1.Effects of Yangxin Tongmai Formula (养心通脉方) on Methylation Key Genes and the PERK/ATF4/CHOP Signaling Pathway in Myocardial Tissue of Coronary Heart Disease Model Rats with Blood Stasis Syndrome
Chun ZHANG ; Shumeng ZHANG ; Yan MAO ; Xing CHEN ; Huifang KUANG ; Yi YANG ; Lingli CHEN ; Jie LI
Journal of Traditional Chinese Medicine 2026;67(7):784-791
ObjectiveTo investigate the mechanism of Yangxin Tongmai Formula (养心通脉方, YTF) in trea-ting coronary heart disease with blood stasis syndrome based on DNA methylation. MethodsSeventy-two SD rats were randomly divided into a control group (n=12) and a modeling group (n=60). The modeling group was subjected to a high-fat diet, intragastric administration of vitamin D3, and subcutaneous injection of isoprenaline to establish the rat model of coronary heart disease with blood stasis syndrome. Forty-one successfully modeled rats were then randomly allocated into model group, YTF low-, medium-, and high-dose groups, and the atorvastatin calcium group, with 8 rats in each group and 1 rat reserved. The YTF low-, medium-, and high-dose groups received YTF at 6, 12, and 18 g/(kg·d) by gavage, respectively. The atorvastatin calcium group received atorvastatin calcium tablets at 1.8 mg/(kg·d) by gavage. The control group and the model group received 0.9% sodium chloride injection at 4 ml/(kg·d) by gavage. All administrations were performed once daily for 3 weeks. Twenty-four hours after the last administration, serum lipid levels including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), myocardial enzymes including cardiac troponin T (cTnT), creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH), and inflammatory factors including interleukin-1β (IL-1β) and interleukin-10 (IL-10) were detected by ELISA. Pathological changes in myocardial tissue were observed via HE staining. Whole blood DNA methylation sequencing was used to analyze differential methylation gene expression among the control group, model group, and YTF high-dose group. Western Blotting was used to verify the protein levels of the key genes and downstream signaling pathways. ResultsCompared to the control group, the model group showed increased levels of TC, TG, LDL-C, cTnT, CK-MB, LDH, and IL-1β, along with decreased levels of HDL-C and IL-10 (P<0.05 or P<0.01). Compared to the model group, all treatment groups exhibited decreased levels of TC, LDL-C, CK-MB, and LDH, along with increased IL-10 levels. Among these, the high-dose YTF group demonstrated superior efficacy in reducing cTnT levels compared to the other TCM groups (P<0.05 or P<0.01). HE staining indicated that the YTF high-dose group ameliorated myocardial cell swelling, disordered arrangement, pyknosis, and disappearance of nuclei, thereby reducing myocardial cell damage. Whole blood DNA methylation sequencing identified 240 differentially methylated genes shared by the control group, model group, and YTF high-dose group, including 109 hypermethylated and 131 hypomethylated genes; eif2ak3 was identified as a key differentially methylated gene. Compared to the control group, the model group exhibited increased protein levels of eukaryotic translation initiation factor 2 alpha kinase 3 (eIf2ak3), phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), and Bax, along with a decreased level of B-cell lymphoma-2 (Bcl-2) protein (P<0.05 or P<0.01). Compared to the model group, the YTF high-dose group showed decreased protein levels of eIf2ak3, p-PERK, ATF4, CHOP, and Bax, and an increased level of Bcl-2 protein (P<0.05 or P<0.01). ConclusionYTF may regulate key differentially methylated genes such as eIf2ak3 and the PERK/ATF4/CHOP signaling pathway, thereby inhibiting endoplasmic reticulum stress, reducing myocardial cell apoptosis, and exerting therapeutic effects in coronary heart disease blood stasis syndrome.
2.Construction of a medication strategy integrating staged modifications of Bushen huoxue decoction with HRT for premature ovarian insufficiency based on the “state-target differentiation and treatment”theory
Lingli WANG ; Qiuwei CHEN ; Xi XIAO ; Tong CHU ; Yue CHEN ; Si CHEN
China Pharmacy 2026;37(10):1329-1334
OBJECTIVE To explore a synergistic medication strategy integrating stage-specific modifications of Bushen huoxue decoction with hormone replacement therapy (HRT) for premature ovarian insufficiency (POI). METHODS The connotation of Academician Tong Xiaolin’s “state-target differentiation and treatment” theory and the disease stage characteristics of POI were summarized. The latent stage, subclinical stage, clinical stage and exhaustion stage of POI were classified into corresponding core pathogenesis “states” and key objective indicator “targets”. Taking Bushen huoxue decoction as the basic prescription, its staged modification scheme and its sequential combination with HRT were analyzed. RESULTS & CONCLUSIONS The four stages of POI correspond to four pathogenic states respectively: kidney yin deficiency, kidney deficiency and blood stasis, heart-kidney disharmony, and deficiency of both yin and yang. Follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), antral follicle count (AFC) and Kupperman score were taken as the evaluation targets of staging. Combined with the “state-target” characteristics of each stage, a medication principle based on Bushen huoxue decoction with syndrome differentiation modification and stage-adjusted administration was established: traditional Chinese medicine dominates in the latent stage, a sequential collaborative regimen is adopted in the subclinical stage, HRT is dominant supplemented by traditional Chinese medicine in the clinical stage, and integrated traditional Chinese and Western medicine is applied to consolidate the root cause in the exhaustion stage.
3.Advances in artificial intelligence-based medical imaging and digital pathology for diagnosis, treatment and prognostic assessment of gastric cancer
Li YU ; Minmin TAO ; Lingli XIE ; Kai CHEN
Chinese Journal of Digestive Surgery 2025;24(1):137-142
Gastric cancer(GC) ranks among the most prevalent cancers and is a leading cause of cancer-related mortality globally. Recently, artificial intelligence(AI) has enhanced the dia-gnosis and treatment of GC, as well as the accuracy and sensitivity of personalized treatment strategies due to its efficient computational and learning capabilities. The authors review the clinical applications of AI-based medical imaging and digital pathology in GC diagnosis and treatment, inclu-ding early screening and diagnosis, differential diagnosis, lymph node and peritoneal metastasis, molecular typing, monitoring of treatment efficacy, and prognostic assessment. In addition, future directions and challenges in the field are discussed, emphasizing the importance of integrating AI technology into clinical practice.
4.Construction of the meridian tapping exercise for frail elderly based on data mining
Lu YAO ; Lingli XU ; Huifen LIN ; Ji CHEN ; Mengxin WANG ; Xueping CHEN
Chinese Journal of Practical Nursing 2025;41(29):2273-2279
Objective:To construct a meridian tapping exercise program for frail elderly, so as to provide daily healthcare options for frail elderly people.Methods:Guided by the theory of meridians and collaterals, data mining was conducted on the database of ancient Chinese medical literature to select acupoints and meridians for tapping. Through literature research, the exercise prescription was improved. A preliminary exercise prescription was formulated through literature review and revised through two rounds of expert consultation in December 2023.Results:The effective response rate for both rounds of expert consultation questionnaires was 7/7. The expert authority coefficients were 0.83 and 0.87, respectively, and the overall Kendall′s coefficient of concordance was 0.301 and 0.302 (both P<0.05). The final meridian tapping exercise for frail elderly comprised 2 primary indicators, 8 secondary indicators, and 23 tertiary indicators. Conclusions:The meridian tapping exercise for the frail elderly is scientific, reliable and practical, which can provide a choice for the frail elderly to carry out targeted traditional Chinese medicine exercises.
5.Defucosylation of anti-West Nile virus NS1 antibody enhances ADCC
Wanlu ZHU ; Lingli WU ; Nan CHEN ; Beifen SHEN ; Jiannan FENG ; Jun ZHANG ; He XIAO
Chinese Journal of Microbiology and Immunology 2025;45(9):740-745
Objective:To obtain fucose-free anti-West Nile virus nonstructural protein 1 (NS1) antibody and evaluate its antibody-dependent cell-mediated cytotoxicity (ADCC).Methods:The guanosine diphosphate-fucose transporter SLC35C1 in CHO cells was knocked out using CRISPR/Cas9 gene editing technology to obtain the fucose-free cell line CHO SLC35C1 -/-. CHO SLC35C1 -/- cells were used to produce fucose-free anti-West Nile virus NS1 antibodies. The binding abilities of the antibodies to the target antigen of West Nile virus NS1 protein and the human high-affinity IgG Fc receptor hFcγRⅠ (hCD64) were detected by ELISA and flow cytometry, respectively. The ADCC activity of the antibodies was detected by ADCC reporter gene assay. One-way analysis of variance was used for statistical analysis. Results:CHO SLC35C1 -/- cells expressed green fluorescent protein but not Lens culinaris agglutinin. The anti-West Nile virus NS1 antibodies produced by CHO SLC35C1 -/- cells with a fucose content of 0.22% could bind to West Nile virus NS1 protein in a concentration-dependent manner. Compared with the wild-type antibodies, the fucose-free anti-West Nile virus NS1 antibodies showed a stronger binding ability to hFcγRⅠ(hCD64), as indicated by a significant increase in fluorescence intensity. The ADCC reporter gene assay showed that the fucose-free anti-West Nile virus NS1 antibodies had increased activity as compared with the wild-type antibodies ( P<0.001). Conclusion:The fucose-free anti-West Nile virus NS1 antibodies may be used to protect against West Nile virus infection.
6.Advances in artificial intelligence-based medical imaging and digital pathology for diagnosis, treatment and prognostic assessment of gastric cancer
Li YU ; Minmin TAO ; Lingli XIE ; Kai CHEN
Chinese Journal of Digestive Surgery 2025;24(1):137-142
Gastric cancer(GC) ranks among the most prevalent cancers and is a leading cause of cancer-related mortality globally. Recently, artificial intelligence(AI) has enhanced the dia-gnosis and treatment of GC, as well as the accuracy and sensitivity of personalized treatment strategies due to its efficient computational and learning capabilities. The authors review the clinical applications of AI-based medical imaging and digital pathology in GC diagnosis and treatment, inclu-ding early screening and diagnosis, differential diagnosis, lymph node and peritoneal metastasis, molecular typing, monitoring of treatment efficacy, and prognostic assessment. In addition, future directions and challenges in the field are discussed, emphasizing the importance of integrating AI technology into clinical practice.
7.Construction of the meridian tapping exercise for frail elderly based on data mining
Lu YAO ; Lingli XU ; Huifen LIN ; Ji CHEN ; Mengxin WANG ; Xueping CHEN
Chinese Journal of Practical Nursing 2025;41(29):2273-2279
Objective:To construct a meridian tapping exercise program for frail elderly, so as to provide daily healthcare options for frail elderly people.Methods:Guided by the theory of meridians and collaterals, data mining was conducted on the database of ancient Chinese medical literature to select acupoints and meridians for tapping. Through literature research, the exercise prescription was improved. A preliminary exercise prescription was formulated through literature review and revised through two rounds of expert consultation in December 2023.Results:The effective response rate for both rounds of expert consultation questionnaires was 7/7. The expert authority coefficients were 0.83 and 0.87, respectively, and the overall Kendall′s coefficient of concordance was 0.301 and 0.302 (both P<0.05). The final meridian tapping exercise for frail elderly comprised 2 primary indicators, 8 secondary indicators, and 23 tertiary indicators. Conclusions:The meridian tapping exercise for the frail elderly is scientific, reliable and practical, which can provide a choice for the frail elderly to carry out targeted traditional Chinese medicine exercises.
8.Predictive Value of Serum miRNA-126a and miRNA-130b Levels in Cognitive Impairment among Patients with Diabetes Mellitus Complicated with Acute Stroke
Lingli LIU ; Ruoxuan WEI ; Wei CHEN ; Caixia KONG ; Zhihong LIU
Journal of Kunming Medical University 2025;46(10):91-96
Objective To explore the relationship between serum miRNA-126a,miRNA-130b levels and cognitive impairment(CI)in patients with diabetes mellitus(DM)complicated with acute stroke(AS).Methods A retrospective analysis was conducted on 70 DM patients with AS admitted to Wuhan First Hospital from January 2019 to December 2021.Patients were divided into CI group(41 cases)and non-CI group(29 cases)based on the occurrence of CI.Real-time fluorescence quantitative PCR was used to detect the relative expression levels of miRNA-126a and miRNA-130b in peripheral blood.Results Compared with non-CI group,the CI group showed increased albumin(P<0.05)and decreased levels of miRNA-126a and miRNA-130b(P<0.05).Logistic regression analysis showed that albumin(OR=19.045,95%CI=2.001~181.230),miRNA-126a(OR=200.603,95%CI=15.663~2569.162),miRNA-130b(OR=11.770,95%CI=1.966~70.474)were related factors affecting CI occurrence in DM patients with AS.ROC curve analysis showed that peripheral blood miRNA-126a had the highest AUC(0.958)for diagnosing CI in DM patients with AS,with a sensitivity of 97.6%and specificity of 89.7%.The AUC for miRNA-130b(0.669)was lower,with a sensitivity of 73.2%and specificity of 62.1%.Conclusion Decreased expression of peripheral blood miRNA-126a has good diagnostic value for CI in DM patients with AS.
9.Pathogenesis and treatment of atherosclerosis in traditional Chinese medicine from the"blood pathway originates from the liver"theory
Liang DONG ; Lingli CHEN ; Jie LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(7):966-972
Atherosclerosis is a degenerative vascular lesion characterized by chronic inflammation of the vessel wall and represents a crucial risk factor for cardiovascular and cerebrovascular events.Although Western medicine has made advances in anti-inflammatory and lipid-lowering treatments,research into the dynamic progression of atherosclerosis and multi-target regulation remains limited.In traditional Chinese medicine,these conditions are classified as"vessel bi"and"pulse accumulation."This study is based on the"blood pathway originates from the liver"theory proposed by KE Qin in the Qing Dynasty in his The Annotated ′Treatise on Cold Pathogenic Diseases′.The aim is to systematically elucidate the connotations of this theory and explore atherosclerosis pathogenesis and treatment.This condition originates in hepatic dysregulation,leading to qi stagnation and blood flow obstruction.It then progresses to disharmony between the liver and heart,where excessive wood and fire injure the vessels.This result in the accumulation of phlegm and blood stasis,causing abnormal qi transformation and lipid stagnation.The underlying deficiency lies in liver and kidney yin deficiency,where essence depletion leads to blood thickening and vessel atrophy,ultimately forming a complex pathology characterized by deficiency in origin and excess at the surface.Therapeutic strategies should prioritize dispersing the liver and regulating the blood,while integrating a multi-faceted approach that includes"dispersing stagnated liver qi for relieving qi stagnation to promote qi flow,invigorating blood and eliminating stasis to open the meridians,transforming phlegm and draining turbidity to clarify the source,nourishing the liver and kidneys to strengthen the foundation,and softening the liver and clearing the heart to harmonize yin and yang."This integrative strategy of"dispersing,dissipating,supplementing,clearing,and harmonizing"offers a novel perspective for the dynamic prevention and multi-target regulation of atherosclerosis,combining both theoretical and practical aspects.
10.Association between body mass index and calcaneus bone mineral density in adults in a cross-sectional study in Tongxiang, Zhejiang Province
Hao WANG ; Kaixu XIE ; Lingli CHEN ; Hao XU ; Zhengjie SHEN ; Jun LYU ; Canqing YU ; Dianjianyi SUN ; Pei PEI ; Jieming ZHONG ; Min YU
Chinese Journal of Epidemiology 2025;46(3):448-454
Objective:To evaluate the association between body mass index (BMI) and bone mineral density of calcaneus in adults.Methods:Data of the second resurvey of China Kadoorie Biobank study from Tongxiang of Zhejiang Province were used. A total of 2 896 participants aged 44-84 years were included in the final analysis. Overweight was defined as 23.0 kg/m 2≤BMI<25.0 kg/m 2, and obesity was defined as BMI ≥25.0 kg/m 2 based on the criteria recommended by WHO/West Pacific Region. Multiple linear regression model was used to evaluate the association between BMI and calcaneus bone mineral density. Restricted cubic splines were used to investigate the dose-response relationship between BMI and calcaneus bone mineral density. Results:The calcaneus bone mineral density in the study subjects were as follow ( x± SE): the broadband ultrasound attenuation was (109.4±12.1) dB/MHz, the speed of ultrasound was (1 545.9±33.8) m/s, and the stiffness index was 85.7±15.8. After adjusting for socio-demographic factors, lifestyle, waist circumference, diabetes and hypertension prevalence, BMI was positively associated with calcaneus stiffness index in non-overweight and non-obese adults, with β of 2.30 (95% CI: 1.11-3.49) for men ( P<0.001) and 1.08 (95% CI: 0.38-1.78) for women ( P=0.003), respectively. In addition, BMI was positively associated with calcaneus stiffness index in overweight and obese women ( β=0.90, 95% CI: 0.38-1.42) ( P<0.001), and null association was found in overweight and obese men ( β=0.06, 95% CI: -0.92-1.04) ( P=0.900). Restricted cubic spline model showed a nonlinear dose-response relationship between BMI and calcaneus stiffness index. Conclusion:Non-linear association was found between BMI with calcaneus bone mineral density in adults.

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