Differential analysis of transcriptome of psychrophilic bacteria under different culture temperatures.

BACKGROUND: Psychrophilic bacteria can survive in a unique living environment. OBJECTIVE: To explore the mechanism of low temperature adaptation and the physiological function of thermophilic metabolic genes. METHOD: Serratia marcescens strain F13 stored in microbial laboratory was cultured at 5∘C, 10∘C and 25∘C respectively, and the obtained strains were sequenced by high-throughput transcriptome. Serratia marcescens strain CAV1761 was used as the reference strain. The data produced by transcriptome sequencing were statistically analyzed by biostatistics software such as soapnuke, soap and edger. The differentially expressed genes were found based on the gene expression, and analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. RESULTS: The results showed that there were 718 differential genes in F13-10 vs F13-5 comparison group, 1614 differential genes in F13-25 vs F13-5 comparison group and 1636 differential genes in F13-25 vs F13-10 comparison group. GO function enrichment analysis showed that the GO term mainly enriched by different genes in the three comparison groups was mostly related to the migration and transport of cellular or subcellular components, cell localization and transmembrane transporter activity, as well as cilia or flagella dependent cell movement. In the enrichment analysis of KEGG pathway, the three comparison groups all enriched the largest number of differential genes in the branch pathway of KEGG metabolism, followed by the branch pathway of environmental information processing. CONCLUSION: In F13-10 vs F13-5, the differential genes were mainly concentrated in 20 pathways such as ATP-binding cassette transport (ABC) transporters, thiamine metabolism and flagella assembly; In F13-25 vs F13-5, the differential genes are mainly concentrated in 20 pathways, such as (ABC) transporters, arginine and proline metabolism, two-component system and so on; In F13-25 vs F13-10, the differential genes are mainly concentrated in 20 pathways such as various types of glycan synthesis, two-component system and arginine metabolism.

Integrated analysis of differentially expressed genes and miRNA expression profiles in dilated cardiomyopathy.

Background: Although dilated cardiomyopathy (DCM) is a prevalent form of cardiomyopathy, the molecular mechanisms underlying its pathogenesis and progression remain poorly understood. It is possible to identify and validate DCM-associated genes, pathways, and miRNAs using bioinformatics analysis coupled with clinical validation methods. Methods: Our analysis was performed using 3 mRNA datasets and 1 miRNA database. We employed several approaches, including gene ontology (GO) analysis, KEGG pathway enrichment analysis, protein-protein interaction networks analysis, and analysis of hub genes to identify critical genes and pathways linked to DCM. We constructed a regulatory network for DCM that involves interactions between miRNAs and mRNAs. We also validated the differently expressed miRNAs in clinical samples (87 DCM ，83 Normal) using qRT-PCR.The miRNAs' clinical value was evaluated by receiver operating characteristic curves (ROCs). Results: 78 differentially expressed genes (DEGs) and 170 differentially expressed miRNAs (DEMs) were associated with DCM. The top five GO annotations were collagen-containing extracellular matrix, cell substrate adhesion, negative regulation of cell differentiation, and inflammatory response. The most enriched KEGG pathways were the Neurotrophin signaling pathway, Thyroid hormone signaling pathway, Wnt signaling pathway, and Axon guidance. In the PPI network, we identified 10 hub genes, and in the miRNA-mRNA regulatory network, we identified 8 hub genes and 15 miRNAs. In the clinical validation, we found 13 miRNAs with an AUC value greater than 0.9. Conclusion: Our research offers novel insights into the underlying mechanisms of DCM and has implications for identifying potential targets for diagnosis and treatment of this condition.

Machine learning-based prediction model for myocardial ischemia under high altitude exposure: a cohort study.

High altitude exposure increases the risk of myocardial ischemia (MI) and subsequent cardiovascular death. Machine learning techniques have been used to develop cardiovascular disease prediction models, but no reports exist for high altitude induced myocardial ischemia. Our objective was to establish a machine learning-based MI prediction model and identify key risk factors. Using a prospective cohort study, a predictive model was developed and validated for high-altitude MI. We consolidated the health examination and self-reported electronic questionnaire data (collected between January and June 2022 in 920th Joint Logistic Support Force Hospital of china) of soldiers undergoing high-altitude training, along with the health examination and second self-reported electronic questionnaire data (collected between December 2022 and January 2023) subsequent to their completion on the plateau, into a unified dataset. Participants were subsequently allocated to either the training or test dataset in a 3:1 ratio using random assignment. A predictive model based on clinical features, physical examination, and laboratory results was designed using the training dataset, and the model's performance was evaluated using the area under the receiver operating characteristic curve score (AUC) in the test dataset. Using the training dataset (n = 2141), we developed a myocardial ischemia prediction model with high accuracy (AUC = 0.86) when validated on the test dataset (n = 714). The model was based on five laboratory results: Eosinophils percentage (Eos.Per), Globulin (G), Ca, Glucose (GLU), and Aspartate aminotransferase (AST). Our concise and accurate high-altitude myocardial ischemia incidence prediction model, based on five laboratory results, may be used to identify risks in advance and help individuals and groups prepare before entering high-altitude areas. Further external validation, including female and different age groups, is necessary.

Wuzi Yanzong Pill relieves MPTP-induced motor dysfunction and neuron loss by inhibiting NLRP3 inflammasome-mediated neuroinflammation.

Parkinson disease (PD) is an age-related neurodegenerative disease, which is associated with the loss of dopaminergic neurons (DA neurons) in the substantia nigra pars compacta (SNpc), and neuroinflammation may lead to the occurrence of PD. Wuzi Yanzong Pill (WYP) has demonstrated neuroprotective and anti-inflammatory properties, but its molecular mechanism of action is still unclear. In this study, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and LPS-mediated BV2 microglia to explore WYP intervention, anti-inflammatory effect and molecular mechanism in vivo and in vitro. The results showed that oral administration of WYP in MPTP-induced PD mice for 2 weeks ameliorated abnormal motor dysfunction, attenuated the loss of TH + neurons in SNpc, protected dopaminergic neurons, and inhibited the activation of microglia in MPTP-induced PD mice and LPS-stimulated BV2 cell. Meanwhile, WYP intervention inhibited the expression of IL-6, TNF-α, Pro-IL-1ß, IL-1ß, Pro-IL-18, IL-18 and enhanced the expression of IL-10 in the SNpc of PD mice. Simultaneously, WYP intervention inhibited the expression of NLRP3 inflammasome, accompanied by the decrease of the TLR4/MyD88/NF-κB pathway. However, the exact target and interaction of WYP on NLRP3 inflammasome and TLR4/MyD88/NF-κB pathway still needs to be further investigated.

Mortality of Escalation and Modulation Antithrombotic Therapy in Coronary Artery Disease Patients: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The net clinical benefit of antithrombotic therapy (ATT) reflects the concomitant effects of bleeding and ischemic events. OBJECTIVES: We sought to assess the overall effect of the modulation or escalation of ATT on all-cause mortality as well as ischemic and bleeding events. METHODS: We performed a meta-analysis of randomized controlled trials comparing escalation or modulation of ATT versus standard ATT in patients with coronary artery disease. A total of 32 studies with 160,659 subjects were enrolled in this analysis. RESULTS: Neither escalation nor modulation of ATT has significant effect on all-cause mortality (escalation: relative risk [RR]: 0.94, 95% confidence interval [CI]: 0.85-1.04; modulation: RR: 0.90; 95% CI: 0.81-1.01). Compared with standard ATT therapy, escalation of ATT was associated with lower risk of myocardial infarction (MI; RR: 0.84, 95% CI: 0.76-0.94), but had a higher risk of major or minor bleeding (RR: 1.38, 95% CI: 1.15-1.66). Modulation of ATT was associated with a similar risk of MI (RR: 1.07, 95% CI: 0.96-1.19), but a reduced risk for major or minor bleeding (RR: 0.58, 95% CI: 0.51-0.66). Meta-regression combining both escalation and modulation studies found that the heterogeneity of all-cause mortality was mainly attributed to the heterogeneity of major or minor bleeding (adjusted R-squared = 100.00%, p = 0.004), but not to MI. CONCLUSION: Either escalation or modulation of ATT has little benefit in all-cause mortality. The variability of the treatment effects on all-cause mortality was mainly attributed to the variability of major or minor bleeding, but not to MI.

Quercetin inhibits testicular toxicity induced by the mixture of three commonly used phthalates in rats.

BACKGROUND: Phthalates (PEs), such as butyl benzyl phthalate, dibutyl phthalate and di(2-ethylhexyl) phthalate, are one of the most widely used plasticizers, and humans are increasingly exposed to them. Phytochemical quercetin (Que) is a typical flavonoid with several biological effects, such as antioxidative and anti-inflammatory. The present study was designed to explore the effect of Que on testicular toxicity caused by the mixture of three commonly used PEs (MPEs), and the underlying mechanism. Forty male Sprague-Dawley rats were randomly and equally divided into five groups (n = 8). Rats in control the group were orally treated with the excipient. Rats in the MPEs group were orally administered with 900 mg kg-1 day-1 MPEs, whereas rats in the MPEs+L-Que, MPEs+M-Que and MPEs+H-Que groups were simultaneously treated with 900 mg kg-1 day-1 MPEs and, respectively, 10, 30 and 90 mg kg-1 day-1 Que for 30 days. RESULTS: Compared with the control group, the testes weight, epididymides weight, serum testosterone, luteinizing hormone, follicle-stimulating hormone and estradiol levels, and anogenital distance in the MPEs group were significantly decreased (P < 0.05). The testicular tissues were injured with atrophy of seminiferous tubules, hyperplasia of Leydig cells and arrest of spermatogenesis in the MPEs group. Testicular steroidogenic proteins (StAR, P450scc, CYP17A1 and 17ß-HSD, P450arom) were up-regulated, whereas P-element-induced wimpy testis proteins (PIWIL1 and PIWIL2) were down-regulated in the MPEs group (P < 0.05). However, the alterations of these parameters were inhibited in the MPEs+M-Que and MPEs+H-Que groups. CONCLUSION: MPEs disturbed steroid hormone metabolism and caused testicular injuries. Que could inhibit testicular toxicity of MPEs, which might relate to the improved regulation of steroid hormone metabolism. © 2022 Society of Chemical Industry.

Protective effect of quercetin against phthalates induced hepatotoxicity in rats.

Humans are increasingly exposed to ubiquitous phthalates (PEs), e.g. butyl benzyl phthalate (BBP), dibutyl phthalate (DBP), and di(2-ethylhexyl) phthalate (DEHP), which are widely used plasticizers in polymer products. This study was aimed to investigate the effect of phytochemical quercetin (Que) on hepatotoxicity caused by the mixture of the 3 commonly used PEs (MPEs), and further to explore the underlying mechanism. Forty male Sprague-Dawley rats were randomly divided into control group, MPEs group, and MPEs combined Que at Low-, Median-, and High-dose groups; rats in MPEs group were orally administered with 900 mg/kg/d MPEs, whereas rats in MPEs combined Que groups were simultaneously treated with 900 mg/kg/d MPEs and respectively 10, 30, and 90 mg/kg/d Que. The intervention last 30 days. Compared with control group, serum ALT, AST, LDH and AKP, and hepatic MDA, SOD, CAT and GPx were significantly increased, whereas, serum albumin and total protein were significantly decreased in MPEs group (P < 0.05); hepatic histopathological observation showed numerous inflammatory cells infiltration, hepatocyte ballooning degeneration, and numerous residual erythrocytes in the central vein in MPEs group. Western-blot analysis showed that hepatic Keap1 was downregulated, whereas Nrf2 and HO-1 were upregulated in MPEs group (P < 0.05). However, the alterations of these parameters were alleviated in MPEs combined Que at Median- and High-dose groups. The results indicated that MPEs-induced hepatic oxidative stress, and caused hepatic injuries; whereas, Que inhibited MPEs' hepatotoxicity, which might relate to Que's ability of quenching free radicals directly, and restored the regulation of Nrf2 signaling pathway.

Development of a highly efficient virus-free regeneration system of Salvia miltiorrhiza from Sichuan using apical meristem as explants.

BCAKGROUND: The dry root and rhizome of Salvia miltiorrhiza are used to treat cardiovascular diseases, chronic pain, and thoracic obstruction over 2000 years in Asian countries. For high quality, Sichuan Zhongjiang is regarded as the genuine producing area of S. miltiorrhiza. Given its abnormal pollen development, S. miltiorrhiza from Sichuan (S.m.-SC) relies on root reproduction and zymad accumulation; part of diseased plants present typical viral disease symptoms and seed quality degeneration. This study aim to detected unknown viruses from mosaic-diseased plants and establish a highly efficient virus-free regeneration system to recover germplasm properties. RESULTS: Tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were detected from mosaic-diseased plants. Primary apical meristem with two phyllo podium in 0.15-0.5 mm peeled from diseased plants were achieved 73.33% virus-free rate. The results showed that the medium containing MS, 0.5 mg/L 6-BA, 0.1 mg/L NAA, 0.1 mg/L GA3, 30 g/L sucrose and 7.5 g/L agar can achieve embryonic-tissue (apical meristem, petiole and leaf callus) high efficient organogenesis. For callus induction, the optimal condition was detected on the medium containing MS, 2 mg/L TDZ, 0.1 mg/L NAA by using secondary petiole of virus-free plants under 24 h dark/d condition for 21 d. The optimal system for root induction was the nutrient solution with 1/2 MS supplemented with 1 mg/L NAA. After transplant, the detection of agronomic metric and salvianolic acid B content confirmed the great germplasm properties of S.m.-SC virus-free plants. CONCLUSIONS: A highly efficient virus-free regeneration system of S.m.-SC was established based on the detected viruses to recover superior seed quality. The proposed system laid support to control disease spread, recover good germplasm properties in S.m.-SC.

Association of serum complement C1q with cardiovascular outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention.

OBJECTIVE: To determine the association of serum complement C1q levels with cardiovascular outcomes among patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), and evaluate the value of C1q modified by high-sensitivity C-reactive protein (hs-CRP) levels as an independent predictor. METHODS: As a single-center prospective observational study, we analyzed 1701 patients who had received primary or elective PCI for ACS at Beijing Anzhen Hospital, Capital Medical University, Beijing, China between June 1, 2016 and November 30, 2017. The associations of C1q modified by hs-CRP with major adverse cardiovascular events (MACE) were determined in survival analysis. RESULTS: Patients with the lowest C1q tertile had the highest cumulative risk of MACE (log-rank P = 0.007). In fully adjusted Cox regression models, stratifying the total population according to hs-CRP dichotomy, C1q was significantly associated with MACE in patients with hs-CRP levels less than 2 mg/L but not in those with 2 mg/L or more (P interaction = 0.02). In patients with hs-CRP levels less than 2 mg/L, with the lowest C1q tertile as reference, the risk of MACE was reduced by 40.0% in the middle C1q tertile [hazard ratio (HR) = 0.600, 95% CI: 0.423-0.852, P = 0.004] and by 43.9% in the highest C1q tertile (HR = 0.561, 95% CI: 0.375-0.840, P = 0.005). CONCLUSIONS: Serum complement C1q is significantly associated with cardiovascular outcomes in patients with ACS undergoing PCI, only when hs-CRP levels are less than 2 mg/L. This finding implicates the usefulness of C1q for the risk stratification in ACS patients with reduced systemic inflammation.

Effect of alirocumab on coronary plaque in patients with coronary artery disease assessed by optical coherence tomography.

BACKGROUND: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been demonstrated to produce significantly greater reduction in LDL cholesterol levels and cardiovascular events than standard statin therapy. However, evidence on the impact of PCSK9 inhibitors on coronary plaque composition and morphology is limited. METHODS: In this open-label randomized study, eligible patients with intermediate coronary lesions and elevated LDL cholesterol values were randomized to either alirocumab 75 mg Q2W plus statin (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) therapy or standard care. Optical coherence tomography (OCT) assessments for target lesions were obtained at baseline and at 36 weeks of follow-up. RESULTS: LDL cholesterol levels were significantly decreased in both the alirocumab and standard care arms, whereas the absolute reduction in LDL cholesterol was significantly greater in patients treated with alirocumab (1.72 ± 0.51 vs. 0.96 ± 0.59, P < 0.0001). Compared with standard care, the addition of alirocumab to statins was associated with significantly greater increases in minimum fibrous cap thickness (18.0 [10.8-29.2] µm vs 13.2 [7.4-18.6] µm; P = 0.029), greater increases in minimum lumen area (0.20[0.10-0.33] mm2 vs 0.13 [0.12-0.24] mm2; P = 0.006) and a greater diminution in maximum lipid arc (15.1̊ [7.8-24.5] vs. 8.4̊ [2.0-10.5]; P = 0.008). CONCLUSIONS: The addition of alirocumab to statins can not only provide additional LDL cholesterol lowering effects but also have a potential role in promoting a more stable plaque phenotype. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04851769 . Registered 2 Mar 2019.

Cobalt-Nickel Phosphate Composites for the All-Phosphate Asymmetric Supercapacitor and Oxygen Evolution Reaction.

Recently, design of cost-effective multifunctional electromaterials for supercapacitors and oxygen evolution reaction (OER) and enhancing their functionalities have become an emphasis in energy storage and conversion. Herein, a series of cheap and functional phosphate composites with different ratios of cobalt and nickel are synthesized using a simple polyalcohol refluxing method, and their excellent capacity and OER properties are systematically studied. Notably, owing to the different major role of Co and Ni elements in the phosphate composites for capacity and OER, the optimal electroconductibility, structural adjustment, electrochemical active sites, and activities for capacity and OER are obtained from the composites with the different ratios of Co/Ni. In addition, using high-capacity BiPO4 (BPO) as the negative electrodes, the new type of all-phosphate asymmetric supercapacitor (CNPO-40//BPO) shows a high energy density and reaches 36.84 W h kg-1 at a power density of 254.52 W kg-1. Its cyclic stability is also more excellent than that of the CNPO-40//AC device using commercial activated carbon as the negative electrodes. This study is beneficial to the more in-depth research on efficient dual-function electromaterials in capacity and OER and provides a high-efficient way to improve the practicality of asymmetric supercapacitors using the high-capacity Bi-based electromaterials as the negative electrodes.

Differential Impact of Cigarette Smoking on Prognosis in Women and Men Undergoing Percutaneous Coronary Intervention.

We sought to compare the effects of smoking on clinical outcomes in women and men with coronary artery disease undergoing percutaneous coronary intervention (PCI). We prospectively followed up 10 369 patients undergoing elective PCI. All patients were stratified according to smoking status and sex. The impacts of smoking on long-term major adverse cardiovascular events (MACEs, the composite of all-cause death, myocardial infarction, or target vessel revascularization) were assessed. Among 7773 men and 2596 women undergoing PCI, the prevalence of cigarette smoking was 66.7% (n = 5185) and 11.0% (n = 286; P < .001). During the 3 years of follow-up (median: 20.6 months), smoking increased MACE in both men and women (men 10.8% vs 8.1%, P < .001; women 23.2% vs 6.4%; P < .001). After adjusting for baseline characteristics, smoking had a greater effect on MACE in women (hazard ratio [HR]: 3.68, 95% confidence interval [CI]: 1.86-7.28; P < .001) compared with men (HR: 1.35, 95% CI: 1.03-1.77; P = .005, interaction P = .026). There was a lower prevalence of smoking in women compared to men among patients undergoing PCI. However, smoking confers a higher excess risk for MACE among women compared with men.

New predictors of in-stent restenosis in patients with diabetes mellitus undergoing percutaneous coronary intervention with drug-eluting stent.

BACKGROUND: Percutaneous coronary intervention (PCI) had become the major therapeutic procedure for coronary artery disease (CAD), but the high rate of in-stent restenosis (ISR) still remained an unsolved clinical problem in clinical practice. Increasing evidences suggested that diabetes mellitus (DM) was a major risk factor for ISR, but the risk predictors of ISR in CAD patients with DM had not been well characterized. The aim of this study was to investigate the clinical and angiographic characteristic predictors significantly associated with the occurrence of ISR in diabetic patients following coronary stenting with drug-eluting stent (DES). METHODS: A total of 920 patients with diabetes who diagnosed CAD and underwent coronary DES implantation at Beijing Anzhen Hospital in China were consecutively enrolled from January 2012 to December 2012. Of these, 440 patients underwent the second angiography within ≥ 6 months due to the progression of treated target lesions. Finally, 368 of these patients who met the inclusion and exclusion criteria were followed up by angiography after baseline PCI. According to whether ISR was detected at follow-up angiography, patients were divided into the ISR group (n = 74) and the non-ISR group (n = 294). The independent predictors of ISR in patients with DM were explored by multivariate Cox's proportional hazards regression models. RESULTS: A total of 368 patients (260 women and 108 men) with a mean ages of 58.71 ± 10.25 years were finally enrolled in this study. Of these, ISR occurred in 74/368 diabetic patients (20.11%) by follow-up angiography. Univariate analysis showed that most baseline characteristics of the ISR and non-ISR group were similar. Patients in the ISR group had significantly higher serum very low density lipoprotein cholesterol (VLDL-C), triglyceride (TG) and uric acid (UA) levels, more numbers of target vessel lesions, higher prevalence of multi-vessel disease, higher SYNTAX score, higher rate of previous but lower rate of drinking compared with patients in the non-ISR group. The independent predictors of ISR in patients with DM after DES implantation included VLDL-C (HR = 1.85, 95% CI: 1.24-2.77, P = 0.002), UA (per 50 µmol/L increments, HR = 1.19, 95% CI: 1.05-1.34, P = 0.006), SYNTAX score (per 5 increments, HR = 1.34, 95% CI: 1.03-1.74, P = 0.031) and the history of PCI (HR = 3.43, 95% CI: 1.57-7.80, P = 0.003) by the multivariate Cox's proportional hazards regression analysis. CONCLUSIONS: The increased serum VLDL-C and UA level, higher SYNTAX score and the history of previous PCI were independent predictors of ISR in patients with DM after coronary DES implantation. It provided new evidence for physicians to take measures to lower the risk of ISR for the better management of diabetic patients after PCI.

Yunnanterpene G, a spiro-triterpene from the roots of Cimicifuga foetida, downregulates the expression of CD147 and MMPs in PMA differentiated THP-1 cells.

A new cycloartane triterpene, yunnanterpene G (1), containing an oxaspiro[5.4]decane moiety, was purified from the roots of Cimicifuga foetida. The new structure was determined from spectroscopic data and the X-ray diffraction method. Biological evaluations revealed that compound 1 significantly inhibited the mRNA expression of the atherosclerosis-related adhesion molecule CD147 (extracellular matrix metalloproteinase inducer, EMMPRIN), and proteolytic enzymes matrix metalloproteinase 2 (MMP-2), MMP-9 and MMP-14, in a dose-dependent manner in phorbol-12-myristate-13-acetate-induced human monocytic THP-1 cells by quantitative real-time PCR method. At the same time, the migration ability of the induced THP-1 cells was potently inhibited. Furthermore, western blot experiments showed that compound 1 at 25 µM strongly suppressed phosphorylation of NF-κB p65 and p38 MAPK in the differentiated THP-1 cells.

Periprocedural heparin bridging in patients receiving oral anticoagulation: a systematic review and meta-analysis.

BACKGROUND: Periprocedural heparin bridging therapy aims to reduce the risk of thromboembolic events in patients requiring an interruption in their anticoagulation therapy for the purpose of an elective procedure. The efficacy and safety of heparin bridging therapy has not been well established. OBJECTIVES: To compare through meta-analysis the effects of heparin bridging therapy on the risk of major bleeding and thromboembolic events of clinical significance among patients taking oral anticoagulants. METHODS: We searched PubMed, EMBASE and the Cochrane library from January 2005 to July 2016. Studies were included if they reported clinical outcomes of patients receiving heparin bridging therapy during interruption of oral anticoagulant for operations. Data were pooled using random-effects modeling. RESULTS: A total of 25 studies, including 6 randomized controlled trials and 19 observational studies, were finally included in this analysis. Among all the 35,944 patients, 10,313 patients were assigned as heparin bridging group, and the other 25,631 patients were non-heparin bridging group. Overall, compared with patients without bridging therapy, heparin bridging therapy increased the risk of major bleeding (OR = 3.23, 95%CI: 2.06-5.05), minor bleeding (OR = 1.52, 95%CI: 1.06-2.18) and overall bleeding (OR = 2.83, 95%CI: 1.86-4.30).While there was no significant difference in thromboembolic events (OR = 0.99,95%CI: 0.49-2.00), stroke or transient ischemic attack(OR = 1.45, 95%CI: 0.93-2.26,) or all-cause mortality (OR = 0.71, 95%CI: 0.31-1.65). CONCLUSIONS: Heparin-bridging therapy increased the risk of major and minor bleeding without decreasing the risk of thromboembolic events and all cause death compared to non-heparin bridging.

Elevated IL-37 levels in the plasma of patients with severe coronary artery calcification.

BACKGROUND: Coronary artery calcification (CAC) is a predictor of cardiovascular events and plaque burden and is closely associated with chronic inflammation. Interleukin (IL)-37 is a newly discovered member of the IL-1 family and is considered an anti-inflammatory cytokine. Our recent study on mice indicated that IL-37 could attenuate atherosclerosis and vascular calcification, which suggests that IL-37 could be associated with the development of atherosclerosis and related diseases. The aim of this study was to investigate if IL-37 plays a role in the progression of CAC in patients. METHODS: Two hundred participants with suspected cardiovascular disease were recruited. The levels of plasma IL-37, osteoprotegerin (OPG), hypersensitive C-reactive protein (hsCRP) together with other biochemical parameters were measured, and a coronary calcium assessment was carried out by multi-detector row CT. A score of < 10 AU (Agatston units) denotes an absence of CAC, a score of 11-100 AU denotes mild CAC, 101-400 denotes moderate CAC, and > 400 AU denotes severe CAC. RESULTS: Our initial data showed that there were no apparent differences in plasma IL-37 levels among patients with or without mild or moderate CAC. However, IL-37 levels were significantly increased in patients with severe CAC (P < 0.001). Similar results were observed for plasma OPG and hsCRP levels. When IL-37 levels in patients with severe calcification were compared with that in all of the other non-severe CAC groups, it became apparent that there was a significant positive correlation between IL-37 level and severe CAC (r = 0.360, P < 0.001; OR = 1.033) using Spearman's correlation and binary logistic regression analysis. CONCLUSIONS: This study demonstrates that the anti-inflammatory cytokine IL-37 is associated with high coronary calcium levels, suggesting that IL-37 expression may be caused by the activation of inflammation and that IL-37 might become a predictor of severe CAC in the future, which requires further investigation.

Atorvastatin attenuates plaque vulnerability by downregulation of EMMPRIN expression via COX-2/PGE2 pathway.

Extracellular matrix metalloproteinase inducer (EMMPRIN) reportedly has a key regulatory role in matrix metalloproteinase (MMP) activities and the progression of atherosclerosis. Statins, which are anti-atherosclerotic pharmacological agents, are widely applied in clinical settings. The aim of the present study was to investigate the pharmaceutical effect of atorvastatin on EMMPRIN expression in atherosclerotic plaques. An atherosclerotic mouse model was established using apoliprotein E-deficient (ApoE-/-) mice raised on a high-fat diet. Additionally, a low (5 mg/kg/day) or high dosage (10 mg/kg/day) of atorvastatin suspension was administered orally for eight weeks, beginning on week 7 or 11 respectively. The effects of atorvastatin on atherosclerotic plaque formation and EMMPRIN expression were subsequently determined. The THP-1 cell line was used to investigate the effect of atorvastatin on EMMPRIN expression in vitro. The results demonstrated that the high-fat diet led to vulnerable plaques (VPs) and increased EMMPRIN expression in VPs in ApoE-/- mice. Atorvastatin treatment decreased EMMPRIN expression in the aortas and plaques of ApoE-/- mice. In vitro, oxidized low-density lipoprotein (ox-LDL) induced the expression of cyclooxygenase-2 (COX-2) and EMMPRIN in THP-1 macrophages, and atorvastatin inhibited ox-LDL-induced expression of PGE2, EMMPRIN and COX-2 in THP-1 macrophages. Therefore, the present data indicated that atorvastatin treatment reduces the vulnerability of atherosclerotic plaques and expression of EMMPRIN, and that the inhibitory effect of atorvastatin on EMMPRIN may occur via the COX-2/PGE2 signaling pathway in macrophages.

MicroRNA-99a inhibits insulin-induced proliferation, migration, dedifferentiation, and rapamycin resistance of vascular smooth muscle cells by inhibiting insulin-like growth factor-1 receptor and mammalian target of rapamycin.

Patients with type 2 diabetes mellitus (T2DM) are characterized by insulin resistance and are subsequently at high risk for atherosclerosis. Hyperinsulinemia has been associated with proliferation, migration, and dedifferentiation of vascular smooth muscle cells (VSMCs) during the pathogenesis of atherosclerosis. Moreover, insulin-like growth factor-1 receptor (IGF-1R) and mammalian target of rapamycin (mTOR) have been demonstrated to be the underlying signaling pathways. Recently, microRNA-99a (miR-99a) has been suggested to regulate the phenotypic changes of VSMCs in cancer cells. However, whether it is involved in insulin-induced changes of VSCMs has not been determined. In this study, we found that insulin induced proliferation, migration, and dedifferentiation of mouse VSMCs in a dose-dependent manner. Furthermore, the stimulating effects of high-dose insulin on proliferation, migration, and dedifferentiation of mouse VSMCs were found to be associated with the attenuation of the inhibitory effects of miR-99a on IGF-1R and mTOR signaling activities. Finally, we found that the inducing effect of high-dose insulin on proliferation, migration, and dedifferentiation of VSMCs was partially inhibited by an active mimic of miR-99a. Taken together, these results suggest that miR-99a plays a key regulatory role in the pathogenesis of insulin-induced proliferation, migration, and phenotype conversion of VSMCs at least partly via inhibition of IGF-1R and mTOR signaling. Our results provide evidence that miR-99a may be a novel target for the treatment of hyperinsulinemia-induced atherosclerosis.

Clinical Characteristics of Patients with Drug-induced Liver Injury.

BACKGROUND: Drug is an important cause of liver injury and accounts for up to 40% of instances of fulminant hepatic failure. Drug-induced liver injury (DILI) is increasing while the diagnosis becomes more difficult. Though many drugs may cause DILI, Chinese herbal medicines have recently emerged as a major cause due to their extensive use in China. We aimed to provide drug safety information to patients and health carers by analyzing the clinical and pathological characteristics of the DILI and the associated drug types. METHODS: A retrospective analysis was conducted in 287 patients diagnosed with DILI enrolled in our hospital from January 2011 to December 2015. The categories of causative drugs, clinical and pathological characteristics were reviewed. RESULTS: Western medicines ranked as the top cause of DILI, accounting for 163 out of the 287 DILI patients (56.79%) in our study. Among the Western medicine, antituberculosis drugs were the highest cause (18.47%, 53 patients) of DILI.   Antibiotics (18 patients, 6.27%) and antithyroid (18 patients, 6.27%) drugs also ranked among the major causes of DILI. Chinese herbal medicines are another major cause of DILI, accounting for 36.59% of cases (105 patients). Most of the causative Chinese herbal medicines were those used to treat osteopathy, arthropathy, dermatosis, gastropathy, leukotrichia, alopecia, and gynecologic diseases. Hepatocellular hepatitis was prevalent in DILI, regardless of Chinese herbal medicine or Western medicine-induced DILI. CONCLUSIONS: Risks and the rational use of medicines should be made clear to reduce the occurrence of DILI. For patients with liver injury of unknown origin, liver tissue pathological examination is recommended for further diagnosis.

Five-year outcomes of ST-elevation myocardial infarction versus non-ST-elevation acute coronary syndrome treated with biodegradable polymer-coated sirolimus-eluting stents: Insights from the CREATE trial.

BACKGROUND: Long-term outcome of drug-eluting stents (DES) for ST-elevation myocardial infarction (STEMI) versus non-ST-elevation acute coronary syndrome (NSTE-ACS) remains unclear. This study sought to compare the long-term outcomes of biodegradable polymer-coated DES in patients with STEMI versus NSTE-ACS. METHODS: We explored a post hoc analysis of the 5-year outcome of the CREATE trial in the subgroup of patients with STEMI (n=318) versus NSTE-ACS (n=1223) who were implanted with biodegradable polymer-coated DES. The primary outcome was the rate of major adverse cardiac events (MACE) at 5 years. Clopidogrel and aspirin for 6 months followed by chronic aspirin therapy were recommended. RESULTS: STEMI patients showed a trend of increase in MACE (8.7% vs. 6.8%, log rank p=0.289) compared to NSTE-ACS patients at 5 years, and a greater risk of cardiac death (5.4% vs. 2.1%, log rank p=0.003), mainly driven by the higher cardiac death rate within the first month after stent placement (log rank p=0.003) and the last year of follow-up (log rank p=0.001). No significant difference in stent thrombosis was found between them (3.1% vs. 2.5%, log rank p=0.653). Prolonged clopidogrel therapy (>6 months) showed no effect on risk of MACE or stent thrombosis between the two groups (both p for interaction >0.1). CONCLUSIONS: STEMI patients have a higher risk of cardiac mortality compared with NSTE-ACS patients after biodegradable polymer-coated DES placement, primarily attribute to more cardiac deaths that happened within the first month after the event and the last year of follow-up.