Predictive value of serum TBA for 2-year MACEs in ACS patients undergoing PCI: a prospective cohort study.

Bile acids play important roles in lipid metabolism and glucose homeostasis. Limited research exist on the association between serum total bile acid (TBA) levels and major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS), particularly those with comorbid type 2 diabetes mellitus (T2DM). This study was conducted to examine the relationship between baseline serum TBA level and T2DM status in patients with ACS after percutaneous coronary intervention (PCI) and to identify the predictive value of TBA levels for a 2-year risk of MACEs. 425 ACS patients underwent PCI were recruited and divided into three groups based on baseline serum TBA concentration. An analysis of the association between the T2DM status and baseline serum TBA levels was conducted using univariate linear regression and multivariate linear regression. The predictive relevance of serum TBA levels was evaluated using the receiver operating characteristic (ROC) curve and Cox regression. Kaplan-Meier curves were employed to analyze the differences among groups in predicting MACEs over a 2-year follow-up period. Baseline serum TBA levels were higher in ACS patients who were diagnosed with T2DM (the median 3.6 µmol/L) than those without T2DM (the median 3.0 µmol/L). T2DM status in ACS patients was positively correlated with baseline serum TBA concentrations (ß: 1.7, 95% confidence interval [CI] 0.3-3.0), particularly in the male (ß: 2.0, 95% CI 0.3-3.6) and 50-69-year-old (ß: 2.5, 95% CI 0.6-4.4) populations. The areas under the ROC curve of baseline serum TBA levels predicted MACEs in ACS and ACS-T2DM patients following PCI were 0.649 (95% CI 0.595-0.703) and 0.783 (95% CI 0.685-0.881), respectively. Furthermore, Cox regression analysis showed that baseline serum TBA level was associated with the occurrence of MACEs in patients with ACS after PCI over a 2-year follow-up period, especially in those diagnosed with T2DM, whose baseline TBA concentration was lower than 10.0 µmol/L. ACS Patients with T2DM had higher serum TBA levels. TBA level at baseline was an independent predictor of MACEs in ACS patients who underwent PCI, especially with comorbid T2DM.

Systemic immune-inflammation index (SII) and the risk of all-cause, cardiovascular, and cardio-cerebrovascular mortality in the general population.

BACKGROUND: An elevated systemic immune-inflammation index (SII) is associated with higher mortality in patients with coronary artery disease and other diseases. However, the potential of SII for predicting mortality in the general population has been underexplored. Therefore, this study aimed to analyze the relationship between the SII and all-cause, cardiovascular disease, and cardiocerebrovascular disease mortality in the general population. METHODS: This study involved 26,855 participants (≥ 18 years) from the National Health and Nutrition Examination Survey 1999-2014 who were grouped according to the SII tertiles. Survival differences between the groups were analyzed using log-rank tests and Kaplan-Meier plots. Furthermore, multivariate Cox regression and restricted cubic spline analyses were used to examine the relationship between the SII and all-cause, cardiovascular, and cardio-cerebrovascular mortality. RESULTS: Overall, 1947 (7.425%) participants died following an average follow-up of 87.99 ± 54.04 months. Among these, 325 (1.210%) deaths were related to cardiovascular diseases and 392 (1.459%) to cardio-cerebrovascular mortality. Kaplan-Meier analysis revealed statistically significant differences in all-cause, cardiovascular, and cerebrovascular mortality between the SII tertiles (log-rank test: all P < 0.001). Multi-adjusted models showed that participants in the highest tertile of SII had a higher risk of death from all-cause (hazard ratio [HR] = 1.48, 95% confidence interval [CI] 1.48-1.48) and cardiovascular mortality (HR = 1.60, 95% CI 1.60-1.61) compared with those in the lowest tertile. In addition, the restricted cubic spline curve indicated a nonlinear association between SII and all-cause mortality (P < 0.001), with threshold value of SII at 18.284. There was a 15% decrease in the risk of all-cause mortality for each twofold change in SII on the left flank (HR = 0.85, 95% CI 0.69-1.05) and a 42% increase (HR = 1.42, 95% CI 1.23-1.64) on the right flank of the inflection point. In addition, the risk of cardiovascular mortality increased nonlinearly by 39% per twofold change in SII (HR = 1.39, 95% CI 1.07-1.81). There was also a nonlinear increase in the risk of cardio-cerebrovascular mortality per twofold change in SII (HR = 1.29, 95% CI 1.00-1.66). CONCLUSIONS: In the general population, the SII was significantly associated with all-cause, cardiovascular, and cardio-cerebrovascular mortality, regardless of the established risk factors.

Case Report: The value of contrast-enhanced ultrasound and contrast-enhanced computed tomography in the diagnosis of hepatic angiosarcoma.

Background: Enhanced imaging techniques have the overwhelming advantages of being noninvasive and sensitive enough to evaluate the microcirculation of lesions, thus making them accurate in the diagnosis of hepatic lesions. Unfortunately, there is very little research on and knowledge of the imaging features of a rare cancerous condition: hepatic angiosarcoma (HA). Case summary: In this study, we retrospectively collected the data of six patients who underwent both contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT), and subsequently obtained a definitive histopathologic diagnosis of HA. We described the imaging appearances of HA by comparing CEUS and CECT images. Furthermore, we analyzed these imaging characteristics from the perspective of histopathology and tumorigenesis. The study included the largest number (six) of histopathologically confirmed HA patients who had received CEUS examinations to date. Conclusion: By offering readers comprehensive knowledge of contrast imaging, especially CEUS, in the diagnosis of HA, our study may reduce misdiagnosis and further improve treatment options.

Ultrasound and clinicopathological characteristics of breast cancer for predicting axillary lymph node metastasis.

OBJECTIVES: The goal of this study was to assess the clinicopathological and ultrasound (US) features of breast cancer for predicting the risk of axillary lymph node metastasis. METHODS: Patients with breast cancer were included in this retrospective, monocentric, observational study. Their preoperative ultrasound features, clinical data, laboratory results and postoperative pathologic results and immunophenotyping were collected. The association of these factors of breast cancer with axillary lymph node metastasis was evaluated by univariate and multivariate analysis. RESULTS: In this study, 471 patients diagnosed with breast cancer at the First Affiliated Hospital of Xi'an Jiaotong University between July 2016 and September 2019 were collected, with a total of 471 nodules, of which 231(49.0%) had axillary lymph node metastasis, and 240(51.0%) did not. The parameters of hyperechoic halo, posterior acoustic decrease, microcalcification, carcinogenic embryonic antigen (CEA), cancer antigen-153 (CA153), CK5/6 (+), Ki67 (≥40%), AR (+) and histological grade (grade II and grade III) were significantly and independently associated with axillary lymph node metastasis (p < 0.05 for all). CONCLUSIONS: The combination of ultrasound features, tumor markers, pathology, and immunohistochemistry can predict axillary lymph node metastasis in breast cancer patients.

Low Ruthenium Content Confined on Boron Carbon Nitride as an Efficient and Stable Electrocatalyst for Acidic Oxygen Evolution Reaction.

To date, only a few noble metal oxides exhibit the required efficiency and stability as oxygen evolution reaction (OER) catalysts under the acidic, high-voltage conditions that exist during proton exchange membrane water electrolysis (PEMWE). The high cost and scarcity of these catalysts hinder the large-scale application of PEMWE. Here, we report a novel OER electrocatalyst for OER comprised of uniformly dispersed Ru clusters confined on boron carbon nitride (BCN) support. Compared to RuO2 , our BCN-supported catalyst shows enhanced charge transfer. It displays a low overpotential of 164 mV at a current density of 10 mA cm-2 , suggesting its excellent OER catalytic activity. This catalyst was able to operate continuously for over 12 h under acidic conditions, whereas RuO2 without any support fails in 1 h. Density functional theory (DFT) calculations confirm that the interaction between the N on BCN support and Ru clusters changes the adsorption capacity and reduces the OER energy barrier, which increases the electrocatalytic activity of Ru.

The Predictive Values of White Blood Cell Indices (Lymphocyte and Eosinophilic Granulocyte) for Heart Failure in Acute Coronary Syndrome Patients Following Percutaneous Coronary Intervention: A Prospective Cohort Study.

Background: White blood cell (WBC) indices are strongly associated with cardiovascular disease, but data on the prognostic values of these parameters in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI) are sparse. The current study aimed to investigate the relationship between baseline WBC indices levels and the incidence of heart failure (HF) in ACS patients after PCI and explore the predictive values over a 2-year follow-up period. Methods: A total of 416 consecutive ACS patients treated with PCI were enrolled and received a median of 27.7 months follow-up. Univariate and multivariate Cox regression analyses and the receiver operating characteristic (ROC) curves were performed. Results: Baseline lymphocyte (LYMPH) count, eosinophil (EO) count and eosinophil percentage (EO %) were higher in patients who experienced HF over a 2-year follow-up. In multivariate Cox proportional hazards analysis, LYMPH count, EO count and EO % were independently associated with the occurrence of HF (hazard ratio [HR] = 12.876, P = 0.025; HR = 16.625, P = 0.004; HR = 1.196, P = 0.031, respectively). The area under the ROC curve of baseline EO count predicting the occurrence of HF in ACS patients following PCI was 0.625 (P = 0.037). For patients aged 60 years and above, who had PCI or history of coronary artery bypass grafting, the higher EO count, the higher the risk of HF. Conclusion: Elevated baseline LYMPH count, EO count and EO % were independently associated with the incidence of HF in ACS patients following PCI, suggesting that WBC indices might be available, simple, and cost-efficient biomarkers with predictive value, especially for patients aged more than 60 years.

Hydrogel Electrolyte with High Tolerance to a Wide Spectrum of pHs and Compressive Energy Storage Devices Based on It.

Normally, hydrogel electrolytes widely used in flexible energy storage devices have limited tolerance to different pHs. Most gel electrolytes will lose their compressible capability when the adaptable pH is changed. Herein, a poly(acrylamide3 -co-(sulfobetaine methacrylate)1 )@polyacrylamide (P(A3 -co-S1 )@PAM) hydrogel electrolyte equipped with a dual crosslinking network (DN) is successfully fabricated, which exhibits excellent tolerance to any pHs, endowing various energy storage devices including batteries and supercapacitors with superior mechanical durability. The batteries with mild and alkaline P(A3 -co-S1 )@PAM electrolytes display superior stability (over 3000 cycles). Additionally, a Zn||MnO2 battery based on the P(A3 -co-S1 )@PAM hydrogel electrolyte (mild) under 50% compression strain also shows excellent charge-discharge stability and high capacity at 152.4 mAh g-1 after 600 cycles. The strong reversible hydrogen bonds and electrostatic forces originating from zwitterionic structures of poly(sulfobetaine methacrylate) play an important role in dissipating and dispersing energy imposed abruptly. Meanwhile, the zwitterionic structure and intermolecular NH⋯OC hydrogen bonds of the hydrogel lead to the property of acid resistance and alkali resistance. The tough and robust covalent crosslinking bonds and the tight arrangement of DN polymer chains enable the hydrogel electrolytes to recover their initial shape fast once unloading.

Hemoglobin within normal range is negatively related to hemoglobin A1c in a nondiabetic American population aged 16 years and older.

BACKGROUND: Protein glycosylated hemoglobin, hemoglobin A1c (HbA1c) binds hemoglobin (Hb) in red blood cells to blood glucose. However, the relationship between Hb and HbA1c remains unclear. AIM: To elucidate their relationship in a nondiabetic population aged ≥ 16 years in the United States, using data from the 1999-2018 National Health and Nutrition Examination Survey. METHODS: This study was based on data from 44560 adults aged ≥ 16 years, excluding those with diabetes. The relationship was estimated using a multivariate regression. We also used piecewise linear regression for subgroup analysis based on age and sex stratification and analysis of the threshold effects of Hb on HbA1c. RESULTS: Hb and HbA1c levels were negatively correlated in the unadjusted model (ß = -0.01; 95%CI: -0.01, -0.01). The correlation was significantly negative when the regression model was minimally regulated and stratified by age and sex, and remained negative when the model was further regulated (more than 10%) to identify covariates with the HbA1c level influence estimates. In subgroup analyses based on age and sex stratification, the association remained negative when the covariates were controlled. A nonlinear relationship was observed between them when the Hb levels reached the tipping point (13.2 g/dL) (adjusted odds ratio, -0.04; 95%CI: -0.05, -0.03) and when the Hb levels exceeded 13.2 g/dL (adjusted odds ratio, -0.10; 95%CI: -0.10, -0.09). CONCLUSION: Our study shows that normal Hb levels are negatively correlated with HbA1c in nondiabetic Americans aged ≥ 16 years.

Structure and pro-inflammatory activities of bran polysaccharides from a novel wheat kernel.

In this study, the structure and pro-inflammatory activities of water-soluble wheat bran polysaccharides (WBP) were evaluated. WBP were heteropolysaccharides consisting 60.34% arabinoxylan as the main component and 31.80% mannose residues characterized with the instrumental analyses. The result of cellular experiment displayed that WBP had significant pro-inflammatory activities by increasing the concentration of nitric oxide (NO) and up-regulating the inflammatory cytokine expressions of inducible nitric oxide synthase (iNOS), interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α). WBP mediated macrophages RAW 264.7 pro-inflammatory response through phosphatidylinositol 3 hydroxykinase/protein kinase B (PI3K/Akt) signaling pathway by significantly promoting Akt and phosphoinositide-dependent kinase 1 (PDK1) phosphorylations. Meanwhile, the expression of related phosphorylated proteins JNK and ERK1/2 was significantly up-regulated which suggested that WBP played pro-inflammatory roles by activating mitogen-activated protein kinases (MAPKs) signaling pathway. PRACTICAL APPLICATIONS: In recent years, wheat bran generally has the phenomenon of high yield and low utilization rate. Wheat bran has rich nutritional value and contains a lot of effective biologically active substances. Based on our findings, the water-soluble polysaccharides extracted from wheat bran have significant effects on regulating immunity and can be utilized as sources of natural immune modulators. The research can develop new functions of wheat bran polysaccharides, and improve processing utilization rate and product added value.

A case report of primary pulmonary artery intimal sarcoma.

BACKGROUND: Pulmonary artery intimal sarcoma (PAS) is a very rare disease, its prevalence is about 0.001-0.003%. PAS is often misdiagnosed as acute or chronic pulmonary thromboembolism due to its clinical presentation and radiological findings. Thus, early diagnosis is very crucial and may improve patient outcome. CASE PRESENTATION: Here, we report a case in a Chinese male where the symptom presentation was episodes of shortness of breath. Transthoracic echocardiography showed a solid mass in the pulmonary valve orifice, which was demonstrated to be a pulmonary artery intimal sarcoma diagnosed by histopathology. In this case, the initial differential diagnosis included pulmonary embolism. Because the initial symptom of primary pulmonary artery sarcoma is extremely similar to the pulmonary embolism, half of them may be misdiagnosed as pulmonary embolism. Imaging studies are very helpful. Ultrasound and CT are the best due to their resolution and ability to assess the relationship of the mass with the surrounding structures. The final diagnosis is mostly made after surgical excision and this is the most effective treatment. At the same time, radiotherapy and chemotherapy after surgery is also an adjuvant treatment. CONCLUSION: We report a very rare case of pulmonary artery intimal sarcoma. Due to late diagnosis and delayed treatment in this case, the patient displayed a poor prognostic. Early diagnosis and right treatment can improve the prognosis of PAS and optimize overall health.

HDL-C/apoA-I Ratio Is Associated with the Severity of Coronary Artery Stenosis in Diabetic Patients with Acute Coronary Syndrome.

BACKGROUND: Emerging evidence demonstrates that the lipid metabolism in acute coronary syndrome (ACS) patients with type 2 diabetes mellitus (T2DM) differs from nondiabetic patients. However, the distinct lipid profiles and their relationships with the severity of coronary artery stenosis and prognosis in patients with T2DM remain elusive. METHOD AND RESULT: This single-center, prospective cohort study enrolled 468 patients diagnosed with ACS undergoing coronary angiography, consisting of 314 non-DM and 154 DM patients. The HDL-C/apoA-I ratio was significantly higher in DM patients with a multivessel (≥3 affected vessels) lesion than a single-vessel (1-2 affected vessels) lesion. Regression analyses showed that the HDL-C/apoA-I ratio was positively correlated to the number of stenotic coronary arteries in DM patients but not non-DM patients. However, Kaplan-Meier survival analysis revealed no significant difference in the major adverse cardiovascular event rate regarding different HDL-C/apoA-I levels in DM or non-DM ACS patients at the end of the 2-year follow-up. CONCLUSION: A higher HDL-C/apoA-I ratio is associated with increased severity of coronary artery stenosis in DM patients with ACS but not with the rate of major adverse cardiovascular events at the end of the 2-year follow-up.

Identification of Key Genes of Prognostic Value in Clear Cell Renal Cell Carcinoma Microenvironment and a Risk Score Prognostic Model.

OBJECTIVE: We aimed at identifying the key genes of prognostic value in clear cell renal cell carcinoma (ccRCC) microenvironment and construct a risk score prognostic model. MATERIALS AND METHODS: Immune and stromal scores were calculated using the ESTIMATE algorithm. A total of 539 ccRCC cases were divided into high- and low-score groups. The differentially expressed genes in immune and stromal cells for the prognosis of ccRCC were screened. The relationship between survival outcome and gene expression was evaluated using univariate and multivariate Cox proportional hazard regression analyses. A risk score prognostic model was constructed based on the immune/stromal scores. RESULTS: The median survival time of the low immune score group was longer than that of the high immune score group (p = 0.044). Ten tumor microenvironment-related genes were selected by screening, and a predictive model was established, based on which patients were divided into high- and low-risk groups with markedly different overall survival (p < 0.0001). Multivariate Cox analyses showed that the risk score prognostic model was independently associated with overall survival, with a hazard ratio of 1.0437 (confidence interval: 1.0237-1.0641, p < 0.0001). CONCLUSIONS: Low immune scores were associated with extended survival time compared to high immune scores. The novel risk predictive model based on tumor microenvironment-related genes may be an independent prognostic biomarker in ccRCC.

Prognostic Value of Admission Mean Corpuscular Volume for Major Adverse Cardiovascular Events following Stent Implantation in Nondiabetic and Diabetic Patients with Acute Coronary Syndrome.

BACKGROUND: One of the key concerns of the clinician is to identify and manage risk factors for major adverse cardiovascular events (MACEs) in nondiabetic and diabetic patients with acute coronary syndrome (ACS) undergoing stent implantation. Mean corpuscular volume (MCV) is a marker of erythrocyte size and activity and is associated with prognosis of cardiovascular disease. However, the role of admission MCV in predicting MACEs following stent implantation in diabetes mellitus (DM), non-DM, or whole patients with ACS remains largely unknown. METHODS AND RESULTS: A total of 437 ACS patients undergoing stent implantation, including 294 non-DM (59.08 ± 10.24 years) and 143 DM (63.02 ± 9.92 years), were analyzed. Admission MCV was higher in non-DM than DM patients. During a median of 31.93 months follow-up, Kaplan-Meier curve demonstrated that higher admission MCV level was significantly associated with increased MACEs in whole and non-DM, but not in DM patients. In Cox regression analysis, the highest MCV tertile was associated with higher MACEs in whole ([HR] 1.870, 95% CI 1.113-3.144, P = 0.018), especially those non-DM ([HR] 2.089, 95% CI 1.077-4.501, P = 0.029) patients after adjustment of several cardiovascular risk factors. MCV did not predict MACEs in DM patients. During landmark analysis, admission MCV showed better predictive value for MACEs in the first 32 months of follow-up than in the subsequent period. Finally, the receiver operating characteristic (ROC) curve was conducted to confirmed the value of admission MCV within 32 months. CONCLUSION: In patients with ACS, elevated admission MCV is an important and independent predictor for MACEs following stent implantation, especially amongst those without DM even after adjusting for lifestyle and clinical risk factors. However, as the follow-up period increased, the admission MCV lost its ability to predict MACEs.

Nomogram Based on microRNA Signature Contributes to Improve Survival Prediction of Clear Cell Renal Cell Carcinoma.

OBJECTIVE: Numerous microRNAs (miRNAs) have been identified in ccRCC and recommended to be used for predicting clear cell renal cell carcinoma (ccRCC) prognosis. However, it is not clear whether a miRNA-based nomogram results in improved survival prediction in patients with ccRCC. METHODS: miRNA profiles from tumors and normal tissues were downloaded from The Cancer Genome Atlas (TCGA) database and analyzed using the "limma" package. The association between differentially expressed miRNAs and patient prognosis was identified using univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Next, all patients were randomly divided into development and validation cohorts at a ratio of 1 : 1. A nomogram was established based on independent prognostic factors in the development cohort. The prognostic performance of the nomogram was validated in both cohorts using the concordance index (C-index) and calibration plots. RESULTS: Multivariate Cox analysis identified the 13-miRNA signature, as well as AJCC stage and age, as independent prognostic factors after adjusting for other clinical covariates. The nomogram was built based on the independent variables. In the development cohort, the C-index for the constructed nomogram to predict overall survival (OS) was 0.792, which was higher than the C-index (0.731) of the AJCC staging system and C-index (0.778) of the miRNA signature. The nomogram demonstrated good discriminative ability in the validation cohort in predicting OS, with a C-index of 0.762. The calibration plots indicated an excellent agreement between the nomogram predicted survival probability and the actual observed outcomes. Furthermore, decision curve analysis (DCA) indicated that the nomogram was superior to the AJCC staging system in increasing the net clinical benefit. CONCLUSIONS: The novel proposed nomogram based on a miRNA signature is a more reliable and robust tool for predicting the OS of patients with ccRCC compared to AJCC staging system, thus, improving clinical decision-making.

Baseline plasma fibrinogen is associated with haemoglobin A1c and 2-year major adverse cardiovascular events following percutaneous coronary intervention in patients with acute coronary syndrome: a single-centre, prospective cohort study.

BACKGROUND: Despite revascularisation, a large proportion of acute coronary syndrome (ACS) patients continue to experience major adverse cardiovascular events (MACEs), which are worsened by diabetes mellitus (DM). Fibrinogen (FIB) is a risk factor for MACEs in coronary artery disease and often elevated in DM. However, the relationships between FIB, glucose metabolism (haemoglobin A1c [HbA1c] and fasting blood glucose [FBG]) and MACEs following percutaneous coronary intervention (PCI) in DM, non-DM or whole patients with ACS remains unknown. METHODS: A total of 411 ACS patients undergoing PCI were enrolled in this study. We compared baseline FIB levels between DM (n = 103) and non-DM (n = 308) patients and divided participants into three groups according to FIB level, i.e. FIB-L, FIB-M and FIB-H, to compare baseline characteristics and MACEs. Linear regression analysis of the relationship between glucose metabolism and FIB, Cox regression, survival and landmark analyses of MACEs were also performed over a median of 27.55 months of follow-up. RESULTS: Patients with DM had higher FIB levels than non-DM patients (3.56 ± 0.99 mg/dL vs. 3.34 ± 0.80 mg/dL, P < 0.05). HbA1c and FBG were significantly positively correlated with FIB in whole and DM patients but not in non-DM patients (all P < 0.05). Compared with the FIB-L group, the FIB-M (hazard ratio [HR] 1.797, 95% CI 1.117-2.892, P = 0.016) and FIB-H (HR 1.664, 95% CI 1.002-2.763, P = 0.049) groups were associated with higher MACEs in whole; the FIB-M (HR 7.783, 95% CI 1.012-59.854, P = 0.049) was associated with higher MACEs in DM patients. FIB was not associated with MACEs in non-DM patients. During landmark analysis, FIB showed better predictive value for MACEs after PCI in the first 30 months of follow up than in the subsequent period. CONCLUSION: In this study from China, FIB was positively associated with glucose metabolism (HbA1c and FBG) in whole and DM populations with ACS. Moreover, elevated baseline FIB levels may be an important and independent predictor of MACEs following PCI, especially amongst those with DM. However, as the follow-up period increased, the baseline FIB levels lost their ability to predict MACEs.

IL-17A contributes to myocardial ischemic injury by activating NLRP3 inflammasome in macrophages through AMPKα/p38MAPK/ERK1/2 signal pathway in mice.

BACKGROUND: Acute myocardial infarction (AMI) is followed by an acute inflammation involving inflammasome activation, thereby inducing cardiac dysfunction. Interleukin-17A (IL-17A) involves in many inflammatory diseases, but its roles in inflammation following AMI are still obscure. The aim of this study is to investigate the roles of IL-17A in the inflammatory response following AMI and its underlying mechanisms. METHODS AND RESULTS: NLRP3 inflammasome and AMPKα/p38MAPK/ERK1/2 signaling pathway were significantly activated under the induction of IL-17A in mouse peritoneal macrophages, which could be inhibited by AMPK inhibitor compound C (CC). Both p38MAPK and ERK1/2 inhibitors could partially inhibit the activation of NLRP3 inflammasome in macrophages treated by IL-17A. In vivo, IL-17A knockout not only decreased the infiltration of macrophages and the activation of NLRP3 inflammasome and AMPKα/p38MAPK/ERK1/2 signaling pathway in ischemic myocardium, but also improved cardiac function and reduced infarction size after the ligation of descending segment from left coronary artery for 3 days in mice, while IL-17A administration further aggravated the myocardial ischemic injury, which were prevented by CC administration. CONCLUSION: IL-17A aggravates inflammatory response during AMI by inducing macrophages infiltration and activating NLRP3 inflammasome through AMPKα/p38MAPK/ERK1/2 pathway.

Combination of the CYP2C19 metabolizer and the GRACE risk score better predicts the long-term major adverse cardiac events in acute coronary syndrome undergoing percutaneous coronary intervention.

INTRODUCTION: Both Global Registry of Acute Coronary Events (GRACE) risk score and CYP2C19 metabolizer status can independently predict major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We investigated whether their combination could better predict MACE occurrence in patients with ACS undergoing PCI. MATERIALS AND METHODS: This retrospective cohort study included 548 consecutive patients with ACS undergoing PCI. A cumulative MACE curve was calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify MACE predictors. The predictive value of GRACE risk score alone and CYP2C19 metabolizer status was estimated by the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: In a median of 28.58 months, 17 patients (3%) were lost to follow-up, and 62 (11.3%) experienced MACEs. Multivariate Cox regression analysis showed that both GRACE score and CYP2C19 metabolizer status were independent MACE predictors (hazard ratio 1.019, 95% CI 1.011-1.027, p < 0.001; hazard ratio 2.383, 95% CI 1.601-3.547, p < 0.001, respectively). Kaplan-Meier analysis showed that CYP2C19 PM increased the MACE risk (log rank test = 10.848, p = 0.004). The GRACE score adjustment by CYP2C19 metabolizer status enhanced the predictive value (AUC increased from 0.682 for GRACE score alone to 0.731 for GRACE score plus CYP2C19 metabolizer). This result was further verified by IDI and NRI. CONCLUSIONS: CYP2C19 metabolizer status and GRACE score are readily available predictive approaches for MACEs, and their combination derives a more accurate long-term MACE prediction in clopidogrel-treated patients with ACS undergoing PCI.

Exclusive Formation of Formic Acid from CO2 Electroreduction by a Tunable Pd-Sn Alloy.

Conversion of carbon dioxide (CO2 ) into fuels and chemicals by electroreduction has attracted significant interest, although it suffers from a large overpotential and low selectivity. A Pd-Sn alloy electrocatalyst was developed for the exclusive conversion of CO2 into formic acid in an aqueous solution. This catalyst showed a nearly perfect faradaic efficiency toward formic acid formation at the very low overpotential of -0.26 V, where both CO formation and hydrogen evolution were completely suppressed. Density functional theory (DFT) calculations suggested that the formation of the key reaction intermediate HCOO* as well as the product formic acid was the most favorable over the Pd-Sn alloy catalyst surface with an atomic composition of PdSnO2 , consistent with experiments.

Hydroxychloroquine, a promising choice for coronary artery disease?

Coronary artery disease is a common disease that seriously threaten the health of more than 150 million people per year. Atherosclerosis is considered to be the main cause of coronary artery disease which begins with damage or injury to the inner layer of a coronary artery, sometimes as early as childhood. The damage may be caused by various factors, including: smoking, high blood pressure, hypercholesterolemia, sedentary lifestyle, diabetes and insulin resistance. Once a coronary artery disease has developed, all patients need to be treated with long term standard treatment, including heart-healthy lifestyle changes, medicines, and medical procedures or surgery. Hydroxychloroquine, an original antimalarial drug, prevents inflammation caused by lupus erythematosus and rheumatoid arthritis. It is relatively safe and well-tolerated during the treatment. Since atherosclerosis and rheumatoid arthritis have resemble mechanism and increasing clinical researches confirm that hydroxychloroquine has an important role in both anti-rheumatoid arthritis and cardiovascular protection (such as anti-platelet, anti-thrombotic, lipid-regulating, anti-hypertension, hypoglycemia, and so on), we hypothesize that hydroxychloroquine might be a promising choice to coronary artery disease patients for its multiple benefits.