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Objectives: To examine serum concentrations of neurotensin, pannexin-1 and sestrin-2, and their correlations with subjective and objective sleep quality and cognitive function in the patients with chronic insomnia disorder (CID). Methods: Sixty-five CID patients were enrolled continuously and fifty-six good sleepers in the same period were served as healthy controls (HCs). Serum levels of neurotensin, pannexin-1 and sestrin-2 were measured by enzyme-linked immunosorbent assays. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and polysomnography, and mood was evaluated by 17-item Hamilton Depression Rating Scale. General cognitive function was assessed with the Chinese-Beijing Version of Montreal Cognitive Assessment and spatial memory was evaluated by Blue Velvet Arena Test (BVAT). Results: Relative to the HCs, the CID sufferers had higher levels of neurotensin (t=5.210, p<0.001) and pannexin-1 (Z=4.169, p<0.001), and lower level of sestrin-2 (Z=2.438, p=0.015). In terms of objective sleep measures, pannexin- 1 was positively associated with total sleep time (r=0.562, p=0.002) and sleep efficiency (r=0.588, p=0.001), and negatively with wake time after sleep onset (r=0.590, p=0.001) and wake time (r=0.590, p=0.001); sestrin-2 was positively associated with percentage of rapid eye movement sleep (r=0.442, p=0.016) and negatively with non-rapid eye movement sleep stage 2 in the percentage (r=0.394, p=0.034). Adjusted for sex, age and HAMD, pannexin-1 was still associated with the above objective sleep measures, but sestrin-2 was only negatively with wake time (r=0.446, p=0.022). However, these biomarkers showed no significant correlations with subjective sleep quality (PSQI score). Serum concentrations of neurotensin and pannexin-1 were positively associated with the mean erroneous distance in the BVAT. Adjusted for sex, age and depression, neurotensin was negatively associated with MoCA score (r=0.257, p=0.044), pannexin-1 was positively associated with themean erroneous distance in the BVAT (r=0.270, p=0.033). [ABSTRACT FROM AUTHOR]

Objectives: To examine serum concentrations of neurotensin, pannexin-1 and sestrin-2, and their correlations with subjective and objective sleep quality and cognitive function in the patients with chronic insomnia disorder (CID). Methods: Sixty-five CID patients were enrolled continuously and fifty-six good sleepers in the same period were served as healthy controls (HCs). Serum levels of neurotensin, pannexin-1 and sestrin-2 were measured by enzyme-linked immunosorbent assays. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and polysomnography, and mood was evaluated by 17-item Hamilton Depression Rating Scale. General cognitive function was assessed with the Chinese-Beijing Version of Montreal Cognitive Assessment and spatial memory was evaluated by Blue Velvet Arena Test (BVAT). Results: Relative to the HCs, the CID sufferers had higher levels of neurotensin (t=5.210, p<0.001) and pannexin-1 (Z=-4.169, p<0.001), and lower level of sestrin-2 (Z=-2.438, p=0.015). In terms of objective sleep measures, pannexin-1 was positively associated with total sleep time (r=0.562, p=0.002) and sleep efficiency (r=0.588, p=0.001), and negatively with wake time after sleep onset (r=-0.590, p=0.001) and wake time (r=-0.590, p=0.001); sestrin-2 was positively associated with percentage of rapid eye movement sleep (r=0.442, p=0.016) and negatively with non-rapid eye movement sleep stage 2 in the percentage (r=-0.394, p=0.034). Adjusted for sex, age and HAMD, pannexin-1 was still associated with the above objective sleep measures, but sestrin-2 was only negatively with wake time (r=-0.446, p=0.022). However, these biomarkers showed no significant correlations with subjective sleep quality (PSQI score). Serum concentrations of neurotensin and pannexin-1 were positively associated with the mean erroneous distance in the BVAT. Adjusted for sex, age and depression, neurotensin was negatively associated with MoCA score (r=-0.257, p=0.044), pannexin-1 was positively associated with themean erroneous distance in the BVAT (r=0.270, p=0.033). Conclusions: The CID patients had increased neurotensin and pannexin-1 and decreased sestrin-2 in the serum levels, indicating neuron dysfunction, which could be related to poor sleep quality and cognitive dysfunction measured objectively. [ABSTRACT FROM AUTHOR]

Background: Primary biliary cholangitis (PBC) is a chronic intrahepatic cholestatic autoimmune liver disease characterized by inflammatory injury of small and medium-sized bile ducts in the liver. The pathogenesis of PBC has yet to be entirely understood. CD47/signal-regulatory protein alpha (SIRPa) is closely related to developing autoimmune diseases by promoting inflammatory response. However, the effect of CD47/SIRPa on inflammatory response in PBC patients is still unclear. Objective: We investigated the expression of CD47/SIRPa and the effect of inflammatory cytokines on the CD47 expression, analyzed potential autoantibodies against CD47 and the effect of anti-CD47 antibody on the inflammatory response in PBC, provided laboratory basis for the study of the pathogenesis and targets for non-invasive diagnosis and treatment on PBC. Methods: The expression levels of CD47 and SIRPa on peripheral blood mononuclear cells (PBMC) were measured in 14 patients with PBC (the PBC group) and 13 healthy subjects (the Control group) by flow cytometry (FCM). The PBMC derived from healthy subjects were stimulated with healthy subjects' serum, PBC patients' serum, IFN-a or TNF-a, and the CD47 expression level on CD14+ monocytes was detected by FCM. The level of serum anti-CD47 antibody or IFN-a in PBC patients and healthy subjects was analyzed by ELISA. FCM was used to examine the TNF-a expression level in CD14+ monocytes of healthy subjects stimulated with isotype control antibody, anti-CD47 antibody, LPS or LPS combined with CD47 antibody. Results: The CD47 expression level on the CD14+ monocytes in PBC patients was statistically higher than that in the Control group (P<0.01). Compared with the Control group (PBMC+healthy serum), the CD47 expression on CD14+ monocyte stimulated with the PBC patients' serum (PBMC+PBC patients' serum) was increased (P<0.001); the CD47 expression on CD14+ monocyte stimulated with IFN-a (PBMC + IFN-a) increased gradually with the increased concentration of IFN-a (P<0.05). However, there was no similar trend on CD14+ monocyte stimulated with the TNF-a (PBMC+TNF-a) (P>0.05). The levels of serum anti-CD47 antibody and IFN-a in the PBC patients were higher than those in healthy subjects (P<0.05). The TNF-a expression level in CD14+ monocyte stimulated with the LPS (PBMC+LPS) or anti-CD47 antibody+LPS group (PBMC +LPS+anti-CD47 antibody) was significantly increased than that in the Control group (PBMC+isotype control antibody) (P<0.01 and P<0.001, respectively). The TNF-a expression level in CD14+ monocyte stimulated with the anti-CD47 antibody + LPS was higher than that with the LPS (P< 0.05). Conclusion: The CD47 may be related to the pathogenesis of PBC by inflammatory response. The CD47/SIRPa signal were imbalanced in PBC patients. The presence of serum anti-CD47 antibodies in PBC patients provides a laboratory basis for clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Few studies have explored the relationships between cold spells and acute myocardial infarction (AMI) using the information of symptom onset. OBJECTIVES: We assessed the impact of cold spells on AMI onset and the potential effect modifiers. METHODS: We conducted a time-stratified case-crossover study among 456,051 eligible patients with AMI from 2,054 hospitals in 323 Chinese cities between January 2015 and June 2021 during cold seasons (November to March). Nine definitions of cold spells were used by combining three relative temperature thresholds (i.e., lower than the 7.5th, 5th, and 2.5th percentiles) and three durations of at least 2–4 consecutive d. Conditional logistic regressions with distributed lag models were applied to evaluate the cumulated effects of cold spells on AMI onset over lags 0–6 d, after adjusting for daily mean temperature. RESULTS: The associations generally appeared on lag 1 d, peaked on lag 3 d, and became nonsignificant approximately on lag 5 d. Cold spells defined by more stringent thresholds of temperature were associated with higher risks of AMI onset. For cold spell days defined by a daily mean temperature of ≤7.5th percentile and durations of ≥2 d, ≥3 d, and ≥4 d, the percentage changes in AMI risk were 4.24% [95% confidence interval (CI): 2.31%, 6.20%], 3.48% (95% CI: 1.62%, 5.38%), and 2.82% (95% CI: 0.98%, 4.70%), respectively. Significant AMI risks associated with cold spells were observed among cases from regions without centralized heating, whereas null or much weaker risks were found among those from regions with centralized heating. Patients ≤65 years of age were more susceptible to cold spells. DISCUSSION: This national case-crossover study presents compelling evidence that cold spells could significantly increase the risk of AMI onset. [ABSTRACT FROM AUTHOR]

Background: Children with autism spectrum disorder (ASD) are at high risk of experiencing externalizing and internalizing problems. This study aimed to reveal how maternal parenting styles and autistic traits influence behavioral problems in children with ASD. Methods: This study recruited 70 2-5 years children with ASD and 98 typically developing (TD) children. The Parental Behavior Inventory (PBI) and Autism Spectrum Quotient (AQ) were used to collect the maternal parenting styles and autistic traits, respectively. The children's behavioral problems were reported by the mothers using the Strengths and Difficulties Questionnaire (SDQ). Hierarchical moderated regression analyses were used to determine whether maternal autistic traits moderated the association between parenting style and behavioral problems in the children. Results: Compared to TD children, children with ASD exhibited more severe externalizing and internalizing problems (t = 4.85, p < 0.01). The ASD group scored lower in the maternal supportive/engaged parenting style than the TD group (t = 3.20, p < 0.01). In the TD group, the maternal AQ attention switching domain was positively correlated with internalizing problems in the children (ß = 0.30, p = 0.03). In the ASD group, hostile/coercive parenting style was significantly correlated with externalizing problems in the children (ß = 0.30, p = 0.02), whereas maternal AQ attention switching domain was negatively correlated with externalizing problems (ß = -0.35, p = 0.02). Moreover, the maternal AQ attention switching domain moderated the association between hostile/coercive parenting style and children's externalizing problems (ß = 0.33, p = 0.04). Conclusion: Among ASD children, a hostile/coercive parenting style can increase the risks of children's externalizing problems, especially in the context of high levels of maternal attention-switching problems. Hence, the current study has important implications for the clinical practice of early family-level interventions for children with ASD. [ABSTRACT FROM AUTHOR]

We have developed a new 2D c-MOF (Cu-TBC) via coordination polymerization of a highly conjugated tribenzocoronene-type organic ligand (6OH-TBC) and Cu2+, which exhibits excellent stability and performance as the electrode for a supercapacitor. [ABSTRACT FROM AUTHOR]

Renal fibrosis commonly occurs in the process of chronic kidney diseases. Here, we explored the role of Jumonji domain containing 3 (Jmjd3)/interferon regulatory factor 4 (IRF4) axis in activation of myeloid fibroblasts and transition of M2 macrophages into myofibroblasts transition (M2MMT) in kidney fibrosis. In mice, Jmjd3 and IRF4 were highly induced in interstitial cells of kidneys with folic acid or obstructive injury. Jmjd3 deletion in myeloid cells or Jmjd3 inhibitor reduced the levels of IRF4 in injured kidneys. Myeloid Jmjd3 depletion impaired bone marrow-derived fibroblasts activation and M2MMT in folic acid or obstructive nephropathy, resulting in reduction of extracellular matrix (ECM) proteins expression, myofibroblasts formation and renal fibrosis progression. Pharmacological inhibition of Jmjd3 also prevented myeloid fibroblasts activation, M2MMT, and kidney fibrosis development in folic acid nephropathy. Furthermore, IRF4 disruption inhibited myeloid myofibroblasts accumulation, M2MMT, ECM proteins accumulation, and showed milder fibrotic response in obstructed kidneys. Bone marrow transplantation experiment showed that wild-type mice received IRF4-/- bone marrow cells presented less myeloid fibroblasts activation in injured kidneys and exhibited much less kidney fibrosis after unilateral ureteral obstruction. Myeloid Jmjd3 deletion or Jmjd3 inhibitor attenuated expressions of IRF4, α-smooth muscle actin and fibronectin and impeded M2MMT in cultured monocytes exposed to IL-4. Conversely, overexpression IRF4 abrogated the effect of myeloid Jmjd3 deletion on M2MMT. Thus, Jmjd3/IRF4 signaling has a crucial role in myeloid fibroblasts activation, M2 macrophages to myofibroblasts transition, extracellular matrix protein deposition, and kidney fibrosis progression. [ABSTRACT FROM AUTHOR]

Renal fibrosis is an important pathological biomarker of chronic kidney disease (CKD). Stimulator of interferon genes/TANK binding kinase 1 (STING/TBK1) axis has been identified as the main regulator of innate immune response and closely related to fibrotic disorder. However, the role of STING/TBK1 signaling pathway in kidney fibrosis is still unknown. In this study, we investigated the effect of pharmacological inhibition of STING/TBK1 signaling on renal fibrosis induced by folic acid (FA). In mice, TBK1 was significantly activated in interstitial cells of FA-injured kidneys, which was markedly inhibited by H-151 (a STING inhibitor) treatment. Specifically, pharmacological inhibition of STING impaired bone marrow-derived fibroblasts activation and macrophage to myofibroblast transition in folic acid nephropathy, leading to reduction of extracellular matrix proteins expression, myofibroblasts formation and development of renal fibrosis. Furthermore, pharmacological inhibition of TBK1 by GSK8612 reduced myeloid myofibroblasts accumulation and impeded macrophage to myofibroblast differentiation, resulting in less deposition of extracellular matrix protein and less severe fibrotic lesion in FAinjured kidneys. In cultured mouse bone marrow-derived monocytes, TGF-β1 activated STING/TBK1 signaling. This was abolished by STING or TBK1 inhibitor administration. In addition, GSK8612 treatment decreased levels of α-smooth muscle actin and extracellular matrix proteins and prevents bone marrow-derived macrophages to myofibroblasts transition in vitro. Collectively, our results revealed that STING/TBK1 signaling has a critical role in bone marrow-derived fibroblast activation, macrophages to myofibroblasts transition, and kidney fibrosis progression. [ABSTRACT FROM AUTHOR]

Background Large-scale real-world data to evaluate the impact of chest pain centre (CPC) accreditation on acute coronary syndrome (ACS) emergency care in heavy-burden developing countries like China are rare. Methods This study is a retrospective study based on data from the Hospital Quality Monitoring System (HQMS) database. This study included emergency patients admitted with ACS to hospitals that uploaded clinical data continuously to the database from 2013 to 2016. Propensity score matching was used to compare hospitals with and without CPC accreditation during this period. A longitudinal self-contrast comparison design with mixed-effects models was used to compare management of ACS before and after accreditation. Results A total of 798 008 patients with ACS from 746 hospitals were included in the analysis. After matching admission date, hospital levels and types and adjusting for possible covariates, patients with ACS admitted to accredited CPCs had lower in-hospital mortality (0R=0.70, 95% CI 0.53 to 0.93), shorter length of stay (LOS; adjustedmultiplicative effect=0.89, 95% CI 0.84 to 0.94) and more percutaneous coronary intervention (PCI) procedures (OR=3.53, 95% CI 2.20 to 5.66) than patients admitted in hospitals without applying for CPC accreditation. Furthermore, when compared with the 'before accreditation' group only in accredited CPCs, the in-hospital mortality and LOS decreased and the usage of PCI were increased in both 'accreditation' (for in-hospital mortality: 0R=0.86, 95% CI 0.79 to 0.93; for LOS: 0.94, 95% CI 0.93 to 0.95; for PCI: OR=1.22, 95% CI 1.18 to 1.26) and 'after accreditation' groups (for in-hospital mortality: 0R=0.90, 95% CI 0.84 to 0.97; for LOS: 0.89, 95% CI 0.89 to 0.90; for PCI: OR=1.36, 95% CI 1.33 to 1.39). The significant benefits of decreased in-hospital mortality, reduced LOS and increased PCI usage were also observed for patients with acute myocardial infarction. Conclusions CPC accreditation is associated with better management and in-hospital clinical outcomes of patients with ACS. CPC establishment and accreditation should be promoted and implemented in countries with high levels of ACS. [ABSTRACT FROM AUTHOR]

Accumulating studies have been conducted to identify risk genes and relevant biological mechanisms underlying major depressive disorder (MDD). In particular, transcriptomic analyses in brain regions engaged in cognitive and emotional processes, e.g., the dorsolateral prefrontal cortex (DLPFC), have provided essential insights. Based on three independent DLPFC RNA-seq datasets of 79 MDD patients and 75 healthy controls, we performed differential expression analyses using two alternative approaches for cross-validation. We also conducted transcriptomic analyses in mice undergoing chronic variable stress (CVS) and chronic social defeat stress (CSDS). We identified 12 differentially expressed genes (DEGs) through both analytical methods in MDD patients, the majority of which were also dysregulated in stressed mice. Notably, the mRNA level of the immediate early gene FOS (Fos proto-oncogene) was significantly decreased in both MDD patients and CVS-exposed mice, and CSDS-susceptible mice exhibited a greater reduction in Fos expression compared to resilient mice. These findings suggest the potential key roles of this gene in the pathogenesis of MDD related to stress exposure. Altered transcriptomes in the DLPFC of MDD patients might be, at least partially, the result of stress exposure, supporting that stress is a primary risk factor for MDD. [ABSTRACT FROM AUTHOR]

Previous studies have shown that nicorandil has a protective effect on cardiomyocytes. However, there is no study to investigate whether perioperative intravenous nicorandil can further reduce the myocardial infarct size in patients with ST-segment elevation myocardial infarction (STEMI) compared to the current standard of percutaneous coronary intervention (PCI) regimen. The CHANGE (China-Administration of Nicorandil Group) study is a multicenter, prospective, randomized, double-blind and parallel-controlled clinical study of STEMI patients undergoing primary PCI in China, aiming to evaluate the efficacy and safety of intravenous nicorandil in ameliorating the myocardial infarct size in STEMI patients undergoing primary PCI and provide evidence-based support for myocardial protection strategies of STEMI patients. [ABSTRACT FROM AUTHOR]

Two different a‐IGZO gate driving circuits (GOA) which used long channel length (GOA_A) and STT (GOA_B) structures were designed and compared. GOA_B shows better performance than that of GOA_A, while the Vth of T53 in GOA_B circuit would shift to a very positive voltage after life test. The large channel width size ratio between T53 and T54 would bring about bigger Vds voltage of T53 which induces large current stress of T53 in GOA_B, so the Vth voltage of T53 in GOA_B would shift to a very positive voltage at life test. The phenomenon which T53 devices were easy to shift to positive bias can be restrained and improved by new design of its pull down holding part in GOA_B by spice simulated results. [ABSTRACT FROM AUTHOR]

Background: Patients who survive non-ST-elevation myocardial infarction (NSTEMI) are at heightened risk of recurrent cardiovascular events. Data on long-term secondary atherothrombotic risk stratification are limited.Objectives: To stratify post-NSTEMI patients for risk of recurrent cardiovascular events to maximise benefit from aggressive secondary prevention strategies using the TIMI Risk Score for Secondary Prevention (TRS 2°P) score in a real-world cohort of NSTEMI patients.Methods and Results: This was a single-centre observational study of 891 post-NSTEMI patients (73.7 ± 12.7 years; male: 54.2%). The TRS 2°P is a nine-point risk stratification tool to predict cardiovascular events in patients with established cardiovascular disease. The primary outcome was a composite endpoint of cardiovascular death, non-fatal MI and non-fatal ischaemic stroke. After a median follow-up of 31 months (IQR: 11.4 - 60.2), 281 patients (31.5%) had developed a primary outcome (13.3%/year) including 196 cardiovascular deaths, 94 non-fatal MIs and 22 non-fatal strokes. The TRS 2°P score was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P score =0 was 1.6%, and increased progressively to 47.4% for those with a TRS 2°P score ≥6 (HR: 20.18, 95% CI: 4.85 to 84.05, p<0.001). Similar associations were also observed between the TRS 2°P score and cardiovascular death and MI (fatal and non-fatal), but not non-fatal ischaemic stroke.Conclusion: The TRS 2°P score stratified post-NSTEMI patients for risk of future cardiovascular events and potentially help guide the selection of more aggressive secondary prevention therapy. [ABSTRACT FROM AUTHOR]

Although increasing the pCO2 for diatoms will presumably down-regulate the CO2-concentrating mechanism (CCM) to save energy for growth, different species have been reported to respond differently to ocean acidification (OA). To better understand their growth responses to OA, we acclimated the diatoms Thalassiosira pseudonana, Phaeodactylum tricornutum, and Chaetoceros muelleri to ambient (pCO2 400 latm, pH 8.1), carbonated (pCO2 800 latm, pH 8.1), acidified (pCO2 400 latm, pH 7.8), and OA (pCO2 800 latm, pH 7.8) conditions and investigated how seawater pCO2 and pH affect their CCMs, photosynthesis, and respiration both individually and jointly. In all three diatoms, carbonation down-regulated the CCMs, while acidification increased both the photosynthetic carbon fixation rate and the fraction of CO2 as the inorganic carbon source. The positive OA effect on photosynthetic carbon fixation was more pronounced in C. muelleri, which had a relatively lower photosynthetic affinity for CO2, than in either T. pseudonana or P. tricornutum. In response to OA, T. pseudonana increased respiration for active disposal of H+ to maintain its intracellular pH, whereas P. tricornutum and C. muelleri retained their respiration rate but lowered the intracellular pH to maintain the cross-membrane electrochemical gradient for H+ efflux. As the net result of changes in photosynthesis and respiration, growth enhancement to OA of the three diatoms followed the order of C. muelleri > P. tricornutum > T. pseudonana. This study demonstrates that elucidating the separate and joint impacts of increased pCO2 and decreased pH aids the mechanistic understanding of OA effects on diatoms in the future, acidified oceans. [ABSTRACT FROM AUTHOR]

Objective: Little is known about left atrial appendage occlusion (LAAO) with WATCHMAN device in patients with atrial fibrillation (AF) in China. The aim of the present study was to evaluate the acute procedural performance and complication rate of LAAO procedures and patient selection in China. Methods: A total of 658 consecutive Chinese patients who were referred to receive LAAO procedures with the WATCHMAN device between 2014 and 2017 were retrospectively included in the study. Patients were divided into four groups according to the year of procedures: Group 2014, Group 2015, Group 2016, and Group 2017. The procedural success, complication rates, and characteristics of Chinese patients, as well as the trends of patients' selection and management, were analyzed. Results: The average age of the patients was 67.7}9.2 years, the CHA2DS2-VASc score was 3.7}1.6, and the HAS-BLED score was 2.5}1.1. Both scores of patients in different years show obvious increasing trends (r=0.126, p=0.001 and r=0.145, p<0.001, respectively). Indications for LAAO included increased bleeding risk (45.6%), recent bleeding under oral anticoagulation (OAC) (9.0%), and non-compliance with OAC (51.4%). The implantation was successful in 643 (97.7%) patients, with a procedural complication rate of 0.6%. Approximately 80.1% of the patients received OAC after LAAO. Conclusion: In China, LAAO with WATCHMAN devices in patients with AF can be performed successfully with a low complication rate. Most of the target population had increased bleeding risk or non-compliance for OAC as indications and received OAC for antithrombotic therapy after the procedure. [ABSTRACT FROM AUTHOR]

Several epidemiological and clinical studies have shown that females with ST-segment elevation myocardial infarction (STEMI) have a higher mortality than males following primary percutaneous coronary intervention (PPCI). Many analyses of sex-based differences following STEMI have revealed conflicting results. Currently, more and more elderly patients with STEMI have undergone emergency interventional therapy. From January 2014 to December 2016, a total of 337 elderly patients with STEMI were enrolled in this study from two chest pain centers, and all patients underwent PPCI. Patients were divided into two groups: elderly females (n=117, mean age 73.4±9.6 years) and elderly males (n=220, mean age 71.7±8.6 years). The prevalence of diabetes was higher in females than in males (29.1% vs. 19.6%, P<0. 01). Typical ischemic chest pain was lower in females than in males (45.3% vs 57.3%, P<0.01). The number of nonsmokers was also significantly higher in females than in males (5.1% vs. 52.3%,P<0. 01). Serum creatinine (sCr) levels (87.6±17.4 umol/L vs 99.5±20.2 umol/L,P<0.01) and body mass index (23.8±2.7 vs 27.3±3.1, P<0.01) were lower in females than in males. The incidences of major adverse cardiac events (MACE) in-hospital showed no significantly difference (P>0.05) between the two groups. However, the cumulative MACE showed a significant difference between the two groups in the 12-month followup (16.8% in male vs 12.8% in female, P = 0.04). Our results suggest that the PPCI is safe and effective in elderly female STEMI patients. The cumulative MACE in females are not higher than in males. PPCI are helpful in elderly STEMI patients. [ABSTRACT FROM AUTHOR]

Background: There is little information about the prognostic value of double product (DP) for acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI). The aim of this study was to investigate whether DP reflects the predictive power of heart rate (HR) or systolic blood pressure (SBP) in ACS patients treated with PCI.Methods: A total of 7590 ACS patients who had undergone PCI, free from cardiac shock, were included. The follow-up duration was two years. The main adverse cardiovascular events (MACEs) included all-cause death, recurrent myocardial infarction and stroke.Results: In the unadjusted model, significantly higher rates of MACEs were recorded in the high DP group (relative risk 1.41, 95%CI 1.08 to 1.83, p = 0.012). However, in the full adjusted models, after including HR and SBP, the predictive value of DP was not significant (relative risk 0.86, 95%CI 0.55 to1.33, p = 0.499). The predictive value of HR for MACEs was statistically significant (relative risk 1.74, 95% CI 1.33-2.28, p < 0.001). It was worth noting that the history of hypertension was strongly associated with MACEs (relative risk 1.53, 95% CI 1.11-2.11, p = 0.009).Conclusion: High DP is associated with MACEs for ACS patients treated with PCI. However, the predictive value of DP weakened when adjusted for HR. Therefore, we have shown that DP may reflect the predictive power of HR for ACS patients treated with PCI. [ABSTRACT FROM AUTHOR]

Ultrathin, transparent and flexible capacitors using graphene as the bottom electrodes were directly fabricated on polyethylene naphthalate (PEN) substrates. ZrO2 dielectric films were deposited on the treated surface of graphene by atomic layer deposition (ALD). The deposition process did not introduce any detectible defects in the graphene, as indicated by Raman measurements, guaranteeing the electrical performances of the graphene electrodes. The Aluminum-doped zinc oxide (AZO) films were prepared as the top electrodes using the ALD technique. The capacitors presented a high capacitance density (10.3 fF/μ m2 at 10 kHz) and a relatively low leakage current (5.3 × 10-6 A/cm2 at 1 V). Bending tests revealed that the capacitors were able to work normally at an outward bending radius of 10 mm without any deterioration of electrical properties. The capacitors exhibited an average optical transmittance of close to 70% at visible wavelengths. Thus, it opens the door to practical applications in transparent integrated circuits. [ABSTRACT FROM AUTHOR]

Background/aim: In addition to its cholesterol-lowering effect, atorvastatin (ATV) has been thought to have multiple cardiovascular benefits, including anti-inflammatory and anti-apoptotic properties. The present study was undertaken to determine whether ATV pretreatment could attenuate myocardial apoptosis and inflammation and improve cardiac function in a swine model of coronary microembolization (CME).Methods: Twenty-four swine were randomly and equally divided into a sham-operated (control) group, CME group, and CME plus ATV group. Swine CME was induced by intracoronary injection of inert plastic microspheres (diameter 42 μm) into the left anterior descending coronary, with or without pretreatment of ATV. Echocardiographic measurements, a pathological examination, terminal deoxynucleotidyl transferase-mediated nick end labeling staining, and Western blotting were performed to assess the functional, morphological, and molecular effects in CME.Results: The expression levels of caspase 3 and tumor necrosis factor-α (TNF-α) were aberrantly upregulated in cardiomyocytes following CME. Downregulation of caspase 3 and TNF-α with ATV pretreatment was associated with improved cardiac function and attenuated serum cardiac troponin I (cTnI) and high-sensitivity C-reactive protein. In addition, through a Pearson correlation analysis, the left ventricular ejection fraction negatively correlated with caspase 3, TNF-α, and cTnI.Conclusion: This study demonstrated that ATV pretreatment could significantly inhibit CME-induced myocardial apoptosis and inflammation and improve cardiac function. The data generated from this study provide a rationale for the development of myocardial apoptosis and inflammation-based therapeutic strategies for CME-induced myocardial injury. [ABSTRACT FROM AUTHOR]

Objective: To find out the association between serum total cholesterol (TC) on admission and in-hospital mortality in patients with acute aortic dissection (AAD). Methods: From January 2007 to January 2014, we enrolled 1492 consecutive AAD patients with serum TC measured immediately on admission. Baseline characteristics and in-hospital mortality were compared between the patients with serum TC above and below the median (4.00 mmol/L). Propensity score matching (PSM) was used to account for known confounders in the study. Cox proportional hazard model was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI) for admission serum TC levels. Results: With the use of PSM, 521 matched pairs of patients with AAD were yielded in this analysis due to their similar propensity scores. Patients with admission serum TC < 4.00 mmol/L, as compared with those with admission serum TC ⩾ 4.00 mmol/L, had higher in-hospital mortality (11.7% vs. 5.8%; HR, 2.06; 95% CI, 1.33-3.19, P = 0.001). Stratified analysis according to Stanford classification showed that the inverse association between admission serum TC and in-hospital mortality was observed in patients with Type-A AAD (24.0% vs. 11.3%; HR, 2.18; 95% CI, 1.33 - 3.57, P = 0.002) but not in those with Type-B AAD (3.8% vs. 2.2%; HR, 1.71; 95% CI, 0.67 - 4.34, P = 0.261). Conclusions: Lower serum TC level on admission was strongly associated with higher in-hospital mortality in patients with Type-A AAD. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effects of cinobufacini injection on the proliferation and expression of topoisomerases in human HepG-2 hepatocarcinoma cells. The cells were divided into a control group and an experimental group, in which 0.105, 0.21, 0.42 mg/l cinobufacini was injected. Cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assay, levels of apoptosis were detected using annexin V/propidium iodide staining and cell cycles were analyzed using flow cytometric analysis. The mRNA and protein expression levels of topoisomerase (TOPO) I and TOPO II were determined by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. Cinobufacini injection significantly inhibited the proliferation of the HepG-2 cells (P<0.05), induced apoptosis (P<0.05) in a dose- and time-dependent manner, induced tumor cell arrest at the S phase in a dose-dependent manner, and downregulated the mRNA and protein expression levels of TOPO I and TOPO II (P<0.05) in a dose-dependent manner. Therefore, cinobufacini was found to inhibit human HepG-2 hepatocellular carcinoma cell proliferation, and downregulation of the expression levels of TOPO I and TOPO II may contribute to the effect on proliferation observed in the Hep-G2 cells following cinobbufacini injection. [ABSTRACT FROM AUTHOR]

Importance The safety and efficacy of bivalirudin compared with heparin with or without glycoprotein IIb/IIIa inhibitors in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are uncertain. Objective To determine if bivalirudin is superior to heparin alone and to heparin plus tirofiban during primary PCI. Design, Setting, and Participants Multicenter, open-label trial involving 2194 patients with AMI undergoing primary PCI at 82 centers in China between August 2012 and June 2013. Interventions Patients were randomly assigned to receive bivalirudin with a post-PCI infusion (n = 735), heparin alone (n = 729), or heparin plus tirofiban with a post-PCI infusion (n = 730). Among patients treated with bivalirudin, a postprocedure 1.75 mg/kg/h infusion was administered for a median of 180 minutes (IQR, 148-240 minutes). Main Outcomes and Measures The primary end point was 30-day net adverse clinical events, a composite of major adverse cardiac or cerebral events (all-cause death, reinfarction, ischemia-driven target vessel revascularization, or stroke) or bleeding. Additional prespecified safety end points included the rates of acquired thrombocytopenia at 30 days, and stent thrombosis at 30 days and 1 year. Results Net adverse clinical events at 30 days occurred in 65 patients (8.8%) of 735 who were treated with bivalirudin compared with 96 patients (13.2%) of 729 treated with heparin (relative risk [RR], 0.67; 95% CI, 0.50-0.90; difference, −4.3%, 95% CI, −7.5% to −1.1%; P = .008); and 124 patients (17.0%) of 730 treated with heparin plus tirofiban (RR for bivalirudin vs heparin plus tirofiban, 0.52; 95% CI, 0.39-0.69; difference, −8.1%, 95% CI, −11.6% to −4.7%; P < .001). The 30-day bleeding rate was 4.1% for bivalirudin, 7.5% for heparin, and 12.3% for heparin plus tirofiban (P < .001). There were no statistically significant differences between treatments in the 30-day rates of major adverse cardiac or cerebral events (5.0% for bivalirudin, 5.8% for heparin, and 4.9% for heparin plus tirofiban, P = .74), stent thrombosis (0.6% vs 0.9% vs 0.7%, respectively, P = .77), acquired thrombocytopenia (0.1% vs 0.7% vs 1.1%; P = .07), or in acute (<24-hour) stent thrombosis (0.3% in each group). At the 1-year follow-up, the results remained similar. Conclusions and Relevance Among patients with AMI undergoing primary PCI, the use of bivalirudin with a median 3-hour postprocedure PCI-dose infusion resulted in a decrease in net adverse clinical events compared with both heparin alone and heparin plus tirofiban. This finding was primarily due to a reduction in bleeding events with bivalirudin, without significant differences in major adverse cardiac or cerebral events or stent thrombosis. [ABSTRACT FROM AUTHOR]

We reported separate absorption and multiplication InAlAs/InGaAs avalanche photodiodes with a p-type multiplication layer. Wedge-shaped electric field profiles with different gradients and peak intensities confined in a thin InAlAs avalanche layer were realized. These devices showed optimum operating gains up to 40 in linear mode with low operating voltages <20 V, small gain slopes, and high-gain uniformity. Moreover, a reduced breakdown voltage temperature coefficient <6 mV/K in the temperature range of 200–350 K was observed, whereas the dark current showed a noticeable increase. Those multiplication performances are attributed to the modified electric field profiles and are ideally suitable for focal plane array imaging applications. [ABSTRACT FROM PUBLISHER]

To evaluate the performance correlated imperfection or defect features of metamorphic InGaAs photodetector structures, a scanning electron microscopy scheme including both plane-view electron beam induced current (EBIC) and secondary electron (SE) images have been used. The abilities, merits and limitations as well as some case-dependent properties of EBIC have been discussed in detail. The devices of similar structures grown on InP or GaAs substrates with quite different lattice mismatch show discriminated defect distribution patterns, prompting their distinct origins, which have been confirmed by cross-sectional transmission electron microscopy observation. Using self-developed image processing software the EBIC features of the samples are statistically analyzed, which validated the qualitative correlation between the EBIC data and device dark current. Fusing of EBIC and SE images has also been attempted to enhance the defect visibility. Results indicate that EBIC is feasible to investigate the effects of defects on the device performance not only in research work, but also for product quality monitor purposes. [ABSTRACT FROM AUTHOR]

Imprinted genes play important roles in placental and embryonic development. Neuronatin (NNAT), first identified as an imprinted gene in human and mouse brains, played important roles in neuronal differentiation in the brain and in glucose-mediated insulin secretion in pancreatic b cells. In the pig, NNAT was reported to be imprinted in eleven tissues. Our previous microarray hybridization study showed that NNAT was differentially expressed in Yorkshire and Meishan pig placentas, but the imprinting status and function of NNAT in the placenta have not been investigated. We demonstrated for the first time that NNAT was monoallelically expressed in the placenta. Immunochemistry analysis showed that NNAT was located in the uterine luminal and glandular epithelium in placentas. We also confirmed the differential expression of NNAT in Meishan and Yorkshire pig placentas by qPCR. Using IPA software and the published literature, we created a model network of the possible relationships between NNAT and glucose transporter genes. A dual luciferase reporter assay demonstrated that the crucial promoter region of NNAT contained a CANNTG sequence in the +210 to +215 positions, which corresponded to the E-box. Our findings demonstrated important roles of NNAT in placenta function. [ABSTRACT FROM AUTHOR]

Background: There is an inverse relationship between febrile infection and the risk of malignancies. Interferon gamma (IFNγ) plays an important role in fever induction and its expression increases with incubation at fever-range temperatures. Therefore, the genetic polymorphism of IFN-γ may modify the association of febrile infection with breast cancer risk. Methodology and Principal Findings: Information on potential breast cancer risk factors, history of fever during the last 10 years, and blood specimens were collected from 839 incident breast cancer cases and 863 age-matched controls between October 2008 and June 2010 in Guangzhou, China. IFN-γ (rs2069705) was genotyped using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. We found that women who had experienced ≥1 fever per year had a decreased risk of breast cancer [ORs and 95% CI: 0.77 (0.61-0.99)] compared to those with less than one fever a year. This association only occurred in women with CT/TT genotypes [0.54 (0.37-0.77)] but not in those with the CC genotype [1.09 (0.77-1.55)]. The association of IFN-c rs2069705 with the risk of breast cancer was not significant among all participants, while the CT/TT genotypes were significantly related to an elevated risk of breast cancer [1.32 (1.03-1.70)] among the women with <1 fever per year and to a reduced risk of breast cancer [0.63 (0.40-0.99)] among women with ≥1 fever per year compared to the CC genotype. A marked interaction between fever frequencies and the IFN-γ genotypes was observed (P for multiplicative and additive interactions were 0.005 and 0.058, respectively). Conclusions: Our findings indicate a possible link between febrile acute infection and a decreased risk of breast cancer, and this association was modified by IFN-γ rs2069705. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the optimal therapeutic dose and time window of picroside II for treating cerebral ischemic injury in rats according to the orthogonal test. The middle cerebral artery occlusion (MCAO) models were established by intraluminally inserting a thread into middle cerebral artery (MCA) from left external carotid artery (ECA). The successful rat models were randomly divided into 16 groups according to the orthogonal layout of [L16(45)] and treated by injecting picroside II intraperitoneally with different doses at various times. The neurological behavioral function was evaluated by Bederson's test and the cerebral infarction volume was measured by tetrazolium chloride (TTC) staining. The expressions of neuron specific enolase (NSE) and neuroglial mark-protein S-100 were determined by immunohistochemisty assay. The results indicated that the optimal compositions of the therapeutic dose and time window of picroside II in treating cerebral ischemic injury were ischemia 1.5 h with 20 mg/kg body weight according to Bederson's test, 1.0 h with 20 mg/kg body weight according to cerebral infarction volume, 1.5 h with 20 mg/kg body weight according to the expressions of NSE and S-100 respectively. Based on the principle of the minimization of medication dose and maximization of therapeutic time window, the optimal composition of the therapeutic dose and time window of picroside II in treating cerebral ischemic injury should be achieved by injecting picroside II intraperitoneally with 20 mg/kg body weight at ischemia 1.5 h. [ABSTRACT FROM AUTHOR]

Bone morphogenetic protein 9 (BMP-9) is a member of the transforming growth factor (TGF)-β/BMP superfamily, and we have demonstrated that it is one of the most potent BMPs to induce osteoblast differentiation of mesenchymal stem cells (MSCs). Here, we sought to investigate if canonical Wnt/β-catenin signalling plays an important role in BMP-9-induced osteogenic differentiation of MSCs. Wnt3A and BMP-9 enhanced each other’s ability to induce alkaline phosphatase (ALP) in MSCs and mouse embryonic fibroblasts (MEFs). Wnt antagonist FrzB was shown to inhibit BMP-9-induced ALP activity more effectively than Dkk1, whereas a secreted form of LPR-5 or low-density lipoprotein receptor-related protein (LRP)-6 exerted no inhibitory effect on BMP-9-induced ALP activity. β-Catenin knockdown in MSCs and MEFs diminished BMP-9-induced ALP activity, and led to a decrease in BMP-9-induced osteocalcin reporter activity and BMP-9-induced expression of late osteogenic markers. Furthermore, β-catenin knockdown or FrzB overexpression inhibited BMP-9-induced mineralization in vitro and ectopic bone formation in vivo, resulting in immature osteogenesis and the formation of chondrogenic matrix. Chromatin immunoprecipitation (ChIP) analysis indicated that BMP-9 induced recruitment of both Runx2 and β-catenin to the osteocalcin promoter. Thus, we have demonstrated that canonical Wnt signalling, possibly through interactions between β-catenin and Runx2, plays an important role in BMP-9-induced osteogenic differentiation of MSCs. [ABSTRACT FROM AUTHOR]