human body. An imbalance in UA production and excretion that disrupts homeostasis leads to elevated blood UA levels and the development of hyperuricemia (HUA). Approximately one-third of UA is excreted through the intestinal tract. As a crucial component of the intestinal microenvironment, the gut microbiota plays a pivotal role in regulating blood UA levels. Alterations or imbalances in gut microbiota composition are linked to the onset of HUA, which implies the potential of gut microbiota as a novel target for the prevention and treatment of HUA. This review introduces the occurrence mechanism and damage of hyperuricemia, examines the association between HUA and the gut microbiota and their metabolites, and explores the molecular mechanisms underlying gut microbiota-targeted therapies for HUA. Furthermore, it discusses the potential applications of probiotics, prebiotics, and traditional Chinese medicine (including both single herbs and compound formulas) with UA-lowering effects, along with cutting-edge technologies such as fecal microbiota transplantation and machine learning in HUA treatment. This review provides valuable perspectives and strategies for improving the prevention and treatment of HUA.
Hyperuricemia/microbiology* ; Humans ; Gastrointestinal Microbiome/physiology* ; Probiotics/therapeutic use* ; Uric Acid/blood* ; Fecal Microbiota Transplantation ; Prebiotics ; Medicine, Chinese Traditional

Postoperative pulmonary complications(PPCs)represent a frequent and severe challenge following surgery,particularly in patients undergoing thoracic or abdominal procedures that necessitate tracheal intubation and mechanical ventilation.PPCs typically manifest within 7 days post-surgery.Effective perioperative management,encompassing optimization of lung-protective ventilation strategies,real-time monitoring of pulmonary ventilation status,and timely interventions,can substantially decrease the incidence of PPCs.As an emerging non-invasive imaging modality,electrical impedance tomography(EIT)has garnered significant attention in recent years for its clinical applications,especially in perioperative lung-protective ventilation.EIT enables real-time and dynamic visualization of lung ventilation distribution,providing a critical foundation for developing personalized ventilation strategies.This significantly enhances the safety and efficacy of mechanical ventilation while improving patient outcomes.The aim of this article is to elucidate the fundamental principles and advantages of EIT,explore its role in perioperative lung protection,and examine its future development prospects,thereby offering additional reference and guidance for clinical practice.