Cardiovascular diseases (CVDs) have emerged as one of the leading causes of global mortality and health burden, with their prevalence and mortality rates demonstrating a persistent upward trend, thereby posing significant challenges to public health worldwide. Tanshinone IIA (Tan IIA), the principal lipophilic bioactive component isolated from Salvia miltiorrhiza Bunge, has gained substantial recognition in cardiovascular therapeutics. Accumulating evidence from recent investigations has demonstrated that Tan IIA exhibits multi-target pharmacological properties and modulates diverse signaling pathways in cardiovascular protection, positioning it as a promising candidate in natural product-based drug discovery. The therapeutic efficacy is mediated through multiple mechanisms, including but not limited to anti-atherosclerotic effects, lipid homeostasis regulation, anti-arrhythmic properties, myocardial functional enhancement, and hemodynamic stabilization. This comprehensive review systematically elucidates the molecular mechanisms and therapeutic targets underlying Tan IIA's cardio-protective effects, particularly focusing on its anti-inflammatory, antioxidant, anti-atherosclerotic, and myocardial preservation properties. Furthermore, we critically evaluate its current clinical applications and propose potential directions for future research to optimize its therapeutic potential in cardiovascular medicine.

South Asians are considered to be at higher risk of dyslipidaemia, a modifiable risk factor for cardiovascular diseases (CVDs). We aimed to identify protein targets for dyslipidaemia and CVDs among people with South Asian ancestry.

We used a two-sample mendelian randomisation (MR) approach, supplemented with MR-Egger, weighted median, colocalisation, and generalised MR (GMR), to evaluate the effect of 2800 plasma proteins on high/low/non-high-density lipoprotein cholesterol (HDL-C/LDL-C/non-HDL-C), total cholesterol, and triglycerides. Observational analyses were conducted on MR findings with strong colocalisation (posterior probability ≥ 80%) and GMR evidence. Univariate MR assessed lipid-associated proteins' effect on CVDs. Finally, we compared the effects of plasma proteins on lipids between South Asian and European populations.

We identified 29 genetically proxied proteins potentially causal to at least one lipid measure, 12 of which showed strong colocalisation and GMR evidence, including angiopoietin-related protein 3 (ANGPTL3), proprotein convertase subtilisin/kexin type 9 (PCSK9), and cadherin EGF LAG seven-pass G-type receptor 2 (CELSR2). Notably, PCSK9 demonstrated a stronger association with LDL-C in Europeans compared to South Asians (βEuropean = 0.37; 95% CI 0.36, 0.38, βSouth Asian = 0.16; 95% CI 0.11, 0.21). Observational analysis suggested statistically significant interaction between PCSK9 levels with LDL-C levels in South Asians with South Asians having a significantly lower effect compared to other ethnicities (PCSK9∗South Asian; β = -0.14; 95% CI -0.174, -0.107). Additionally, we showed that CELSR2 is also linked with coronary artery disease in South Asians.

Our study highlighted potential causal links between plasma proteins, dyslipidaemia, and CVDs in South Asians and highlighted protein targets, including CELSR2, PCSK9, ANGPTL3, and Apolipoprotein(a) (LPA). Notably, our study indicated that PCSK9 has a significantly weaker effect on LDL-C in South Asians than Europeans.

This work is supported by the British Heart Foundation Research Excellence Award (4) (RE/24/130023). IT and AR are supported by NIHR01 HL162300-02.

Osteoarthritis (OA) and cardiovascular disease (CVD) are two highly prevalent conditions that often coexist, especially in older adults. This paper explores the complex relationship between OA and CVD, highlighting their shared risk factors, such as aging, obesity, inflammation, and metabolic dysfunction. It delves into how age-related changes in both the joints and the cardiovascular system contribute to disease progression. The role of oxidative stress, chondrocyte senescence, and endothelial dysfunction are examined as key mechanisms linking these conditions. Pharmacological treatments commonly used in OA, including non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, are discussed in terms of their cardiovascular implications. In addition, the paper reviews current diagnostic approaches for CVD in OA patients and suggests that a more comprehensive and personalized strategy is needed. It also evaluates lifestyle and pharmacologic interventions that could benefit both joint and cardiovascular health. While evidence supports a connection between OA and increased cardiovascular risk, the paper emphasizes the need for further research to clarify causation, improve risk prediction, and guide multidisciplinary treatment strategies. Ultimately, integrating cardiovascular care into OA management can lead to better outcomes and quality of life for affected individuals.

Gas exchange measurements, such as oxygen uptake ( V ˙ O 2 ) and carbon dioxide output ( V ˙ C O 2 ), of cardiopulmonary exercise testing (CPET), are the key and gold standard for human cardiopulmonary functional evaluation. However, in terms of quality control, they are unstable and inaccurate. We used a metabolic simulator (MS) to detect measurement errors and enhance quality control.

In the Fuwai CPET laboratory, we performed CPET after systems had: (I) passed all the steps of regular system calibrations for flow and the partial pressure of O₂ and CO₂; and (II) passed the MS validation of V ˙ O 2 and V ˙ C O 2 at low, medium, and high metabolic rates (MRs) daily from 2014 to 2023 for eight different CPET carts/systems. The absolute percentage difference of the 1^st validation of both V ˙ O 2 and V ˙ C O 2 was calculated as follows: |[(measured - ideal) / ideal] × 100%|. A difference of <10% was set as the 1^st validation pass standard to run the laboratory, while a difference of ≥10% was classified as a 1^st validation failure. The absolute percentage difference of the 1^st validation among the eight carts/systems was compared using the Kruskal-Wallis H test. The rate of the 1^st validation failure, the number of validation days, and the median absolute percentage difference of the 1^st validation among the different CPET carts/systems were clustered using the hierarchical clustering method.

In total, we completed 1,810 validation days for the eight CPET carts/systems, and found a 10,860 absolute percentage difference of the 1^st validation of V ˙ O 2 and V ˙ C O 2 . The number of validation days completed by each cart/system and the 1^st validation failure rates were as follows: 8 (87.50%), 10 (90.00%), 54 (48.15%), 349 (43.27%), 20 (45.00%), 759 (21.21%), 525 (29.52%), and 85 (22.35%), respectively. The overall absolute percentage difference of the 1^st validation of each cart/system was 7.32% (P₂₅, P₇₅: 3.67%, 13.82%), 9.12% (P₂₅, P₇₅: 3.33%, 30.4%), 6.82% (P₂₅, P₇₅: 4.31%, 9.06%), 5.40% (P₂₅, P₇₅: 2.60%, 8.26%), 4.90% (P₂₅, P₇₅: 2.21%, 9.68%), 4.32% (P₂₅, P₇₅: 2.17%, 6.78%), 5.62% (P₂₅, P₇₅: 2.96%, 8.19%), and 5.35% (P₂₅, P₇₅: 2.55%, 7.81%), respectively. The Kruskal-Wallis H test results revealed significant differences among the eight carts/systems (H=274.86, P<0.001), and the pairwise comparisons showed that cart/system F had the lowest absolute percentage difference of 4.32% (P₂₅, P₇₅: 2.17%, 6.78%). The hierarchical cluster classified carts/systems A and B as one cluster, carts/systems C, E, and H as another cluster, and carts/systems D, F, and G as yet another cluster.

Using an MS can decrease measurement errors and variability for CPET. It can also improve the quality control of CPET.

This study is based on the theory of Holistic Integrative Physiology and Medicine (HIPM), which emphasizes a comprehensive understanding of the interplay of respiratory-circulatory-metabolic integration regulation. Within this theory, we recognize that left heart failure (LHF) and right heart failure (RHF) present distinct pathophysiological profiles, especially when assessed through cardiopulmonary exercise testing (CPET). We seek to elucidate the similarities and differences in CPET responses between LHF and RHF, thereby enhancing our understanding of their unique exercise pathophysiology.

In this retrospective study, we included 123 patients diagnosed with LHF and 101 patients with RHF, all of whom were treated at Fuwai Hospital between 2018 and 2023. Each patient underwent standard CPET, along with routine medical examinations. During the CPET, we calculated the key parameters, identified the presence of oscillatory breathing (OB), and assessed the occurrence of exercise-induced right-to-left shunting (R-LShunt) using standard methodologies. Additionally, a control group comprising 81 normal subjects (NS) also underwent CPET to provide a baseline for comparison. The data collected from all three groups-LHF patients, RHF patients, and NS-were then subjected to a comprehensive analysis. We used analysis of variance (ANOVA)-based statistical methods to analyze the differences in CPET parameters among these groups.

Peak oxygen uptake ( V ˙ O 2 ) in LHF [48.04±17.14 percentage of predicted (%pred)] and RHF (53.68±15.10 %pred) was significantly lower than in NS (85.37±14.01 %pred) (NS versus LHF and RHF, both P<0.001). Notably, the LHF demonstrated markedly lower exercise capacity in both peak (%pred) and anaerobic threshold (AT, %pred), but higher oxygen uptake efficiency plateau (OUEP, %pred) than the RHF group (P=0.008, 0.009, and <0.001, respectively). In the LHF group, OB manifestations were observed in 72 cases (59%), and in the RHF group, R-LShunt manifestations appeared in 64 cases (63%). Within the LHF subgroup, those with OB showed a significantly lower peak V ˙ O 2 (39.95±12.84 %pred) compared to those without OB (59.46±15.99 %pred, P<0.001). In the RHF group, peak V ˙ O 2 was also lower in the R-LShunt subgroup (50.1±12.52 %pred) compared to the no R-LShunt subgroup (59.87±17.24 %pred, P=0.001). Additionally, the R-LShunt group displayed an aberrant pattern of almost persistently decreased partial pressure of end-tidal carbon dioxide (PETCO₂) during CPET.

LHF patients exhibited lower exercise tolerance, in contrast to RHF patients, but showed a relatively small decrease in gas exchange capacity. Nevertheless, both LHF and RHF exhibited general functional limitations during CPET. Notably, patients exhibiting OB in the context of LHF, and those with R-LShunt in RHF, presented with even more pronounced functional limitations compared to their counterparts without these specific pathophysiological features.

Human sleep is characterized by alternating cycles of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, with cardiovascular regulation differing across sleep stages. Sleep deprivation (SD) is prevalent in modern societies and can be associated with worsened cardiovascular outcomes. Previous research on SD has primarily focused on epidemiological concerns and the effects of total SD, while clinical data on the hemodynamic impact of selective SD during different sleep stages remain scarce. This study aimed to investigate the hemodynamic alterations in healthy volunteers undergoing acute selective SD of either REM or slow-wave sleep (SWS) under polysomnography guidance. Additionally, the cardiovascular stability of healthy individuals under selective SD and its potential correlation with cardiovascular diseases were examined.

A total of 30 healthy volunteers (male:female ratio =1:1; age 26.27±4.479 years) were enrolled in this study. Each participant underwent a 3-day experimental protocol: the first night involved normal sleep, the second night selective SD (either SWS or REM), and the third night recovery sleep. After an initial night of normal sleep, participants were randomly assigned to either the REMSD group (n=15) or the SWSSD group (n=15). During the SD night, participants were repeatedly awakened during REM or SWS sleep, with a total of three full-night deprivations. Hemodynamic parameters were recorded synchronously during SD interventions, with measurements taken 5 minutes before and after the first SD event, as well as before sleep onset and upon awakening. The hemodynamic parameters assessed included heart rate (), stroke volume index, cardiac index, cardiac power index, total peripheral resistance index, systolic blood pressure, and diastolic blood pressure.

In the SWSSD group, after SD, the heart rate significantly increased, while stroke volume index decreased (t=-4.37 to 2.21; P<0.05), whereas cardiac index, cardiac power index, and total peripheral resistance index showed no significant changes (P>0.05). In the REMSD group, heart rate, cardiac index, and cardiac power index increased, while total peripheral resistance index decreased (t=-5.91 to 2.39; P<0.05), with no significant changes in stroke volume index (P>0.05). Additionally, both groups had a significantly higher post deprivation DBP than a pre-SD diastolic blood pressure (t=-2.660; P<0.05).

Healthy individuals demonstrated resilience to minor hemodynamic fluctuations. However, abrupt awakening from SWS could elevate the risk of cardiovascular events. Since REM sleep is associated with heightened sympathetic nervous system activity as compared to NREM sleep, selective REMSD may exacerbate cardiovascular physiological vulnerability during SD.

Chinese Clinical Trial Registry identifier: ChiCTR1900020622.

The prevalence of chronic diseases continues to rise. Personalized accurate intensity exercise based on an overall functional evaluation is a useful supplement to medication therapy. The aim of this study is to provide a simple method for detecting human function and evaluating the role of individualized exercise.

This retrospective cohort study included 30 patients with chronic diseases and 30 healthy subjects. A cardiopulmonary exercise test (CPET) was performed on all participants to determine their functional state. An individualized exercise intensity was set based on the CPET results, and exercise was performed for 30 minutes at that intensity. Pulse waves were recorded for 50 seconds each before exercise and at 10, 20, and 30 minutes after exercise. This study compared pulse wave parameters before and after exercise, including radial artery pulse pressure difference (ΔYP1), upstroke time (UT), upstroke time per cardiac cycle (UTCC), diastolic time to systolic time ratio (DT/ST), reflection index (RI), stiffness index (SI), and dicrotic wave rate.

Compared with healthy subjects, patients with chronic diseases were older and had greater body mass index (BMI) (P<0.001). All pulmonary function indicators of patients were significantly lower than those of healthy subjects (P<0.05). Patients had lower measured-to-estimated values for peak oxygen uptake (peak V ˙ O 2 ) (P<0.001). After eliminating the influence of age differences, the two-way repeated-measures analysis of variance demonstrated significant time difference for DT/ST (P=0.001), RI (P<0.001) and SI (P=0.005). Significant group differences were observed in ΔYP1 (P=0.03), UT (P=0.03) and SI (P=0.009). Patients have a lower incidence of dicrotic waves before and after exercise (P<0.001).

Personalized intensity exercise can reveal nonobvious functional decline and may benefit patients with chronic diseases, as well as the importance of pulse waves in the early detection of chronic diseases and reflecting patients' cardiovascular function state.

Oxidative stress and mitochondrial dysfunction play critical roles in the pathology of cardiovascular diseases. However, the effects of Astragaloside IV (As-IV) on mitochondrial function remain unclear. This study is aimed at evaluating the protective effects and mechanism of As-IV against H₂O₂-induced mitochondrial dysfunction in H9c2 cells. H9c2 cells were exposed to 200 μM H₂O₂ with or without As-IV. The level of apoptosis and reactive oxygen species (ROS) was measured by flow cytometry. Confocal microscopy and transmission electron microscopy were performed to detect the changes in mitochondrial membrane potential (MMP), mitochondrial morphology, and autophagosome. Mitochondrial dynamics and mitophagy-related proteins were measured by Western blot. The results indicated that As-IV decreased H₂O₂-induced apoptosis and ROS generation. Meanwhile, As-IV significantly increased MMP, exerted regulatory effects on mitochondrial dynamics, and ameliorated the damaged mitochondrial morphology in H₂O₂-injured cardiomyocytes. Additionally, As-IV decreased the amount of autophagosome and expressions of PINK1 and Parkin, but upregulated the expressions of PI3K, p-AKT, and p-mTOR proteins. However, cotreatment with LY294002 diminished the upregulation of PI3K, p-AKT, and p-mTOR induced by As-IV. In the study, we demonstrated that As-IV protected H9c2 cells from H₂O₂-induced mitochondrial dysfunction by inhibiting mitophagy, which might be related to the PI3K/AKT/mTOR pathway.

IgG4-related disease (IgG4-RD) is a chronic fibrotic inflammatory condition characterized by elevated serum IgG4 levels and the infiltration of IgG4-bearing plasma cells in affected organs. It can involve various organs, particularly large vessels. IgG4-related aortitis/periaortitis and periarteritis (IgG4-related PAO/PA) predominantly affect the abdominal aorta and iliac arteries, with a higher prevalence in elderly males. This condition exhibits distinct clinical, histologic, and radiological features compared to IgG4-RD without vascular involvement and other immune-associated vasculitides. IgG4-related PAO/PA diagnosis primarily relies on histopathological findings and imaging studies. Glucocorticoids (GCs) are the mainstay of treatment, often combined with immunosuppressants (IMs), while B- and T-cell-targeted therapies are under investigation. Although most patients respond well to treatment, the disease can be life-threatening due to complications such as myocardial infarction, aortic dissection, and aneurysmal rupture. Therefore, understanding these characteristics is crucial for clinicians to make accurate diagnoses and implement effective treatment strategies. This review provides a comprehensive overview of the current understanding of the pathogenesis, histopathological characteristics, clinical features, diagnosis, treatment, and prognosis of IgG4-related PAO/PA.

Behçet's disease (BD) is a systemic inflammatory disorder characterized by recurrent oral and genital ulcers, skin lesions, and ocular involvement, often presenting with retinal vasculitis as a severe complication. Although mixed cryoglobulinemia, typically associated with hepatitis C virus (HCV) infection, is well-documented in other autoimmune diseases, its coexistence with BD is exceedingly rare. This report details the case of a 56-year-old male presenting with BD complicated by HCV-related mixed cryoglobulinemia, manifesting as retinal vasculitis, purpuric skin lesions, and systemic vasculitis. Despite initial corticosteroid treatment, the patient required escalated therapy, including immunosuppressants and antiviral agents, to achieve disease stability. This case underscores the need for a multidisciplinary approach in managing BD with secondary cryoglobulinemia and highlights the complex interplay between autoimmune and viral-induced vasculitis. Our findings contribute to the literature by documenting a rare presentation of BD and providing insights into comprehensive treatment strategies for similar cases.