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 improvement effect and mechanism of processed Oxytropis falcata on renal fibrosis （RF） in rats. METHODS RF model was induced by adenine. After modeling， the rats were divided into the model group， positive control group （colchicine， 0.45 mg/kg）， and processed O. falcata low-， medium- and high-dose groups （0.5， 1， 2 g/kg）， respectively. Additionally， a blank group without modeling was set up， with 8 rats in each group. The positive control group and the various dosage groups of processed O. falcata were given the corresponding medicinal solutions intragastrically， while the blank group and model group were given equal volume of normal saline intragastrically， once daily for 28 consecutive days. The appearance and histopathological morphology of the rats’ kidneys were observed. Serum levels of renal function indexes [bl ood urea nitrogen （BUN）， creatinine （Cr） ] and inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） ] in rats were detected. Protein expressions of fibronectin （FN）， α -smooth muscle actin （ α -SMA） and collagen type Ⅰ （Col-Ⅰ） in renal tissue of rats were determined. mRNA expressions of transforming growth factor-β 1 （TGF-β 1 ）， Smad3 and extracellular signal-regulated kinase 1/2 （ERK1/2） in renal tissues were measured. Protein expression of TGF-β 1 and phosphorylation levels of Smad3 and ERK1/2 in renal tissues were detected. RESULTS Compared with the blank group， the rats in the model group exhibited enlarged kidneys with pale color， rough and uneven surface. There was a significant infiltration of inflammatory cells and vacuolated cells in the renal tubules， along with marked proliferation of collagen fibers. Serum levels of BUN， Cr， IL-6 and TNF-α， protein expressions of α -SMA， Col-Ⅰ and FN in renal tissues， mRNA expressions of TGF-β 1 ， Smad3， ERK1 and ERK2 and protein expression of TGF-β 1 as well as phosphorylation levels of Smad3 and ERK1/2 in renal tissues were increased significantly （ P ＜0.05）. Compared with the model group， renal pathological changes of rats were alleviated in processed O. falcata groups， with reduced infiltration of inflammatory cells and proliferation of collagen fibers. The levels of the aforementioned quantitative indicators were all significantly reversed （ P ＜0.05）. CONCLUSIONS Processed O. falcata can improve renal function in RF rats， alleviate inflammatory responses， and reduce abnormal collagen fiber deposition. Its mechanism of action may be related to the inhibition of the activity of the TGF-β 1 /Smad signaling pathway.

Objective To explore the functional impact of A-to-I editing in the seed region of miR-411 during post-myocardial infarction (MI) fibrosis and elucidate its therapeutic potential. Methods Integrating GEO database with myocardial RNA-seq data from MI mouse models, we identified dynamic A-to-I RNA editing in small noncoding RNAs across MI progression (1 day to 8 weeks post-MI). Four miRNAs exhibited differential editing rates between MI and controls, with miR-411 showing progressive editing enhancement at seed region position 4 (P＜0.01). This editing event was validated in both murine MI models and human heart failure specimens. Results The A-to-I editing ratio change of the 4th nucleotide in the seed region of miR-411 mainly occurs in cardiac fibroblasts rather than cardiomyocytes, and the editing at this site depends on ADAR2 rather than ADAR1. Edited miR-411 (ED-miR-411) diverged from wild-type miR-411 (WT-miR-411) in suppressing collagen-related pathways (extracellular matrix [ECM]-receptor interaction, collagen-containing ECM, ECM organization; P＜0.01) in cardiac fibroblasts. Mechanistically, dual-luciferase assays confirmed ED-miR-411 directly targeted the 3′UTR and suppressed expression of type Ⅱ transforming growth factor (TGF)-beta receptor (TGFBR2) and CD44, which were key drivers of TGF-β-mediated fibroblast activation. ED-miR-411 overexpression blunted TGF-β-induced collagen synthesis and myofibroblast proliferation (P＜0.05). In vivo, intramyocardial delivery of ED-miR-411 mimics at 1 week post-MI reduced fibrosis by 40% and improved ejection fraction by 15% (P＜0.01 vs controls), whereas WT-miR-411 showed no therapeutic effect. Conclusions A-to-I editing of miR-411 emerges as an endogenous anti-fibrotic mechanism by repressing TGFBR2 and CD44, thereby disrupting TGF-β signaling and ECM dysregulation. Our findings highlight ED-miR-411 as a novel RNA-based therapeutic candidate to mitigate post-infarction cardiac remodeling.

Education is a crucial element in the development of acupuncture as a discipline, providing essential talent support for its future advancement. A structured interview was conducted with renowned acupuncture expert Professor ZHAO Jiping, focusing on key topics such as the core of acupuncture education, the connotation and development of acupuncture textbooks, and acupuncture teaching models. Through in-depth discussion, the current problems in acupuncture education were analyzed, and possible solutions were explored, aiming to offer ideas for the innovative development of acupuncture education.
Acupuncture/trends* ; Humans ; Acupuncture Therapy ; China

Objective: To investigate the association between emotional intelligence and sleep problems at the symptom level among junior and senior high school students, so as to provide new insights for interventions targeting junior and senior high school students sleep disorders. Methods: From November 2023 to May 2024, a stratified cluster random sampling method was employed to select 3 531 first year junior high school and first year senior high school students from 6 schools in Guangyuan City and Liangshan Yi Autonomous Prefecture in Sichuan Province, as well as Lhasa City in Tibet Autonomous Region. The Insomnia Severity Index Scale and the Wong and Law Emotional Intelligence Scale(WLEIS) were used to assess sleep problems and emotional intelligence. A network analysis was performed to explore the relationship between emotional intelligence and sleep disorders, and a gender based network comparison analysis was conducted. Results: The reported rate of sleep problems among junior and senior high school students was 47.3%, with severe sleep problems of 2.2%. Difficulty maintaining sleep, worry about sleep, and emotional application were the core symptoms in the network (node strength values: 1.11, 0.98, and 0.82, respectively). Dissatisfaction with sleep and emotional application served as bridge symptoms connecting emotional intelligence and sleep problems (bridge strength values: 1.77 and 1.59, respectively). The edge weights of the emotional intelligence and sleep problems network differed significantly between genders (maximum difference in edge weight values was 0.13， P <0.05). Conclusions Emotional application ability and dissatisfaction with sleep are the key nodes in the network connecting emotional intelligence and sleep problems. Targeted efforts to enhance emotional application ability may effectively reduce the risk of sleep problems among junior and senior high school students.

Objective:To discuss the effects of bone marrow-derived mesenchymal stem cells(BMSCs)transplantation on mitophagy in the vascular dementia(VaD)rats through reactive oxygen species(ROS)/nuclear factor erythroid 2-related factor 2(Nrf2)signaling,and to clarify its mechanism.Methods:Forty-five male adult SD rats were randomly divided into sham operation group,model group,unloaded group,BMSCs group,and MSCs+ML385(Nrf2 inhibitor)group(combination group),and there were 9 rats in each group.After intraperitoneal anesthesia,the VaD models were established in all groups except sham operation group.Morris water maze test was used to detect the learning and memory abilities of the rats in various groups;HE staining was used to observe the histopathological morphology of brain tissue of the rats in various groups;Nissl staining was used to observe the changes of Nissl bodies in hippocampus region of brain tissue of the rats in various groups;transmission electron microscope was used to observe the ultrastructure of hippocampus region of the rats in various groups;fluorescence probe method was used to detect the ROS levels in hippocampus neurons in various groups;Western blotting method was used to detect the expression levels of Nrf2,heme oxygenase-1(HO-1),PTEN-induced putative kinase 1(PINK1),parkin RBR E3 ubiquitin protein ligase(Parkin),Beclin-1,ubiquitin-binding protein p62(P62),and microtubule-associated protein 1A/1B-light chain 3(LC3-Ⅱ/LC3-Ⅰ)ratio in brain tissue of the rats in various groups.Results:The Morris water maze results showed that compared with sham operation group,the escape latency of the rats in model group was significantly increased(P<0.01),while the number of crossing time and residence time were significantly decreased(P<0.01).Compared with model group,the escape latency of the rats in BMSCs group was significantly decreased(P<0.01),while the number of crossing time and residence time were significantly increased(P<0.01).Compared with BMSCs group,the escape latency of the rats in combination group was significantly increased(P<0.01),while the number of crossing time and residence time were significantly decreased(P<0.01).The HE staining results showed that hippocampus neurons of the rats in sham operation group were normal in quantity and morphology,with uniform staining and clear structure.Compared with sham operation group,the hippocampus tissue of the rats in model group showed sparse arrangement,disordered structure,reduced neuronal quantity,varied morphology,uneven staining,nuclear pyknosis,and partial neuronal necrosis.Compared with model group,the neuronal damage of the rats in hippocampus regio in BMSCs group was alleviated,with restored morphology and improved neuronal loss.Compared with BMSCs group,the neurons of the rats in hippocampus region in combination group showed irregular morphology,disordered structure,unclear cell boundaries,uneven staining,and nuclear pyknosis.The Nissl staining results showed that the hippocampal neurons in sham operation group were tightly arranged with intact morphology,obvious nucleoli,and abundant darkly stained Nissl bodies.Compared with sham operation group,the neurons in hippocampus region of the rats in model group showed pyknosis,vacuolization,and sparse Nissl bodies.Compared with model group,the BMSCs group showed reduced neuronal pyknosis,relatively intact morphology,and increased Nissl bodies.Compared with BMSCs group,the combination group showed neuronal pyknosis,loss of morphological integrity,and fragmented Nissl bodies.The transmission electron microscope results showed that mitochondria in sham operation group exhibited oval shape with intact double-membrane structure and cristae.Compared with sham operation group,the mitochondria in model group showed swelling,disrupted membranes,broken cristae,and numerous autophagosomes.Compared with model group,the BMSCs group showed improved mitochondrial structure and reduced autophagosomes.Compared with BMSCs group,the combination group showed swollen mitochondria,disrupted membranes,broken cristae,and visible autophagosomes.The fluorescence probe results showed that compared with sham operation group,the ROS levels in the hippocampus neurons in brain tissue of the rats in model group were significantly increased(P<0.01);compared with model group,the ROS levels in hippocampus neurons in brain tissue of the rats in BMSCs group were significantly decreased(P<0.01);compared with BMSCs group,the ROS levels in hippocampus neurons in brain tissue of the rats in combination group were significantly increased(P<0.01).The Western blotting results showed that compared with sham operation group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in model group were significantly decreased(P<0.01);compared with model group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in BMSCs group were significantly increased(P<0.01);compared with BMSCs group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in combination group were significantly decreased(P<0.01);compared with sham operation group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,and LC3-Ⅱ/LC3-Ⅰ ratio of the rats in model group were significantly increased(P<0.01),while the expression level of P62 protein was significantly decreased(P<0.01);compared with model group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,as well as the LC3-Ⅱ/LC3-Ⅰ ratio,of the rats in BMSCs group were significantly decreased(P<0.01),while the expression level of P62 protein was significantly increased(P<0.01);compared with BMSCs group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,as well as the LC3-Ⅱ/LC3-Ⅰ ratio,of the rats in combination group were significantly increased(P<0.01),while the expression level of P62 protein was significantly decreased(P<0.01).Conclusion:BMSCs can alleviate the hippocampal neuronal pathological changes and improve cognitive function in the VaD rats,and its mechanism may be related to the regulation of ROS/Nrf2 signaling pathway to inhibit mitophagy.

In epidemiological statistics, the incidence rate and mortality rate of malignant lung tumors rank among the top. Non-small cell lung cancer (NSCLC) constitutes an important part of lung cancer and has become a key focus of clinical research and treatment. Among the genomic characteristics of NSCLC, the Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is one of the main tumor drivers, accounting for approximately 25% of all NSCLC cases. The existence of this mutation is closely related to the treatment response and prognosis of patients. Therefore, the treatment strategy for KRAS-mutated NSCLC is an important topic in the field of tumor research. In the current era, immunomodulatory therapy has rapidly gained popularity and developed rapidly in oncology due to its unique mechanism of action and remarkable clinical efficacy. The treatment strategies targeting the KRAS-mutated of NSCLC have gradually become a research hotspot. The advent of immune checkpoint inhibitors (ICIs) has opened up a new therapeutic avenue for patients with such cancers, and clinical studies have shown significant effects in improving survival rates. Nevertheless, there are still many challenges in the application of immunotherapy, such as the complexity of the tumor microenvironment, individual differences among patients, and drug resistance mechanisms. This article reviews the progress of immunotherapy for KRAS-mutated NSCLC, focusing on the specific application of immunotherapy, the exploration of combination therapies, and the results of related clinical trials. At the same time, it discusses the possible future development directions of KRAS-mutated NSCLC treatment, providing a reference for clinical treatment practice.
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Humans ; Carcinoma, Non-Small-Cell Lung/immunology* ; Lung Neoplasms/immunology* ; Proto-Oncogene Proteins p21(ras)/immunology* ; Immunotherapy/methods* ; Mutation ; Animals

To address the problem of large reconstruction errors in 3D pulse signals caused by excessively small out-of-plane displacement of the contact membrane in the existing traditional Chinese medicine fingertip tactile binocular vision detection technology, this study proposes a 3D pulse image detection method based on subtle motion magnification technology and explores its application in pulse pattern recognition. Firstly, a 3D pulse image detection system based on binocular vision to obtain pulse image signals is developed as experimental data. Then, the phase motion video magnification algorithm is used to amplify the original signals, and the amplified signals are reconstructed in three dimensions to obtain 3D pulse signals. On this basis, nine features are extracted from the 3D pulse signals and features selection is performed using a two-sample Kolmogorov-Smirnov test. Finally, machine learning algorithms such as decision trees and random forests are used to identify the five types of pulse conditions: deep pulse, intermittent pulse, flooding pulse, slippery pulse, and rapid pulse. The experimental results show that compared to the methods without subtle motion magnification technology, the proposed method significantly improves waveform clarity, amplitude stability, and periodic regularity. Meanwhile, the average accuracy in pulse pattern recognition reaches 96.29%±0.26%.
Algorithms ; Imaging, Three-Dimensional/methods* ; Pattern Recognition, Automated ; Medicine, Chinese Traditional ; Motion ; Humans ; Pulse ; Signal Processing, Computer-Assisted ; Machine Learning

Loss-of-function variants of low-density lipoprotein receptor-related protein 5 (LRP5) can lead to reduced bone formation, culminating in diminished bone mass. Our previous study reported transcription factor osterix (SP7)‍-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration. However, the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown. In this study, we used mice with a conditional knockout (cKO) of LRP5 in mature osteoblasts, which presented decreased osteogenesis. The in vitro experimental results showed that SP7 could promote LRP5 expression, thereby upregulating the osteogenic markers such as alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2), and β‍-catenin (P<0.05). For the in vivo experiment, the SP7 overexpression virus was injected into a bone defect model of LRP5 cKO mice, resulting in increased bone mineral density (BMD) (P<0.001) and volumetric density (bone volume (BV)/total volume (TV)) (P<0.001), and decreased trabecular separation (Tb.‍Sp) (P<0.05). These data suggested that SP7 could ameliorate bone defect healing in LRP5 cKO mice. Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.
Animals ; Low Density Lipoprotein Receptor-Related Protein-5/metabolism* ; Osteoporosis/genetics* ; Mice ; Mice, Knockout ; Sp7 Transcription Factor/physiology* ; Osteogenesis ; Bone Density ; Osteoblasts/metabolism* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Mice, Inbred C57BL ; beta Catenin/metabolism*

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.