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 investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

ObjectiveTo evaluate the pregnancy outcomes of assisted reproductive technology （ART） in women with a history of thyroid cancer who retained fertility intentions after completing cancer treatment. MethodsA retrospective analysis was performed on 61 patients with a history of thyroid cancer who underwent in vitro fertilization/intracytoplasmic sperm microinjection and embryo transfer （IVF/ICSI-ET）. These patients were included as the case group. A total of 122 non-cancer patients who received ART during the same period were selected as the control group using 1∶2 matching based on age and oocyte retrieval time. Baseline characteristics， outcomes of the first ART cycle， and cumulative pregnancy outcomes were compared between the two groups. ResultsThere was no significant difference in the basic data， the total amount of gonadotropin （Gn） and the days of use between the case group and the control group （P>0.05）. However， the case group had significantly fewer retrieved oocytes， mature oocytes （MII）， lower fertilization and cleavage rates， and fewer transferable and high-quality embryos， as well as fewer embryos transferred during the first cycle （P < 0.05）. However， there was no significant difference in the rate of first embryo implantation and first clinical pregnancy between the two groups （P>0.05）. In the analysis of cumulative outcomes， the two groups did not show statistically significant differences in the cumulative pregnancy rate， clinical pregnancy rate per transfer cycle， the number of oocyte retrieval cycles required per live birth， the number of embryo transfer cycles required per live birth， and the number of embryos used for each live birth （P>0.05）. However， the cumulative live birth rate was significantly lower in the case group compared to the control group （P=0.005）. ConclusionAfter treatment for thyroid cancer， when ART is used to help pregnant women， the pregnancy outcome is comparable to that of women without tumors. Individualized reproductive management and timely fertility preservation strategies are recommended to optimize reproductive outcomes in this population.

Objective To evaluate the short-term effects of comprehensive health management interventions for stroke high-risk population screening on the prevention and treatment of ischemic stroke, and to provide reference and basis for improving and exploring health management and prevention strategies for stroke high-risk population. Methods From 2018 to 2022, 13 community health service centers in Jiading District, Shanghai were selected in the present study. Based on information push platform, stroke risk assessment and health intervention follow-up were conducted for community residents through convenience sampling. The residents were divided into a full course intervention group (intervention group) and a routine intervention group (control group) according to different health intervention measures and forms. The incidence of ischemic stroke in the two groups of survey subjects was tracked within 36 months. Results A total of 52144 subjects were included in the study. The total number of patients in the full course intervention group was 14227, with an incidence density of 577.32/100 000 (556.49/100 000-598.12/100 000), which was lower than that of the conventional intervention group (37 917), with an incidence density of 1 485.47/100 000 (1 464.99/100 000-1 505.94/100 000) (χ²=2490.212, P<0.001). The relative risk of the full course intervention group was 0.39, and the relative risk of stroke risk factors in the full course intervention group from low to high was 0.33, 0.43, 0.45, and 0.49, respectively. The incidence density of males in the full course intervention group was 660.76 (627.46/100 000 - 694.05/100 000), with a relative risk of 0.43, and the incidence density of female patients was 509.71/100 000 (483.37/100 000 - 536.05/100 000), with a relative risk of 0.35. The overall incidence density of the population under 62 years old gourp, 62-75 years old group and over 75 years old group was 197.45/100 000 (173.09/100 000 -221.80/100 000), 608.36/100 000 (580.19/100 000-636.54/100 000), and 1 025.06/100 000 (958.51/100 000-1 091.61/100 000), with relative risks of 0.51, 0.44, and 0.38, respectively. Conclusion Comprehensive health management measures can effectively reduce the short-term risk of ischemic stroke, and should be further promoted and improved to enhance the effectiveness of stroke prevention and control.

Purpose: Due to the preservation of the entire stomach after endoscopic resection, the occurrence of metachronous gastric cancer (MGC) remains a possibility. In this study, we investigated the incidence and risk factors for MGC in patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) and successfully eradicatedHelicobacter pylori. Materials and Methods: A retrospective analysis was conducted of 1,191 patients who underwent ESD and successfully eradicated H. pylori at the Affiliated Drum Tower Hospital of Nanjing University. Endoscopic surveillance was performed at 3, 6, and 12 months post-resection, and annually thereafter. MGC was defined as the development of a new cancer at a site other than the primary gastric cancer site, at least 1 year after the initial endoscopic resection. Results: A total of 77 patients were diagnosed with MGC during a median follow-up of 41.5 months. Kaplan-Meier analysis showed a 5-year cumulative incidence of MGC of 9.4% after successful H. pylori eradication. Multivariate analysis of the training set using Cox proportional hazards models identified male sex, severe atrophic gastritis, multiple gastric cancers before H. pylori eradication, and smoking history as independent risk factors for MGC.The nomogram exhibited favorable discrimination, with area under the curves of 0.767 and 0.822 in the training set and 0.724 and 0.745 in the testing set at 3 and 5 years, respectively. Conclusions Patients with gastric cancer who undergo endoscopic resection, even after successful H. pylori eradication, should undergo annual and continuous endoscopic surveillance for MGC.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

γδ T cells possess both innate and adaptive immune characteristics. Their antigen recognition is independent of major histocompatibility complex presentation， and they can directly recognize abnormal tumor metabolism， showing unique application potential in tumors with low immune infiltration. This paper systematically sorts out the biological characteristics and antitumor immune functions of γδ T cells， and mainly reviews the relevant mechanisms by which active ingredients of traditional Chinese medicine regulate γδ T cells to exert antitumor immune functions. Glycyrrhiza polysaccharide and Astragalus polysaccharide can enhance the antitumor immune function of γδ T cells by promoting the expression of various cytokines， regulating intestinal flora and alleviating immunosuppressive state. Quercetin and puerarin can strengthen γδ T cell-mediated tumor cell killing by regulating the proliferation of γδ T cells， the expression of cytotoxic effector molecules and related signaling pathways. Toosendanin can potentiate γδ T cell-induced tumor cell killing by down-regulating the expression of anti-apoptotic protein in tumor cells. Artesunate can boost γδ T cell-mediated antitumor immune responses by enhancing the effector function of γδ T cells and weakening tumor immune escape. Future research shall focus on exploring the synergistic effects and molecular mechanisms of the combined application of active ingredients of traditional Chinese medicine and γδ T cell immunotherapy， and identifying the key targets for γδ T cells to exert antitumor immune functions.

γδ T cells possess both innate and adaptive immune characteristics. Their antigen recognition is independent of major histocompatibility complex presentation， and they can directly recognize abnormal tumor metabolism， showing unique application potential in tumors with low immune infiltration. This paper systematically sorts out the biological characteristics and antitumor immune functions of γδ T cells， and mainly reviews the relevant mechanisms by which active ingredients of traditional Chinese medicine regulate γδ T cells to exert antitumor immune functions. Glycyrrhiza polysaccharide and Astragalus polysaccharide can enhance the antitumor immune function of γδ T cells by promoting the expression of various cytokines， regulating intestinal flora and alleviating immunosuppressive state. Quercetin and puerarin can strengthen γδ T cell-mediated tumor cell killing by regulating the proliferation of γδ T cells， the expression of cytotoxic effector molecules and related signaling pathways. Toosendanin can potentiate γδ T cell-induced tumor cell killing by down-regulating the expression of anti-apoptotic protein in tumor cells. Artesunate can boost γδ T cell-mediated antitumor immune responses by enhancing the effector function of γδ T cells and weakening tumor immune escape. Future research shall focus on exploring the synergistic effects and molecular mechanisms of the combined application of active ingredients of traditional Chinese medicine and γδ T cell immunotherapy， and identifying the key targets for γδ T cells to exert antitumor immune functions.

The molecular mechanisms underlying the develop-ment and metastasis of prostate cancer remain elusive.This comprehensive review delves into the intricate role of cofilin,an actin-binding protein,in the pathogenesis and progression of prostate cancer.Cofilin is a significant protein in cytoskeletal dynamics,and any dysregulation may result in the morphological changes in normal cells and the invasion and metastasis of tumor cells.Research has revealed that the activity of cofilin is regula-ted by various mechanisms,including phosphorylation/dephos-phorylation and interactions with other molecules.Moreover,this review discusses promising therapeutic interventions,such as co-filin inhibitors and gene therapy,which have demonstrated effica-cy in preclinical models.The challenge of clinically preventing the transition to castration-resistant prostate cancer and tumor metastasis is widely recognized,necessitating the development of precise drug treatments and biomarker identification.As a key regulatory protein,cofilin provides a more comprehensive refer-ence for the prevention and treatment of prostate diseases.

Aim To explore the action mechanism of isoquercitrin(IQ)in ameliorating anxiety based on network pharmacology,cellular transcriptomics,molecu-lar docking and animal experiments.Methods The common targets of anxiety disorders and IQ were ob-tained by using relevant databases.The protein-protein interaction network,the biological function and signa-ling pathway enrichment analysis were conducted by u-sing the common targets.Primary hippocampal neurons were cultured in vitro,and corticosterone was added to induce neurons to establish a corticosterone injury mod-el.IQ treatment was added to the culture system,and transcriptomics was used to screen for differentially ex-pressed genes and enrich for differentially expressed pathways.Subsequently,the results were validated by quantitative real-time polymerase chain reaction(qRT-PCR).Possible targets and signaling pathways for IQ treatment on anxiety were speculated and screened u-sing network pharmacology,transcriptomics and molec-ular docking.The anxiety rat model was constructed,and the anxiety state of rats was evaluated after IQ in-tervention,and the protein expression level of hippo-campus was detected to verify the relevant mechanism.Results Network pharmacology,cellular transcrip-tome,and molecular docking analyses revealed that the key mechanism of IQ for anxiety may be related to the BDKRB2/PI3K/Akt signaling pathway.Animal exper-iments showed that IQ was effective in improving anxie-ty behaviour and learning memory ability in rats.IQ increased the movement distance and residence time in the central area of the open field,the time and number percentage of entries into the open arm in the elevated plus maze,and the spontaneous alternations score in the Y maze in rats,and significantly elevated protein expression of BDKRB2,PI3K,Akt and decreased pro-tein expression of NF-κB in the hippocampus.Conclu-sions Isoquercitrin can effectively treat anxiety,and the mechanism of action may be related to the regula-tion of BDKRB2/PI3K/Akt signaling pathway in hip-pocampus.