Abstract Cardiovascular diseases are the leading cause of death, requiring innovative approaches for prevention, diagnosis, and treatment. Personalized medicine customizes interventions according to individual characteristics, with artificial intelligence (AI) playing a key role in analyzing complex data to improve diagnostic accuracy, predict outcomes, and optimize therapies. AI can identify patterns in imaging and biomarkers, facilitating the earlier detection of medical conditions. Wearable devices and health applications facilitate continuous monitoring and personalized care. Emerging fields such as digital Chinese medicine offer additional perspectives by integrating traditional diagnostic principles with modern digital tools, contributing to holistic and individualized cardiovascular care. This study examines the advancements and challenges in personalized cardiovascular medicine, highlighting the need to address issues such as data privacy, algorithmic bias, and accessibility to promote the equitable application of personalized medicine.

Objective: To investigate the mechanism of in alleviating colonic mucosal inflammation in ten-eleven translocation (TET) protein 2 gene knockout (TET2-/-) mice with ulcerative colitis (UC) by regulating DNA methyltransferase (DNMT) and DNA hydroxymethylase. Methods: Male specific pathogen-free (SPF) grade C57BL/6J wild-type (WT) mice (n = 8) and TET2-/- mice (n = 20) were used to establish UC models by freely drinking 3% dextran sulfate sodium solution for 7 d. After UC model validation through histopathological examination in two mice from each type, the remaining mice were divided into four groups (n = 6 in each group): WT model (WT + UC), TET2-/- model (TET2-/- + UC), TET2-/- mild moxibustion (TET2-/- + MM), and TET2-/- electroacupuncture (TET2-/- + EA) groups. TET2-/- + MM group received mild moxibustion on Tianshu (ST25) and Qihai (CV6) for 10 min daily for 7 d. The TET2-/- + EA group also applied electroacupuncture (1 mA, 2/100 Hz) at the same acupoints for 10 min daily for 7 d. The disease activity index (DAI) scores of each group of mice were accessed daily. The colon lengths of mice in groups were measured following intervention. The pathological changes in the colon tissues were observed with hematoxylin and eosin (HE) staining. The concentrations of interleukin (IL)-6, C-C motif chemokine 17 (CCL17), and C-X-C motif chemokine ligand 10 (CXCL10) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression of DNMT proteins (DNMT1, DNMT3A, and DNMT3B) in the colon tissues was detected by immunohistochemistry. The expression of 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC), histone deacetylase 2 (HDAC2), and DNA hydroxymethylase family proteins (TET 1 and TET3) was detected using immunofluorescence, which also determined the co-localization of TET1 and IL-6 protein. Results: Compared with WT + UC group, TET2-/- + UC group exhibited significantly higher DAI scores and shorter colon lengths (P < 0.01). Both mild moxibustion and electroacupuncture significantly decreased DAI scores and ameliorated colon shortening in TET2-/- mice (P < 0.001). Histopathological scores of TET2-/- + UC mice were significantly higher than those of WT + UC group (P < 0.001) and were significantly reduced after both mild moxibustion and electroacupuncture interventions (P < 0.001). Serum levels of IL-6, CCL17, and CXCL10 were significantly elevated in TET2-/- + UC group compared with WT + UC group (P < 0.001). Mild moxibustion significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.001, P < 0.001, and P < 0.01, respectively), while electroacupuncture also significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.05, P < 0.01, and P < 0.01, respectively). TET2-/- + UC mice showed increased expression levels of DNMT1, DNMT3A , DNMT3B, and 5-mC (P < 0.05, P < 0.01 and P < 0.001, respectively), with decreased expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001). Mild moxibustion significantly reduced DNMT1, DNMT3B, and 5-mC levels (P < 0.05, P < 0.01, and P < 0.001, respectively), while increasing expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001, P < 0.001, P < 0.05, and P < 0.001, respectively). Electroacupuncture significantly decreased 5-mC and DNMT3B levels (P < 0.001 and P < 0.01, respectively) and increased 5-hmC and HDAC2 levels (P < 0.05 and P < 0.001, respectively), but did not significantly affect TET1 and TET3 expression (P > 0.05). Compared with TET2-/- + MM group, TET2-/- + EA group showed significantly higher 5-mC expression (P < 0.001). TET2-/- + UC group exhibited markedly increased IL-6 expression and higher co-localization of TET1 and IL-6 in mucosal epithelium, whereas minimal IL-6 expression was observed in the other groups. Conclusion Mild moxibustion and electroacupuncture significantly ameliorate colonic inflammation exacerbated by TET2 deficiency in UC mice via epigenetic modulation. Distinct mechanisms exist between the two interventions: mild moxibustion regulates both DNMT and hydroxymethylase, whereas electroacupuncture primarily affects DNMT.

Objective: To evaluate the antibacterial potential of bioactive compounds from Persicaria hydropiper (L.) (P. hydropiper) against bacterial virulence proteins through molecular docking (MD) and experimental validation. Methods: Six bioactive compounds from P. hydropiper were investigated: catechin (CAT1), hyperin (HYP1), ombuin (OMB1), pinosylvin (PSV1), quercetin 3-sulfate (QSF1), and scutellarein (SCR1). Their binding affinities and potential binding pockets were assessed through MD against four bacterial target proteins with Protein Data Bank identifiers (PDB IDs): topoisomerase IV from Escherichia coli (E. coli) (PDB ID: 3FV5), Staphylococcus aureus (S. aureus) gyrase ATPase binding domain (PDB ID: 3U2K), CviR from Chromobacterium violaceum (C. violaceum) (PDB ID: 3QP1), and glycosyl hydrolase from Pseudomonas aeruginosa (P. aeruginosa) (PDB ID: 5BX9). Molecular dynamics simulations (MDS) were performed on the most promising compound-protein complexes for 50 nanoseconds (ns). Drug-likeness was evaluated using Lipinski's Rule of Five (RO5), followed by absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis using SwissADME and pkCSM web servers. Antibacterial activity was evaluated through disc diffusion assays, testing both individual compounds and combinations with conventional antibiotics [cefotaxime (CTX1, 30 μg/disc), ceftazidime (CAZ1, 30 μg/disc), and piperacillin (PIP1, 100 μg/disc)]. Results: MD revealed strong binding affinity (ranging from – 9.3 to – 5.9 kcal/mol) for all compounds, with CAT1 showing exceptional binding to 3QP1 (– 9.3 kcal/mol) and 5BX9 (– 8.4 kcal/mol). MDS confirmed the stability of CAT1-protein complexes with binding free energies of – 84.71 kJ/mol (5BX9-CAT1) and – 95.59 kJ/mol (3QP1-CAT1). Five compounds (CAT1, SCR1, PSV1, OMB1, and QSF1) complied with Lipinski's RO5 and showed favorable ADMET profiles. All compounds were non-carcinogenic, with CAT1 classified in the lowest toxicity class (VI). In antibacterial assays, CAT1 demonstrated significant activity against both gram-positive bacteria [Streptococcus pneumoniae (S. pneumoniae), S. aureus, and Bacillus cereus (B. cereus)] [zone diameter of inhibition (ZDI): 10 – 22 mm] and gram-negative bacteria [Acinetobacter baumannii (A. baumannii), E. coli, and P. aeruginosa] (ZDI: 14 – 27 mm). Synergistic effects were observed when CAT1 was combined with antibiotics and the growth inhibitory indices (GII) was 0.69 – 1.00. Conclusion P. hydropiper bioactive compounds, particularly CAT1, show promising antibacterial potential through multiple mechanisms, including direct inhibition of bacterial virulence proteins and synergistic activity with conventional antibiotics. The favorable pharmacological properties and low toxicity profiles support their potential development as therapeutic agents against bacterial infections.

Abstract Traditional Chinese medicine (TCM) has demonstrated unique advantages in the prevention and treatment of chronic diseases such as glycolipid metabolism disorder. However, its widespread application has been hindered by the unclear biological essence of TCM syndromes and therapeutic mechanisms. As an emerging interdisciplinary field, phenomics integrates multi-dimensional data including genome, transcriptome, proteome, metabolome, and microbiome. When combined with TCM's holistic philosophy, it forms TCM phenomics, providing novel approaches to reveal the biological connotation of TCM syndromes and the mechanisms of herbal medicine. Taking glycolipid metabolism disorder as an example, this paper explores the application of TCM phenomics in glycolipid metabolism disorder. By analyzing molecular characteristics of related syndromes, TCM phenomics identifies differentially expressed genes, metabolites, and gut microbiota biomarkers to elucidate the dynamic evolution patterns of syndromes. Simultaneously, it deciphers the multi-target regulatory networks of herbal formulas, demonstrating their therapeutic effects through mechanisms including modulation of insulin signaling pathways, improvement of gut microbiota imbalance, and suppression of inflammatory responses. Current challenges include the subjective nature of syndrome diagnosis, insufficient standardization of animal models, and lack of integrated multi-omics analysis. Future research should employ machine learning, multimodal data integration, and cross-omics longitudinal studies to establish quantitative diagnostic systems for syndromes, promote the integration of precision medicine in TCM and western medicine, and accelerate the modernization of TCM.

[Objective] : To systematically evaluate the overall efficacy of external application of traditional Chinese medicine (EA-TCM) in combination with oral three-step analgesic ladder therapy for patients suffering from cancer-induced bone pain (CIBP). [Methods] : We conducted a literature search of randomized controlled trials on the combination of EA-TCM and three-step analgesic ladder therapy for CIBP across ten databases and two registration systems. It included four Chinese databases [Chinese Biomedical Literature Database (SinoMed), China National Knowledge Infrastructure (CNKI), Wanfang Database, and China Science and Technology Journal Database (VIP) ], six English databases (Scopus, Embase, Web of Science, PubMed, Cochrane Library, and OpenGrey), and two registration systems (Chinese Clinical Trial Registry and ClinicalTrials.gov). The timeframe for the literature search extended from the inception of each database to December 31, 2023. Meta-analysis was performed using RevMan (v5.4.1), and the outcome indicators (pain relief rate, analgesic duration, quality of life, pain intensity, breakthrough pain frequency, and adverse reactions) were graded using GRADE profiler (v3.6). [Results] : According to the established inclusion and exclusion criteria, a total of 43 studies was deemed eligible, involving 3 142 participants with CIBP. The results of meta-analysis showed that compared with oral three-step analgesic ladder therapy alone, the combined therapy of EA-TCM and three-step analgesic ladder has a significant improvement in pain relief rate [risk ratio (RR) = 1.32, 95% confidence interval (CI): 1.24 to 1.41, P < 0.000 01], analgesic duration [mean difference (MD) = 1.33, 95% CI: 0.97 to 1.69, P < 0.000 01], and quality of life (MD = 5.66, 95% CI: 4.88 to 6.44, P < 0.000 01). Furthermore, the combined therapy significantly reduced pain intensity (MD = – 1.00, 95% CI: – 1.19 to – 0.80, P < 0.000 01), breakthrough pain frequency (MD = – 0.43, 95% CI: – 0.51 to – 0.36, P < 0.000 01), and adverse reactions (RR = 0.60, 95% CI: 0.53 to 0.68, P < 0.000 01) in CIBP patients. Based on the GRADE assessment, the level of evidence varied from low to moderate. [Conclusion] EA-TCM combined with the three-step analgesic ladder therapy can effectively alleviate pain symptoms in patients with CIBP and improve their quality of life. Additionally, the EA-TCM can effectively reduce the incidence of adverse reactions associated with three-step analgesic therapy.

Abstract Digitization is the inevitable path for the natural development of traditional Chinese medicine (TCM) in the context of the Fourth Industrial Revolution. The goal of TCM digitization is to generate intelligence from numbers. Originating from the reasoning paradigm of Xiangshu (象数, image-number) or phenotype-numerology thinking, TCM came with a deep correlation of clinical observations with digits and laid a strong theoretical basis for digitization. The digitization of TCM should start from the clinical aspect, solve the problem of electronic medical records, achieve standardization and informatization, and on this basis, form a TCM knowledge base through knowledge-building. This process depends on the combined efforts of multiple disciplines such as medicine, mathematics, and engineering to achieve the digitization and intelligent transformation of TCM. This era calls for TCM to break down barriers, embrace opportunities, and move towards digitization. However, during the transformation, it should maintain its essence, avoid simplistic conversions, be guided by scientific value, leverage cutting-edge technologies, and enhance the depth and breadth of the interpretation of TCM connotations. The digitization of TCM will also improve its service capabilities, create an innovative digitally-intelligent TCM service platform, and contribute to the development of “Healthy China” initiatives with wisdom and solutions.

[Objective] : To predict the autophagy-related pathogenesis and key diagnostic genes of diabetic kidney disease (DKD) through bioinformatics analysis, and to identify related Chinese medicines. [Methods] : Data from sequencing microarrays GSE30528, GSE30529, and GSE1009 in the Gene Expression Omnibus (GEO) were employed. Differentially expressed genes (DEGs) with adjusted P < 0.05 from GSE30528 and GSE30529 were identified. Combining these DEGs with the human autophagy gene database, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and protein-protein interaction (PPI) network analysis were conducted on the obtained DKD autophagy-related genes. Subsequently, the least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms were adopted to select autophagy-related genes. The diagnostic capability of these genes was assessed through analysis with the external validation set from microarray GSE1009, and relevant Chinese medicines were inversely predicted using the SymMap database. [Results] : A total of 2 014 DEGs were selected from GSE30528 and GSE30529, leading to the identification of 37 DKD autophagy-related genes. GO analysis indicated 681 biological mechanisms, including autophagy regulation and plasma membrane microdomain activity. KEGG enrichment analysis identified 112 related signaling pathways. PPI network analysis showed a marked enrichment of autophagy-related genes in DKD. Through LASSO regression and SVM-RFE, four core diagnostic genes for autophagy in DKD were identified: protein phosphatase 1 regulatory subunit 15A (PPP1R15A), hypoxia inducible factor 1 alpha subunit (HIF1α), deleted in liver cancer 1 (DLC1), and ceroid lipofuscinosis neuronal 3 (CLN3). The external validation set demonstrated high diagnostic efficiency for these genes. Finally, 146 kinds of potential Chinese medicines were predicted using the SymMap database, with heatclearing and detoxifying medicine and blood-activating and stasis-eliminating medicine accounting for the largest proportion (25/146 and 13/146, respectively). [Conclusion] This study analyzed and validated bioinformatics sequencing databases to elucidate the potential molecular mechanisms of DKD autophagy and predicted key diagnostic genes, potential therapeutic targets, and related Chinese medicines, laying a solid foundation for clinical research and application.

[Objective] : To explore the clinical characteristics and methods for syndrome differentiation prediction, as well as to construct a predictive model for Qi deficiency and blood stasis syndrome in patients with acute ischemic stroke (AIS). [Methods] : This study employed a retrospective case-control design to analyze patients with AIS who received inpatient treatment at the Neurology Department of The First Hospital of Hunan University of Chinese Medicine from January 1, 2013 to December 31, 2022. AIS patients meeting the diagnostic criteria for Qi deficiency and blood stasis syndrome were stratified into case group, while those without Qi deficiency and blood stasis syndrome were stratified into control group. The demographic characteristics (age and gender), clinical parameters [time from onset to admission, National Institutes of Health Stroke Scale (NIHSS) score, and blood pressure], past medical history, traditional Chinese medicine (TCM) diagnostic characteristics (tongue and pulse), neurological symptoms and signs, imaging findings [magnetic resonance imaging-diffusion weighted imaging (MRI-DWI)], and biochemical indicators of the two groups were collected and compared. The indicators with statistical difference (P < 0.05) in univariate analysis were included in multivariate logistic regression analysis to evaluate their predictive value for the diagnosis of Qi deficiency and blood stasis syndrome, and the predictive model was constructed by receiver operating characteristic (ROC) curve analysis. [Results] : The study included 1 035 AIS patients, with 404 cases in case group and 631 cases in control group. Compared with control group, patients in case group were significantly older, had extended onset-to-admission time, lower diastolic blood pressure, and lower NIHSS scores (P < 0.05). Case group showed lower incidence of hypertension history (P < 0.05). Regarding tongue and pulse characteristics, pale and dark tongue colors, white tongue coating, fine pulse, astringent pulse, and sinking pulse were more common in case group. Imaging examinations demonstrated higher proportions of centrum semiovale infarction, cerebral atrophy, and vertebral artery stenosis in case group (P < 0.05). Among biochemical indicators, case group showed higher proportions of elevated fasting blood glucose and glycated hemoglobin (HbA1c), while lower proportions of elevated white blood cell count, reduced hemoglobin, and reduced high-density lipoprotein cholesterol (HDL-C) (P < 0.05). Multivariate logistic regression analysis identified significant predictors for Qi deficiency and blood stasis syndrome including: fine pulse [odds ratio (OR) = 4.38], astringent pulse (OR = 3.67), superficial sensory abnormalities (OR = 1.86), centrum semiovale infarction (OR = 1.57), cerebral atrophy (OR = 1.55), vertebral artery stenosis (OR = 1.62), and elevated HbA1c (OR = 3.52). The ROC curve analysis of the comprehensive prediction model yielded an area under the curve (AUC) of 0.878 [95% confidence interval (CI) = 0.855 – 0.900]. [Conclusion] This study finds out that Qi deficiency and blood stasis syndrome represents one of the primary types of AIS. Fine pulse, astringent pulse, superficial sensory abnormalities, centrum semiovale infarction, cerebral atrophy, vertebral artery stenosis, elevated blood glucose, elevated HbA1c, pale and dark tongue colors, and white tongue coating are key objective diagnostic indicators for the syndrome differentiation of AIS with Qi deficiency and blood stasis syndrome. Based on these indicators, a syndrome differentiation prediction model has been developed, offering a more objective basis for clinical diagnosis, and help to rapidly identify this syndrome in clinical practice and reduce misdiagnosis and missed diagnosis.

Abstract In the wave of digital and intelligent applications, artificial intelligence (AI) is transforming the development trajectories of industries across the globe. Traditional Chinese medicine (TCM), as a cultural treasure of the Chinese nation, carries thousands of years of wisdom and practical experience. However, in the context of the rapid advancements in modern medicine and technology, TCM faces dual challenges: preserving its heritage while innovating. DeepSeek, a major achievement in the field of AI, offers a new opportunity for the development of TCM with its powerful technological capabilities. Exploring the integration of DeepSeek with TCM not only helps modernize the practice but also promises unique contributions to global health.