Atherosclerosis (AS), the primary pathological contributor to cardiovascular diseases (CVDs), has increasingly affected younger populations due to modern dietary habits and sedentary lifestyles. Current diagnostic modalities, including ultrasound, MRI, and CT, primarily identify advanced lesions and inadequately evaluate plaque vulnerability, thereby hindering early detection. Conventional treatments, which involve long-term medications associated with side effects such as hepatic injury and surgical interventions that carry risks of restenosis and hemorrhage, underscore the urgent need for non-invasive, cost-effective early diagnostic methods and targeted therapies. Gut microbiota metabolites are pivotal in AS pathogenesis, with trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs) serving as functionally opposing biomarkers. TMAO is produced when gut bacteria, specifically Firmicutes and Proteobacteria, metabolize dietary choline and carnitine into trimethylamine (TMA), which the liver subsequently converts to TMAO via flavin-containing monooxygenase 3 (FMO3); TMAO is then excreted in urine. Variability in TMAO levels is influenced by marine food consumption and FMO3 modulation, which can be affected by genetics, age, and diet. Mechanistically, TMAO exacerbates AS by disrupting cholesterol metabolism, inducing endothelial dysfunction through the elevation of reactive oxygen species (ROS) and pro-inflammatory cytokines such as IL-6, and reducing nitric oxide levels. Additionally, TMAO activates NF-κB and NLRP3 pathways while enhancing platelet reactivity. Clinically, elevated TMAO levels correlate with early AS and serve as predictors of mortality in patients with stable coronary artery disease (CAD) and acute coronary syndrome (ACS), as well as major adverse cardiovascular events (MACE) in stroke patients. Conversely, SCFAs—namely acetate, propionate, and butyrate—are produced by gut bacteria such as Akkermansia muciniphila and Faecalibacterium prausnitzii through the fermentation of dietary fiber. These metabolites exert anti-AS effects: acetate aids in maintaining metabolic homeostasis; propionate protects endothelial function and reduces plaque area; and butyrate fortifies intestinal barriers while suppressing inflammation. Furthermore, SCFAs cross-regulate bile acid metabolism, thereby influencing TMAO levels, and antagonize the pro-inflammatory and lipid-disrupting effects of TMAO. The use of TMAO and SCFAs as standalone biomarkers is constrained by limitations. TMAO lacks specificity, while SCFA levels fluctuate based on gut microbiota and dietary intake. Traditional AS risk assessment tools, which include clinical indicators, imaging techniques, and single biomarkers such as CRP, LDL-C, and ASCVD scores, overlook gut metabolism and demonstrate inadequate performance in younger populations. This review advocates for an “antagonistic-complementary” combined strategy: utilizing acetate and TMAO for early AS, propionate and TMAO for progressive AS, and butyrate and TMAO for advanced AS, addressing endothelial dysfunction, lipid deposition, and plaque stability/thrombosis risk, respectively. For clinical application, standardization of detection methods is crucial; liquid chromatography-mass spectrometry (LC-MS) is the gold standard, necessitating a unified sample pretreatment protocol, such as extraction with 1% formic acid in methanol. Additionally, dried blood spots (DBS) facilitate non-invasive testing, provided that dietary controls are implemented prior to detection, including a 12-hour fast and avoidance of high-choline and high-fiber foods. Existing challenges encompass the absence of standardized systems, limited large-scale validation, and ambiguous interactions with conditions such as hypertension. The authors’ team has previously established connections between gut metabolites and AS, including the reduction of TMAO as a preventive measure for AS, thereby reinforcing this proposed strategy. Future research should prioritize standardization, the development of machine learning-optimized models, validation of interventions, and the exploration of multi-omics-based “gut microbiota-metabolite-vascular” networks. In conclusion, the combined detection of TMAO and SCFAs offers a novel framework for AS risk assessment, facilitating early diagnosis and targeted interventions while enhancing the integration of gut metabolism into cardiovascular disease management.

Atherosclerosis (AS), the primary pathological contributor to cardiovascular diseases (CVDs), has increasingly affected younger populations due to modern dietary habits and sedentary lifestyles. Current diagnostic modalities, including ultrasound, MRI, and CT, primarily identify advanced lesions and inadequately evaluate plaque vulnerability, thereby hindering early detection. Conventional treatments, which involve long-term medications associated with side effects such as hepatic injury and surgical interventions that carry risks of restenosis and hemorrhage, underscore the urgent need for non-invasive, cost-effective early diagnostic methods and targeted therapies. Gut microbiota metabolites are pivotal in AS pathogenesis, with trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs) serving as functionally opposing biomarkers. TMAO is produced when gut bacteria, specifically Firmicutes and Proteobacteria, metabolize dietary choline and carnitine into trimethylamine (TMA), which the liver subsequently converts to TMAO via flavin-containing monooxygenase 3 (FMO3); TMAO is then excreted in urine. Variability in TMAO levels is influenced by marine food consumption and FMO3 modulation, which can be affected by genetics, age, and diet. Mechanistically, TMAO exacerbates AS by disrupting cholesterol metabolism, inducing endothelial dysfunction through the elevation of reactive oxygen species (ROS) and pro-inflammatory cytokines such as IL-6, and reducing nitric oxide levels. Additionally, TMAO activates NF-κB and NLRP3 pathways while enhancing platelet reactivity. Clinically, elevated TMAO levels correlate with early AS and serve as predictors of mortality in patients with stable coronary artery disease (CAD) and acute coronary syndrome (ACS), as well as major adverse cardiovascular events (MACE) in stroke patients. Conversely, SCFAs—namely acetate, propionate, and butyrate—are produced by gut bacteria such as Akkermansia muciniphila and Faecalibacterium prausnitzii through the fermentation of dietary fiber. These metabolites exert anti-AS effects: acetate aids in maintaining metabolic homeostasis; propionate protects endothelial function and reduces plaque area; and butyrate fortifies intestinal barriers while suppressing inflammation. Furthermore, SCFAs cross-regulate bile acid metabolism, thereby influencing TMAO levels, and antagonize the pro-inflammatory and lipid-disrupting effects of TMAO. The use of TMAO and SCFAs as standalone biomarkers is constrained by limitations. TMAO lacks specificity, while SCFA levels fluctuate based on gut microbiota and dietary intake. Traditional AS risk assessment tools, which include clinical indicators, imaging techniques, and single biomarkers such as CRP, LDL-C, and ASCVD scores, overlook gut metabolism and demonstrate inadequate performance in younger populations. This review advocates for an “antagonistic-complementary” combined strategy: utilizing acetate and TMAO for early AS, propionate and TMAO for progressive AS, and butyrate and TMAO for advanced AS, addressing endothelial dysfunction, lipid deposition, and plaque stability/thrombosis risk, respectively. For clinical application, standardization of detection methods is crucial; liquid chromatography-mass spectrometry (LC-MS) is the gold standard, necessitating a unified sample pretreatment protocol, such as extraction with 1% formic acid in methanol. Additionally, dried blood spots (DBS) facilitate non-invasive testing, provided that dietary controls are implemented prior to detection, including a 12-hour fast and avoidance of high-choline and high-fiber foods. Existing challenges encompass the absence of standardized systems, limited large-scale validation, and ambiguous interactions with conditions such as hypertension. The authors’ team has previously established connections between gut metabolites and AS, including the reduction of TMAO as a preventive measure for AS, thereby reinforcing this proposed strategy. Future research should prioritize standardization, the development of machine learning-optimized models, validation of interventions, and the exploration of multi-omics-based “gut microbiota-metabolite-vascular” networks. In conclusion, the combined detection of TMAO and SCFAs offers a novel framework for AS risk assessment, facilitating early diagnosis and targeted interventions while enhancing the integration of gut metabolism into cardiovascular disease management.

Plant-derived exosome-like nanovesicles (PELNs), characterized by a natural lipid bilayer membrane, have rapidly emerged as a prominent research frontier in medicine owing to their unique biological properties and robust therapeutic potential. This review comprehensively examines the biological profiles, mechanistic functions, and recent engineering advancements of PELNs. In terms of composition, PELNs are uniquely enriched in plant-specific glycolipids, phosphatidylserine, secondary metabolites, and highly stable 2'-O-methylated miRNAs. This distinct molecular makeup endows them with exceptional biocompatibility, negligible immunogenicity, and the capacity for cross-species molecular communication. Mechanistically, PELNs demonstrate profound anti-inflammatory efficacy by suppressing the NF-κB and NLRP3 inflammasome pathways. They also serve as potent immune modulators, driving macrophage M1/M2 polarization and regulating T cell activity. Additionally, PELNs exhibit promising antitumor capabilities, targeting malignancies via reactive oxygen species (ROS) induction, TRAIL pathway activation, and tumor microenvironment remodeling. Crucially, the plant miRNAs encapsulated within PELNs remain highly stable in the gastrointestinal tract, allowing them to selectively alter gene expression in specific gut microbiota communities. This interaction deeply influences host immunity and metabolism, highlighting the vital role in cross-species regulation. Advancements in bioengineering have further expanded the clinical utility of PELNs. Targeted delivery efficiency can be significantly amplified via surface functionalization (e.g., folate and RGD sequences) and state-of-the-art drug loading technologies such as sonication and electroporation. Consequently, engineered PELNs surpass traditional synthetic nanocarriers in penetrating natural physiological barriers, particularly for oral and transdermal drug administration. Despite these advantages, clinical translation is currently hindered by the lack of standardized isolation protocols, challenges in scalable manufacturing, and the need for robust quality control frameworks. Looking forward, the integration of multi-omics approaches and AI-driven “molecular fingerprinting”—coupled with the design of synthetic biomimetic vesicles—will be instrumental in overcoming these bottlenecks, ultimately establishing PELNs as a next-generation platform for precision medicine and targeted nanotherapeutic delivery.

Purpose To explore the characteristics of left and right ventricular myocardial strain in hypertensive heart disease(HHD)assessed by magnetic resonance feature tracking technique,and to assess the effect of HHD on right ventricular function.Materials and Methods A retrospective analysis was performed on 40 patients with HHD at the General Hospital of Ningxia Medical University from January 2022 to August 2023.Among these 40 HHD patients,19 presented with a left ventricular ejection fraction(LVEF)of≥50%,and 21 presented with an LVEF of<50%.Additionally,25 healthy controls were enrolled.All subjects underwent cardiac magnetic resonance imaging.The cine sequence images were imported into cardiac post-processing analysis software(QIR suite software).The left ventricular radial strain(LVRS),left ventricular circumferential strain(LVCS),left ventricular longitudinal strain(LVLS)and right ventricular longitudinal strain(RVLS)were measured,and left and right ventricular strain parameters of the three groups were analyzed statistically.Results The absolute values of LVRS,LVCS,LVLS and RVLS in the HHD group with LVEF<50%were lower than those in the normal control group(t=7.48,-12.69,-8.19,-6.32,all P<0.001)and those in the HHD group with LVEF≥50%(t=5.97,-8.88,-4.50,-4.90,all P<0.001);the area under the curve values of LVRS,LVCS,LVLS and RVLS for distinguishing HHD from normal controls were 0.804,0.785,0.829,0.832,respectively,and the cut-off values of LVRS,LVCS,LVLS and RVLS were 22.9%,-10.0%,-11.9%and-18.7%,respectively.Conclusion Magnetic resonance feature tracking technique can detect left and right ventricular myocardial dysfunction in HHD at an early stage and can provide a new basis for evaluating cardiac function.

In recent years,the incidence and mortality rates of hepatocellular carcinoma in China have gradually become close to each other,reflecting persistent limitations in current diagnostic and therapeutic strategies.Given the close association between hepatocellular carcinoma development and the progression of precancerous lesions,the expert panel released the first edition of the Multidisciplinary Experts Consensus on Diagnosis and Treatment of Precancerous Lesions of Hepatocellular Carcinoma in 2020 and updated it in 2023,aiming to advance early-intervention strategies and improve overall patient survival rates.This article provides an in-depth interpretation of the key imaging diagnostic points outlined in the consensus,aiming to offer radiologists at all levels with a robust reference for early identification and diagnosis of hepatocellular carcinoma precancerous lesions,thereby facilitating critical support for timely patient intervention and treatment.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Aim To investigate the mechanism of Guanxinning injection regulating cardiac immune mi-croenvironment to improve myocardial infarction in mice.Methods In this study,MI model was estab-lished by permanent ligation of left anterior descending coronary artery in mice.The mice were divided into five groups:sham operation group,model group,Guanxinning injection low dose group,Guanxinning in-jection high dose group and positive drug captopril group.Hearts were weighed,heart tissues were collect-ed,and Masson staining was used for pathological anal-ysis of heart tissues;immunofluorescence staining was used to detect apoptosis and CCL21 expression in the infarct border zone;flow cytometry was used to detect the proportion of immune cells in myocardial ischemia tissues and lymph nodes;PCR was used to detect CCL21 expression in heart and in vitro human lymphat-ic endothelial cells(HLEC).Results Compared with the model group,the low and high dose groups of Guanxinning injection significantly improved cardiac hypertrophy.Apoptosis in the border zone of myocardi-al infarction was reduced in the low and high dose groups of Guanxinning injection and captopril group.Compared with the model group,the proportion of leu-kocytes in the infarct border zone was dreduced and the proportion of CD4+T cells,Treg cells,and CD8+T cells in the mediastinal lymph nodes and infarct border zone of the heart was regulated in the low and high dose groups of Guanxinning injection;CCL21 secretion by the heart and lymphatic vessels increased.Conclu-sions Guanxinning injection can significantly improve cardiac hypertrophy and fibrosis in MI mice,reduce ap-optosis in the infarct border zone,and play a role in an-ti-myocardial ischemia injury by promoting CCL21 ex-pression in lymphatic vessels to regulate the proportion of mediastinal lymph nodes and cardiac T cells after myocardial infarction.

Objectives:To investigate the incidence and related risk factors of mid-term postoperative cognitive impairment by a single cognitive function test among heart transplant recipients.Methods:The heart transplant recipients who visited our heart transplant outpatient department from May to October of 2019 were recruited and received cognitive function test.Their heart transplantation,anesthesia,cardiopulmonary bypass and immunosuppressive therapy were performed by the same heart transplant team.Mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)were used to test the study population and diagnose cognitive impairment.The patients were divided into cognitive impairment group and non-cognitive impairment group,and the clinical characteristics,perioperative characteristics of heart transplantation,hospital outcomes and donor characteristics were compared between the two groups.After excluding those with missing data(n=34),48 patients in the cognitive impairment group and 50 patients in the non-cognitive impairment group were analyzed.Univariate and multivariate logistic regression were used to analyze the potential influencing factors of cognitive impairment diagnosed by a single assessment after heart transplantation.Results:The median time of cognitive test after surgery was 2(1,4)years.The incidence of mid-term postoperative cognitive impairment by a single test among heart transplant recipients was 50.0%(66/132).Compared with the non-cognitive impairment group,patients in the cognitive impairment group were older at heart transplant([40.2±13.4]years vs.[46.4±11.0]years)and at cognitive test([42.3±13.0]years vs.[49.2±11.2]years),with a higher proportion of males(68.0%vs.87.5%),a higher proportion of those with lower education(less than high school)(31.9%vs.63.8%),and a longer postoperative hospital stay(32.0[26.0,38.8]d vs.38.0[20.3,50.0]d),and the differences between groups were statistically significant(all P<0.05).Multivariate logistic regression analysis showed that older age at cognitive test(OR=1.067,95%CI:1.019-1.117,P=0.005),longer postoperative in-hospital stay(OR=1.051,95%CI:1.006-1.097,P=0.025)were associated with higher risk of mid-term postoperative cognitive impairment by a single test,while the education level higher than high school was an independent protective factor(OR=0.132,95%CI:0.029-0.607,P=0.009)of mid-term postoperative cognitive impairment.Conclusions:The incidence of mid-term postoperative cognitive impairment by a single test among heart transplant recipients is high.Patients with an older age,low education level,long postoperative in-hospital stay face increased risk of mid-term postoperative cognitive impairment,these patients need to be monitored for cognitive function during follow up to achieve early recognition and treatment of cognitive decline.

Objectives:To investigate the incidence and related risk factors of mid-term postoperative cognitive impairment by a single cognitive function test among heart transplant recipients.Methods:The heart transplant recipients who visited our heart transplant outpatient department from May to October of 2019 were recruited and received cognitive function test.Their heart transplantation,anesthesia,cardiopulmonary bypass and immunosuppressive therapy were performed by the same heart transplant team.Mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)were used to test the study population and diagnose cognitive impairment.The patients were divided into cognitive impairment group and non-cognitive impairment group,and the clinical characteristics,perioperative characteristics of heart transplantation,hospital outcomes and donor characteristics were compared between the two groups.After excluding those with missing data(n=34),48 patients in the cognitive impairment group and 50 patients in the non-cognitive impairment group were analyzed.Univariate and multivariate logistic regression were used to analyze the potential influencing factors of cognitive impairment diagnosed by a single assessment after heart transplantation.Results:The median time of cognitive test after surgery was 2(1,4)years.The incidence of mid-term postoperative cognitive impairment by a single test among heart transplant recipients was 50.0%(66/132).Compared with the non-cognitive impairment group,patients in the cognitive impairment group were older at heart transplant([40.2±13.4]years vs.[46.4±11.0]years)and at cognitive test([42.3±13.0]years vs.[49.2±11.2]years),with a higher proportion of males(68.0%vs.87.5%),a higher proportion of those with lower education(less than high school)(31.9%vs.63.8%),and a longer postoperative hospital stay(32.0[26.0,38.8]d vs.38.0[20.3,50.0]d),and the differences between groups were statistically significant(all P<0.05).Multivariate logistic regression analysis showed that older age at cognitive test(OR=1.067,95%CI:1.019-1.117,P=0.005),longer postoperative in-hospital stay(OR=1.051,95%CI:1.006-1.097,P=0.025)were associated with higher risk of mid-term postoperative cognitive impairment by a single test,while the education level higher than high school was an independent protective factor(OR=0.132,95%CI:0.029-0.607,P=0.009)of mid-term postoperative cognitive impairment.Conclusions:The incidence of mid-term postoperative cognitive impairment by a single test among heart transplant recipients is high.Patients with an older age,low education level,long postoperative in-hospital stay face increased risk of mid-term postoperative cognitive impairment,these patients need to be monitored for cognitive function during follow up to achieve early recognition and treatment of cognitive decline.

In clinical practice,the diagnosis of hepatocellular carcinoma primarily relies on imaging findings.For cases with atypical imaging features or insufficient diagnostic specificity,pathological analysis remains essential.With the advancement of precision medicine,research focus has expanded from pure diagnostic evaluation to therapeutic efficacy prediction.Imaging-based prognostic biomarkers have emerged as a key research frontier in hepatocellular carcinoma management.Although accurate diagnosis remains paramount,current investigations increasingly prioritize the identification of biomarkers for treatment response prediction and outcome stratification.Recent studies demonstrate that radiological characteristics not only reflect tumor heterogeneity but also carry prognostic implications for hepatocellular carcinoma.These imaging biomarkers enable non-invasive outcome prediction and provide objective evidence to optimize therapeutic decision-making.This comprehensive review summarizes MRI-derived imaging features associated with hepatocellular carcinoma prognosis,aiming to guide personalized treatment strategies and ultimately improve survival outcomes for hepatocellular carcinoma patients.