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Objective To investigate the relationship between admission diastolic blood pressure (DBP) and subsequent cardiovascular and all-cause mortality in elderly patients with acute coronary syndrome (ACS). Methods This is a retrospective observational study. Consecutive patients ≥65 years of age admitted for ACS at a 2,300-bed tertiary hospital from December 2012 to July 2019 were included. The association between admission DBP and cardiovascular and all-cause mortality during hospitalization and over the follow-up period among this population were analyzed using multivariate COX regression model. Results were presented according to DBP quartiles: Q1, less than 67 mm Hg; Q2, from 67 to 72 mm Hg; Q3, from 73 to 80 mm Hg; and Q4, above 80 mm Hg. Results A total of 6 785 patients were included in this cohort study. Mean (SD) patient age was 74.0 (6.5) years, and 47.6% were women. Mean (SD) follow-up time was 2.54 (1.82) years. A non-linear relation was observed between DBP at admission and cardiovascular and all-cause mortality during hospitalization and over the follow-up period using restricted cubic splines. After adjustment for potential confounders, patients in Q3 or Q2 had lower risk for 2-year cardiovascular death by Cox proportional hazard model compared with patients in Q4 (hazard ratio [HR] 0.66; 95% confidence interval [CI], 0.48–0.90, P=0.010, for Q3 vs Q4; and HR 0.72; 95% CI, 0.53–0.99, P=0.041, for Q2vs Q4), while patients in Q1 had similar risk for cardiovascular death with that of patients in Q4. Meanwhile, when compared with patients in Q1, patients in Q3 had lower risk for 2-year cardiovascular death (HR, 0.72; 95% CI, 0.53–0.97, P=0.033). However, lower or higher admission DBP was not an independent predictor of 2-year all-cause mortality in this population. Conclusion Among patients aged ≥65 years admitted for ACS, there is a J-curve relationship between supine admission DBP and risk for 2-year cardiovascular death, with a nadir at 73–80 mm Hg. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support Study population and selectionAdjusted multivariate COX regression

Among all types of tea, black tea is produced in the largest amount worldwide, and its consumption is still increasing. Enzymatic fermentation is considered majorly contribute to quality formation of black tea, and the information about the roles of bacterial community in black tea processing is scarce. This study aimed to analyze the dynamic changes in composition, structure, and function of microbial communities during black tea processing and reveal the roles of bacterial community in black tea processing. Results showed that the genera Sphingomonas and Variovorax were dominant throughout the processing of black tea. Prediction function analysis of bacterial community showed that the mean proportions of glucuronoarabinoxylan endo - 1,4 - beta - xylanase, aminopeptidase B, phosphoserine phosphatase, homoserine O-acetyltransferase, glycolysis related enzymes, pyruvate dehydrogenase, tricarboxylic acid cycle related enzymes, and glyoxylate bypass were significantly elevated in the rolling and fermentation stages. The contents of amino acids, soluble sugar, theaflavins, thearubigins, and theabrownins increased greatly during the rolling and fermentation processes. Redundancy and Pearson's correlation analyses showed that the relative abundance of bacteria was closely related to the contents of water extract, tea polyphenols, epigallocatechin, epicatechin gallate, catechin gallate, thearubigins, theaflavins, and theabrownins. Overall, the findings provided new insights into the variation of bacterial community during black tea processing and improved our understanding of the core functional bacteria involved in black tea processing.

Microneedles composed of arrays of micro-sized needles assembled on a patch, has attracted increasing interest in transdermal drug delivery due to its ease of use and lack of painful responses. Here, a bibliometric analysis was conducted to determine a hotspot and trend of microneedles in the biomedical field.All relevant articles about microneedles between 2011 and 2020 were obtained from the databases of Web of Science (WOS) and PubMed of the National Center for Biotechnology Information (NCBI). A series of software such as VOSviwewer, the online bibliometric analysis website, CiteSpace, BICOMB and gCLUTO were used to process the data and get visual images. Processed data and visualized images were conducted to predict the trend of this research field.The number of articles published over the last decade had increased rapidly (37 in 2011, 165 in 2020), the Journal of Controlled Release was the most productive journal in microneedle studies. The United States was the most productive country, while the Queens Univ Belfast topped the other institutions. Ryan F Donnelly was the most productive author in the field, while the two most cited articles were published by Gu Zhen group. More importantly, the research trend of microneedles had ranged from physicochemical properties and pharmacokinetics to insulin transdermal injection and vaccine development over the past decade. The four hot spots in microneedle studies, including skin rejuvenation, vaccines, fabrication technology and insulin delivery, were identified. Microneedle vaccination shows promising application prospects, and polymers are considered as the most promising materials for microneedles manufacturing.This study will help researchers understand the hot spots and trends of microneedles in the biomedical field accurately and quickly. Moreover, the exploitation of novel polymeric microneedles will be a solid direction for subsequent research and development of transdermal drug delivery.

Lignin is a phenylpropanoid-derived polymer that functions as a major component of cell walls in plant vascular tissues. Biosynthesis of the aromatic amino acid Phe provides precursors for many secondary metabolites, including lignins and flavonoids. Here, we discovered that MYB transcription factors MYB20, MYB42, MYB43, and MYB85 are transcriptional regulators that directly activate lignin biosynthesis genes and Phe biosynthesis genes during secondary wall formation in Arabidopsis (Arabidopsis thaliana). Disruption of MYB20, MYB42, MYB43, and MYB85 resulted in growth development defects and substantial reductions in lignin biosynthesis. In addition, our data showed that these MYB proteins directly activated transcriptional repressors that specifically inhibit flavonoid biosynthesis, which competes with lignin biosynthesis for Phe precursors. Together, our results provide important insights into the molecular framework for the lignin biosynthesis pathway.

Flavonoids are major secondary metabolites derived from the plant phenylpropanoid pathway that play important roles in plant development and also have benefits for human health. So-called MBW ternary complexes involving R2R3-MYB and basic helix-loop-helix (bHLH) transcription factors along with WD-repeat proteins have been reported to regulate expression of the biosynthetic genes in the flavonoid pathway. MYB4 and its closest homolog MYB7 have been suggested to function as repressors of phenylpropanoid metabolism. However, the detailed mechanism by which they act has not been fully elucidated. Here, we show that Arabidopsis thaliana MYB4 and its homologs MYB7 and MYB32 interact with the bHLH transcription factors TT8, GL3 and EGL3 and thereby interfere with the transcriptional activity of the MBW complexes. In addition, MYB4 can also inhibit flavonoid accumulation by repressing expression of the gene encoding Arogenate Dehydratase 6 (ADT6), which catalyzes the final step in the biosynthesis of phenylalanine, the precursor for flavonoid biosynthesis. MYB4 potentially represses not only the conventional ADT6 encoding the plastidial enzyme but also the alternative isoform encoding the cytosolic enzyme. We suggest that MYB4 plays dual roles in modulating the flavonoid biosynthetic pathway in Arabidopsis.

This study investigated whether a novel index of stress hyperglycemia might have a better prognostic value compared to admission glycemia alone in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). The acute-to-chronic glycemic ratio was expressed as admission blood glucose (ABG) devided by the estimated average glucose (eAG), and eAG was derived from the glycated hemoglobin (HbA1c). A total of 1300 consecutive patients with STEMI treated with PCI were included. Baseline data and outcomes were analyzed. The study end point was a composite of in-hospital all-cause death, cardiogenic shock, and acute pulmonary edema. Accuracy was defined with area under the curve (AUC) by a receiver–operating characteristic (ROC) curve analysis. After multivariate adjustment, both ABG/eAG and ABG were closely associated with an increased risk of the composite end point in nondiabetic patients. However, only ABG/eAG (odds ratio = 2.45, 95% confidence interval: 1.24-4.82, P = .010), instead of ABG, was associated with the outcomes in diabetic patients. Compared to ABG, ABG/eAG had an equivalent predictive value in nondiabetic patients but a superior discriminatory ability in diabetic patients (AUC improved from 0.52-0.63, P < .001). Taken together, ABG/eAG provides more significant in-hospital prognostic information than ABG in diabetic patients with STEMI after PCI.

The prognostic value of the CHA2DS2-VASc score in acute coronary syndrome (ACS) patients without atrial fibrillation (AF) who underwent percutaneous coronary intervention remains uncertain. We examine the association of the CHA2DS2-VASc score and major adverse cardiovascular events (MACE) in this population and compared its risk prediction with 2 other commonly used risk scores (Global Registry of Acute Coronary Events [GRACE] and thrombolysis in myocardial infarction [TIMI]). A total of 3,745 consecutive ACS patients without AF who underwent percutaneous coronary intervention during 2013 to 2017 were classified into 4 groups according to the CHA2DS2-VASc score: low (0 to 1), moderate (2 to 3), high (4 to 5), and very high (>5). Incidences of MACE including cardiovascular death, nonfatal myocardial infarction, or stroke in-hospital and during a median follow-up of 33 months were compared among the 4 groups. Receiver-operating characteristic curves were generated to compare CHA2DS2-VASc with GRACE and TIMI for risk prediction. The incidences of in-hospital MACE (3.5%, 6.6%, 7.6%, and 9.1%, p

Severe haemorrhagic transformation (HT), a common complication of recombinant tissue plasminogen activator (rtPA) treatment, predicts poor clinical outcomes in acute ischaemic stroke. The search for agents to mitigate this effect includes investigating biomolecules involved in neovascularization. This study examines the role of Cathepsin K (Ctsk) in rtPA-induced HT after focal cerebral ischaemia in mice. After knockout of Ctsk, the gene encoding Ctsk, the outcomes of Ctsk+/+ and Ctsk−/− mice were compared 24 h after rtPA-treated cerebral ischaemia with respect to HT severity, neurological deficits, brain oedema, infarct volume, number of apoptotic neurons and activated microglia/macrophage, blood–brain barrier integrity, vascular endothelial growth factor (VEGF) expression and Akt-mTOR pathway activation. We observed that haemoglobin levels, brain oedema and infarct volume were significantly greater and resulted in more severe neurological deficits in Ctsk−/− than in Ctsk+/+ mice. Consistent with our hypothesis, the number of NeuN-positive neurons was lower and the number of TUNEL-positive apoptotic neurons and activated microglia/macrophage was higher in Ctsk−/− than in Ctsk+/+ mice. Ctsk knockout mice exhibited more severe blood–brain barrier (BBB) disruption, with microvascular endothelial cells exhibiting greater VEGF expression and lower ratios of phospo-Akt/Akt and phospo-mTOR/mTOR than in Ctsk+/+ mice. This study is the first to provide molecular insights into Ctsk-regulated HT after cerebral ischaemia, suggesting that Ctsk deficiency may disrupt the BBB via Akt/mTOR/VEGF signalling, resulting in neurological deficits and neuron apoptosis. Ctsk administration has the potential as a novel modality for improving the safety of rtPA treatment following stroke.

TiB2-TiC reinforced Ni55 matrix composite coatings were in-situ fabricated via plasma cladding on steels using Ti, B4C, and Ni55 as precursor materials at different proportions. Effects of TiB2+TiC content of ceramics phase on the microstructure and wear resistance were studied. The results showed that ceramic phases TiB2 and TiC were in-situ synthesized by plasma cladding, and the ceramic phase content significantly affected tribological performance and the wear mechanism of coatings under different loads. The composite ceramics protected coatings from further delamination wear by crack-resistance under a load of 30 N. Severe abrasive wear and adhesive wear were prevented when the load increased to 60 N because of the high hardness and strength of ceramic phases. Moreover, a compacted layer appeared on the wear surface of coatings with high content of ceramic phases, which effectively decreased the friction coefficient and wear rate. The TiB2-TiC composite ceramics significantly improved the wear performance of metal matrix composite coatings by different mechanisms under loads of 30 and 60 N.

The aim of this study is to explore the usability of multiple forms of television remote control interfaces for older adult users and users with mild cognitive impairment (MCI) to clarify the operation performance requirements of these two user groups. The test interfaces were constructed through programming and were capable of recording participants’ task completion time, operation errors, and the locations of their taps. The results show that users with MCI could not perform their initial action quickly and accurately; buttons with larger sizes provided greater operation performance for older adult users and users with MCI.

Light is an important environmental factor for plant growth and development. Phytochrome B (phyB), a classical red/far-red light receptor, plays vital role in controlling plant photomorphogenesis and light-induced stomatal opening. Phytohormone abscisic acid (ABA) accumulates rapidly and triggers a series of physiological and molecular events during the responses to multiple abiotic stresses. Recent studies showed that phyB mutant synthesizes more ABA and exhibits improved tolerance to salt and cold stress, suggesting that a crosstalk exists between light and ABA signaling pathway. However, whether ABA signaling components mediate responses to light remains unclear. Here, we showed that SnRK2.6 (Sucrose Nonfermenting 1-Related Protein Kinase 2.6), a key regulator in ABA signaling, interacts with phyB and participates in light-induced stomatal opening. First, we checked the interaction between phyB and SnRK2s, and found that SnRK2.2/2.3/2.6 kinases physically interacted with phyB in yeast and in vitro. We also performed co-IP assay to support that SnRK2.6 interacts with phyB in plant. To investigate the role of SnRK2.6 in red light-induced stomatal opening, we obtained the snrk2.6 mutant and overexpression lines, and found that snrk2.6 mutant exhibited a significantly larger stomatal aperture under red light treatment, while the two independent overexpression lines showed significantly smaller stomatal aperture, indicative of a negative role for SnRK2.6 in red light-induced stomatal opening. The interaction of SnRK2.6 with red light receptor and the negative role of SnRK2.6 in red light-induced stomatal opening provide new evidence for the crosstalk between ABA and red light in guard cell signaling.

Background: Inflammation plays an important role in diabetes mellitus (DM) and its related complications, including atherosclerosis and acute ischemic stroke (AIS). The mechanisms of excessive inflammation in DM are not fully understood. Specialized pro-resolving mediators (SPMs) are key regulators that promote resolution of inflammation. Unbalance of pro-resolving and pro-inflammatory signals may be the key pathogenesis in DM and DM-related diseases. We examined the resolution function in macrophages of DM patients with AIS.Methods: Macrophages were derived from peripheral blood mononuclear cells of AIS and none-AIS patients with or without DM. The cultured macrophages were treated with oxidized low-density lipoprotein. Resolution and inflammatory pathway markers were analyzed in the culture medium and cells. Results: In AIS patients, the ratios of SPMs to leukotriene B4 (LTB4) released by macrophages were decreased in those with DM compared to those without DM. Oxidized low-density lipoprotein treatment further reduced the ratios of SPMs/LTB4 in DM patients with AIS, but such a reduction was not observed in none-DM AIS patients. Analysis of M2/M1 polarization and MAPK/NFkB pathway markers also demonstrated un-resolved inflammation in macrophages of AIS patients with DM. Treatment with one of the SPMs, resolvin D2, rescued the resolution function and ameliorated inflammation in macrophages from these patients.Conclusions: Our data demonstrated that resolution of inflammation is disturbed by DM in macrophages of AIS patients, implicating a novel mechanism of un-resolved inflammation in DM-related vascular disorder. Exogenous SPMs treatment can rescue resolution and downregulate inflammatory signals, and may thus be beneficial in DM-related AIS.

Introduction: Medically underserved (US) populations have an increased level of atherosclerotic cardiovascular disease (ASCVD) risk, however, few studies investigated ASCVD risk reduction in US. Methods: Of 217 subjects with ApoB ≥120 mg/dL and carotid atherosclerosis (≥15% stenosis by ultrasound) enrolled in the Carotid Plaque Composition by MRI (CPC) study between 2005 and 2011, US (n=33) was defined as those without adequate healthcare insurance, while AS (n=184) included those with adequate healthcare coverage. All subjects received atorvastatin-based lipid therapies and lifestyle intervention for 2 years. Metabolic and inflammatory risk factors were compared between AS and US. Results: At baseline, compared to AS, US displayed higher levels of metabolic and inflammatory risk including systolic blood pressure (140±27 vs. 131±18 mmHg, p=0.04), fasting glucose (125±59 vs. 102±22 mg/dL, p=0.03) and fasting insulin (39±33 vs. 28±20 µU/dL, p=0.03) which resulted in higher insulin resistance (HOMA-IR 2.2±0.4 vs. 1.3±0.1, p=0.03), and hsCRP (5.6±1.5 vs. 2.8±0.2 mg/L, p=0.03). Over 2 years of intervention, US and AS showed similar reductions in LDL-C (-10.7% vs. -16% per year, p=0.2), triglycerides (-16.7% vs. -15.9% per year, p=0.4), and hsCRP (-0.11% vs. -0.04% per year, p=0.1). However, US continued to show significantly higher levels of fasting blood glucose (115±6.0 vs. 101±2.0 mg/dL, p=0.03) and HOMA-IR (1.9±0.2 vs. 1.5±0.1, p=0.047), and hsCRP (3.9±0.7 vs. 1.9±0.2 mg/L, p

IntroductionAtherosclerosis has become a worldwide medical burden. Our previous studies have shown that Artemisinin(ART) had the capability to reduce atherosclerosis. Emerging evidence indicates that Long non-coding RNAs(lncRNAs) are engaged in the formation of atherosclerosis. However, whether lncRNAs might participate in the mechanism through which artemisinin mitigates atherosclerosis has not been reported.Material and methodsEight-week-old apolipoprotein E deficient (APOE-/-) mice were divided into two groups, one of which was treated with Artemisinin. Red oil O staining was used to measure the sizes of Atherosclerotic lesion. We conducted deep sequencing to investigate lncRNA profiles in the aorta tissue in high-fat diet fed APOE knockdown mice with and without artemisinin treatment. CeRNA network, Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) analyses were constructed through bioinformatics analysis. RT-PCR was used to validate the differentially expressed lncRNAs.ResultsA total of 102 lncRNAs and 4,630 mRNAs were differentially expressed (pConclusionsThese findings indicated the possible mechanism and therapeutic role of lncRNAs in Artemisinin treatment of atherosclerosis and provided a theoretical basis for the future application of Artemisinin in patients with atherosclerosis.

Neddylation is a ubiquitylation-like pathway that is critical in various cellular functions by conjugating NEDD8 to target proteins. However, the roles of neddylation in stroke, remain elusive. Here, we report that NEDD8 conjugation increased after ischemic stroke and was abundantly present in neutrophils, whereas cullin-1, a key substrate of neddylation, was upregulated in endothelium. Inhibition of neddylation by MLN4924, inactivated cullin-RING E3 ligase (CRL), reduced brain infarction and improved functional outcomes. MLN4924 treatment induced accumulation of the CRL substrate NF1. Knockdown of NF1 abolished MLN4924-dependent inhibition of neutrophil trafficking. These effects were mediated through activation of endothelial P-selectin and ICAM-1. Moreover, NF1 silencing blocked MLN4924-afforded BBB protection and neuroprotection through activation of PKCδ, MARCKS and MLC in cerebral microvessels. Our results demonstrate that increased neddylation promoted neutrophil trafficking and thus exacerbated injury of the BBB and stroke outcomes. We suggest that the neddylation inhibition may be beneficial in ischemic stroke.

AIM To evaluate the prognostic value of triglyceride-glucose (TyG) index in nondiabetic patients with acute coronary syndrome (ACS) with low-density lipoprotein cholesterol (LDL-C) below 1.8 mmol/L. METHODS A total of 1655 nondiabetic patients with ACS with LDL-C below 1.8 mmol/L were included in the analysis. Patients were stratified into two groups. The incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, and major adverse cardiac and cerebral event during a median of 35.6-month follow-up were determined and compared between the two groups. The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL)×fasting plasma glucose (mg/dL)/2]. RESULTS Compared with the TyG index ＜8.33 group, the TyG index ≥ 8.33 group had a significantly higher incidence of AMI (21.2% vs. 15.2%, p=0.014) and larger infarct size in patients with AMI [the peak value of troponin I: 10.4 vs. 4.8 ng/ml, p=0.003; the peak value of Creatine kinase MB: 52.8 vs. 22.0 ng/ml, p=0.006; the peak value of myoglobin: 73.7 vs. 46.0 ng/ml, p=0.038]. Although there was no significant difference in mortality between the two groups, the incidence of revascularization of the TyG index ≥ 8.33 group was significantly higher than that of the TyG index ＜8.33 group (8.9% vs. 5.0%, p=0.035). A multivariable Cox regression revealed that the TyG index was positively associated with revascularization [hazard ratio, 1.67; 95% confidence interval, 1.02-2.75; p=0.043]. CONCLUSIONS In nondiabetic patients with ACS with LDL-C below 1.8 mmol/L, a high TyG index level was associated with higher incidence of AMI, larger infarct size, and higher incidence of revascularization. A high TyG index level might be a valid predictor of subsequent revascularization.

Patients undergoing successful percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) with normal left ventricular ejection fraction (LVEF) are generally considered to have successful clinical outcomes; however, there are still significant differences in clinical outcomes among these patients. The aim of the study was to find a common indicator to predict the risk of major adverse cardiac and cerebrovascular events (MACCE) in this population.A total of 3986 patients with ACS were divided into 4 groups based on the quartile (Q) values of peak N-Terminal pro-brain natriuretic peptide (NT-proBNP) measured during hospitalization. The incidence of MACCE was compared among Q1-Q4 groups during follow up. Multivariate Cox regression analysis was performed to identify independent prognostic factors of MACCE. Receiver operating characteristic (ROC) curve was generated to compare the area under the curve (AUC) for MACCE by adding NT-proBNP to the Thrombolysis in Myocardial Infarction (TIMI) risk score.NT-proBNP was significantly positively correlated with peak values of cardiac troponin I (cTnI) (r = 0.418), high-sensitivity C-reactive protein (hs-CRP) (r = 0.397) and left ventricular end-diastolic diameter (LVEDD) (r = 0.075) (P0.001). The risks of composite MACCE (5.6%, 9.1%, 13.0%, 20.1%, P0.001), all-cause death (1.0%, 2.5%, 4.1%, 8.4%, P0.001) and non-fatal myocardial infarction (2.0%, 3.4%, 4.8%, 6.2%, P0.001) were significantly higher in the higher Q groups. In multivariate analysis, the Q4 group displayed an independent 2.2-fold increase for MACCE compared to Q1 (HR: 2.16; 95%CI: 1.57-2.99; P0.001). Compared with TIMI risk score alone, TIMI+NT-proBNP showed improved AUCs: cardiovascular death (P = 0.0008), and heart failure requiring hospitalization (P = 0.0017).In patients with ACS with successful PCI and normal LVEF, elevated NT-proBNP was significantly associated with poor clinical outcomes. These results suggest that NT-proBNP is a useful biomarker for prognosis and risk stratification in this population.

Saccharification, the conversion of cellulose to sugar for fermentation-based biofuels, remains problematic for lignocellulosic feedstocks such as wood. Genetic modifications to reduce the amount or change the structure of lignin can improve saccharification efficiency but often result in dwarf plants. Here, we report that overexpression of Pag-MIR408 in hybrid poplar results in a near doubling saccharification efficiency, with no requirement for acid-pretreatment, increased accessibility of secondary cell walls to fungal cellulase and scaffoldin cellulose-binding modules, accompanied by enhanced photosynthesis, and increased number of cambium zone layers, xylem width and vessel diameter. Conversely, Pag-MIR408 loss-of-function plants by CRISPR/Cas9 showed decreased cell wall accessibility. Moreover, miR408 targets LACCASE 19/25, leading to delayed lignification, and modestly reduced lignin content, S/G ratio, as well as the degree of lignin polymerization. This study provides a unique insight into enhanced saccharification efficiency altered wood structure through modulation of the balance between secondary development and lignification.

Alzheimer's disease (AD) is a major neurodegenerative disorder. The functions of lncRNA RMRP have been characterized mainly in various human cancers. However, the functional network of RMRP in AD progression remains unknown.Human serum samples, AD transgenic (Tg) mice as well as SH-SY5Y cells were used in this study. The RNA expression patterns of RMRP, miR-3142 and TRIB3 were assessed by quantitative real-time PCR (qRT-PCR). Levels of apoptosis- or autophagy-associated biomarkers and TRIB3 level were evaluated using immunohistochemistry (IHC), western blotting or immunofluorescence assays, respectively. Bioinformatics methods and luciferase assays were used to predict and validate the interactions among RMRP, miR-3142, and TRIB3. Flow cytometry, TUNEL staining and EdU assays were used to examine the apoptosis and proliferation of neurons, respectively.The elevated RMRP and TRIB3 expressions and activation of autophagy were observed in AD. Knockdown of RMRP restrained neuronal apoptosis and autophagy activation in vitro and in vivo. Interestingly, TRIB3 overexpression reversed the biological effects of RMRP silencing on AβThese data illustrated that knockdown of RMRP inhibited autophagy and apoptosis via regulating miR-3142/TRIB3 axis in AD, suggesting that inhibition of RMRP maybe a therapeutic strategy for AD.

In this paper, two design schemes based on irregular subarray are proposed to verify the user-defined DoF control strategy. The relationship between the sensor array radiation performance and manufacturing cost is analyzed and compared. Firstly, the optimal configuration of the subarray is found via the array element grid theory modeling and heuristic iterative convex relaxation optimization. Then corresponding scanning electrical performance is analyzed for different structures and uses the subarray-level weighting vector to effectively suppress the grating lobes. Numerical experiments are provided to validate the effectiveness and potential of the proposed method.

In this paper, a small-scale wide-angle planar phased-array design based on irregular subarrays is presented. Considering that the control nodes are placed at the subarray level, the increase of scanning angle will generate quantized lobe to form a finite field of view. Increasing the control nodes to reduce the influence of quantization error, the iterative convex relaxation programming is used to achieve the precise aperture coverage and the multitask Bayesian compressive sensing (MT-BCS) solver is adopted to obtain a heuristic initial iteration points to improve the performance of the scanning radiation pattern. Numerical experiments are provided to validate the feasibility of this method.

Background Triglyceride glucose (TyG) index is considered a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular (CV) outcomes. However, the prognostic value of TyG index in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI) remains unclear. Methods A total of 1932 consecutive patients with T2DM and AMI were enrolled in this study. Patients were divided into tertiles according to their TyG index levels. The incidence of major adverse cardiac and cerebral events (MACCEs) was recorded. The TyG index was calculated as the ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. Results Competing risk regression revealed that the TyG index was positively associated with CV death [2.71(1.92 to 3.83), p p = 0.001], cardiac rehospitalization [2.42(1.81 to 3.24), p p p p p Conclusions The TyG index was significantly associated with MACCEs, suggesting that the TyG index may be a valid marker for risk stratification and prognosis in patients with T2DM and AMI. Trial registration Retrospectively registered.

Background PCSK9 inhibition has emerged as a potent pharmaceutical approach to lowering LDL cholesterol (LDL-C). Monoclonal anti-PCSK9 antibodies have been shown in recent clinical trials to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease, but the underlying mechanisms are not fully understood. Meanwhile, circulatory inflammation markers were not reduced with PCSK9 inhibitors, thus their effects on plaque inflammation remain elusive. Vessel wall imaging with magnetic resonance (VW-MRI) has enabled serial monitoring of changes in carotid plaque lipid content and inflammation noninvasively that correlates with coronary and carotid vascular events. Purpose Using serial VW-MRI, we studied the effects and time course of PCSK9 inhibition with alirocumab on carotid plaque lipid content and inflammation. Methods Patients with LDL-C ≥70 mg/dl on ≤70 mg per week atorvastatin or an equivalent (due to statin intolerance or treating-physician discretion) and soft carotid plaque(s) identified on ultrasound underwent carotid VW-MRI. Those with confirmed lipid-rich plaque(s) on VW-MRI received alirocumab (150 mg subcutaneously every other week) and were re-scanned at 3, 6, and 12 months after treatment. Carotid VW-MRI included pre- and post-contrast images for measuring percent lipid-rich necrotic core volume (%LRNC) and dynamic contrast-enhanced images for measuring the extravasation rate of gadolinium contrast (Ktrans, reflecting tissue blood flow, endothelial surface area, and microvessel permeability), a marker of plaque inflammation. The co-primary endpoints were changes in %LRNC and Ktrans at 12 months from baseline. Results Of 31 patients enrolled, 27 completed the study (mean age: 69±9; male: 67%; on statins and/or ezetimibe: 41%; median LDL-C: 120 mg/dl [interquartile range: 99, 158]). Alirocumab induced a 59% reduction in LDL-C (p Conclusions Serial VW-MRI documented plaque-stabilizing effects of PCSK9 inhibition with alirocumab, including plaque delipidation and attenuation of plaque inflammation. The reduction in plaque lipid content was apparent as early as 3 months. The reduction in Ktrans was not seen until 12 months of treatment and may indicate a later effect on microvascular structure and/or function. This observation represents the earliest time course of plaque morphology modification by non-statin therapy reported to date. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): The study was funded by an investigator-initiated grant from Regeneron and Sanofi.

Background Serum calcium levels were reported to be associated with risk of cardiovascular diseases. The aim of this study was to analyze the association between serum calcium levels and all-cause mortality in patients with acute myocardial infarction (AMI). Methods A total of consecutive 3886 AMI patients with serum calcium data available were included in this analysis. The baseline characteristics, including clinical and laboratory parameters were collected. Patients were classified into 4 equally-sized groups based on serum calcium values (≤2.15, 2.16–2.23, 2.24–2.31, ≥2.32 mmol/L). Serum calcium tests were finished within 12 hours after admission. Patients were followed up for a median of 2.0 years (interquartile range 0.6–4.0). The primary endpoint was all-cause mortality. Results Compared to upper quartiles of serum calcium groups, subjects in the lowest quartile group (≤2.15 mmol/L) were older, lower body mass index (BMI), had lower levels of LDL-C and albumin, but higher level of NTproBNP. During a median follow-up period of 2.0 years, all-cause death occurred significantly more in the lowest quartile group (19.8%, 11.9%, 8.0% and 9.2% among the 4 groups from lowest to highest quartile, p Conclusion Low serum calcium levels on admission independently predict mortality in patients with AMI. Further studies are required to determine whether calcium supplementation could improve outcomes in AMI patients with hypocalcemia. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Beijing Natural Science Foundation (no. 7194253);Scientific Research Common Program of Beijing Municipal Commission of Education (KM201910025017)

Background Whether elderly women over 80 years old with acute coronary syndrome (ACS) should actively receive PCI treatment is still controversial. Purpose We assessed the effectiveness and long-term clinical outcomes of PCI in very elderly women patients, and detected predictive factors which contributed to the major adverse cardiovascular and cerebrovascular events (MACCE). Methods Female ACS patients aged ≥80 years were continuously enrolled from the hospital database bank (n=729, a mean age of 83.6±3.1 years). All patients were followed up for MACCE: non-fatal MI, stroke, heart failure (HF) re-hospitalization, cardiovascular (CV) death, and the composite of them. Before and after Propensity Score (PS) Matching (1:1), the incidences of MACCE were compared between female PCI group (n=232) and medical group (n=497). Clinical and coronary artery characteristics were analyzed in PCI treatment patients with (n=56) and without MACCE (n=176). Multivariate Cox regression analysis was performed to identify risk factors which independently associated with MACCE in female PCI patients. Results A total of 31.8% women (n=232) received PCI treatment in the retrospective study.Compared to medical group, PCI treatment significantly reduced the incidences of non-fatal MI (6.2%, 20.2%, p Conclusion In very elderly women with ACS, PCI treatment significantly decreased the risks of MACCE and improves the long-term clinical outcomes.STEMI and elevated NT-proBNP value were independently associated with the increase of the composite MACCE after PCI in this population. Funding Acknowledgement Type of funding source: None

Understanding the quantitative relationship between multi-scale landscape pattern and water quality is of important theoretical significance for rational landscape configuration and non-point source pollution control. Using water quality data at nine monitoring sites on the Baihe River in the upper reaches of the Miyun Reservoir in Beijing, a correlation analysis and a multiple stepwise regression were used to determine the effects of the landscape characteristics on the water quality at different riparian buffer zone scales (100, 200, 300, 500, and 1000 m). The results showed that the impact of the landscape pattern, composed of both landscape composition and configuration, on the surface water quality, varied significantly with spatial scales. The landscape characteristics for the 300 m and 100 m buffer zones appeared to have slightly greater effects on the water quality index TN and TP, respectively. The patch density of cultivated land and the aggregation index of grassland were recognized as the dominant indices influencing TN for the 300 m buffer zone. The area proportion of rural residential at the 100 m buffer zone was the dominant index influencing TP. It is very important to optimize the landscape pattern within a 300 m width of a riparian buffer zone. In particular, the reasonable allocation of cultivated land, forest, and grassland, to improve the connectivity and aggregation of agricultural landscapes, and the control of rural residential areas and pollutant discharge along the river bank, will enhance the ecological function of the water quality of the Baihe River in Beijing. This will ensure drinking water safety from the Miyun Reservoir.

Background To explore the relevant factors for early liver transplantation (LT) after Kasai portoenterostomy (KP). Methods Retrospective analysis was performed for 200 children with biliary atresia, who underwent LT with hepatic failure after KP. According to the interval between KP and LT, they were divided into three groups: G1 (≤6-month), G2 (6-month~ 2-year) and G3 (> 2-year). Gender, age of Kasai portoenterostomy, jaundice-clearance, cholangitis after KP and liver function indexes before LT were compared among the three groups. Results The proportion of patients with age of KP (≤90-day) in G1 was lower than that in G3 (P = 0.003). Jaundice-clearance occurred in 6 (7.6%), 26(28.6%) and 26 (86.7%) patients after KP in G1, G2 and G3 respectively (P P = 0.035, 90-day was lower than that of children at operation age ≤ 90-day (P = 0.002). The NLS rate of the children with jaundice-clearance after KP was significantly better than that of the children without jaundice-clearance (P P = 0.026). The NLS rate of patients of G2 and G3 with cholangitis after KP was lower than that in children without cholangitis (P = 0.017). Multiple logistic regression analysis showed uncleared jaundice after KP was a risk factor for the NLS time in patients. Conclusion The age of KP (> 90-day), jaundice-unclear and early cholangitis could reduce the NLS time after KP, which were related to early liver transplantation. Jaundice-unclear was a risk factor for early liver transplantation.

Background: To evaluate the prognostic value of triglyceride glucose (TyG) index in non-diabetic acute coronary syndrome (ACS) patients with low-density lipoprotein cholesterol (LDL-C) below 1.8mmol/L.Methods: A total of 1655 non-diabetic ACS patients with LDL-C below 1.8mmol/L were included in the analysis. Patients were stratified into 2 groups. Incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, and major adverse cardiac and cerebral event (MACCE) during a median of 35.6-month follow-up were determined and compared between the 2 groups. The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL) ×fasting plasma glucose (mg/dL)/2].Results: Compared with the TyG index p =0.014) and larger infarct size in patients with AMI (pTNI: 10.4 vs. 4.8 ng/ml, p =0.003; pCKMB: 52.8 vs. 22.0 ng/ml, p =0.006; pMyo: 73.7 vs. 46.0 ng/ml, p =0.038). Although there was no significant difference in mortality between the 2 groups, the incidence of revascularization of TyG index ≥8.33 group was significantly higher than that of TyG index p =0.035). Multivariable Cox regression revealed that the TyG index was positively associated with revascularization [HR (95% CI): 1.67 (1.02,2.75), p=0.043].Conclusion: In non-diabetic ACS patients with LDL-C below 1.8mmol/L, the high TyG index level was associated with higher incidence of AMI, larger infarct size, and higher incidence of revascularization. The high TyG index level might be a valid predictor of subsequent revascularization.Trial registration: retrospectively registered.

Thrombolysis is the only approved therapy for acute ischemic stroke, but its success is limited by secondary hemorrhage. Wang and colleagues report that infusion of tissue plasminogen activator (tPA) in a murine stroke model results in increased neutrophil extracellular trap (NET) formation. NETs disrupt the blood-brain barrier and increase brain hemorrhage that can be decreased by DNase I or inhibition of NET production. Targeting NETs could improve the safety of tPA administration for stroke., Key Points NETs contribute to cerebrovascular complications of tPA via cGAS-STING activation and type 1 interferon response in ischemic brain.Targeting NETs or cGAS improves thrombolytic therapy by blocking tPA-associated BBB breakdown and hemorrhage., Intracerebral hemorrhage associated with thrombolytic therapy with tissue plasminogen activator (tPA) in acute ischemic stroke continues to present a major clinical problem. Here, we report that infusion of tPA resulted in a significant increase in markers of neutrophil extracellular traps (NETs) in the ischemic cortex and plasma of mice subjected to photothrombotic middle cerebral artery occlusion. Peptidylarginine deiminase 4 (PAD4), a critical enzyme for NET formation, is also significantly upregulated in the ischemic brains of tPA-treated mice. Blood–brain barrier (BBB) disruption after ischemic challenge in an in vitro model of BBB was exacerbated after exposure to NETs. Importantly, disruption of NETs by DNase I or inhibition of NET production by PAD4 deficiency restored tPA-induced loss of BBB integrity and consequently decreased tPA-associated brain hemorrhage after ischemic stroke. Furthermore, either DNase I or PAD4 deficiency reversed tPA-mediated upregulation of the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). Administration of cGAMP after stroke abolished DNase I–mediated downregulation of the STING pathway and type 1 interferon production and blocked the antihemorrhagic effect of DNase I in tPA-treated mice. We also show that tPA-associated brain hemorrhage after ischemic stroke was significantly reduced in cGas−/− mice. Collectively, these findings demonstrate that NETs significantly contribute to tPA-induced BBB breakdown in the ischemic brain and suggest that targeting NETs or cGAS may ameliorate thrombolytic therapy for ischemic stroke by reducing tPA-associated hemorrhage., Visual Abstract

Introduction: The impact of early-onset peritonitis (EOP) on patients with diabetes undergoing peritoneal dialysis (PD) has not been adequately addressed. We therefore sought to investigate the effects of EOP on the therapeutic response to management and long-term prognostic outcomes in patients with diabetes undergoing PD. Methods: For this retrospective cohort study, we analyzed the data for patients with end-stage renal disease, who were also suffering from diabetes mellitus and had undergone PD between January 1, 2013, and December 31, 2018. EOP was defined as the first episode of peritoneal dialysis-related peritonitis (PDAP) occurring within 12 months of PD initiation. All patients were divided into an EOP group and a later-onset peritonitis (LOP) group. Clinical data, treatment results, and outcomes were compared between groups. Results: Ultimately, 202 patients were enrolled for the analysis. Compared to the EOP group, the LOP group had more Streptococcus (p = 0.033) and Pseudomonas (p = 0.048). Patients with diabetes in the EOP group were less likely to have PDAP-related death (OR 0.13, CI: 0.02–0.82, p = 0.030). Patients with diabetes in the EOP group were more likely to have multiple episodes of PDAP and had higher rates of technical failure and poorer patient survival than those in the LOP group, as indicated by Kaplan-Meier analysis (p = 0.019, p = 0.004, and p < 0.001). In the multivariate Cox proportional hazards model, EOP was a significant predictor for multiple PDAP (HR 4.20, CI: 1.48–11.96, p = 0.007), technical failure (HR 6.37, CI: 2.21–18.38, p = 0.001), and poorer patient survival (HR 3.09, CI: 1.45–6.58, p = 0.003). Conclusions: The occurrence of EOP is significantly associated with lower rates of PDAP-related death and poorer clinical outcomes in patients with diabetes undergoing PD.

Vehicle following is a very important micro traffic model in traffic flow theory. In the actual traffic network, most of the vehicles are in vehicle following state, especially when the traffic flow density is large, and there are only small gap between the adjacent vehicles in a same lane. The speed is relatively slow in such case, and the phenomenon of vehicle following is particularly obvious. Because the vehicle movement is manually controlled, the driver is a very important factor in the analysis of vehicle movement. In this paper, we consider the regular law of driver's perception on the surrounding environment from the driver's point of view, and a car following model based on driving psychology field is proposed. Simulation is carried out based on MATLAB software, and the results validate this novel vehicle following model.

PCSK9 inhibitors lower low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events. The clinical benefits presumably result from favorable effects on atherosclerotic plaques. Lipid-core and plaque inflammation have been recognized as main determinants of risk for plaque rupture and cardiovascular events. Both can be noninvasively assessed with carotid MRI. We studied if PCSK9 inhibition with alirocumab induces regression in lipid-core or plaque inflammation within 6 months as measured by MRI. Patients with non-calcified carotid plaque(s) and baseline LDL-C ≥ 70 mg/dl, who were statin-intolerant or taking a low-dose statin (≤ 10 mg per day of atorvastatin or an equivalent), received subcutaneous alirocumab 150 mg every 2 weeks. Carotid MRI was performed at baseline and 6 months after treatment, including pre- and post-contrast images for measuring percent lipid-core volume (%LC) and dynamic contrast-enhanced images for measuring microvessel leakiness (K

Background: Does N-Terminal pro-brain natriuretic peptide (NT-proBNP) predict subsequent major adverse cardiovascular and cerebral event (MACCE) in patients received successful percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and had normal left ventricular ejection fraction (LVEF)? Methods: 3986 ACS patients were divided into 4 groups based on the quartile (Q) values of peak NT-proBNP measured during hospitalization. All patients were followed for MACCE, a composite of all-cause death, non-fatal myocardial infarction (MI) or stroke, and heart failure requiring hospitalization (HFRH), during a median of 35 months. The incidence of MACCE was compared among Q1-Q4. Receiver operation characteristic curves (ROC) were generated to compare the area under the curve (AUC) for MACCE, cardiovascular (CV) death and HFRH by adding NT-proBNP to the TIMI (thrombolysis in myocardial infarction) risk score.Results: The incidences of MACCE (5.6%, 9.1%, 13.0%, 20.1%, P P P P P =0.438). Each median level (337pg/ml) increase in NT-proBNP was significantly and independently associated with increased risk of MACCE (HR 1.02, 95%CI, 1.01-1.03; P P =0.0008), and HFRH (0.68 vs. 0.66, P =0.0017), MACCE (0.70 vs. 0.69, P =0.0012), respectively. Conclusion: NT-proBNP was significantly and independently associated with increased risk of subsequent MACCE in 3 years in ACS patients who received successful PCI and had normal LVEF, and improved the prognosis of major adverse events in addition to the TIMI risk score.

Ionizing irradiation kills pathogens by destroying nucleic acids without protein structure destruction. However, how pathogens respond to irradiation stress has not yet been fully elucidated. Here, we observed that Pseudomonas aeruginosa PAO1 could release nucleic acids into the extracellular environment under X-ray irradiation. Using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), X-ray irradiation was observed to induce outer membrane vesicle (OMV) formation in P. aeruginosa PAO1. The size distribution of the OMVs of the irradiated PAO1 was similar to that of the OMVs of the non-irradiated PAO1 according to nanoparticle tracking analysis (NTA). The pyocin-related proteins are involved in OMV production in P. aeruginosa PAO1 under X-ray irradiation conditions, and that this is regulated by the key SOS gene recA. The OMV production was significantly impaired in the irradiated PAO1 Δlys mutant, suggesting that Lys endolysin is associated with OMV production in P. aeruginosa PAO1 upon irradiation stress. Meanwhile, no significant difference in OMV production was observed between PAO1 lacking the pqsR, lasR, or rhlR genes and the parent strain, demonstrating that the irradiation-induced OMV biosynthesis of P. aeruginosa was independent of the Pseudomonas quinolone signal (PQS).

Neovascularization and vascular remodeling are functionally important for brain repair after stroke. We show that neutrophils accumulate in the peri-infarct cortex during all stages of ischemic stroke. Neutrophils producing intravascular and intraparenchymal neutrophil extracellular traps (NETs) peak at 3–5 days. Neutrophil depletion reduces blood-brain barrier (BBB) breakdown and enhances neovascularization at 14 days. Peptidylarginine deiminase 4 (PAD4), an enzyme essential for NET formation, is upregulated in peri-ischemic brains. Overexpression of PAD4 induces an increase in NET formation that is accompanied by reduced neovascularization and increased BBB damage. Disruption of NETs by DNase 1 and inhibition of NET formation by genetic ablation or pharmacologic inhibition of PAD increases neovascularization and vascular repair and improves functional recovery. Furthermore, PAD inhibition reduces stroke-induced STING-mediated production of IFN-β, and STING knockdown and IFN receptor-neutralizing antibody treatment reduces BBB breakdown and increases vascular plasticity. Collectively, our results indicate that NET release impairs vascular remodeling during stroke recovery., Following ischemic insult, neovascularization and vascular remodelling play an essential part in the repair of brain damage. Here the authors show that neutrophil extracellular traps serve a detrimental role in the regeneration process, limiting the functional recovery of the brain post injury.

Background Triglyceride glucose (TyG) index is considered a new marker for metabolic disorders. Although recent studies have found an association between TyG index level and vascular disease development, the prognostic value of TyG index in patients with acute myocardial infarction (AMI) remains unclear. Methods A total of 3181 patients with AMI, who underwent coronary angiography, were identified from the Cardiovascular Center of Beijing Friendship Hospital Database Bank and included in the analysis. Patients were stratified into 2 groups according to their baseline TyG index levels: the TyG index 2, smoker, diabetes mellitus, estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2, high-density lipoprotein cholesterol ≥ 1.01 mmol/L and left ventricular ejection fraction (LVEF) ≥ 0.50. The results also revealed that diabetes mellitus, previous AMI, eGFR, LVEF, and multi-vessel/left main coronary artery lesions were independent predictors of MACEs in patients with AMI (all P

Research on vibration characteristics of hydraulic valves is helpful to improve the performance of the hydraulic valve. In this article, a visualization experimental method is designed to capture the cone valve core vibration, and the image sequence of the vibration is obtained. And the least-squares contour fitting of the valve core is proposed to analyze the vibration characteristics of the valve core, which could eliminate noise in the vibration signal and improve accuracy. The difference of the least-squares variance between adjacent data points obtained by least-squares contour fitting is one order of magnitude smaller than corner detection method, while the signal-to-noise ratio is more than twice the corner detection. Furthermore, the frequency spectrum and amplitude of the valve core vibration are also discussed. The deviation of the valve core from the coordinate origin will increase with increasing of the pressure difference and decreasing of the pre-compression of the spring and the amplitude of vibration increases too. The vibration signal of the valve core under different conditions has similar frequency spectrum, which is mainly composed of the vibration signal spectrum caused by the fluctuation of oil pressure and turbulence of the liquid system.

To evaluate the efficacy of acupuncture therapy in the treatment of chronic urticaria.Randomized controlled trials of acupuncture treatment of chronic urticaria published from January of 2008 to October of 2018 were searched from databases of CNKI, VIP, Wanfang, CBM, PubMed, Embase and Cochrane Library by using key words "urticaria or urticarias" "acupuncture therapy" "acupuncture treatment" and "randomized controlled trial (RCT)". The retrieved RCT papers were input into EndNote X8 document management software for screening the qualified ones, followed by evaluating the quality of the screened papers. The data extraction table was designed, and the information and data needed for the research were accurately extracted. Finally, Review Manager 5.3 software was used to analyze the included literature.A total of 1 095 articles were retrieved, and 16 RCTs were included finally. The Meta-analysis showed that the total therapeutic efficacy wasAcupuncture treatment is significantly better than antihistamine administration alone in the treatment of chronic urticaria, with lower recurrence rate. High-quality clinical studies with rigorous design and large sample sizes are needed for providing more reliable evidence.

Background Current guidelines recommend angiotensin-converting-enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) as a first-line therapy in diabetic hypertensive patients and for secondary prevention in patients with obstructive coronary artery disease (OCAD). However, the effects of using ACEI/ARB before the initial diagnosis of OCAD on major adverse cardiac and cerebral event (MACCE) in diabetic hypertensive patients remain unclear. This study investigated whether using ACEI/ARB before the initial diagnosis of OCAD could be associated with improved clinical outcomes in diabetic hypertensive patients. Methods A total of 2501 patients with hypertension and diabetes, who were first diagnosed with OCAD by coronary angiography, were included in the analysis. Of the 2501 patients, 1300 did not used ACEI/ARB before the initial diagnosis of OCAD [the ACEI/ARB(-) group]; 1201 did [the ACEI/ARB(+) group]. Propensity score matching at 1:1 was performed to select 1050 patients from each group. Incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, heart function, and subsequent MACCE during a median of 25.4-month follow-up were determined and compared between the 2 groups. Results Compared with the ACEI/ARB(-) group, the ACEI/ARB(+) group had significantly lower incidence of AMI (22.5% vs. 28.4%, p Conclusions In diabetic hypertensive patients, treatment with ACEI/ARB before the initial diagnosis with OCAD was associated with decreased incidence of AMI, smaller infarct size, improved heart function, and lower incidences of non-fatal stroke and composite MACCE. Trial registration Retrospectively registered

Background ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) plays a vital role in preventing microvascular thrombosis and inflammation. Reduced ADAMTS13 levels in plasma have been detected in multiple sclerosis (MS) patients. In the present study, we have determined the role of ADAMTS13 in the disease progression of MS using a mouse model of experimental autoimmune encephalomyelitis (EAE). Methods Female C57BL/6 mice were immunized with MOG35–55 peptide and then treated with ADAMTS13 or vehicle in preventive and therapeutic settings. Mice were analyzed for clinical deficit, white matter demyelination and inflammatory cell infiltration. To explore the underlying mechanism, VWF expression and blood-spinal cord barriers (BSCB) were determined. Results Plasma ADAMTS13 activity was suppressed in EAE mice. ADAMTS13-treated EAE mice exhibited an ameliorated disease course, reduced demyelination, and decreased T lymphocyte, neutrophil and monocyte infiltration into the spinal cord. Consistently, ADAMTS13 treatment reduced VWF levels and inhibited BSCB breakdown in the spinal cords of EAE mice. However, leukocytes in the blood and spleen of EAE mice remained unaffected by ADAMTS13 administration. Conclusion Our results demonstrate that ADAMTS13 treatment ameliorates inflammatory responses, demyelination and disease course in EAE mice. Therefore, our study suggests that ADAMTS13 may represent a potential therapeutic strategy for MS patients.