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.

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.

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.

Objective To explore the mechanism of Huoxin pill(HXP)in the prevention and treatment of heart failure(HF)based on transcriptomics and network pharmacology.Methods The mice were randomly divided into the normal control group,model control group,positive control group treated with sacubitril/valsartan(60 mg·kg-1),low-dose group treated with HXP(31.2 mg·kg-1),and high-dose group treated with HXP(62.4 mg·kg-1).The model control group and each drug treat-ment group were subcutaneously injected with an equal volume of ISO(5 mg·kg-1)for modeling,while the normal control group was given an equal volume of sterile saline.Six hours later,each drug administration group was gavaged with the corresponding drug for intervention,and the normal control and model control groups were gavaged with an equal volume of sterile water.The modeling and drug administration were continued for 21 days.The cardiac function parameters of the mice were measured using color Doppler ultrasound imaging;ELISA was used to detect the levels of mouse serum cAMP,NT-proBNP,and BNP;HE staining and Masson's trichrome staining were used to evaluate the pathological morphology of cardiac tissue,and the CVF was calculated.Network pharmacology combined with transcriptomics was used to predict potential targets and signaling pathways of HXP in the prevention and treatment of HF,and molecular biology methods were used for validation.Results Compared with the normal control group,the model control group showed an increase in LVESd and LVEDd(P＜0.01),and a decrease in LVEF and LVFS(P＜0.01);BNP,NT-proBNP,and cAMP levels were increased(P＜0.01);myocardial collagen fibers increased and CVF in-creased(P＜0.01).Compared with the model control group,the HXP low-dose group,HXP high-dose group,and positive control groups showed a decrease in LVESd and LVEDd(P＜0.01),and an increase in LVEF and LVFS(P＜0.01);serum levels of BNP,NT-proBNP,and cAMP decreased(P＜0.05);the degree of myocardial fibrosis decreased and CVF decreased(P＜0.01).Network pharmacology combined with transcriptomics predicted 10 key targets for HXP in the prevention and treatment of HF:CACNA1H,SCN10A,FGF12,PVALB,ACAN,LGALS3,SERPINE1,MMP3,GSTM1,VDR.Western blot results showed that the protein activation levels of PKA and CREB in myocardial tissue were increased in the model control group compared with the nor-mal control group(P＜0.01).Compared with the model control group,HXP low-dose group、HXP high-dose group,and positive control groups showed a decrease in the protein activation levels of PKA and CREB in myocardial tissue(P＜0.05).Conclusion HXP has an improvement effect on ISO-induced HF in mice,which may involve numerous targets and the cAMP/PKA signaling pathway.

Objective To explore the effect of sitagliptin and metformin combined with zoledronic acid in the treatment of type 2 diabetes mellitus(T2DM)complicated with osteoporosis(OP)on the levels of glucose and lipid metabolism and bone metabolism in patients.Methods Patients with T2DM combined with OP admitted to Nantong Second People's Hospital from January 2021 to January 2024 were selected as the research subjects and randomly divided into the combined group(sitagliptin and metformin combined with zoledronic acid)and the control group(zoledronic acid only).After 6 months of treatment,the clinical efficacy,glucose and lipid metabolism indicators[fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),glycated hemoglobin(HbA1c),total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)],bone metabolism indicators[osteoprotegerin(OPG),bone-specific alkaline phosphatase(BALP),osteocalcin(OC)]levels,changes in bone density,and incidence of adverse reactions were compared between the two groups before and after treatment.Results A total of 120 patients were included,with 60 patients in each group.After treatment,the total effective rate of the combination group was 93.33％,significantly higher than the control group's 73.33％(P＜0.05).The levels of FBG,2hPG,HbA1c,TC,TG,and LDL-C in two groups were significantly lower than those before treatment,while the levels of HDL-C,OPG,BALP,OC,and bone density in the femoral neck and lumbar spine were significantly higher than before treatment(P＜0.05);and all indicators of the combined group were better than those of the control group(P＜0.05).There was no statistically significant difference in the total incidence of adverse reactions between the two groups(P＞0.05).Conclusion Sitagliptin and metformin combined with zoledronic acid in the treatment of patients with T2DM complicated with OP is more effective in regulating their glycolipid metabolism and bone metabolism levels,increasing bone density,improving therapeutic effects,and it has better safety than zoledronic acid alone.

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.

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.

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.

Cultural confidence is an important part of nurturing"confidence in the path,theory,system,and culture of social-ism with Chinese characteristics"students,as well as the important direction of ideological and political courses,and play an impor-tant role for establishing the core values of Chinese socialism.This paper summarized the reform exploration and practical experience of the Basic Immunology and Pathogen Biology through deeply excavating the core ideas of Chinese medicine culture based on the course content for improving the cultural confidence.The object of this paper is to improving the effectiveness of education.

Objective To explore whether miR-146b can participate in the brain injury process of diabetic rats with cerebral infarction(DM-CI)by regulating the extracellular regulatory protein kinase(ERK1/2)-activated protein-1(AP-1)signaling pathway.Methods 80 SD rats were randomly divided into sham operation group,DM-CI group,low miR-146b expression group and ERK1/2 inhibition group,with 20 rats in each group.The National Institutes of Health Stroke Scale(NIHSS)score measures brain function in rats.The mRNA levels of miR-146b,ERK1/2 and AP-1 in rat brain tissue were detected by RT-qPCR.Western blotting detected ERK1/2,AP-1 protein levels in rat brain tissue.TTC staining was used to detect cerebral infarction volume in rats.H&E staining was used to detect brain histopathological changes.Random blood glucose levels were detected by glucose meter in rats.Results Compared with sham operation group,mRNA expression levels of miR-146b,ERK1/2 and AP-1 in brain tissue of rats in DM-CI group were significantly increased,with statistically differences(t=10.86,15.62,9.87,all P<0.05).ERK1/2 and AP-1 protein levels increased,with statistically differences(t=11.18,23.81,P<0.05).NIHSS score increased and random blood glucose level increased(t=44.49,30.02,all P<0.05),and increased cerebral infarction volume(t=51.05,P<0.05),the structure of brain tissue was disorganized and loose,and edema can be seen in the pericellular space.Compared with the DM-CI group,the mRNA expression levels of miR-146b,ERK1/2 and AP-1 in the brain tissue of rats with low expression of miR-146b were decreased,with statistically differences(t=38.00,20.03,24.25,all P<0.05).the protein expression of EPK1/2 and AP-1 decreased,and the differences were statistically significant(t=12.30,26.70,all P＜0.05).NIHSS score and random blood glucose level were decreased,with statistically differences(t=38.11,33.77,all P<0.05),cerebral infarction volume decreased(t=16.70,P<0.05),the degree of brain tissue in jury and edema was improved,and the expression levels of ERK1/2 and AP-1 protein and mRNA in brain tissue of rats inhibited by ERK1/2 were decreased,with statistically differences(t=13.61～38.00,all P<0.05),the NIHSS score of rats was decreased,and the random blood glucose level was decreased,with statistically differences(t=16.48,26.61,all P<0.05).Conclusion MiR-146b may be involved in brain functional and structural damage in DM-CI rats by regulating ERK1/2-AP-1 signaling pathway.