Objectives:This study aims to explore the causal relationships between immune cells and serum metabolites in the development of coronary heart disease(CHD)using Mendelian randomization(MR)methods.Methods:We conducted a two-sample MR analysis utilizing data from the FinnGen Project's genome-wide association study(GWAS)on CHD,alongside data on metabolites and immune cells from the GWAS catalog.For the identified associated metabolites,we further employed mediation MR methods to evaluate their mediating roles in the influence of immune cells on CHD.Results:The MR analysis indicated that three immune cells(IgD-CD24-%B cell,CD11b on CD14+monocyte,HLA DR on DC)had stable causal relationship with CHD(under the premise of inverse variance weighted[IVW]method P<0.05,both MR-Egger and weighted median methods also showed P<0.05).Furthermore,these immune cells were associated with CHD through four metabolites(N-acetylneuraminic acid levels,the ratio of desmethyltaurine to taurine,X-24801 and X-18779).Conclusions:This study reveals the causal relationships between immune cells and serum metabolites in the pathogenesis of CHD,providing new biomarkers for early prediction and risk assessment of CHD.

Objective:The predictive value of oxidized low density lipoprotein(ox-LDL)and electrocardiogram(ECG)ischaemia grade for major adverse cardiovascular events(MACE)in patients with ST elevation myocardial infarction(STEMI)after percutaneous coronary intervention(PCI)was assessed by a retrospective cohort study de-sign.Methods:A total of 336 STEMI patients admitted to Cangzhou People's Hospital between October 2019 and May 2022 were selected,and the medical record information was obtained through the hospital medical record sys-tem,and all patients received PCI and physician-recommended basic treatment.With occurrence of MACE with in 12-month follow-up as the evaluation index,they were divided into MACE group(n=65)and no MACE group(n=271).Multifactorial Logistic regression model was used to study the influencing factors of MACE after PCI in STEMI patients,and Spearman test for association of ox-LDL level,ECG ischaemia grade with MACE after PCI.ROC curve was used to evaluate the predictive efficacy of ox-LDL,ECG ischaemia grade and their combination for MACE after PCI.Results:The overall MACE incidence was 19.35％.Compared with patients in no MACE group,those in MACE group had significant higher ox-LDL level[46.34(29.46,66.29)U/L vs.33.00(23.02,50.03)U/L]and proportion of ECG grade Ⅲ ischaemia(64.62％vs.42.80％)(P＜0.01 all).Multifactorial Logistic re-gression analysis showed that ox-LDL(OR=1.022,95％CI 1.011～1.033,P=0.001)and ECG grade Ⅲ ischae-mia(OR=1.878,95％CI 1.007～3.504,P=0.048)were the independent risk factors of post-PCI MACE in STEMI patients.Spearman test showed that ox-LDL and ECG grade Ⅲ ischaemia were positively correlated with post-PCI MACE(r=0.209,0.173,P＜0.001 all).ROC curve analysis showed that the AUCs of ox-LDL,ECG grade Ⅲ ischaemia and their combination in predicting post-PCI MACE were respectively 0.653(95％CI 0.599～0.704),0.609(95％CI 0.555～0.662)and 0.758(95％CI 0.709～0.803),in which the predictive value of the combination of the two was significantly higher than any single detection(Z=2.030,3.097,P=0.042,0.002).Conclusion:ox-LDL combined with ECG ischaemia grading has a high predictive value for the occurrence of MACE with in 12 months after PCI in STEMI patients.

Fear of disease progression(FoP)is a common psychological state among patients with coronary heart dis-ease(CHD),which exists throughout the course of disease and seriously affects the prognosis.High level of FoP not only harms the mental health of patients but also do not benefit their rehabilitation after discharge.This concept was first proposed by foreign researchers studying the psychological state of cancer patients.In recent years,there have been numerous studies on the influencing factors and qualitative aspects of FoP in CHD patients,while related inter-vention studies remain few.This paper reviews the concept,scales and related influencing factors of FoP,providing ideas for medical staff to provide targeted interventions for CHD patients.

Objective:Using ecological niche width and situation model,the operation and management of public Traditional Chinese Medicine(TCM)hospitals in 16 cities in Shandong Province were evaluated to put forward countermeasures.Methods:The relevant index data of public TCM hospitals in 16 cities in Shandong Province from 2019 to 2022 were collected to analyze the development status.The ecological niche width model and niche situation model were applied to evaluate the operation and management of public TCM hospitals in 16 cities in Shandong.Results:The top three public TCM hospitals in terms of average ecological niche width were City G,City P and City F.The ecological niche situation value of public TCM hospitals in City K,City A and City J ranked the top three.Conclusion:The dimensions of operation management structure of public TCM hospitals in Shandong need to be enhanced and the development of operation management space needs to be balanced.It is feasible to evaluate operation management by using ecological niche width and situation model.It is suggested to improve the allocation efficiency of health personnel,facilities,funds and other resources;promote the spatial balanced development of operation management;promote the application of ecological niche width and situation model in the field of medicine and health management.

Background:Bushen Zhuanggu Formula(BZF),derived from the classic Yougui Pills,has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head(NONFH),particularly by promoting bone repair.However,its underlying mechanisms remain unclear.Objective:This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH.Materials and methods:A total of 518 potential BZF targets were identified from the ETCM v2.0 database.Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls.A drug target-disease gene interaction network was constructed to identify candidate BZF targets involved in NONFH pathogenesis.In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH.Results:Network analysis identified key pathways associated with blood circulation obstruction,immune-inflammatory imbalance,and abnormal bone metabolism.Protein kinase C alpha(PKCA),Ras proto-oncogene(RAS),mitogen-activated protein kinase 3(ERK),ETS proto-oncogene 1(ETS1),and receptor activator of nuclear factor-κB ligand(RANKL)formed a signaling axis implicated in NONFH pathogenesis.BZF treatment alleviated joint inflammation,preserved trabecular bone morphology,reduced bone loss,and promoted bone repair.Mechanistically,BZF significantly downregulated the expression of PKCA,RAS,ERK,ETS1,and RANKL,improved blood circulation,and inhibited osteoclast activation while promoting osteoblast activation.Conclusion:BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis,thereby reversing dysregulated bone metabolism.

Objective:To investigate the bone marrow and peripheral blood cytological characteristics and prognosis in acute myeloid leukemia(AML)with FLT3-ITD mutation.Methods:A total of 106 newly diagnosed AML patients who were hospitalized in the First Affiliated Hospital of Xi'an JiaoTong University from January 2021 to December 2023 were collected,and divided into mutation group and non-mutation group according to the results of high-throughput sequencing of bone marrow specimens.The cytological characteristics of bone marrow smears and peripheral blood smears of patients in the two groups were analyzed at the time of initial diagnosis.The differences in the degree of hyperplasia,the proportion of leukemic cells,and the erythroblasts and megakaryocytes were compared between the two groups.What's more,the relationship between FLT3-ITD mutation status and characteristics of bone marrow and peripheral blood cells was analyzed.Results:AML patients with FLT3-ITD mutation accounted for 24.53％of the hospitalized AML patients during the same period.Patients with peripheral blood leukocyte counts＞30 × 109/L accounted for 53％,and＞100 × 109/L accounted for 15％in FLT3-ITD mutation group.Compared with non-mutation group,the peripheral blood leukocyte count was significantly higher in the mutation group(P＜0.001),and the degree of hemoglobin decline was milder(P＜0.05).The level of platelet was not significantly different between the two groups(P＞0.05).The highest proportion of FAB subtypes were M2a and M5a in mutation group,which accounted for 38％and 27％,respectively.The proportion of extreme hyperplasia of bone marrow in the mutation group was 38.46％,which was higher than 23.75％in the non-mutation group.The proportion of peripheral blood and bone marrow leukemic cells in patients with high-frequency mutation were significantly higher than those in patients with low-frequency mutation(both P＜0.01).The complete remission(CR)rate after the first induction chemotherapy was 38.46％and 65.00％in the mutation group and non-mutation group,respectively,and the CR rate after 2 courses of induction chemotherapy was 50.00％and 73.75％,respectively.Conclusion:The FLT3-ITD mutation results in high proliferation and rapid progression of the bone marrow feature in AML patients,with less suppression of normal erythropoiesis.Increased mutation frequency is accompanied by increased leukemic tumor burden in the bone marrow and circulation,and patients with FLT3-ITD mutation have a low response rate to early induction therapy.

Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.

Numerous studies on the formation and consolidation of memory have shown that memory processes are characterized by phase-dependent and dynamic regulation. Memory retrieval, as the only representation of memory content and an active form of memory processing that induces memory reconsolidation, has attracted increasing attention in recent years. Although the molecular mechanisms specific to memory retrieval-induced reconsolidation have been gradually revealed, an understanding of the time-dependent regulatory mechanisms of this process is still lacking. In this study, we applied a transcriptome analysis of memory retrieval at different time points in the recent memory stage. Differential expression analysis and Short Time-series Expression Miner (STEM) depicting temporal gene expression patterns indicated that most differential gene expression occurred at 48 h, and the STEM cluster showing the greatest transcriptional upregulation at 48 h demonstrated the most significant difference. We then screened the differentially-expressed genes associated with that met the expression patterns of those cluster-identified genes that have been reported to be involved in learning and memory processes in addition to dipeptidyl peptidase 9 (DPP9). Further quantitative polymerase chain reaction verification and pharmacological intervention suggested that DPP9 is involved in 48-h fear memory retrieval and viral vector-mediated overexpression of DPP9 countered the 48-h retrieval-induced attenuation of fear memory. Taken together, our findings suggest that temporal gene expression patterns are induced by recent memory retrieval and provide hitherto undocumented evidence of the role of DPP9 in the retrieval-induced reconsolidation of fear memory.
Animals ; Fear/physiology* ; Male ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics* ; Memory Consolidation/physiology* ; Time Factors ; Mental Recall/drug effects* ; Mice ; Gene Expression Profiling

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

A scoping review was performed to systematically search and summarize the clinical research in the treatment of dysmenorrhea with oral Chinese patent medicines. The oral Chinese patent medicines for treating dysmenorrhea in three major drug lists, guidelines, and textbooks were screened, and the relevant clinical trials were retrieved from eight Chinese and English databases. The key information of the included trials was extracted and visually analyzed. A total of 50 Chinese patent medicines were included, among which oral Chinese patent medicines for the dysmenorrhea patients with the syndrome of Qi stagnation and blood stasis accounted for the highest proportion, and the average daily cost varied greatly among Chinese patent medicines. A total of 150 articles were included, involving 22 Chinese patent medicines, among which Guizhi Fuling Capsules/Pills, Sanjie Zhentong Capsules, and Dan'e Fukang Soft Extract were the most frequently studied. These articles mainly reported randomized controlled trial(RCT), which mainly focused on the comparison of the intervention effect between Chinese patent medicines combined with western medicine and western medicine alone, and the sample size was generally 51-100 cases. The high-frequency outcome indicators belonged to nine domains such as effective rate, adverse reactions, and laboratory examinations. This study showed that oral Chinese patent medicines had advantages in the treatment of dysmenorrhea, and the annual number of related clinical trials showed an overall growing trend. However, there were still problems such as insufficient safety information and vague description of traditional Chinese medicine(TCM) syndromes types in the instructions of Chinese patent medicines. The available clinical research had shortcomings such as uneven distribution of Chinese patent medicines, limited research scale, poor methodological rigor, and insufficient standardization of outcome indicators. In the future, it is necessary to deepen the development of high-quality clinical research and improve the contents of the instructions to ensure the effectiveness and safety of the clinical application of oral Chinese patent medicines in the treatment of dysmenorrhea.
Dysmenorrhea/drug therapy* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Administration, Oral ; Nonprescription Drugs/administration & dosage*