The correlation between healthy lifestyle habits and all-cause and cardiovascular mortality in Guangxi.

BACKGROUND: Adherence to healthy lifestyle habits has become a mainstream approach for lessening the burden of cardiovascular disease (CVD) during initial prevention efforts. The purpose of this study was to investigate the prevalence of four healthy lifestyle habits, the associated factors, and their impact on all-cause and cardiovascular mortality among residents of Guangxi Zhuang Autonomous Region. METHODS: From 2015 to 2019, individuals between the ages of 35 and 75 from Guangxi Zhuang Autonomous Region were recruited through the ChinaHeart Million Person Project. Our study examined four healthy lifestyle habits: not smoking, no or moderate amounts of alcohol, sufficient leisure time physical activity (LTPA) and a balanced diet. RESULTS: Out of the 19,969 individuals involved, the majority, 77.3% did not smoke, while 96.7% had limited alcohol intake, 24.5% engaged in sufficient LTPA, 5.5% followed a balanced diet, and merely 1.7% adhered to all four healthy lifestyle habits. Participants who were women, older, nonfarmers, living in cities, with a high income or level of education, or had hypertension or diabetes were more likely to follow all four healthy lifestyle habits (p < 0.001). People who followed the three healthy lifestyle habits had reduced chances of death from all cause (HR 0.34[95% CI:0.15,0.76]) and cardiovascular-related death (HR 0.23 [95% CI: 0.07, 0.68]) (p < 0.01) over a median period of 3.5 years. CONCLUSIONS: In Guangxi Province, the level of adherence to healthy lifestyle habits is very minimal. Therefore, population-specific health promotion strategies are urgently needed.

Anti-IL-17 Inhibits PINK1/Parkin Autophagy and M1 Macrophage Polarization in Rheumatic Heart Disease.

Rheumatic heart disease (RHD) is an important and preventable cause of cardiovascular death and disability, but the lack of clarity about its exact mechanisms makes it more difficult to find alternative methods or prevention and treatment. We previously demonstrated that increased IL-17 expression plays a crucial role in the development of RHD-related valvular inflammatory injury. Macrophage autophagy/polarization may be a pro-survival strategy in the initiation and resolution of the inflammatory process. This study investigated the mechanism by which IL-17 regulates autophagy/polarization activation in macrophages. A RHD rat model was generated, and the effects of anti-IL-17 and 3-methyladenine (3-MA) were analyzed. The molecular mechanisms underlying IL-17-induced macrophage autophagy/polarization were investigated via in vitro experiments. In our established RHD rat model, the activation of the macrophage PINK1/Parkin autophagic pathway in valve tissue was accompanied by M1 macrophage infiltration, and anti-IL-17 treatment inhibited autophagy and reversed macrophage inflammatory infiltration, thereby attenuating endothelial-mesenchymal transition (EndMT) in the valve tissue. The efficacy of 3-MA treatment was similar to that of anti-IL-17 treatment. Furthermore, in THP-1 cells, the pharmacological promotion of autophagy by IL-17 induced M1-type polarization, whereas the inhibition of autophagy by 3-MA reversed this process. Mechanistically, silencing PINK1 in THP-1 blocked autophagic flux. Moreover, IL-17-induced M1-polarized macrophages promoted EndMT in HUVECs. This study revealed that IL-17 plays an important role in EndMT in RHD via the PINK1/Parkin autophagic pathway and macrophage polarization, providing a potential therapeutic target.

Potential Involvement of M1 Macrophage and VLA4/VCAM-1 Pathway in the Valvular Damage Due to Rheumatic Heart Disease.

BACKGROUND: Rheumatic heart disease (RHD) is caused by inflammatory cells mistakenly attacking the heart valve due to Group A Streptococcus (GAS) infection, but it is still unclear which cells or genes are involved in the process of inflammatory cells infiltrating the valve. Inflammatory infiltration into the target tissue requires an increase in the expression of phosphorylated vascular endothelial-cadherin (p-VE-cad), p-VE-cad can increase the endothelial permeability and promote the migration of inflammatory cells across the endothelium. P-VE-cad is potentially regulated by RAS-related C3 botulinum substrate 1 (RAC1), together with phosphorylated proline-rich tyrosine kinase 2 (p-PYK2). While RAC1/p-PYK2/p-VE-cad is triggered by the activation of vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 is related to M1 macrophages adhering to the endothelium via very late antigen 4 (VLA4). Inflammatory infiltration into the valve is extremely important in the early pathogenesis of RHD. However, there is no relevant research on whether M1/VLA4/VCAM-1/RAC1/p-PYK2/p-VE-cad is involved in RHD; therefore, what we explored in this study was whether M1/VLA4/VCAM-1/RAC1/p-PYK2/p-VE-cad is involved. METHODS: We established a rat model of RHD and a cell model of M1 macrophage and endothelial cell cocultivation. Subsequently, we measured the degree of inflammatory cell infiltration, the levels of IL-6/IL-17, the degree of fibrosis (COL3/1), and the expression levels of fibrosis markers (FSP1, COL1A1 and COL3A1) in the heart valves of RHD rats. Additionally, we detected the expression of M1/M2 macrophage biomarkers in rat model and cell model, as well as the expression of M1/VLA4/VCAM-1/RAC1/p-PYK2/p-VE-cad. We also tested the changes in endothelial permeability after coculturing M1 macrophages and endothelial cells. RESULTS: Compared to those in the control group, the levels of inflammatory cell infiltration and fibrotic factors in the heart valves of RHD rats were significantly higher; the expression of M1 macrophage biomarkers (iNOS, CD86 and TNF-α) in RHD rats was significantly higher; and significantly higher than the expression of M2 macrophage biomarkers (Arg1 and TGF-ß). And the expression levels of VLA4/VCAM-1 and RAC1/p-PYK2/p-VE-cad in the hearts of RHD rats were significantly higher. At the cellular level, after coculturing M1 macrophages with endothelial cells, the expression levels of VLA4/VCAM-1 and RAC1/p-PYK2/p-VE-cad were significantly higher, and the permeability of the endothelium was significantly greater due to cocultivation with M1 macrophages. CONCLUSIONS: All the results suggested that M1 macrophages and the VLA4/VCAM-1 pathway are potentially involved in the process of inflammatory infiltration in RHD.

Y4 RNA fragments from cardiosphere-derived cells ameliorate diabetic myocardial ischemia‒reperfusion injury by inhibiting protein kinase C ß-mediated macrophage polarization.

The specific pathophysiological pathways through which diabetes exacerbates myocardial ischemia/reperfusion (I/R) injury remain unclear; however, dysregulation of immune and inflammatory cells, potentially driven by abnormalities in their number and function due to diabetes, may play a significant role. In the present investigation, we simulated myocardial I/R injury by inducing ischemia through ligation of the left anterior descending coronary artery in mice for 40 min, followed by reperfusion for 24 h. Previous studies have indicated that protein kinase Cß (PKCß) is upregulated under hyperglycemic conditions and is implicated in the development of various diabetic complications. The Y4 RNA fragment is identified as the predominant small RNA component present in the extracellular vesicles of cardio sphere-derived cells (CDCs), exhibiting notable anti-inflammatory properties in the contexts of myocardial infarction and cardiac hypertrophy. Our investigation revealed that the administration of Y4 RNA into the ventricular cavity of db/db mice following myocardial I/R injury markedly enhanced cardiac function. Furthermore, Y4 RNA was observed to facilitate M2 macrophage polarization and interleukin-10 secretion through the suppression of PKCß activation. The mechanism by which Y4 RNA affects PKCß by regulating macrophage activation within the inflammatory environment involves the inhibition of ERK1/2 phosphorylation In our study, the role of PKCß in regulating macrophage polarization during myocardial I/R injury was investigated through the use of PKCß knockout mice. Our findings indicate that PKCß plays a crucial role in modulating the inflammatory response associated with macrophage activation in db/db mice experiencing myocardial I/R, with a notable exacerbation of this response observed upon significant upregulation of PKCß expression. In vitro studies further elucidated the protective mechanism by which Y4 RNA modulates the PKCß/ERK1/2 signaling pathway to induce M2 macrophage activation. Overall, our findings suggest that Y4 RNA plays an anti-inflammatory role in diabetic I/R injury, suggesting a novel therapeutic approach for managing myocardial I/R injury in diabetic individuals.

Reactive oxygen species act as the key signaling molecules mediating light-induced anthocyanin biosynthesis in Eucalyptus.

Light plays a pivotal role in regulating anthocyanin biosynthesis in plants, and the early light-responsive signals that initiate anthocyanin biosynthesis remain to be elucidated. In this study, we showed that the anthocyanin biosynthesis in Eucalyptus is hypersensitive to increased light intensity. The combined transcriptomic and metabolomic analyses were conducted on Eucalyptus leaves after moderate (ML; 100 µmol m-2 s-1) and high (HL; 300 µmol m-2 s-1) light intensity treatments. The results identified 1940, 1096, 1173, and 2756 differentially expressed genes at 6, 12, 24, and 36 h after HL treatment, respectively. The metabolomic results revealed the primary anthocyanin types, and other differentially accumulated flavonoids and phenylpropane intermediates that were produced in response to HL, which well aligned with the transcriptome results. Moreover, biochemical analysis showed that HL inhibited peroxidase activity and increased the ROS level in Eucalyptus leaves. ROS depletion through co-application of the antioxidants rutin, uric acid, and melatonin significantly reduced, and even abolished, anthocyanin biosynthesis induced by HL treatment. Additionally, exogenous application of hydrogen peroxide efficiently induced anthocyanin biosynthesis within 24 h, even under ML conditions, suggesting that ROS played a major role in activating anthocyanin biosynthesis. A HL-responsive MYB transcription factor EgrMYB113 was identified to play an important role in regulating anthocyanin biosynthesis by targeting multiple anthocyanin biosynthesis genes. Additionally, the results demonstrated that gibberellic acid and sugar signaling contributed to HL-induced anthocyanin biosynthesis. Conclusively, these results suggested that HL triggers multiple signaling pathways to induce anthocyanin biosynthesis, with ROS acting as indispensable mediators in Eucalyptus.

Integrative description of a new species of Dugesia (Platyhelminthes, Tricladida, Dugesiidae) from Shennongjia, Central China.

A new species of the genus Dugesia (Platyhelminthes, Tricladida, Dugesiidae) from Xiangxi River, Shennongjia Forestry District, Hubei Province, China, is described on the basis of an integrative approach, involving morphology, and molecular systematics. The new species Dugesia saccaria A-T. Wang & Sluys, sp. nov. is characterized by the following features: a dumb-bell-shaped, muscularized hump located just anterior to the knee-shaped bend in the bursal canal; a ventrally displaced ejaculatory duct, which, however, opens terminally through the dorsal portion of the blunt tip of the penis papilla; a ventrally located seminal vesicle, giving rise to a vertically running duct that eventually curves downwards to communicate with the ejaculatory duct via a small diaphragm; oviducts opening asymmetrically into the dorsal portion of the common atrium and at the knee-shaped part of the bursal canal. The phylogenetic position of the new species was determined using four molecular markers (18S rDNA; ITS-1; 28S rDNA; COI), which suggested that it groups with other species of Dugesia from the Australasian and Oriental biogeographical regions.

Clinical characteristics of systemic sclerosis patients with occupational silicosis.

To explore the clinical characteristics of systemic sclerosis complicated with silicosis. The systemic sclerosis patients treated in the Guangxi Workers' Hospital and the People's Hospital of Guangxi Zhuang Autonomous Region from January 2000 to December 2020 were divided into the systemic sclerosis with silicosis group and the systemic sclerosis without silicosis group. Survival analysis was performed using Kaplan-Meier estimates the Cox proportional hazards model. A propensity score matching was applied in order to avoid the selection bias.Over the past 20 years, 72 systemic sclerosis patients with silicosis and 238 systemic sclerosis patients without silicosis were treated in the two hospitals. The systemic sclerosis patients with silicosis group had more males (P < 0.000),lower mean age at onset of SSc (P < 0.000), more frequent occurrence of weight loss (P = 0.028), smoking (P < 0.000), tuberculosis (P < 0.000), cardiac involvement (P < 0.000), ILD (P = 0.017), pulmonary hypertension (P = 0.024), elevated BNP (P < 0.000). With regards to the multivariate Cox regression analysis, silicosis was related with a higher overall mortality before (HR = 3.666, 95% CI = 1.440-11.234, p = 0.025) and after the propensity score matching analysis (HR = 2.817, 95% CI = 1.196-10.764, p = 0.014). Independent risk factors for overall mortality were Gangrene (HR = 3.003, 95% CI = 1.343-9.431), Cardiac involved (HR = 5.370, 95% CI = 1.910-15.472), Scl-70 (HR = 3.569, 95% CI = 1.333-10.869), Elevated BNP (HR = 2.135, 95% CI = 1.293-9.564).Concomitant silicosis worsens systemic sclerosis patients' prognoses. Gangrene, Scl-70, elevated BNP and cardiac involvement are independent risk factors for overall mortality. Key Points •Concomitant silicosis worsens SSc patients' prognoses. •For individuals with occupational exposure, close observation of the symptoms of SSc, early diagnosis, and interruption of exposure may improve the prognosis. •Gangrene, Scl-70, elevated BNP and cardiac involvement are independent risk factors for overall mortality.

Lipidomic diversity and proxy implications of archaea from cold seep sediments of the South China Sea.

Cold seeps on the continental margins are characterized by intense microbial activities that consume a large portion of methane by anaerobic methanotrophic archaea (ANME) through anaerobic oxidation of methane (AOM). Although ANMEs are known to contain unique ether lipids that may have an important function in marine carbon cycling, their full lipidomic profiles and functional distribution in particular cold-seep settings are still poorly characterized. Here, we combined the 16S rRNA gene sequencing and lipidomic approaches to analyze archaeal communities and their lipids in cold seep sediments with distinct methane supplies from the South China Sea. The archaeal community was dominated by ANME-1 in the moderate seepage area with strong methane emission. Low seepage area presented higher archaeal diversity covering Lokiarchaeia, Bathyarchaeia, and Thermoplasmata. A total of 55 core lipids (CLs) and intact polar lipids (IPLs) of archaea were identified, which included glycerol dialkyl glycerol tetraethers (GDGTs), hydroxy-GDGTs (OH-GDGTs), archaeol (AR), hydroxyarchaeol (OH-AR), and dihydroxyarchaeol (2OH-AR). Diverse polar headgroups constituted the archaeal IPLs. High concentrations of dissolved inorganic carbon (DIC) with depleted δ13CDIC and high methane index (MI) values based on both CLs (MICL) and IPLs (MIIPL) indicate that ANMEs were active in the moderate seepage area. The ANME-2 and ANME-3 clades were characterized by enhanced glycosidic and phosphoric diether lipids production, indicating their potential role in coupling carbon and phosphurus cycling in cold seep ecosystems. ANME-1, though representing a smaller proportion of total archaea than ANME-2 and ANME-3 in the low seepage area, showed a positive correlation with MIIPL, indicating a different mechanism contributing to the IPL-GDGT pool. This also suggests that MIIPL could be a sensitive index to trace AOM activities performed by ANME-1. Overall, our study expands the understanding of the archaeal lipid composition in the cold seep and improves the application of MI using intact polar lipids that potentially link to extent ANME activities.

Mediating effect of body fat percentage in the association between ambient particulate matter exposure and hypertension: a subset analysis of China hypertension survey.

BACKGROUND: Hypertension caused by air pollution exposure is a growing concern in China. The association between air pollutant exposure and hypertension has been found to be potentiated by obesity, however, little is known about the processes mediating this association. This study investigated the association between fine particulate matter (aerodynamic equivalent diameter ≤ 2.5 microns, PM2.5) exposure and the prevalence of hypertension in a representative population in southern China and tested whether obesity mediated this association. METHODS: A total of 14,308 adults from 48 communities/villages in southern China were selected from January 2015 to December 2015 using a stratified multistage random sampling method. Hourly PM2.5 measurements were collected from the China National Environmental Monitoring Centre. Restricted cubic splines were used to analyze the nonlinear dose-response relationship between PM2.5 exposure and hypertension risk. The mediating effect mechanism of obesity on PM2.5-associated hypertension was tested in a causal inference framework following the approach proposed by Imai and Keele. RESULTS: A total of 20.7% (2966/14,308) of participants in the present study were diagnosed with hypertension. Nonlinear exposure-response analysis revealed that exposure to an annual mean PM2.5 concentration above 41.8 µg/m3 was associated with increased hypertension risk at an incremental gradient. 9.1% of the hypertension burden could be attributed to exposure to elevated annual average concentrations of PM2.5. It is noteworthy that an increased body fat percentage positively mediated 59.3% of the association between PM2.5 exposure and hypertension risk, whereas body mass index mediated 34.3% of this association. CONCLUSIONS: This study suggests that a significant portion of the estimated effect of exposure to PM2.5 on the risk of hypertension appears to be attributed to its effect on alterations in body composition and the development of obesity. These findings could inform intersectoral actions in future studies to protect populations with excessive fine particle exposure from developing hypertension.

Hsa_ circ_0006867 regulates ox-LDL-induced endothelial injury via the miR-499a-3p/ADAM10 axis.

Circular RNAs (circRNAs) have been reported to participate in the development of various diseases. In this study, we investigated the potential mechanism underlying the role of circRNAs in atherosclerosis. Human umbilical vein endothelial cells (HUVECs) were treated with 100µg/mL oxidized low-density lipoprotein (ox-LDL) to simulate atherosclerosis. We observed that hsa_circ_0006867 (circ_0006867), a circRNA markedly increased in ox-LDL-treated endothelial cells, acted as a molecular sponge of miR-499a-3p and regulated its expression. This interaction led to changes in the downstream target gene ADAM10, thus affecting cell apoptosis and migration. Thus, our study suggests that circ_0006867 regulates ox-LDL-induced endothelial injury via the circ_0006867/miR-499a-3p/ADAM10 axis, indicating its potential as an exploitable therapeutic target for atherosclerosis.

Human Leukocyte Antigen Polymorphism HLA-A*24:02 is Associated with Acute Liver Disease in HBV-Infected Han Chinese Adults.

BACKGROUND: Whether polymorphic Human Leukocyte Antigen (HLA)-A, HLA-B and HLA-DRB1 alleles were associated with acute liver disease after hepatitis B virus (HBV) infections was investigated. METHODS: In this study, from initially 100 participants in each group, HLA-A, HLA-B and HLA-DRB1 sequences were available from 86 acute hepatitis B (AHB) patients and from 84 HBV-resistant individuals (controls), using sequencing-based typing allele groups and alleles that exhibited differences in distribution between the case and control groups were subjected to chi-squared and logistic regression analyses to identify those associated with AHB. A dose response analysis was also performed on the effect of HLA-A*24:02 allele number on acute liver disease following HBV infection. RESULTS: The frequency distribution of HLA-B and HLA-DRB1 alleles in the control group were in Hardy-Weinberg Equilibrium (P > .05). HLA-A*24:02 (χ2 = 6.949, P = .008) occurred most frequently in the AHB and HLA-DRB1*12:02 (χ2 = 7.768, P = .005) in the control group. With adjustment for sex, the logistic regression model showed that the HLA-A*24:02 allele was significantly associated with AHB liver injury (P = .0326, OR = 2.270, 95% CI: 1.070-4.816), whereas the other HLA-A, HLA-B, and HLA-DRB1 alleles were not (P > .05). A linear response was observed for the association between HLA-A*24:02 allele number and acute liver disease after HBV infections (χ2 = 4.428, P = .025). CONCLUSION: The HLA-A*24:02 allele may influence the severity of the cellular response to HBV infection, increasing the elimination of HBV-infected hepatocytes. The HLA-A*24:02 allele may be a potential screening marker for identifying people or regional populations in China at higher risk of acute liver disease following HBV infection.

Exploring Myocardial Ischemia-Reperfusion Injury Mechanism of Cinnamon by Network Pharmacology, Molecular Docking, and Experiment Validation.

Myocardial ischemia-reperfusion injury (MIRI) is a common complication of acute myocardial infarction that seriously endangers human health. Cinnamon, a traditional Chinese medicine, has been used to counteract MIRI as it has been shown to possess anti-inflammatory and antioxidant properties. To investigate the mechanisms of action of cinnamon in the treatment of MIRI, a deep learning-based network pharmacology method was established to predict potential active compounds and targets. The results of the network pharmacology showed that oleic acid, palmitic acid, beta-sitosterol, eugenol, taxifolin, and cinnamaldehyde were the main active compounds, and phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt), mitogen-activated protein kinase (MAPK), interleukin (IL)-7, and hypoxia-inducible factor 1 (HIF-1) are promising signaling pathways. Further molecular docking tests revealed that these active compounds and targets exhibited good binding abilities. Finally, experimental validation using a zebrafish model demonstrated that taxifolin, the active compound of cinnamon, has a potential protective effect against MIRI.

Inhibition of miR-143-3p alleviates myocardial ischemia reperfusion injury via limiting mitochondria-mediated apoptosis.

MicroRNA (miR)-143-3p is a potential regulatory molecule in myocardial ischemia/reperfusion injury (MI/RI), wherein its expression and pathological effects remains controversial. Thus, a mouse MI/RI and cell hypoxia/reoxygenation (H/R) models were built for clarifying the miR-143-3p's role in MI/RI. Following myocardial ischemia for 30 min, mice underwent reperfusion for 3, 6, 12 and 24 h. It was found miR-143-3p increased in the ischemic heart tissue over time after reperfusion. Cardiomyocytes transfected with miR-143-3p were more susceptible to apoptosis. Mechanistically, miR-143-3p targeted B cell lymphoma 2 (bcl-2). And miR-143-3p inhibition reduced cardiomyocytes apoptosis upon H/R, whereas it was reversed by a specific bcl-2 inhibitor ABT-737. Of note, miR-143-3p inhibition upregulated bcl-2 with better mitochondrial membrane potential (Δψm), reduced cytoplasmic cytochrome c (cyto-c) and caspase proteins, and minimized infarction area in mice upon I/R. Collectively, inhibition of miR-143-3p might alleviate MI/RI via targeting bcl-2 to limit mitochondria-mediated apoptosis. To our knowledge, this study further clarifies the miR-143-3p's pathological role in the early stages of MI/RI, and inhibiting miR-143-3p could be an effective treatment for ischemic myocardial disease.

The relationship between homocysteine and cardiopulmonary exercise testing in patients with acute coronary syndrome after percutaneous coronary intervention.

OBJECTIVE: The purpose of this study was to investigate the relationship between homocysteine (Hcy) levels and cardiopulmonary exercise testing (CPET) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). We also explored the relationship between Hcy levels and cardiac ultrasonography. METHODS: This study comprised 261 patients with ACS who underwent coronary angiography and PCI at Yulin First Hospital from January 2020 to June 2021. All subjects completed basic data collection, laboratory examination, CPET and cardiac ultrasonography. The CPET includes the peak oxygen uptake (peak VO2), anaerobic threshold (AT), metabolic equivalents (METs), exercise load (load), oxygen pulse (O2 pulse), end-tidal CO2 partial pressure (PETCO2), ventilatory equivalents for carbon dioxide (VE/VCO2) and Oxygen uptake efficiency (OUES). Cardiac ultrasonography was used to evaluate the left ventricular end diastolic diameter (LVEDD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT) and left ventricular ejection fraction (LVEF). A serum Hcy level ≥ 15 µmol/L was defined as hyperhomocysteinemia (HHcy). The patients were divided into the Hcy < 15 µmol/L group (n = 189) and the Hcy ≥ 15 µmol/L group (n = 72). RESULTS: The average age of the participating patients was 58.9 ± 10.1 years. The majority of participants were male (86.6%). The CPET indices of METs, load, VO2/kg, and PETCO2 were significantly decreased in the Hcy ≥ 15 µmol/L group compared with the Hcy < 15 µmol/L group. Additionally, the CPET index of the VE/VCO2 slope and the cardiac ultrasonography indices of IVST and LVPWT were significantly increased in the Hcy ≥ 15 µmol/L group compared with the Hcy < 15 µmol/L group. These differences were statistically significant (P < 0.05). Correlation analysis showed that Hcy levels were negatively correlated with METs, VO2/kg and PETCO2 and positively correlated with the VE/VCO2 slope (P < 0.05). Partial correlation analysis showed that Hcy levels were negatively correlated with METs and VO2/kg in the AT state. The correlation coefficients were - 0.172 and - 0.172, respectively (P < 0.05). Hcy levels were negatively correlated with METs, VO2/kg and PETCO2 in the peak state. The correlation coefficients were - 0.177, -0.153 and - 0.129, respectively (P < 0.05). After further adjustment for confounders, multiple linear regression analysis showed that Hcy levels were negatively correlated with METs and VO2/kg in the AT state and peak state. The standardized regression coefficients were - 0.035, -0.122, -0.048 and - 0.128, respectively (P < 0.05). Correlation analysis showed that Hcy levels were positively correlated with the IVST and LVPWT (P < 0.05), but after adjusting for confounding factors, partial correlation analysis showed that there was no correlation between them. CONCLUSION: A high Hcy level is associated with lower METs and VO2/kg and worse cardiopulmonary function in patients with ACS after PCI.

Rational design, synthesis and biological evaluation of novel 2-(substituted amino)-[1,2,4]triazolo[1,5-a]pyrimidines as novel tubulin polymerization inhibitors.

Following our previously reported compound 3, we designed and synthesized a series of new 2-(substituted amino)- [1,2,4]triazolo[1,5-a]pyrimidines as potential tubulin polymerization inhibitors. Among them, analogue 4k, having a 3-hydroxy-4-methoxyphenylamino group, was observed to display excellent antiproliferative activity toward HeLa, HCT116, A549, and T47D with the IC50 values of 0.31, 1.28, 3.99 and 10.32 µM, respectively, which were approximately 32, 48, 4, and 5-fold improvement compared with 3. Importantly, 4k possessed significant selectivity in inhibiting cancer cell lines over the normal HEK293 cells. Moreover, futher mechanism analysis demonstrated that 4k caused G2/M arrest, induced cells apoptosis in HeLa cells, and manifested significant tubulin polymerization inhibitory activity with the IC50 value of 4.9 µM, which is comparable to CA-4 (IC50 = 4.2 µM). The observations performed in this study reveal that 2-arylamino- [1,2,4]triazolo[1,5-a]pyrimidines represent a novel class of tubulin polymerization inhibitors with potent antiproliferative efficacy.

Atorvastatin Inhibits Ferroptosis of H9C2 Cells by regulatingSMAD7/Hepcidin Expression to Improve Ischemia-Reperfusion Injury.

Background: Ferroptosis plays a key role in cardiomyopathy. Atorvastatin (ATV) has a protective effect on ischemia-reperfusion (I/R) cardiomyopathy. The purpose of this study is to elucidate the mechanism of ATV in I/R injury. Methods: H9C2 cells and cardiomyopathy rats were induced by hypoxia/reoxygenation (H/R) and I/R to construct in vitro and in vivo models. Cell viability was determined by CCK8. Cardiac histopathology was observed by HE staining. Transmission electron microscope (TEM) was used to observe the mitochondrial morphology. The reactive oxygen species (ROS) content in cells was analyzed by the biochemical method. ELISA was conducted to calculate the concentrations of total iron/Fe2+ and hepcidin. The expression of ferroptosis and SMAD pathway-related genes were detected by qPCR. Western blot was performed to detect the expression levels of ferroptosis and SMAD pathway-related proteins. Results: In H9C2 cells, ATV reversed the decline in cell viability, mitochondrial shrinkage, and ROS elevation induced by erastin or H/R. The concentration of total iron and Fe2+ in H/R-induced H9C2 cells increased, and the protein expression of FPN1 decreased. After ATV treatment, the concentration of total iron and Fe2+ decreased, and the protein expression of FPN1 increased. The expression of the SMAD7 gene in H/R-induced H9C2 cells decreased, and the expression of the hepcidin gene increased, which were reversed by ATV. When SMAD7 was knocked down, ATV treatment failed to produce the above effect. ATV also improved ferroptosis in I/R rat myocardium through the SMAD7/hepcidin pathway. Conclusions: ATV reversed the decline in H9C2 cell viability, mitochondrial shrinkage, and ROS elevation, and improved the myocardium ferroptosis through the SMAD7/hepcidin pathway in I/R rat.

Healthcare quality and safety assessment based on annual scorekeeping.

Objective: To explore the practice of medical quality and safety evaluation system based on annual score under the background of establishing modern hospital management system and strengthening national public hospital performance evaluation. Methods: Statistical analysis was used to study the improvement of medical quality and safety in hospitals after the implementation of score evaluation, and the existing problems were analyzed according to the actual situation and related requirements. Results: The hospital's medical quality and safety evaluation system ran smoothly, the evaluation indexes could be implemented, and the evaluation results were used properly. The improvement of hospital medical quality and operation efficiency has achieved good results. Conclusion: The evaluation system of medical quality and safety for physicians and medical technicians based on annual score can achieve the whole process, all-round, personalized and information-based evaluation, and promote the high-quality development of hospitals. It is necessary to further improve the range of evaluation and carry out the evaluation of the evaluation system by relevant personnel.

Predictive value of ST-segment deviation in aVR in patients suffering from acute coronary syndrome: A retrospective cohort study.

Changes in the ST-segment in aVR of electrocardiogram have been used to predict the morbidity of left main and/or 3-vessel disease (LM/3-VD) in patients with acute coronary syndrome (ACS). However, the association with patient prognosis has rarely been reported. A total of 274 patients diagnosed with ACS were retrospectively evaluated following allocation into 1 of 3 groups: the ST-segment elevation (STE) group ≥ 0.05 mV, ST-segment depression (STD) group ≥ 0.05 mV, and the Isoelectric group in aVR. A comparison of clinical characteristics, coronary angiography results, major adverse cardiovascular events (MACE), and GRACE risk score was made. Patients in the STE and STD groups were older and had a lower LVEF, a greater number of MACE and higher GRACE risk score, compared with patients in the isoelectric group. Patients in the STE group had significantly greater morbidity due to LM/3-VD than did the non-STE groups. In addition, as the amplitude of STE in aVR increased, the number of MACE, GRACE risk score, and the incidence of LM/3-VD increased. Furthermore, after adjusting for other clinical factors, multivariate statistical results indicated that STE ≥ 0.05 mV in aVR was the only predictor of LM/3-VD, whereas STD ≥ 0.05 mV was not. It was found that STE or STD ≥ 0.05 mV in aVR was an independent predictor of MACE. STE ≥ 0.05 mV in aVR is associated with LM/3-VD. Furthermore, ST-segment deviation in aVR may have prognostic value of MACE and associated with higher GRACE risk scores in patients with ACS.

Identification of hub genes and their correlation with immune infiltration in coronary artery disease through bioinformatics and machine learning methods.

Background: Coronary artery disease (CAD) is a multifactorial disease and its pathogenesis remains unclear. We aimed to explore the optimal feature genes (OFGs) for CAD and to investigate the function of immune cell infiltration of CAD. It will be helpful for better understanding of the pathogenesis and the development of genetic prediction of CAD. Methods: Datasets related to CAD were obtained from the Gene Expression Omnibus (GEO) database. Cases from the datasets met diagnostic criteria including clinical symptoms, electrocardiographic (ECG) and angiographic evidence. We identified differentially expressed genes (DEGs) and conducted functional enrichment analysis. OFGs were obtained from the least absolute shrinkage and selection operator (LASSO) algorithm, support vector machine recursive feature elimination (SVM-RFE) algorithm, and random forest (RF) algorithm. CIBERSORT was used to compare immune infiltration between CAD patients and normal controls, and the correlation between OFGs and immune cells was analyzed. Results: DEGs were involved in the interleukin (IL)-17 signaling pathway, nuclear factor (NF)-kappa B signaling pathway, and tumor necrosis factor (TNF) signaling pathway. Gene Ontology (GO) analysis revealed DEGs were enriched in lipopolysaccharide (LPS), tertiary granule, and pattern recognition receptor activity. Disease Ontology (DO) analysis suggested DEGs were enriched in lung disease, arteriosclerotic cardiovascular disease (CVD). Matrix metalloproteinase 9 (MMP9), Pellino E3 ubiquitin protein ligase 1 (PELI1), thrombomodulin (THBD), and zinc finger protein 36 (ZFP36) were screened by the intersection of OFGs obtained from LASSO, SVM-REF, and RF algorithms. CAD patients had a lower proportion of memory B cells (P=0.019), CD8 T cells (P<0.001), resting memory CD4 T cells (P<0.001), regulatory T cells (P=0.028), and gamma delta T cells (P<0.001) than normal controls, while the proportion of activated memory CD4 T cells (P=0.014), resting natural killer (NK) cells (P<0.001), monocytes (P<0.001), M0 macrophages (P=0.023), activated mast cells (P<0.001), and neutrophils (P<0.001) in CAD patients were higher than normal controls. MMP9, PELI1, THBD, and ZFP36 were correlated with immune cells. Conclusions: MMP9, PELI1, THBD, and ZFP36 may be predicted biomarkers for CAD. The OFGs and association between OFGs and immune infiltration may provide potential biomarkers for CAD prediction along with the better assessment of the disease.

Micron channel length ZnO thin film transistors using bilayer electrodes.

Micro light-emitting diodes (Micro-LEDs) are currently attracting more and more attention. Thin film transistors (TFTs) with micron channel lengths can be used to drive Micro-LEDs. The key parameters of TFTs, such as mobility, ION/IOFF and threshold voltage, still need to be improved. In this study, we propose and experimentally demonstrate ZnO TFTs using bilayer electrodes to overcome the short channel effects when the channel length is scaled down to 3 µm. Ti, Mo and Sn interlayers not only serve as diffusion barriers to prohibit migration of Cu atoms from the top electrodes, but also enhance adhesive energy of the metal electrodes on ZnO channel layers. ZnO TFTs using Cu/Ti bilayer electrodes exhibit the best performance, e.g., a high mobility of 45.3 cm2V-1s-1, a high ION/IOFF ratio of 4.28 × 109, a low subthreshold of 0.24 V/dec and a proper threshold voltage of 1.13 V. The high mobility can be attributed to a significant decrease of the barrier height and a slight narrowing of the space charge layer, and the high ratio of ION/IOFF is concerned with the high electron concentration under an ON-state condition. Thus, ZnO TFTs using Cu/Ti bilayer electrodes can be used in next-generation displays.