Coronary microembolism (CME) is commonly seen in the peri-procedural period of Percutaneous Coronary Intervention (PCI), where local platelet activation and endothelial cell inflammation crosstalk may lead to micro thrombus erosion and rupture, with serious consequences. Qihuang Zhuyu Formula (QHZYF) is a Chinese herbal compound with high efficacy against coronary artery disease, but its antiplatelet mechanism is unclear. This study aimed to elucidate the effects and mechanisms of QHZYF on sodium laurate-induced CME using network pharmacology and in vitro and in vivo experiments. We employed high-performance liquid chromatography mass spectrometry to identify the main components of QHZYF. Network pharmacology analysis, molecular docking and surface plasmon resonance (SPR) were utilized to predict the primary active components, potential therapeutic targets, and intervention pathways mediating the effects of QHZYF on platelet activation. Next, we pretreated a sodium laurate-induced minimally invasive CME rat model with QHZYF. In vivo experiments were performed to examine cardiac function in rats, to locate coronary arteries on heart sections to observe internal microthrombi, to extract rat Platelet-rich plasma (PRP) for adhesion assays and CD62p and PAC-1 (ITGB3/ITGA2B) flow assays, and to measure platelet-associated protein expression in PRP. In vitro clot retraction and Co-culture of HUVECs with PRP were performed and the gene pathway was validated through flow cytometry and immunofluorescence. Combining UPLC-Q-TOF/MS technology and database mining, 78 compounds were finally screened as the putative and representative compounds of QHZYF, with 75 crossover genes associated with CME. QHZYF prevents CME mainly by regulating key pathways of the inflammation and platelets, including Lipid and atherosclerosis, Fluid shear stress, platelet activation, and PI3K-Akt signaling pathways. Five molecules including Calyson, Oroxin A, Protosappanin A,Kaempferol and Geniposide were screened and subjected to molecular docking and SPR validation in combination with Lipinski rules (Rule of 5, Ro5). In vivo experiments showed that QHZYF not only improved myocardial injury but also inhibited formation of coronary microthrombi. QHZYF inhibited platelet activation by downregulating expression of CD62p receptor and platelet membrane protein αIIbβ3 and reduced the release of von Willebrand Factor (vWF), Ca²⁺ particles and inflammatory factor IL-6. Further analysis revealed that QHZYF inhibited the activation of integrin αIIbβ3, via modulating the PI3K/Akt pathways. In in vitro experiments, QHZYF independently inhibited platelet clot retraction. Upon LPS induction, the activation of platelet membrane protein ITGB3 was inhibited via the PI3K/Akt pathway, revealing an important mechanism for attenuating coronary microthrombosis. We performed mechanistic validation using PI3K inhibitor LY294002 and Akt inhibitor MK-2206 to show that QHZYF inhibited platelet membrane protein activation and inflammation to improved coronary microvessel embolism by regulating PI3K/Akt/αIIbβ3 pathways, mainly by inhibiting PI3K and Akt phosphorylation. QHZYF interferes with coronary microthrombosis through inhibition of platelet adhesion, activation and inflammatory crosstalk, thus has potential in clinical anti-platelet applications. Calyson, Oroxin A, Protosappanin A, Kaempferol and Geniposide may be the major active ingredient groups of QHZYF that alleviate coronary microthrombosis.

The findings of the 2021 Global Burden of Disease (GBD) study can offer valuable insights for the development of screening and prevention strategies targeting ischemic heart disease (IHD). We aim to investigate trends in IHD incidence, mortality, and disability-adjusted life years (DALYs), while exploring associated risk factors for IHD-associated death from 1990 to 2021. The cross-sectional study utilized data from the GBD 2021, covering 204 countries and regions. The analysis included individuals aged 55 and above. We analyzed the trends in IHD incidence, all cause and cause-specific deaths, DALYs, and corresponding estimated annual percentage changes (EAPCs) from 1990 to 2021. These indicators were further stratified by geographical region, country, age group, gender, and sociodemographic index (SDI). The global incidence rate, mortality rate, and DALYs rate for individuals aged 55 and above with IHD have shown a decreasing trend. However, the number of incident cases, death cases, and DALYs has been increasing from 1990 to 2021. Both the high-middle and high SDI regions exhibit a significant decline in these rates from 1990 to 2021. However, the low SDI, low-middle SDI, and middle SDI regions show less noticeable changes. The region with low-middle SDI experiences the largest increase in mortality rate (EAPC: 0.38; 95%CI, 0.33–0.44) and DALYs rate (EAPC: 0.17; 95%CI, 0.12–0.22). The region with middle SDI experiences the largest increase in incidence rate (EAPC: 0.37; 95%CI, 0.27–0.46). Regionally, East Asia exhibits the greatest increase in incidence rate (EAPC: 0.94; 95% CI, 0.79–1.10), mortality rate (EAPC: 1.68; 95% CI, 1.40–1.94), and DALYs rate (EAPC: 0.94; 95% CI, 0.69–1.20). Among the 12 risk factors associated with mortality from IHD, high systolic blood pressure, dietary risks, high low-density lipoprotein (LDL) cholesterol levels, and air pollution are identified as the primary contributors to global mortality. This study reveals that in high SDI regions, the incidence, mortality, and DALYs rate of IHD are declining. Conversely, in low to middle SDI regions, the disease burden of IHD is increasing. It highlights global inequality in IHD burden. Recommendations include early screening, risk management, and strengthening primary care, especially in middle and low SDI regions. Countries should also invest in environmental governance and air pollution control. Future research should focus on evaluating the effects of health policies in different countries, exploring the impact of socio-economic and cultural factors on the burden of IHD, and developing big data-based prediction models to optimize resource allocation and intervention strategies.

Objectives: Previous studies have shown that there may be a positive correlation between serum uric acid levels and hyperthyroidism. However, the relationship between thyroid function and serum uric acid in healthy people is unclear. This study analyzed the relationship between impaired thyroid hormone sensitivity and serum uric acid levels, and presented them in quantitative form. Research design and methods: This is a cross-sectional study of 4460 adults (male: 2300; female: 2160) who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2010. Parameters representing central sensitivity to thyroid hormones were calculated as: thyroid feedback quantile-based index (TFQI_FT4), thyroid stimulating hormone index (TSHI), and total thyroxine (T4) resistance index (TT4RI); Peripheral sensitivity to thyroid hormone was evaluated by FT3/FT4 ratio. In addition, we have innovated total triiodothyronine (T3) resistance index (TT3RI) and TFQI_FT3 indexes based on FT3 and TSH. Multiple linear regression models were used to evaluate the correlation between thyroid resistance index and serum uric acid, and the results were presented graphically as smooth curve fittings. Results: Higher levels of serum uric acid were associated with decreased sensitivity to thyroid hormones in euthyroid individuals. In conjunction with an increase in the thyroid hormone sensitivity index value, uric acid levels gradually increased as well. Furthermore, we found a segmented relationship between TT3RI and serum uric acid changes. The saturation and threshold analyses indicated that 18.85 was the turning point (logarithmic likelihood ratio test = 0.036). When TT3RI < 18.85, the relationship between serum uric acid and TT3RI was not significant [β(95% CI) 0.47 (− 0.05, 1.00), P = 0.077], but when TT3RI > 18.85, there was a significant rise in serum uric acid with an increase in TT3RI [β(95% CI) 3.94 (0.94, 6.95), P = 0.010]. A further finding of the interaction test was that impaired thyroid hormone sensitivity and uric acid changes vary among different age groups and BMI levels. Conclusions: Decreased sensitivity to thyroid hormones was associated with high levels of serum uric acid in people with normal thyroid function. The interaction test shows that different age groups and BMI groups impact the association between impaired thyroid hormone sensitivity and serum uric acid. Furthermore, smooth curve fitting revealed a segmental relationship between TT3RI and serum uric acid levels.

At present, due to the limitations of drug therapy targets for atherosclerosis, some patients fail to achieve satisfactory efficacy. Cholesterol efflux dysfunction and endothelial cell inflammation are considered to be important factors in the development of atherosclerosis. Peroxisome proliferator‐activated receptor gamma (PPARγ), a promising therapeutic target for atherosclerosis, plays a dual role in regulating cholesterol efflux and endothelial cell inflammation. However, the use of PPARγ agonist in clinical practice is greatly limited as it could lead to water and sodium retention and hence result in congestive heart failure. Qihuang Zhuyu Formula (QHZYF) is a hospital preparation of Jiangsu Province Hospital of Chinese Medicine which has definite effect in the treatment of atherosclerosis, but its pharmacological mechanism has not been clear. In this study, we successfully predicted that QHZYF might regulate cholesterol efflux and endothelial inflammation via targeting PPARγ‐mediated PPARγ/LXRα/ABCA1‐ABCG1 and PPARγ/NF‐κB p65 pathways by using UPLC‐Q‐TOF/MS, network pharmacology, bioinformatics analysis, and molecular docking technology. Subsequently, we confirmed in vivo that QHZYF could attenuate atherosclerosis in ApoE^−/− mice and regulate the expression levels of related molecules in PPARγ/LXRα/ABCA1‐ABCG1 and PPARγ/NF‐κB p65 pathways of ApoE^−/− mice and C57BL/6 wild‐type mice. Finally, in in vitro experiments, we found that QHZYF could reduce lipid content and increase cholesterol efflux rate of RAW 264.7 cells, inhibit the inflammatory response of HUVECs, and regulate the expression levels of related molecules in the two pathways. In addition, the above effects of QHZYF were significantly weakened after PPARγ knockdown in the two kinds of cells. In conclusion, our study revealed that QHZYF attenuates atherosclerosis via targeting PPARγ‐mediated PPARγ/LXRα/ABCA1‐ABCG1 and PPARγ/NF‐κB p65 pathways to regulate cholesterol efflux and endothelial cell inflammation. More importantly, our study offers a promising complementary and alternative therapy which is expected to make up for the limitation of current drug treatment methods and provide a valuable reference for new drugs development in the future.

Background: Soluble Klotho (S-Klotho) is an anti-aging protein mainly secreted by the kidneys. Hyperuricemia is prevalent among middle-aged and elderly individuals, which affects the development of various chronic diseases. However, there are relatively few studies investigating the association between plasma S-Klotho levels and hyperuricemia in middle-aged and elderly individuals. This study sought to clarify the relationship between S-Klotho and the risk of hyperuricemia in middle-aged and elderly people. Methods: During 2007–2016, a total of 50,588 people participated in the National Health and Nutrition Examination Survey. Finally, 12,441 middle-aged and elderly people (aged 40–79) completed the soluble Klotho tests and had obtained complete data. S-Klotho was detected by ELISA kit, and the relationship between S-Klotho and hyperuricemia was assessed by multiple logistic regression. Hyperuricemia is defined as serum uric acid levels higher than or equal to 420 mmol/l in men and 360 mmol/l in women. Results: In the middle-aged and elderly, plasma S-Klotho levels were negatively correlated with hyperuricemia, and there was a saturation effect. The inflection point of S-Klotho was 927.8 pg/ml (logarithmic likelihood ratio test = 0.002). When plasma S-Klotho < 927.8 pg/ml, the prevalence of hyperuricemia in middle-aged and elderly individuals with higher levels of S-Klotho decreased by 25.6% compared with those with low levels of S-Klotho [Q4 vs Q1, OR: 0.744, 95%CI: (0.634, 0.874), P < 0.001]; In different age groups, S-Klotho had a significantly greater effect on hyperuricemia in middle-aged people [age: 40–65 years, Q4 vs Q1, OR (95%CI): 0.69 (0.58, 0.82), P < 0.001; Age > 65 years: Q4 vs Q1, OR (95%CI): 0.72 (0.56, 0.92), P = 0.008)].When the level of S-Klotho was higher, the risk of hyperuricemia in men was lower than that in women [male: Q4 vs Q1, OR (95%CI): 0.67 (0.56, 0.81), P < 0.001; female: Q4 vs Q1 (95%CI):0.72 (0.58, 0.88), P < 0.001]. Conclusions: In middle-aged and elderly individuals, plasma S-Klotho levels were inversely correlated with hyperuricemia, with a saturation effect. Given the limitations of the research results, the underlying mechanism between S-Klotho and hyperuricemia should be further explored.

Background: In a meta-analysis, we investigated the effects of angiotensin receptor blockers (ARBs) in comparison to placebo or other classes of antihypertensive drugs on endothelial function, which was measured by brachial flow-mediated vasodilation (FMD). Methods: We searched for randomized controlled trials that compared ARBs with placebo or other classes of antihypertensive drugs in improving FMD. A random-effect model was used to compute pooled estimates. Results: In 13 trials (n = 529), ARBs were more efficacious in improving brachial FMD than placebo [pooled weighted mean change difference (WMD) 1.34%, 95% CI, 0.93-1.75%, p < 0.001]. In 15 trials (n = 918), treatment with ARBs had a significant effect on brachial FMD when compared with other antihypertensive drugs (pooled WMD 0.59%, 95% CI, 0.20-0.98%, p = 0.003 with significant heterogeneity). ARBs were also more efficacious in improving brachial FMD than calcium channel blockers (CCBs; pooled WMD 1.61%, 95% CI, 0.72-2.49%, p < 0.001) but not the other classes of drugs (p ≥ 0.072). Conclusions: This meta-analysis shows that ARBs improve brachial FMD, a marker of endothelial function, and that they are superior to placebo and CCBs. There was no significant difference in the effect on brachial FMD between ARBs and the other antihypertensive drugs.