BackgroundAnthracycline-induced cardiotoxicity is a major factor affecting the long-term prognosis of cancer patients. Atrial arrhythmias, as common manifestations of cardiotoxicity, significantly impair quality of life and may compromise the effectiveness of anticancer therapy, representing a significant clinical challenge. Wenxin Keli (WXKL), a traditional Chinese medicine formulation with the effects of replenishing qi, nourishing yin, and promoting blood circulation, has demonstrated potential anti-arrhythmic benefits. However, high-quality evidence supporting its application in the field of cardio-oncology remains limited. This study aims to systematically evaluate the efficacy and safety of WXKL in patients with anthracycline-induced atrial arrhythmias.MethodsThis is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 152 eligible participants will be enrolled and randomly assigned to receive either WXKL or placebo for 3 months, followed by a 3-month follow-up period. The primary outcome is the proportion of patients free from atrial arrhythmias at 3 months, defined as the absence of atrial fibrillation (AF) episodes lasting ≥30 s or premature atrial contractions (PACs) ≥100 beats per 24 h on Holter monitoring. Secondary outcomes include AF burden, PACs count, echocardiographic parameters, cardiac biomarkers (cTnI and NT-proBNP), quality of life (FACT-G), functional status (ECOG), clinical symptom scores, and anxiety scores (SAS) at 3 and 6 months, as well as safety assessments.DiscussionThis study is designed to provide high-level clinical evidence for the use of WXKL in the treatment of anthracycline-induced atrial arrhythmias. By incorporating both PACs and AF as a composite endpoint, the study aims to more comprehensively capture the overall burden and dynamic progression of atrial arrhythmias, and to inform cardio-protective strategies during cancer therapy.Trial registration:http://itmctr.ccebtcm.org.cn/zh-CN, International Traditional Medicine Clinical Trial Registry Platform, ITMCTR2025000704.

Sepsis-induced cardiomyopathy (SIC), a severe complication of sepsis, is strongly associated with significantly increased patient mortality, yet targeted therapeutic strategies remain lacking. Emerging evidence has established ferroptosis, an iron-dependent, lipid peroxidation-mediated regulated cell death pathway, as a critical pathogenic mechanism underlying SIC. Iron metabolism dysregulation plays a central role in SIC. Although sepsis reduces circulating iron levels, iron paradoxically accumulates in myocardial tissues. This abnormal redistribution of iron leads to uncontrollable lipid peroxidation in cardiac tissue, ultimately aggravating myocardial injury. In recent years, the application of traditional Chinese medicine (TCM) in the treatment of sepsis has become increasingly widespread. Moreover, due to its multi-target and multi-pathway advantages, TCM has shown considerable potential in the intervention of ferroptosis. However, due to the lack of understanding of the precise molecular mechanism, the therapeutic potential of TCM and its active components in SIC has not been fully explored. This review summarizes the mechanism of ferroptosis in the pathogenesis of SIC, and comprehensively synthesizes the mechanism and application potential of TCM targeting ferroptosis for SIC intervention, aiming to provide a theoretical basis for the development of innovative treatment strategies and the improvement of prognosis of SIC.

BACKGROUND:Ibrutinib, a frontline therapy for chronic lymphocytic leukemia (CLL), has been associated with an approximately 10-fold increased risk of atrial fibrillation (AF) during treatment. Wenxin Granules, as a multi-component and multi-target drug, exert therapeutic effects on AF. METHODS:We conducted electrophysiological studies in ibrutinib-treated mice models to assess AF inducibility and the therapeutic efficacy of Wenxin Granules. Through network pharmacology screening, we identified potential molecular targets of Wenxin Granules. Subsequent proteomic analysis revealed specific targets through which Wenxin Granules may prevent ibrutinib-associated AF. These targets were further validated in mice model experiments. RESULTS:Our study demonstrates that Wenxin Granules treatment in mice significantly reduces AF inducibility, shortens AF duration, and attenuates pathological cardiac remodeling, including left atrial (LA) enlargement and myocardial fibrosis (p < 0.05). Through comprehensive analysis integrating proteomics with network pharmacology-predicted molecular targets, we systematically screened and identified 25 core therapeutic targets of Wenxin Granules, which are primarily associated with oxidative stress and calcium protein-related signaling pathways. The ibrutinib treatment group demonstrated significantly elevated expression of reactive oxygen species (ROS)-related proteins, including NOX2, NOX4, p22-phox, and XO. Additionally, ibrutinib substantially increased the expression of ox-CaMKII, p-CaMKII (Thr-286), and p-RyR2 (Ser2814), resulting in enhanced abnormal sarcoplasmic reticulum (SR) Ca2+ release, altered mitochondrial structures, and atrial fibrosis. Notably, Wenxin Granules administration reduced the expression of these proteins (p < 0.05). CONCLUSIONS:These findings demonstrate that Wenxin Granules can ameliorate the occurrence and progression of AF induced by ibrutinib treatment, thereby laying the groundwork for further research and potential clinical applications in AF therapy.

In oncology clinics, anthracyclines remain a cornerstone of cancer therapy. However, their clinical benefits are accompanied by substantial toxicities. As cumulative exposure increases and patient survival improves, the incidence of treatment-related adverse effects also increases, particularly those affecting the heart and kidneys. Rather than existing in isolation, these two forms of damage often interact: impaired cardiac function can accelerate renal injury through hemodynamic changes and neuroendocrine activation, whereas renal dysfunction further exacerbates cardiac injury via toxin accumulation and inflammation. This interaction leads to the well-recognized cardiorenal vicious cycle, which substantially limits the safe use of anthracyclines in clinical practice. Although dexrazoxane is currently the only approved cardioprotective agent, its renoprotective effect remains limited. Moreover, there are no clear guidelines or standardized strategies for preventing or managing anthracycline-induced cardiorenal toxicity. Therefore, a deeper understanding of the underlying mechanisms, along with effective monitoring and intervention strategies, is crucial for optimizing anthracycline therapy and improving patient survival. This review explores the pathological basis, molecular mechanisms, risk factors, monitoring approaches, and treatment strategies related to anthracycline-induced cardiorenal toxicity. It aims to develop a comprehensive strategy to protect both cardiac and renal function and to provide a scientific foundation for the development of safer and more effective cancer treatment regimens.

Chinese herbal medicines(CHMs)and their bioactive compounds have demonstrated clinical effectiveness in treating and managing membranous nephropathy(MN),as evidenced by a comprehensive analysis of clinical trials,systematic reviews,and meta-analyses.The bioactive constituents of CHMs exert their therapeutic effects by modulating various signaling pathways,resulting in antioxidant,anti-inflammatory,and antifibrotic properties,as well as the regulation of autophagy.In contrast to conventional single-target approaches,traditional Chinese medicines formulas and phytochemicals employ a multi-target therapeutic strategy for MN,which has shown significant clinical efficacy and the potential to mitigate or reverse the damage.This evaluation provides a foundation for a comprehensive clinical understanding of the protective role of CHMs in the context of MN,highlighting their benefits and prospects in addressing this condition.

Anthracycline chemotherapy leads to cardiotoxicity in patients with breast cancer. We performed a double-blind randomized controlled trial to assess the efficacy of crocin (crocin tablets) in reducing anthracycline-induced cardiotoxicity in breast cancer patients. Eligible patients were randomly assigned to receive either treatment with crocin tablets or placebo for 6 months. Primary efficacy outcome was the proportion of patients with a drop in left ventricular ejection fraction (LVEF) of at least 10 % from baseline until 6 months. We randomized 200 patients; 7 of them had no valid randomization as the change in chemotherapy scheme. A total of 193 eligible participants (mean [SD] age, 50.9 [9.6] years; all women) were randomly assigned to receive crocin tablets or placebo. The incidence of the primary efficacy outcome was 7.2 % (7/97) in the crocin group and 17.7 % (17/96) in the placebo group (P = 0.027). At 6 months, there were significant differences in the mean change of Nterminal pro-brain natriuretic peptide (NT-pro BNP) between the groups (3.06 [-25.18-6.95] vs. 3.06 [-4.85-24.98] pg/ml; P = 0.017). The changes in heart rate from baseline to 6 months showed a significant difference as the mean difference of -4.00 (95 %CI, -6.95 to -1.05) bpm (P = 0.008). Conclusively, among patients with breast cancer treated with anthracycline-based chemotherapy, crocin tablets reduced the incidence of LVEF reduction. This finding indicated that crocin tablets might be a safe and effective therapy to prevent the cardiotoxicity in this population. (Chictr.org.cn, ID Number: ChiCTR2000041134).

Increased cardiomyocyte-specific activation of the NLRP3 inflammasome contributes to the development of atrial fibrillation (AF). Berberine (BBR) exhibits numerous beneficial effects on the cardiovascular system. This study investigated how the NLRP3 inflammasome regulates susceptibility to hypertension-induced AF and the effects of BBR on this susceptibility. Blood pressure was monitored in mice using a tail pressure sensor device. AF was induced by burst stimulation of the esophagus. The target proteins of BBR were screened by network pharmacology, and molecular docking was performed. The changes in atrial tissue structure were observed by pathological tissue staining and transmission electron microscopy. Western blot analysis was used for protein verification. Intracellular Ca2+ release was detected by confocal laser microscopy and the IonOptix system. We found that in angiotensin II (Ang II)-induced AF, NLRP3 inflammasome activation was inhibited, ultimately inhibiting hypertensive AF susceptibility. In a recombinant adeno-associated virus 9 (rAAV9)-NLRP3 overexpression model, BBR mitigated the increase in systolic blood pressure and the development and progression of AF by inhibiting the NLRP3 inflammasome. This study provides hitherto undocumented evidence that the NLRP3 inflammasome acts as a critical regulator in the progression of Ang II-induced AF and that BBR may serve as a viable treatment for AF by inhibiting NLRP3.

Importance:Prehypertension increases the risk of developing hypertension and other cardiovascular diseases. Early and effective intervention for patients with prehypertension is highly important. Objective:To assess the efficacy of Tai Chi vs aerobic exercise in patients with prehypertension. Design, Setting, and Participants:This prospective, single-blinded randomized clinical trial was conducted between July 25, 2019, and January 24, 2022, at 2 tertiary public hospitals in China. Participants included 342 adults aged 18 to 65 years with prehypertension, defined as systolic blood pressure (SBP) of 120 to 139 mm Hg and/or diastolic BP (DBP) of 80 to 89 mm Hg. Interventions:Participants were randomized in a 1:1 ratio to a Tai Chi group (n = 173) or an aerobic exercise group (n = 169). Both groups performed four 60-minute supervised sessions per week for 12 months. Main Outcomes and Measures:The primary outcome was SBP at 12 months obtained in the office setting. Secondary outcomes included SBP at 6 months and DBP at 6 and 12 months obtained in the office setting and 24-hour ambulatory BP at 12 months. Results:Of the 1189 patients screened, 342 (mean [SD] age, 49.3 [11.9] years; 166 men [48.5%] and 176 women [51.5%]) were randomized to 1 of 2 intervention groups: 173 to Tai Chi and 169 to aerobic exercise. At 12 months, the change in office SBP was significantly different between groups by -2.40 (95% CI, -4.39 to -0.41) mm Hg (P = .02), with a mean (SD) change of -7.01 (10.12) mm Hg in the Tai Chi group vs -4.61 (8.47) mm Hg in the aerobic exercise group. The analysis of office SBP at 6 months yielded similar results (-2.31 [95% CI, -3.94 to -0.67] mm Hg; P = .006). Additionally, 24-hour ambulatory SBP (-2.16 [95% CI, -3.84 to -0.47] mm Hg; P = .01) and nighttime ambulatory SBP (-4.08 [95% CI, -6.59 to -1.57] mm Hg; P = .002) were significantly reduced in the Tai Chi group compared with the aerobic exercise group. Conclusions and Relevance:In this study including patients with prehypertension, a 12-month Tai Chi intervention was more effective than aerobic exercise in reducing SBP. These findings suggest that Tai Chi may help promote the prevention of cardiovascular disease in populations with prehypertension. Trial Registration:Chinese Clinical Trial Registry Identifier: ChiCTR1900024368.

Intracerebral hemorrhage (ICH), a common subtype of hemorrhagic stroke, often causes severe disability or death. ICH induces adverse events that might lead to secondary brain injury (SBI), and there is currently a lack of specific effective treatment strategies. To provide a new direction for SBI treatment post-ICH, the systematic review discussed how thrombin impacts secondary injury after ICH through several potentially deleterious or protective mechanisms. We included 39 studies and evaluated them using SYRCLE’s ROB tool. Subsequently, we explored the potential molecular mechanisms of thrombin-mediated effects on SBI post-ICH in terms of inflammation, iron deposition, autophagy, and angiogenesis. Furthermore, we described the effects of thrombin in endothelial cells, astrocytes, pericytes, microglia, and neurons, as well as the harmful and beneficial effects of high and low thrombin concentrations on ICH. Finally, we concluded the current research status of thrombin therapy for ICH, which will provide a basis for the future clinical application of thrombin in the treatment of ICH.

Cardio-oncology has emerged as a new translational and clinical field owing to the growing repertory of cancer therapy. To date, there is a lack of effective pharmacological therapy to target cardiotoxicity. Cardio-oncology, which began by investigating the negative effects of cancer medicines on cardiovascular system, has since grown to include research into the similarities between cardiovascular disease (CVD) and cancer. Thioredoxin domain-containing protein 5 (TXNDC5) belongs to the protein disulfide isomerase (PDI) family. Many diseases, including CVD and cancer, improperly express TXNDC5. This review provides a comprehensive analysis of the expression patterns of TXNDC5 in diseases. It outlines the processes via which TXNDC5 contributes to the advancement of malignant diseases such as CVD and cancer. Additionally, it summarizes prospective therapeutic approaches that can be used to target TXNDC5 for the treatment of these diseases. This will offer novel perspectives for enhancing anticancer therapy and advancing cardio-oncology research and drug development.

With the prolonged survival of individuals with cancer, the emergence of cardiovascular diseases (CVD) induced by cancer treatment has become a significant concern, ranking as the second leading cause of death among cancer survivors. This review explores three distinct types of programmed cell death (PCD): ferroptosis, cuproptosis, and PANoptosis, focusing on their roles in chemotherapy-induced cardiotoxicity. While ferroptosis and cuproptosis are triggered by excess iron and copper (Cu), PANoptosis is an inflammatory PCD with features of pyroptosis, apoptosis, and necroptosis. Recent studies reveal intricate connections among these PCD types, emphasizing the interplay between cuproptosis and ferroptosis. Notably, the role of intracellular Cu in promoting ferroptosis through GPX4 is highlighted. Additionally, ROS-induced PANoptosis is influenced by ferroptosis and cuproptosis, suggesting a complex interrelationship. This review provides insights into the molecular mechanisms of these PCD modalities and their distinct contributions to chemotherapy-induced cardiotoxicity. Furthermore, we discuss the potential application of cardioprotective drugs in managing these PCD types. This comprehensive analysis aims to advance the understanding, diagnosis, and therapeutic strategies for cardiotoxicity associated with cancer treatment.

BackgroundThe therapeutic effects of vitamin D supplementation on Coronavirus disease 2019 (COVID-19) aggravation remain controversial and inconclusive. To probe into this contentious issue, we performed the present meta-analysis of randomized controlled trials (RCTs).MethodsLiterature published up to June 2023 was retrieved from Cochrane Library, PubMed, Web of Science and Embase. RCTs assessing mortality, intensive care unit (ICU) admission, mechanical ventilation (MV), length of hospitalization (LOH), and inflammatory markers containing C-reactive protein (CRP), D-dimer, interleukin-6 (IL-6), lactate dehydrogenase (LDH) were included. 19 RCTs were involved in the analysis and were conducted subgroup analyses on the baseline COVID-19 severity and vitamin D administration.ResultsIn the severity subgroup, statistically significant effects in moderate to severe group were observed in ICU admission (OR 0.43, 95% CI 0.23, 0.80; p = 0.008), MV (OR 0.44, 95% CI 0.27, 0.72; p = 0.001) and LOH (SMD –0.49, 95% CI –0.92, −0.06; p = 0.027). In the administration subgroup, effects of ICU admission (OR 0.39, 95% CI 0.16, 0.97; p = 0.044), MV (OR 0.18, 95% CI 0.07, 0.46; p = 0.000) and LOH (SMD –0.50, 95% CI –0.96, −0.04; p = 0.034) were more pronounced in patients supplied with multiple-dose vitamin D than single-dose. Although the result of mortality showed no statistically significant effect, it indicated a reduced trend (OR 0.87, 95% CI 0.63, 1.12; p > 0.05). The results of inflammatory markers reached no statistical differences.ConclusionThis meta-analysis revealed that moderate to severe COVID-19 patients supplied with multiple doses of vitamin D were less apt to need ICU admission, mechanical ventilation and have shorter hospital stays.

AIMS:Atrial fibrillation (AF) has high mortality and morbidity rates. However, the intracellular molecular complexity of the atrial tissue of patients with AF has not been adequately assessed. METHODS AND RESULTS:We investigated the cellular heterogeneity of human atrial tissue and changes in differentially expressed genes between cells using single-cell RNA sequencing, fluorescence in situ hybridization, intercellular communication, and cell trajectory analysis. Using genome-wide association studies (GWAS) and proteomics, we discovered cell types enriched for AF susceptibility genes. We discovered eight different cell types, which were further subdivided into 23 subpopulations. In AF, the communication strength between smooth muscle cells (SMCs) and fibroblast (FB) 3 cells increased and the relevant signaling pathways were quite similar. Subpopulations of endothelial cells (ECs) are mainly involved in fibrosis through TXNDC5 and POSTN. AF susceptibility genes revealed by GWAS were especially enriched in neuronal and epicardial cells, FB3, and lymphoid (Lys) cells, whereas proteomic sequencing differential proteins were concentrated in FB3 cells and SMCs. CONCLUSIONS:This study provides a cellular landscape based on the atrial tissue of patients with AF and highlights intercellular changes and differentially expressed genes that occur during the disease process. A thorough description of the cellular populations involved in AF will facilitate the identification of new cell-based interventional targets with direct functional significance for the treatment of human disease.

Single-cell RNA sequencing (scRNA-seq) is a new technology that can be used to explore molecular changes in complex cell clusters at the single-cell level. Single-cell spatial transcriptomic technology complements the cell-space location information lost during single-cell sequencing. Coronary artery disease is an important cardiovascular disease with high mortality rates. Many studies have explored the physiological development and pathological changes in coronary arteries from the perspective of single cells using single-cell spatial transcriptomic technology. This article reviews the molecular mechanisms underlying coronary artery development and diseases as revealed by scRNA-seq combined with spatial transcriptomic technology. Based on these mechanisms, we discuss the possible new treatments for coronary diseases.

Intracerebral hemorrhage (ICH) is a stroke subtype characterized by non-traumatic rupture of blood vessels in the brain, resulting in blood pooling in the brain parenchyma. Despite its lower incidence than ischemic stroke, ICH remains a significant contributor to stroke-related mortality, and most survivors experience poor outcomes that significantly impact their quality of life. ICH has been accompanied by various complex pathological damage, including mechanical damage of brain tissue, hematoma mass effect, and then leads to inflammatory response, thrombin activation, erythrocyte lysis, excitatory amino acid toxicity, complement activation, and other pathological changes. Accumulating evidence has demonstrated that activation of complement cascade occurs in the early stage of brain injury, and the excessive complement activation after ICH will affect the occurrence of secondary brain injury (SBI) through multiple complex pathological processes, aggravating brain edema, and pathological brain injury. Therefore, the review summarized the pathological mechanisms of brain injury after ICH, specifically the complement role in ICH, and its related pathological mechanisms, to comprehensively understand the specific mechanism of different complements at different stages after ICH. Furthermore, we systematically reviewed the current state of complement-targeted therapies for ICH, providing a reference and basis for future clinical transformation of complement-targeted therapy for ICH.

Anthracyclines (ANTs) are a class of anticancer drugs widely used in oncology. However, the clinical application of ANTs is limited by their cardiotoxicity. The mechanisms underlying ANTs-induced cardiotoxicity (AIC) are complicated and involve oxidative stress, inflammation, topoisomerase 2β inhibition, pyroptosis, immunometabolism, autophagy, apoptosis, ferroptosis, etc. Ferroptosis is a new form of regulated cell death (RCD) proposed in 2012, characterized by iron-dependent accumulation of reactive oxygen species (ROS) and lipid peroxidation. An increasing number of studies have found that ferroptosis plays a vital role in the development of AIC. Therefore, we aimed to elaborate on ferroptosis in AIC, especially by doxorubicin (DOX). We first summarize the mechanisms of ferroptosis in terms of oxidation and anti-oxidation systems. Then, we discuss the mechanisms related to ferroptosis caused by DOX, particularly from the perspective of iron metabolism of cardiomyocytes. We also present our research on the prevention and treatment of AIC based on ferroptosis. Finally, we enumerate our views on the development of drugs targeting ferroptosis in this emerging field.

基于中医药理论,结合抗肿瘤药物及放疗、化疗引起心血管毒性相关的现代研究,认为肿瘤心脏病病位在心络,涉及肝、脾、肾,核心病机为"毒损心络".以"毒损"为病机关键,以"络虚"为发病基础.放射线(热)及抗肿瘤药物(寒)作为"外毒"蓄于心络,影响气血、津液的运行,日久化为瘀痰等"内毒".二者相互结合、相互转化,使"毒"结于心络而不解,发为肿瘤心脏病.

介绍邢雁伟教授论治肿瘤心脏病经验.邢雁伟教授于长期临证实践体悟中积累了丰富的经验,以寒毒为肿瘤心脏病的重要致病因素,提出"寒毒内侵,毒损心络"的病机,认为"心阳不振为本,寒毒损络为标".针对化疗引起的窦性心动过缓,治疗时以麻黄附子细辛汤加味辛温散寒、温阳通脉、安神定悸;对于化疗引起的心功能不全,治以四逆汤合真武汤加减温阳通脉、益气利水.邢教授临证中辨证清晰,用药灵活,正邪兼顾,临床疗效显著.

Ischemic heart disease (IHD) is currently one of the leading causes of death among cardiovascular diseases worldwide. In addition, blood reflow and reperfusion paradoxically also lead to further death of cardiomyocytes and increase the infarct size. Multiple evidences indicated that mitochondrial function and structural disorders were the basic driving force of IHD. We summed up the latest evidence of the basic associations and underlying mechanisms of mitochondrial damage in the event of ischemia/reperfusion (I/R) injury. This review then reviewed natural plant products (NPPs) which have been demonstrated to mitochondria-targeted therapeutic effects during I/R injury and the potential pathways involved. We realized that NPPs mainly maintained the integrality of mitochondria membrane and ameliorated dysfunction, such as improving abnormal mitochondrial calcium handling and inhibiting oxidative stress, so as to protect cardiomyocytes during I/R injury. This information will improve our knowledge of mitochondrial biology and I/R-induced injury’s pathogenesis and exhibit that NPPs hold promise for translation into potential therapies that target mitochondria.