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Paroxysmal atrial fibrillation is a common arrhythmia, and its development process and prediction of the degree of atrial fibrosis are of great significance for treatment and management. Optical imaging technology provides a new means for non-invasive observation of atrial electrical activity. The aim of this study is to investigate the predictive effect of sinus node recovery time on the degree of atrial fibrosis in patients with paroxysmal atrial fibrillation, and to provide a basis for the application of optical imaging technology in the study of atrial fibrosis. The study collected clinical and optical imaging data from a group of patients with paroxysmal atrial fibrillation, and used statistical analysis methods to investigate the relationship between sinus node recovery time and the degree of atrial fibrosis. The research results indicate that there is a significant correlation between the recovery time of the sinus node and the degree of atrial fibrosis, that is, there is a positive correlation between the prolonged recovery time of the sinus node and the aggravation of atrial fibrosis. SNRT can serve as an effective indicator for evaluating atrial matrix and can be applied to predict recurrence after catheter ablation of paroxysmal atrial fibrillation. Shortening SNRT through catheter ablation can become an important predictor of effective catheter ablation., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study underscores the significance of precisely manipulating the morphology of the active layer in organic solar cells (OSCs). By blending polymer donors of D18 with varying molecular weights, a multiscale interpenetrating fiber network structure within the active layer is successfully created. The introduction of 10% low molecular weight D18 (LW-D18) into high molecular weight D18 (HW-D18) produces MIX-D18, which exhibits an extended exciton diffusion distance and orderly molecular stacking. Devices utilizing MIX-D18 demonstrate superior electron and hole transport, improves exciton dissociation, enhances charge collection efficiency, and reduces trap-assisted recombination compared to the other two materials. Through the use of the nonfullerene acceptor L8-BO, a remarkable power conversion efficiency (PCE) of 20.0% is achieved. This methodology, which integrates the favorable attributes of high and low molecular weight polymers, opens a new avenue for enhancing the performance of OSCs., (© 2024 Wiley‐VCH GmbH.)

Introduction: Pulmonary arterial hypertension (PAH) is a serious complication of systemic lupus erythematosus (SLE) with increased mortality. A prothrombotic state may contribute to pathogenesis of SLE-PAH. Extracellular vesicles (EVs) are known to be associated with thrombosis. Here, we investigated circulating EVs and their associations with SLE-PAH., Methods: Eighteen SLE-PAH patients, 36 SLE-non-PAH patients, and 36 healthy controls (HCs) were enrolled. Flow cytometry was used to analyze circulating EVs from leukocytes (LEVs), red blood cells (REVs), platelets (PEVs), endothelial cells (EEVs), and Annexin V + EVs with membrane phosphatidylserine (PS) exposure., Results: Plasma levels of all EV subgroups were elevated in SLE patients with or without PAH compared to HCs. Furthermore, plasma Annexin V + EVs, LEVs, PEVs, REVs, EEVs, and Annexin V + REVs were significantly elevated in SLE-PAH patients compared to SLE-non-PAH patients. Additionally, PAH patients with moderate/high SLE showed a significant increase in LEVs, PEVs, REVs, Annexin V + EVs, and Annexin V + REVs compared to SLE-non-PAH patients. However, PAH patients with inactive/mild SLE only exhibited elevations in Annexin V + EVs, REVs, and Annexin V + REVs. In the SLE-PAH patients, EEVs were positively correlated with pulmonary arterial systolic pressure, while PEVs and EEVs were positively correlated with right ventricular diameter. Moreover, the receiver operating characteristic curve indicated that Annexin V + EVs, LEVs, PEVs, REVs, EEVs and Annexin V + REVs could predict the presence of PAH in SLE patients. Importantly, multivariate logistic regression analysis showed that circulating levels of LEVs or REVs, anti-nRNP antibody, and serositis were independent risk factors for PAH in SLE patients., Discussion: Findings reveal that specific subgroups of circulating EVs contribute to the hypercoagulation state and the severity of SLE-PAH. Higher plasma levels of LEVs or REVs may serve as biomarkers for SLE-PAH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ding, Qi, Liu, Wang, Zhang, Lyu, Sun, Du, Song, Hou, Guo, Wang, Liu and Wei.)

Mimotope, a kind of peptide vaccine, is developed to bind natural receptor and inhibit the downstream signaling. We have demonstrated that the vaccination of Tocilizumab mimotopes could alleviate the renal fibrosis by interfering with both IL-6 and ferroptosis signaling. However, the effect of the vaccination of Tocilizumab mimotopes on the fibroblast was not investigated in previous study. Thus, we sought to explore the changes in the fibroblast induced by the Tocilizumab mimotopes vaccination. Bleomycin instillation was performed to construct the pulmonary fibrosis model after the immunization of Tocilizumab mimotopes. Lung histological analysis showed that the Tocilizumab mimotopes could significantly reduce the maladaptive repairment and abnormal remodeling. Immunoblotting assay and fluorescence staining showed that Immunization with the Tocilizumab mimotopes reduces the accumulation of fibrosis-related proteins. High level of lipid peroxidation product was observed in the animal model, while the Tocilizumab mimotopes vaccination could reduce the generation of lipid peroxidation product. Mechanism analysis further showed that Nrf-2 signaling, but not GPX-4 and FSP-1 signaling, was upregulated, and reduced the lipid peroxidation. Our results revealed that in the BLM-induced pulmonary fibrosis, high level of lipid peroxidation product was significantly accumulation in the lung tissues, which might lead to the occurrence of ferroptosis. The IL-6 pathway block therapy could inhibit lipid peroxidation product generation in the lung tissues by upregulating the Nrf-2 signaling, and further alleviate the pulmonary fibrosis.

Recent evidence suggests that glia maturation factor β (GMFβ) is important in the pathogenesis of pulmonary arterial hpertension (PAH), but the underlying mechanism is unknown. To clarify whether GMFβ can be involved in pulmonary vascular remodeling and to explore the role of the IL-6-STAT3 pathway in this process, the expression of GMFβ in PAH rats is examined and the expression of downstream molecules including periostin (POSTN) and interleukin-6 (IL-6) is measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The location and expression of POSTN is also tested in PAH rats using immunofluorescence. It is proved that GMFβ is upregulated in the lungs of PAH rats. Knockout GMFβ alleviated the MCT-PAH by reducing right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and pulmonary vascular remodeling. Moreover, the inflammation of the pulmonary vasculature is ameliorated in PAH rats with GMFβ absent. In addition, the IL-6-STAT3 signaling pathway is activated in PAH; knockout GMFβ reduced POSTN and IL-6 production by inhibiting the IL-6-STAT3 signaling pathway. Taken together, these findings suggest that knockout GMFβ ameliorates PAH in rats by inhibiting the IL-6-STAT3 signaling pathway., (© 2024 The Authors. Advanced Biology published by Wiley‐VCH GmbH.)

Objective: We examine how state spending on children is associated with the size of socioeconomic gaps in maternal childcare time., Background: Persistent socioeconomic divides in the amount and nature of parental time with children have prompted consideration of the factors that mitigate inequalities within the family. At both the national and local levels, the welfare state plays an important role in structuring opportunities for children. Thus it is important to understand the institutional factors that shape parental behavior. Yet, little research examines how the social safety net is associated with family processes., Method: Using rich data on maternal time with children from the American Time Use Surveys (2003-2016), combined with longitudinal data on public spending in states on major programs affecting children and families, we examine how state spending on children is associated with the size of socioeconomic gaps in maternal childcare time., Results: We found that higher levels of state spending were associated with significant increases in childcare time among low-educated mothers at both the extensive and intensive margin, increasing the likelihood of spending any minutes on primary childcare in a typical day, as well as increasing the number of minutes spent on childcare. In contrast, we observed no variation in the behavior of highly-educated mothers as state spending changes., Implications: State-level investments could meaningfully narrow socioeconomic gaps in maternal time with children.

Purpose: To evaluate the consistency on the target heart rate for exercise determined by simple target heart rate (sTHR) based on resting heart rate (HRrest) and heart rate at anaerobic threshold (HRAT) in cardiopulmonary exercise test (CPET) for patients with chronic heart failure., Methods: This is a retrospective cohort study, in which CHF patients who underwent CPET in Tongji Hospital Cardiac Rehabilitation Center Affiliated to Tongji University from March 2007 to December 2018 were enrolled. The clinical data of the patients from the electronic medical record system, HRrest and HRAT measured by CPET were collected. Patients were further divided into subgroups according to gender, age (<60 years group and ≥ 60 years group), with or without beta-blocker therapy and subgroup of heart failure (heart failure with reduced, mid-range and preserved ejection fraction). The sTHR (HRrest plus 10, 15, 20, 25 and 30 bpm) and HRAT were all calculated in each patient. Paired t-test was used for the difference between the two methods, correlation analysis was shown by pearson analysis and intraclass correlation coefficient (ICC) was calculated for consistency test., Results: A total of 547 CHF patients were enrolled, including 447 males (81.7%), aged 63 (56,69) years, with BMI of 25.2 (23.5,26.4) kg/m 2 and LVEF of 45.0 (36.0, 52.0) %. The target heart rate determined by HRAT method was (93.59 ± 13.95) bpm, and its counterpart determined by HRrest plus 20 bpm (HRrest +20 ) was (93.16 ± 7.69) bpm. There was no significant difference between the two methods (P>0.05). However, it was statistically different between HRrest plus 10, 15, 25, 30 bpm and HRAT respectively (P<0.001). And HRrest +20 was positively correlated with HRAT (r = 0.418, P<0.001). Therefore, HRrest +20 below was regarded as sTHR. The ICC of the consistency test between sTHR and HRAT was 0.523,95%CI 0.435-0.596 (P < 0.001) in all patients (n = 547). In patients with beta-blocker therapy (n = 464), the ICC of sTHR and HRAT consistency test was 0.534,95%CI 0.441-0.612, P < 0.001; The ICC of the consistency test between sTHR and HRAT of patients without beta-blocker therapy (n = 83) was 0.407,95%CI 0.083-0.616, P < 0.05. In the sinus rhythm group (n = 466), the ICC of sTHR and HRAT consistency test was 0.527,95%CI 0.433-0.606, P < 0.001; The ICC of the consistency test between sTHR and HRAT of atrial fibrillation patients in group (n = 81) was 0.482,95%CI 0.195-0.667, P < 0.05.The ICC of the consistency test between sTHR and HRAT was 0.501,95%CI 0.338-0.623 (P < 0.001) in patients under 60 years old (n = 195); The ICC of the consistency test between sTHR and HRAT in patients ≥60 years old (n = 352) was 0.533,95%CI 0.424-0.621, P < 0.001. In the male group (n = 447), the ICC of sTHR and HRAT consistency test was 0.577,95%CI 0.491-0.649, P < 0.001; The ICC of the consistency test between sTHR and HRAT of female patients in group (n = 100) was 0.344,95%CI 0.025-0.559, P < 0.05. The ICC of sTHR and HRAT consistency test in HFrEF group (n = 170) was 0.395,95%CI 0.181-0.553, P < 0.01; The ICC values of the consistency test between sTHR and HRAT was 0.543, 95%CI 0.405-0.649 (P < 0.001) in patients with HFmrEF (n = 222); In HFpEF group (n = 155), the ICC of sTHR and HRAT consistency test was 0.620,95%CI 0.478-0.723, P < 0.001., Conclusion: The exercise target heart rate calculated by HRrest is consistent with that determined by HRAT in patients with CHF. For primary hospitals without CPET, exercise prescription equivalent to AT intensity for patients with CHF can be determined by HRrest. However, the target heart rate calculated by HRrest can't replace that determined by HRAT in this patient cohort completely., Competing Interests: Declaration of Competing Interest The authors report none., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the diagnostic value of circulating integrins β 1, 2, and 3 in venous thrombosis (VTE)., Materials and Methods: A total of 474 VTE patients and 306 patients with nonhigh risk for VTE as the control group were studied. Levels of adhering integrins β 1, 2, and 3 were detected by flow cytometry. Levels of circulating integrins β 1, 2, and 3 in serum were measured by enzyme-linked immunosorbent assay., Results: We found that integrins β 1, 2, and 3 were expressed highly both in serum and on the surface of leukocytes and platelets in venous thromboembolism. The levels of circulating integrins β 1, 2, and 3 are positively correlated with adhering integrins. It showed excellent clinical diagnostic performance of circulating integrins β 1, 2, and 3 in venous thromboembolism., Conclusions: Integrin subunit β can be used as a diagnostic marker with high sensitivity and specificity for venous thromboembolism., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Fan Yang et al.)

Two structurally intriguing Ru-containing isopolyoxometalates [(Ru(OH)) 2 O(W 5 O 18 ) 2 ] 8- ( 1 ) and [(W 5 O 18 )(Ru 2 W 8 O 31 )] 12- ( 2 ) were constructed from subtly different conditions. Single-crystal X-ray diffraction indicated that the precise pH modification has allowed us to trap a diruthenium-oxo core within different isopolyoxotungstate species. Compound 1 is the first sandwich-type ruthenium isopolyoxotungstate consisting of a linear {(HO)Ru-O-Ru(OH)} unit and two Lindqvist-type {W 5 } building blocks, while a ligand replacement of {W 5 } with an unusual {W 8 } ring in the case of compound 1 produced a unique embedded-type compound 2 with a quasi-linear {Ru-O-Ru} core. In addition to being determined in the solid state, crystal structures of 1 and 2 were also confirmed by 183 W nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization-mass spectrometry (ESI-MS) in solution. 183 W NMR spectrum demonstrated that the two-line pattern of 1 (with approximately 4:1 relative intensities) is consistent with the pseudo- D 2 h symmetry observed in the solid state. However, two other lines were observed in 2 according to the C 2 v symmetry but not in accord with the expected 4/4/4/1 ratio in the crystalline state, which indicated that the structure of 2 could not be maintained completely in aqueous solution. After recrystallizing the solid sample of 2 in water, the crystal structure of 2 partly converted to the structure of 1 , and the transformation was determined by the combined results of 183 W NMR, ESI-MS and single-crystal X-ray diffraction measurements. Catalytic investigations showed that their sodium salts presented excellent photocatalytic activities toward the benzylamine oxidation reaction induced by visible light (λ > 400 nm). The structures of the two compounds can still be maintained without a significant yield decrease after five continuous reaction cycles. Furthermore, both catalysts 1 and 2 could proceed with the oxidative coupling reaction smoothly for most of the primary benzylamine derivatives bearing various functional groups (H, F, Cl, Br, and Me) in good to excellent yields.

In the United States, high marital instability calls for more research on union transitions after marital dissolution. Previous studies focus on remarriage and pay little attention to rising post-dissolution cohabitation. In this study, I apply marital search theory to examine the level, pace, and differentials of repartnering (remarriage or cohabitation vs. staying single) and the exit from cohabitation (remarriage or dissolution vs. staying cohabiting). Adopting union history data from the pooled National Survey of Family Growth (2011-2017), I track union transitions among a sample of N = 2129 women. Analyses based on life tables and discrete-time event history analyses reveal important findings. First, most women repartner after marital dissolution. Compared to remarriage, cohabitation occurs more frequently and shows a quicker pace. Second, post-dissolution cohabitation is short-lived, and its transition to remarriage is more common than to dissolution. Third, these union transitions differ by demographic and socioeconomic predictors, including age, race and ethnicity, and education. Overall, I reveal that post-dissolution union transition is a divergent and unequal process, and I further discuss the implications on theory and family inequality., Competing Interests: Conflict of interest The authors declared that they have no conflict of interest.

Infant sex ratios that differ from the biological norm provide a measure of gender status inequality that is not susceptible to social desirability bias. Ratios may become less biased with educational expansion through reduced preference for male children. Alternatively, bias could increase with education through more access to sex-selective medical technologies. Using National Vital Statistics data on the population of live births in the United States for 1969-2018, we examine trends in infant sex ratios by parental race/ethnicity, education, and birth parity over five decades. We find son-biased infant sex ratios among Chinese and Asian Indian births that have persisted in recent years, and regressions suggest son-biased ratios among births to Filipino and Japanese mothers with less than a high school education. Infant sex ratios are more balanced at higher levels of maternal education, particularly when both parents are college educated. Results suggest greater equality of gender status with higher education in the United States., (Copyright © 2022 The Authors.)

This paper presents a search-theoretic model of union formation among women, aged 55 and older. Specifically, it provides new estimates of gender differentials in cohabitation and marriage at older ages, and documents recent patterns of assortative mating using data from the 2008-2017 American Community Survey. Our analyses reveal that cohabitation represents a much smaller share of all older unmarried women, all partnered women, and all women in comparison to patterns observed among their male counterparts. The results also reveal highly uneven patterns of union formation by age, race and marital history, which reflect demographically uneven constraints and preferences. Our analyses also document, for the first time, patterns of assortative mating at older ages. Shortages of similarly-aged men, especially among older African American women, seemingly heighten the likelihood of demographically mismatched unions. Older women are less likely to form unions with same-race or economically attractive partners, defined as men having a college-degree. This study shows that older single women, in general, are at a comparative disadvantage in the marriage market, both in forming co-residential unions and in finding partners who match their own social, demographic, and economic profiles. This paper highlights considerable heterogeneity in the experiences of America's older women. It calls for new theoretical approaches that acknowledge the unequal resources and bargaining power among older women in the marriage market., (Copyright © 2021. Published by Elsevier Inc.)

Bruton's tyrosine kinase (BTK) is an attractive therapeutic target in the treatment of cancer, inflammation, and autoimmune diseases. Covalent and noncovalent BTK inhibitors have been developed, among which covalent BTK inhibitors have shown great clinical efficacy. However, some of them could produce adverse effects, such as diarrhea, rash, and platelet dysfunction, which are associated with the off-target inhibition of ITK and EGFR. In this study, we disclosed a series of pteridine-7(8 H )-one derivatives as potent and selective covalent BTK inhibitors, which were optimized from 3z , an EGFR inhibitor previously reported by our group. Among them, compound 24a exhibited great BTK inhibition activity (IC 50 = 4.0 nM) and high selectivity in both enzymatic (ITK >250-fold, EGFR >2500-fold) and cellular levels (ITK >227-fold, EGFR 27-fold). In U-937 xenograft models, 24a significantly inhibited tumor growth (TGI = 57.85%) at a 50 mg/kg dosage. Accordingly, 24a is a new BTK inhibitor worthy of further development.

Background: Long noncoding RNA urothelial cancer-associated 1 (lnc-UCA1) targets microRNA-26a (miR-26a) and microRNA-195 (miR-195) to participate in coronary heart disease (CHD) progression via regulation of vascular smooth muscle cell and microvascular endothelial cell viability and mobility. Therefore, this study set out to further explore the relationship between lnc-UCA1 and miR-26a and miR-195, along with their roles in the management of patients with CHD., Methods: One hundred and thirty-six CHD patients and 70 age-/gender-matched controls were recruited in this case-control study. Their peripheral blood mononuclear cell samples were collected for lnc-UCA1, miR-26a, and miR-195 measurement. Furthermore, serum samples from CHD patients were obtained for inflammatory cytokines and cell adhesion molecules measurement. The Gensini score was used to evaluate the stenosis severity in CHD patients., Results: Lnc-UCA1 expression tend to be increased, while miR-26a and miR-195 expressions were reduced in patients with CHD compared to that of controls (all p < 0.001). In CHD patients, lnc-UCA1 was negatively correlated with miR-26a (p < 0.001) and miR-195 (p = 0.014). Besides, lnc-UCA1 was positively correlated with Gensini score (p < 0.001), total cholesterol (p = 0.019), low-density lipoprotein cholesterol (p = 0.002), and C-reactive protein (p < 0.001), while miR-26a (p < 0.001) and miR-195 (p = 0.002) were negatively correlated with Gensini score. What's more, lnc-UCA1 was positively correlated with tumor necrosis factor (TNF)-α (p = 0.004), interleukin (IL)-1β (p = 0.041), vascular cell adhesion molecule-1 (VCAM-1) (p = 0.010), and intercellular adhesion molecule-1 (ICAM-1) (p < 0.001). While miR-26a was negatively correlated with some of the individual inflammatory cytokines and cell adhesion molecules., Conclusion: Lnc-UCA1, miR-26a, and miR-195 may serve as potential biomarkers for CHD management., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Rapid changes in American families have reshaped inequalities in child well-being. This paper examines the unequal consequences of family structures for infant health, focusing on birthweight. Existing studies mainly address the average association between marriage (versus singlehood) and birthweight. I extend the literature by 1) explicitly considering cohabitation and 2) exploring the heterogeneous associations based on mother's likelihood of union formation at conception. Pooling nationally representative data from the National Survey of Family Growth 2011-17, I analyze a sample of recent births (N = 4,376) born to mothers aged between 20 and 49 years. Propensity score methods are used to address selections. Results show that 1) compared to single mothers, married mothers reap birthweight benefits, while cohabiting mothers do not; 2) married mothers with a higher likelihood to marry at conception (i.e., more advantaged) reap even larger birthweight benefits than their low-likelihood counterparts (i.e., less advantaged). Overall, the findings reveal important and nuanced roles of family structure in the reproduction of intergenerational inequality through infant health., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To develop a weakly supervised deep learning (WSDL) method that could utilize incomplete/missing survival data to predict the prognosis of extranodal natural killer/T cell lymphoma, nasal type (ENKTL) based on pretreatment 18 F-FDG PET/CT results., Methods: One hundred and sixty-seven patients with ENKTL who underwent pretreatment 18 F-FDG PET/CT were retrospectively collected. Eighty-four patients were followed up for at least 2 years (training set = 64, test set = 20). A WSDL method was developed to enable the integration of the remaining 83 patients with incomplete/missing follow-up information in the training set. To test generalization, these data were derived from three types of scanners. Prediction similarity index (PSI) was derived from deep learning features of images. Its discriminative ability was calculated and compared with that of a conventional deep learning (CDL) method. Univariate and multivariate analyses helped explore the significance of PSI and clinical features., Results: PSI achieved area under the curve scores of 0.9858 and 0.9946 (training set) and 0.8750 and 0.7344 (test set) in the prediction of progression-free survival (PFS) with the WSDL and CDL methods, respectively. PSI threshold of 1.0 could significantly differentiate the prognosis. In the test set, WSDL and CDL achieved prediction sensitivity, specificity, and accuracy of 87.50% and 62.50%, 83.33% and 83.33%, and 85.00% and 75.00%, respectively. Multivariate analysis confirmed PSI to be an independent significant predictor of PFS in both the methods., Conclusion: The WSDL-based framework was more effective for extracting 18 F-FDG PET/CT features and predicting the prognosis of ENKTL than the CDL method., (© 2021. The Author(s).)

Systemic vasculitis is a heterogeneous group of multisystem autoimmune disorders characterized by inflammation of blood vessels. Although many progresses in diagnosis and immunotherapies have been achieved over the past decades, there are still many unanswered questions about vasculitis from pathological understanding to more advanced therapies. Extracellular vesicles (EVs) are double-layer phospholipid membrane vesicles harboring various cargoes. EVs can be classified into exosomes, microvesicles (MVs), and apoptotic bodies depending on their size and origin of cellular compartment. EVs can be released by almost all cell types and may be involved in physical and pathological processes including inflammation and autoimmune responses. In systemic vasculitis, EVs may have pathogenic involvement in inflammation, autoimmune responses, thrombosis, endothelium injury, angiogenesis and intimal hyperplasia. EV-associated redox reaction may also be involved in vasculitis pathogenesis by inducing inflammation, endothelial injury and thrombosis. Additionally, EVs may serve as specific biomarkers for diagnosis or monitoring of disease activity and therapeutic efficacy, i.e. AAV-associated renal involvement. In this review, we have discussed the recent advances of EVs, especially their roles in pathogenesis and clinical involvements in vasculitis., (Published by Elsevier Inc.)

Background: To investigate the protective efficacy of miR-155 on down regulating NADPH oxidase isoform subunit A1 (NoxA1) gene expression, resulting in inhibition of VSMC migration and over proliferation and thus ameliorating the progression of arterial atherosclerosis in AS mouse model. Therefore, to further explore the regulatory effect of miR-155 on neointima formation in AS and locate potential anti-atherosclerosis target., Methods: The mouse vascular aorta smooth muscle cell (MOVAS) was cultured and transfected with recombinant Pad2YFG adenovirus fluorescent vector with miR-155 fragment into 4 groups. Western blotting and RT-PCR were performed to identify the expression of NoxA1 under different circumstances. Fluorescence microscope was applied to observe the transfection rate of miR-155 into adenovirus. Twelve-week fatty food induced atherosclerotic ApoE -/- mouse model was established as host to accept miR-155 transfected adenovirus transplantation to observe its effect on VSMC in AS progression. Carotid and thoracic artery were extracted at 1 month after dosing. Distribution of miR-155 was quantified via expression levels of protein and RNA to detect NoxA1, Nox1, p47phox and NADPH expression. Immunohistochemistry, fluorescence imaging and other methods were performed in arteries section to compare the thickness of neointima and assess the severity of AS in each group., Results: Luciferase reporter gene assay showed significant expression of miR-155 in mimic group indicating that miR-155 had target binding effect with NoxA1 gene. Western blotting and RT-PCR results both showed significantly decreased NoxA1 expression in miR-155 mimic group while increased with its inhibitor. The miR-155 distribution was observed varied at 1 month after in control, miR-155 mimic and inhibitor groups. The NoxA1, NADPH, Nox1 and pp47phox protein expression in VSMC was decreased in mimic group vs control and inhibitor groups (P<0.05); no significant difference of NADPH expression was observed in all groups. The NoxA1, Nox1 and p47phox gene expression in VSMC were both found reduced compared with those of control group at week 4 (P<0.05). Immunohistochemistry staining of artery frozen sections figured out that the thickness of neointima of carotid artery in miR-155 mimic group was significantly lower vs control and inhibitor groups (P<0.01) at week 4., Conclusions: miR-155 played an important role in NoxA1-related signaling pathway. miR-155 transfection into VSMC may have anti-inflammatory regulatory effect on NoxA1 expression in vivo and resulting in amelioration of atherosclerotic lesion in AS mouse model. In summary, miR-155 specifically plays in a negative feedback loop and demonstrates a protective role during atherosclerosis-associated VSMC proliferation and neointima formation through the miR-155-NoxA1-p47phox complex signaling pathway., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-518). The authors have no conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Repeated practice is fundamental to the acquisition of skills, which is typically accompanied by increasing reliability of neural representations that manifested as more stable activation patterns for the trained stimuli. However, large-scale neural pattern induced by learning has been rarely studied. Here, we investigated whether global connectivity patterns became more reliable as a result of motor learning using a novel analysis of the multivariate pattern of functional connectivity (MVPC). Human participants were trained with a finger-tapping motor task for five consecutive days and went through Functional magnetic resonance imaging (fMRI) scanning before and after training. We found that motor learning increased the whole-brain MVPC stability of the primary motor cortex (M1) when participants performed the trained sequence, while no similar effects were observed for the untrained sequence. Moreover, the increase of MVPC stability correlated with participants' improvement in behavioral performance. These findings suggested that the acquisition of motor skills was supported by the increased connectivity pattern stability between the M1 and the rest of the brain. In summary, our study not only suggests global neural pattern stabilization as a neural signature for effective learning but also advocates applying the MVPC analysis to reveal mechanisms of distributed network reorganization supporting various types of learning., (Copyright © 2020 Yu, Song, Huang, Song and Liu.)

Aims: Previously we identified four Tocilizumab mimotopes and antibodies induced by these mimotopes could bind to IL-6R (interleukin-6 receptor) and regulate the downstream signaling pathways. On the basis of obtained research data, we sought to investigate whether the therapeutic strategies by Tocilizumab mimotope vaccination could be effective in the renal fibrosis model and show the desired activity by inhibiting IL-6 signaling in current study., Main Methods: We immunized the mice with the Tocilizumab mimotope and then performed the unilateral ureteric obstruction (UUO) surgery. Masson-trichrome staining and immunohistochemistry were performed to evaluate the renal fibrosis. The activations and differentiations of F4/80+ cells in the spleens and kidneys were detected by flow cytometry, immunohistochemistry and immunofluorescence. Signaling pathways involved IL-6, pro-fibrotic and ferroptosis were analyzed by immunoblot assay. The free iron and lipid oxidation end product were performed by Prussian blue staining and immunohistochemistry. The injury and apoptosis in the kidneys were evaluated by immunofluorescence., Key Findings: The results showed the mimotope vaccination could reduce the level of fibrosis, injury and apoptosis by down-regulating the pro-fibrotic proteins, alleviating the activations and differentiations of macrophage F4/80+ cells in UUO models. IL-6/ERK signaling pathway was inhibited with the mimotope vaccination. The ferroptosis inhibited proteins significantly increased after the mimotope vaccination. On the contrary, the levels of free iron and lipid oxidation end product were observed to decrease in the mimotope treatment group., Significance: Our results suggested that the Tocilizumab mimotope vaccination might be an alternative therapy to against renal fibrosis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The study aimed to investigate the relationship between the aerobic exercise intensity determined by 6-minute walking distance (6MWD) and its counterpart based on anaerobic threshold (AT) in chronic heart failure (CHF) individuals for exploring suitable means for CHF exercise rehabilitation., Methods: We retrospectively analyzed data in patient with CHF, who performed cardiopulmonary exercise test (CPET) and 6-minute walking test (6MWT) uniformly. Anthropometric characteristics, left ventricular ejection fraction (LVEF), and multiple parameters of 6MWT and AT were collected., Results: The results of the analysis revealed that the 6MWD was correlated with the AT positively [CHF group: r=0.433, heart failure with reduced ejection fraction (HFrEF) group: r=0.395, heart failure with intermediate ejection fraction (HFmEF) group: r=0.477, heart failure with preserved ejection fraction (HFpEF) group: r=0.445; all P<0.05]. The regression analysis showed that the linear equation model developed can predict exercise intensity based on AT (EIAT) by exercise intensity based on 6MWD (EI6MWD), the aerobic exercise intensity based on AT and 6MWD respectively, of CHF patients., Conclusions: There is a correlation between EI6MWD and EIAT. 74.6-87.4% of EI6MWD in patients with CHF is equivalent to EIAT. It is feasible to establish the aerobic exercise intensity of patients with CHF equivalent to AT based on 6MWD.

With the development and improvement of new techniques in cell biology, molecular biology and biostatistics, increasing studies have been conducted to investigate the mechanism of venous thromboembolism (VTE). Some studies have found that the pathogenesis of VTE is largely related to the abnormality of the immune system as demonstrated by the thrombosis in mice infected with H1N1 influenza and the changes in the expression of genes related to immune system. According to the protein-protein interaction analysis of the differential expression of the immune system in VTE patients, the presence of venous thrombosis was related to the abnormal expression of molecules in JAK/STAT signaling pathway. We discussed the mechanism of VTE and provided two novel therapeutic targets for venous thrombosis: AKT1 and AOX1. Our review may be helpful for better understanding of the current research status of VTE, and provide evidence on the molecular mechanism of VTE.

Context: The pathogenesis of cardiomyocyte death is closely associated with mitochondrial homeostasis via poorly understood mechanisms. Objective: The aim of our study is to explore the contribution of large tumor suppressor kinase 2 (LATS2) to the apoptosis of cardiomyocyte H9C2 cells. Materials and Methods: Adenovirus-mediated LATS2 overexpression was carried out in H9C2 cells. The cell viability and apoptosis rate were measured via an MTT assay, TUNEL staining, western blotting, an ELISA, and an LDH release assay. Mitophagy was quantified using immunofluorescence and western blotting. Results: The overexpression of LATS2 in H9C2 cells drastically promoted cell death. Molecular investigations showed that LATS2 overexpression was associated with mitochondrial injury, as evidenced by increased mitochondrial ROS production, reduced antioxidant factor levels, increased cyt-c liberation into the nucleus and activated mitochondrial caspase-9-dependent apoptotic pathway activity. Furthermore, our results demonstrated that LATS2-mediated mitochondrial malfunction by repressing mitophagy and that the reactivation of mitophagy could sustain mitochondrial integrity and homeostasis in response to LATS2 overexpression. Furthermore, we found that LATS2 inhibited mitophagy by inactivating the Prx3-Mfn2 axis. The reactivation of Prx3-Mfn2 pathways abrogated the LATS2-mediated inhibition of mitochondrial apoptosis in H9C2 cells. Conclusions: The overexpression of LATS2 induces mitochondrial stress by repressing protective mitophagy in a manner dependent on Prx3-Mfn2 pathways, thus reducing the survival of H9C2 cells.

Immune activation and inflammation participate in the progression of chronic heart failure (CHF). Th17 cells and CD4+CD25+ regulatory T (Treg) cells both come from naive Th cells and share reciprocal development pathways but exhibit opposite effects. We hypothesized that the Th17/Treg balance was impaired in patients with CHF, and exercise can improve it. Rats with ischemic cardiomyopathy were prepared by ligaturing the left anterior descending branch of the left coronary artery. Rats in training group were trained with treadmill; Th17 cells increased significantly while Treg cells significantly decreased in s by flow cytometry, and the peripheral blood level of IL-6, IL-17, and TNF-α was obviously elevated by ELISA assay. We found that Th17/Treg balance is impaired in CHF rats, suggesting Th17/Treg imbalance potentially plays a role in the pathogenesis of CHF. Exercise can improve Th17/Treg imbalance, which also improves cardiac function of CHF.

Background: To evaluate the natural innate and adaptive immunity through gene expression and cytology levels in peripheral blood mononuclear cells in patients with acute myocardial infarction (AMI), stable angina pectoris (SAP) and controls. Methods : 210 patients with AMI, 210 with SAP, and 250 clinical controls were recruited. Whole human genome microarray analysis was performed in 20 randomly chosen subjects per group were examined to detect the expressions of complement markers, natural killer cells, T cells and B cells. The quantity of these cells and related cytokines as well as immunoglobulin levels were measured in all subjects. Results: In AMI group, the mRNA expressions of late complement component, markers of natural killer cells, CD3+, CD8+ T cells and B cells were down-regulated, while those of early complement component and CD4+T cells were up-regulated (p<0.05). In both AMI and SAP patients, the quantity of natural killer cells, CD3+, CD8+ T cells, B cells, IgM and IgG were significantly lower than those of the controls. CD4+ T cells, CH50, C3, C4, IL-2, IL-4, IL-6 and IFN-γ were significantly higher (p<0.05). Conclusions : In AMI patients, both of gene expressions related to complement, natural killer cells, CD3+, CD8+ T cells, B cells and the quantity of these immune cells decreased while cell number reduced in SAP patients. Immune function in both AMI and SAP patients decreased especially in AMI patients with declined gene and protein levels. To improve the immune system is a potential target for medical interventions and prevention in AMI., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Objectives: This study's aim was to evaluate the protective effects of salvianolate on contrast-induced nephropathy after primary percutaneous coronary intervention (PPCI) compared with normal saline (NS) hydration., Methods: We enrolled patients with acute myocardial infarction who underwent PPCI in 3 centers in Shanghai. The patients were randomly assigned to the salvianolate group or the NS group. The incidence of CIN, the changes in renal function parameters, and the occurrence of adverse events after the procedure were compared between the 2 groups. We used a multivariate logistic regression analysis to determine the independent correlates of CIN after PPCI., Results: A total of 484 patients were finally included in the statistical analysis. Compared with the control group, salvianolate reduced the incidence of CIN (9.1 vs. 16.3%, p = 0.018) after PPCI. The renal function parameters after PPCI in the salvianolate group were superior to those of the control group (p < 0.05). The composite adverse events rate was significantly lower in the salvianolate group within 1 month after the procedure (9.5 vs. 15.5%, p = 0.046). A higher peak of troponin I and loop diuretic therapy were the independent correlates of CIN after PPCI., Conclusions: Salvianolate reduces the incidence of CIN and protects renal function after PPCI, and the effects were superior to those of NS hydration., (© 2017 S. Karger AG, Basel.)

The aim of the present study was to evaluate differences in the expression of complement system genes, and serum levels of CH50, C3 and C4 in peripheral blood mononuclear cells from patients with myocardial infarction (AMI), stable angina pectoris (SA) and controls. A total of 100 patients with AMI, 100 with SA and 100 clinical controls were recruited in the present study. In each group, 20 randomly selected individuals were examined using whole human genome microarray analysis to detect the expression of genes of the complement system. The serum levels of CH50, C3 and C4 were measured in all 300 subjects. In the patients with AMI, the expression levels of genes encoding C1qα, C1qβ, C1qγ, C1r, Factor P, C5a (complement component), CR1, integrin αM, integrin αX, integrin β2, C5aR, CRIg (complement receptors) and CD46, CD55 and CD59 (complement regulators) were significantly higher, compared with the respective genes in the SA patients and controls (P<0.05), whereas the mRNA levels of C1s, C7, C8β and C9 were the lowest in this group (P<0.05). No statistically significant differences were found in the gene expression levels of complement components or regulators between the SA and control groups. The serum levels of CH50, C3 and C4 were significantly increased in the AMI and SA groups, compared with the controls. In the AMI and SA groups, the complement system was activated. However, the differential mRNA expression of complement components, receptors and regulators in the AMI group suggested the dysfunction of the C5b-9 complex. The depression of complement system immunity in the patients with AMI may be associated with the pathogenesis of AMI.

The current study aimed to identify differentially expressed B cell‑associated genes in peripheral blood mononuclear cells and observe the changes in B cell activation at different stages of coronary artery disease. Groups of patients with acute myocardial infarction (AMI) and stable angina (SA), as well as healthy volunteers, were recruited into the study (n=20 per group). Whole human genome microarray analysis was performed to examine the expression of B cell‑associated genes among these three groups. The mRNA expression levels of 60 genes associated with B cell activity and regulation were measured using reverse transcription‑quantitative polymerase chain reaction. The mRNA expression of the B cell antigen receptor (BCR)‑associated genes, CD45, NFAM, SYK and LYN, were significantly upregulated in patients with AMI; however, FCRL3, CD79B, CD19, CD81, FYN, BLK, CD22 and CD5 mRNA expression levels were significantly downregulated, compared with patients in the SA and control group. The mRNA levels of the T‑independent B cell‑associated genes, CD16, CD32, LILRA1 and TLR9, were significantly increased in AMI patients compared with SA and control patients. The mRNA expression of genes associated with T‑dependent B cells were also measured: EMR2 and CD97 were statistically upregulated, whereas SLAMF1, LY9, CD28, CD43, CD72, ICOSL, PD1, CD40 and CD20 mRNAs were significantly downregulated in AMI group patients compared with the two other groups. Additionally the gene expression levels of B cell regulatory genes were measured. In patients with AMI, CR1, LILRB2, LILRB3 and VAV1 mRNA expression levels were statistically increased, whereas, CS1 and IL4I1 mRNAs were significantly reduced compared with the SA and control groups. There was no statistically significant difference in B cell‑associated gene expression levels between patients with SA and the control group. The present study identified the downregulation of genes associated with BCRs, B2 cells and B cell regulators in patients with AMI, indicating a weakened T cell‑B cell interaction and reduced B2 cell activation during AMI. Thus, improving B2 cell‑mediated humoral immunity may be a potential target for medical intervention in patients with AMI.

Intracranial hemorrhage remains the most feared complication in tissue plasminogen activator (tPA) thrombolysis for ischemic stroke. However, the underlying molecular mechanisms are still poorly elucidated. In this study, we reported an important role of caveolin-1 (Cav-1) s-nitrosylation in matrix metalloproteinase (MMP)-2 and 9 secretion from tPA-treated ischemic endothelial cells. Brain vascular endothelial cells (bEND3) were exposed to oxygen-glucose deprivation (OGD) for 2 h before adding recombinant human tPA for 6 h. This treatment induced a significant increase of MMP2 and 9 in the media of bEND3 cells and a simultaneous degradation of fibronectin and laminin β-1, the two main components of extracellular matrix (ECM). Inhibition of MMP2 and 9 with SB-3CT completely blocked the degradation of fibronectin and laminin β-1. ODG+tPA treatment led to Cav-1 shedding from bEND3 cells into the media. Notably, OGD triggered nitric oxide (NO) production and S-nitrosylationof Cav-1 (SNCav-1). Meanwhile tPA induced activation of ERK signal pathway and stimulates the secretion of SNCav-1. Pretreatment of bEND3 cells with C-PTIO (a NO scavenger) or U0126 (a specific ERK inhibitor) significantly reduced OGD-induced S-nitrosylation of Cav-1 in cells and blocked the secretion of Cav-1 and MMP2 and 9 into the media as well as the degradation of fibronectin and laminin β-1 in OGD and tPA-treated cells. These data indicate that OGD-triggered Cav-1 S-nitrosylation interacts with tPA-induced ERK activation to augment MMP2 and 9 secretion and subsequent ECM degradation, which may account for the exacerbation of ischemic blood brain barrier damage following tPA thrombolysis for ischemic stroke.

Background: Cardiopulmonary exercise testing has been widely used to risk stratify patients with chronic heart failure (CHF). Peak oxygen consumption (peakVO2) was regarded as a powerful predictor of survival, as it is a surrogate for peak cardiac output (CO), which by most is considered the "true" measure of heart failure. Therefore, it is reasonable to hypothesize that CO is an even stronger predictor than peak VO2. The present study is aimed to investigate the prognostic value of peak cardiac power output (peak CPO) in comparison with peakVO2 in Chinese patients with CHF., Methods: Participants provided written informed consent to participate in this study. Totally 129 patients with CHF underwent symptom-limited cardiopulmonary exercise testing (CPET), with mean age 59.1 ± 11.4 years, 87.6% male, 57.4% ischemic etiology, body mass index (BMI) 24.7 ± 3.7 kg/m(2) and LVEF 38 ± 9%. CO was measured using an inert gas rebreathing method. The primary endpoints are cardiac deaths., Results: Over median 33.7-month follow-up, 19 cardiac deaths were reported. Among peak VO2,VE/VCO2 slope and Peak CPO, their area under ROC were 0.64, 0.67, 0.68, respectively (Ρ<0.05).The optimal thresholds for predicting cardiac deaths were peak VO2 ≤ 13.4 ml.kg(-1).min(-1), and VE/VCO2 slope ≥ 39.3 and peak CPO≤ 1.1 respectively by ROC analysis. Finally, in patients with a peak VO2 ≤ 13.4 ml.kg(-1).min(-1) those with peak CPO>1.1W had better survival than those with peak CPO ≤ 1.1W. However, by multivariate analysis adjusted for age, sex, BMI, resting heart rate, LVMI, LVEF, Peak CPO was not an independent predictor of cardiac deaths (P> 0.05)., Conclusions: Peak CPO was not a predictor of cardiac death in Chinese CHF patients.

Objective: To identify differentially expressed T cells-related genes in peripheral blood mononuclear cells and compare their differences in T cell activation and subset functions in different stages of coronary atherosclerosis disease (CAD)., Methods: 20 patients with acute myocardial infarction patients (AMI), 20 patients with stable angina pectoris (SA) and 20 healthy volunteers were recruited into the study. Whole human genome microarray analysis was used to detect the expression of T cell related genes among three groups., Results: mRNA expression of 68 genes involved in T cell was detected. 1) Antigen recognition: in the AMI patients 12 genes were down-regulated and 9 were significantly down-regulated among all 13 genes, compared with those of the SA and the control group, respectively. 2) Co-stimulators and regulators of T cell activation: among 16 genes in the AMI patients, 15 genes were lower and 8 were significantly lower than the other two groups. 3) T cell subsets, CTL: all 11 genes in the AMI patients were down-regulated, particularly GZMM and CASP8 were significantly down-regulated compared with the SA patients and controls. Th1/Th2: in the AMI patients, gene expressions including IL1 and IL18 were significantly higher, whereas GATA3 mRNA was significantly lower than those in other two groups. Th17/Treg: in the AMI group, RORC and CCR6 mRNAs were significantly down-regulated compared with the control group, while CD25 and CD127 expressions were significantly lower than SA group. There was no difference in T cell related genes between the SA patients and the controls., Conclusions: In the AMI patients, the mRNA expression of T cell antigen recognition, activation and subset functions was imbalanced or decreased, indicating the dysfunction of cellular immunity in patients with AMI. Then improving T cell mediated cellular immunity may be considered as a potential target for medical interventions in the patients with AMI.

Objective: The high morbidity, mortality and misdiagnosis rate render pulmonary embolism (PE) as a worldwide health problem. However, the etiology and pathogenesis of this disease have not been well characterized. Increasing studies indicate infection and immunity play a crucial role in PE. Natural killer (NK) cells act as a bridge between the innate immune and acquired immune. This study aimed to investigate the possible function of NK cells in PE., Methods: Human cDNA microarray analysis was employed to detect genes associated with NK cells in peripheral blood mononuclear cells (PBMCs). Random variance model corrected t-test was used for statistical analysis of differential gene expression. Flow cytometry was performed to detect the CD16+CD56+ NK cells., Results: In the present study, based on gene expression microarray analysis, we showed four inhibitory receptors (KLRB1, KLRD1, KLRF1, KLRG1) and four activating receptors (KLRC1, KLRC3, KLRK1 and NCR1) on NK cells were remarkably down-regulated and the cytological experiment demonstrated the proportion of CD16+CD56+ NK cells among PBMCs decreased in the PE group., Conclusions: We confirmed the presence of reduced expression of critical activating as well as inhibitory NK cell receptors and low proportion of CD16+CD56+ NK cells in PE. The consistence between genomic and cytological examination suggests compromised NK cells may contribute to the pathogenesis of PE.

Aim: This study was to carry out exome sequencing in a Han Chinese family with venous thromboembolism., Methods: Three venous thromboembolism (VTE) patients and five members from a Han Chinese family were evaluated by exome sequencing., Results: Among the 3 VTE patients, mutations of 2 genes including PRF1 and HTR2A were identified and predicted to be functionally damaged to their encoded proteins. In addition, the PRF1 mutation and the HTR2A mutation identified in our study were absent in 100 non-related controls, indicating that venous thromboembolism has a genetic component. The R357W mutation is located in the membrane attack complex/perforin domain of PRF1 protein, which exists in both the perforin. The steps of killing foreign or pathological antigen cells by NK cells, CD8 (+)T cells and the membrane attack complex include membrane perforation and release of the granzyme, either of which is abnormal can lead to immune dysfunction., Conclusions: The mutations of immune related genes in familial VTE might provide new understanding of the pathogenesis of familial venous thromboembolism.

Objective: To investigate the differences of T lymphocyte subgroups and high-sensitivity C reactive protein (HsCRP) levels among patients with venous thromboembolism (VTE), VTE patients with infection, simple infection patients and the normal controls., Method: 289 patients were enrolled in this study and divided into control group, VTE group, VTE with infection group and simple infection group., Result: Compared with the control group, the serum levels of CD3(+), CD4(+), CD8(+) T lymphocytes significantly decreased and CD4(+)/CD8(+) ratio significantly increased in simple infection group (P < 0.05); CD3(+) and CD8(+) T lymphocytes significantly decreased and CD4(+)/CD8(+) ratio significantly increased in VTE and VTE with infection group (P < 0.05); the proportion of declined CD3(+) and CD8(+) T lymphocytes increased, and the proportion of increased CD4(+)/CD8(+) ratio statistically elevated in three disease groups. As an important inflammatory factor, all HsCRP levels in three disease groups significantly increased when compared with the control group., Conclusion: Immune dysfunction exists in both of VTE and infection patients, while VTE patients tend to be accompanied with infections. The changes of T lymphocyte subgroups in VTE patients, who were independent from infection, could cause T lymphocyte immune dysfunction, suggesting that there were abnormalities of T lymphocyte immune function in VTE itself. The overall T lymphocyte functions of recognizing antigens and transducing activation signals decline in VTE patients. Besides, the function of T lymphocyte of directly killing virus microbes declines significantly and the inflammatory mechanisms are involved in the occurrence and development of venous thrombosis.

The aim of the present study was to explore the function and interaction of differentially expressed genes (DEGs) in pulmonary embolism (PE). The gene expression profile GSE13535, was downloaded from the Gene Expression Omnibus database. The DEGs 2 and 18 h post‑PE initiation were identified using the affy package in R software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the DEGs were analyzed using Database for Annotation Visualization and Integrated Discovery (DAVID) online analytical tools. In addition, protein‑protein interaction (PPI) networks of the DEGs were constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins. The PPI network at 18 h was modularized using Clusterone, and a functional enrichment analysis of the DEGs in the top three modules was performed with DAVID. Overall, 80 and 346 DEGs were identified 2 and 18 h after PE initiation, respectively. The KEGG pathways, including chemokine signaling and toll‑like receptor signaling, were shown to be significantly enriched. The five highest degree nodes in the PPI networks at 2 or 18 h were screened. The module analysis of the PPI network at 18 h revealed 11 hub nodes. A Gene Ontology terms analysis demonstrated that the DEGs in the top three modules were associated with the inflammatory, defense and immune responses. The results of the present study suggest that the DEGs identified, including chemokine‑related genes TFPI2 and TNF, may be potential target genes for the treatment of PE. The chemokine signaling pathway, inflammatory response and immune response were explored, and it may be suggested that these pathways have important roles in PE.

The minute ventilation/carbon dioxide production (VE/VCO 2 ) slope has been widely demonstrated to have strong prognostic value in patients with chronic heart failure (CHF), and the risk of mortality is believed to increase when the VE/VCO 2 slope is >32.8; however, there is little evidence concerning the prognostic value of the VE/VCO 2 slope in Chinese patients. In the present study, the prognostic value of the VE/VCO 2 slope was investigated in patients with CHF. A total of 258 subjects underwent symptom-limited cardiopulmonary exercise testing (CPET) and were divided into CHF (113 males and 16 females; LVEF <0.49) and control (106 males and 23 females) groups. The cardiac-related events over a median 33.7-month follow-up period subsequent to the CPET were evaluated using receiver operating characteristic curve analysis. The VE/VCO 2 slope was significantly different between the CHF and control groups (P<0.001). The area under the curve (AUC) for the VE/VCO 2 slope in predicting cardiac-related mortalities in the patients with CHF was 0.670 (P<0.05), and the sensitivity and specificity of the VE/VCO 2 slope were 0.667 and 0.620, respectively. The optimal threshold of the VE/VCO 2 slope for predicting cardiac-related mortalities in patients with CHF was ≥39.3. The AUC for the VE/VCO 2 slope in predicting cardiac-related hospitalizations in patients with CHF was 0.682 (P<0.05), and the sensitivity and specificity of the VE/VCO 2 slope were 0.631 and 0.778, respectively. The optimal threshold of the VE/VCO 2 slope for predicting cardiac-related hospitalizations in patients with CHF was ≥32.9. In conclusion, ventilatory efficiency decreases in patients with CHF. The VE/VCO 2 slope is a strong predictor of cardiac-related mortalities in the patients with CHF analyzed.

Background: To compare different expression of core proteins among venous thromboembolism (VTE) and those with risk factor groups and analyze the relative risk for VTE after integrating integrin β1, β2 and β3 expression., Methods: A total of 1006 subjects were recruited and divided into VTE group, risk factor groups and control (non- risk factor) group. Flow cytometry was performed to detect the expression of integrin β1, β2 and β3. The relative risk for VTE was evaluated with independent, parallel and serial methods., Results: The expression of integrin β1 increased markedly in VTE patients, and those with risk factors (acute infection, malignancy, and autoimmune diseases), respectively (P < 0.001 or 0.01). The expression of integrin β1 in trauma/surgery group was not significantly different with control group (P > 0.05). The expression of integrin β2 or β3 significantly increased in VTE group, but that in risk factor groups was not significantly increased (P > 0.05). Multivariate analysis revealed the trauma/surgery groups had no significantly increased risk for VTE., Conclusions: VTE group patients have significantly increased expression of integrin β1, β2 and β3, and risk factor groups (acute infection, malignancy and autoimmune disease) have significantly increased expression of integrin β1. The significant increase in integrin β2, β3 expression is a marker differentiating of VTE group patients with other risk factor groups. Trauma/surgery group has no increased expression of integrin β1, β2 and β3 as other risk factors. Thus, that trauma/surgery may be not the "true" risk factor for VTE.

Background: To investigate the mechanism of smoking on cardiovascular diseases., Material and Methods: 576 elderly patients with cardiovascular diseases in stable condition were consecutive recruited, asked about the living habits and smoking history in a way of face to face., Results: Of all the enrolled patients, current smoking rate was 34.8% for males and 3.4% for females. Average smoking quantity was 17 cigarettes per day and incidence of hyperhomocysteinemia was 38.0%. The homocysteine level in current smokers was significantly higher than that in never smokers (P = 0.004); while the serum folic acid and serum superoxide dismutase (SOD) level were significantly lower those in never smokers (P = 0.012; P = 0.004). The daily smoking consumption and the pack-years of smoking were significantly positively correlated with total homocysteine (tHcy) level (P = 0.020; P = 0.003). The reduced serum SOD level might be associated with increased risk of hypertension (P = 0.023), coronary heart disease (P = 0.018), and stroke (P = 0.035). However, the elevated serum tHcy level was not correlated with increased risk of hypertension and coronary heart disease, while may increase the risk of ischemic stroke (P = 0.075)., Conclusions: Smoking status is still prevalent among Chinese elderly patients with cardiovascular diseases, which causes the increase of serum tHcy and the decrease of serum folate as well as SOD; smoking consumption per day and pack-years of smoking have indirect effects on tHcy. And decrease of serum SOD is a risk factor for cardiovascular diseases, increase of serum tHcy may be associated with changes of metabolism caused by oxidative damage.

Aim: Poly-l-lactic acid (PLLA) based bioabsorbable stents with or without amorphous calcium phosphate (ACP) were implanted and compared the inflammation in coronary arteries., Methods: 6 PLLA and 6 PLLA/ACP based paclitaxel-eluting stents were randomly implanted into the coronary arteries of 12 healthy mini-pigs. The segments with stent were used to evaluate inflammation score and endothelialization score by hematoxylin-eosin staining., Results: At the 28th day after stent implantation, no in-stent restenosis or stent thrombosis was found in both PLLA and PLLA/ACP group. Histological analysis indicated that the inflammation score in PLLA/ACP group was less than that of in PLLA group (2.20±0.42 vs. 2.80±0.48, P<0.05). Consist with that, the expression of NF-κB was lower in PLLA/ACP group. The results from immunohistochemistry showed that the expressions of endothelial nitric oxide synthase (eNOS) and CD 31 in PLLA/ACP group were dramatically higher than those in PLLA group respectively. The serum levels of vascular endothelial growth factor (VEGF) and nitric oxide (NO) in PLLA/ACP group were significantly higher than those in PLLA group respectively (509.86±49.37 pg/ml vs. 322.04±35.16 pg/ml and 139.46±7.52 μmol/L vs. 29.55±16.55 μmol/L, P<0.05)., Conclusion: The application of ACP helps to reduce the inflammation caused by PLLA, and is also helpful in endothelial formation and function for PLLA-based bioabsorbable stent.

Introduction: We aim to compare the midterm outcomes between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in diabetic patients who had multivessel coronary artery diseases (CAD)., Material and Methods: A comprehensive literature search was conducted to identify the related clinical studies with a follow-up for 1 year at least. The endpoints were death, myocardial infarction, and major adverse cardiac and cerebrovascular events (MACCE)., Results: Finally, the analysis of ten studies involving 5,264 patients showed that patients with CABG had worse baseline characteristics, a higher rate of stable angina pectoris, a higher percentage of triple-vessel disease, higher incidence of chronic total occlusion and a higher SYNTAX score. However, there was no significant difference in mortality between the two groups. Additionally, the rates of myocardial infarction and MACCE were markedly decreased in the CABG group., Conclusions: The strategy of CABG is better than PCI for diabetic patients with multivessel CAD. The CABG can significantly reduce the rates of myocardial infarction and MACCE and is comparable in mortality despite the worse baseline characteristics.

Introduction and Objectives: Recent studies have shown that the major risk factors for arterial thrombotic diseases are closely associated with venous thromboembolism (VTE). This study aimed to investigate the expression of CD3, CD4 and CD8 in T lymphocytes, the CD4/CD8 ratio and high-sensitivity C-reactive protein (hs-CRP) levels in patients with VTE, coronary artery atherosclerosis (CAA) and healthy subjects., Methods: A total of 82 healthy subjects, 51 VTE patients and 114 CAA patients were recruited, and the expression of CD3, CD4 and CD8 in T lymphocytes and the CD4/CD8 ratio were determined. Serum hs-CRP was also measured., Results: Compared to healthy subjects, VTE patients had significantly reduced CD3 expression (p=0.019), comparable CD4 expression (p=0.868), significantly reduced CD8 expression (p<0.001) and increased CD4/CD8 ratio (p=0.044). However, VTE patients had comparable expression of CD3, CD4 and CD8 and CD4/CD8 ratio to CAA patients. In addition, among patients with VTE or CAA, the proportion of patients with reduced CD3+ and CD8+ T lymphocytes or increased CD4/CD8 ratio was significantly higher than in healthy subjects. In addition, hs-CRP in both VTE and CAA groups was significantly higher than in healthy subjects., Conclusions: The antigen recognition and signal transduction activation of T cells is significantly reduced in patients with VTE or CAA, and the killing effect of T cells on pathogens, including viruses, is also significantly compromised. In addition, inflammatory and immune mechanisms are involved in the occurrence and development of venous and arterial thrombosis., (Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Background: Atherosclerosis is a chronic inflammatory process, in which oxidative stress is the key event. Gamma-glutamyl transferase (GGT) is a cellular production of oxidants. We aimed to elucidate the relationship of serum GGT levels and coronary artery disease (CAD) in a Chinese population., Material and Methods: A total of 513 adult subjects who had undergone coronary angiography were enrolled in the study. Clinical characteristics, coronary angiography, and serum samples were collected from all the patients and analyzed for the serum GGT, blood lipids, and cardiovascular risk factors., Results: Subjects with CAD had significantly increased activity of serum GGT (p=0.003). Serum GGT levels exhibited positive correlations with alcohol intake (β=0.177, p<0.001), coronary complexity (β=0.068, p<0.001), and triacylglycerol (β=0.058, p<0.001). High-density lipoprotein cholesterol levels (β=0.157, p=0.008) and age (β=0.004, p=0.002) were negatively correlated with serum GGT in the CAD group. The coronary complexity presented a negative correlation with Ig-apolipoprotein AI (β=-2.517, p=0.001) and positive correlations with smoking (β=0.640, p<0.001), Ig-GGT (β=0.613, p=0.004), Ig high sensitivity-C reactive protein (β=0.320, p<0.001), and hypertension (β=0.286, p<0.026)., Conclusions: The study showed a positive correlation between serum GGT and CAD in a Chinese population. Serum GGT levels may be a potential biomarker for CAD.

Introduction: Pulmonary embolism (PE) is a disease with a high mortality and morbidity rate, and the pathogenesis of PE remains still unclear. We aimed to investigate the gene expression differences of the complement system in peripheral blood mononuclear cells (PBMCs) from patients with symptomatic PE and controls., Methods: Twenty cases of PE patients and twenty sex and age matched controls were recruited into the study. Human cDNA microarray analysis was used to detect the gene expression difference of the complement system between the two groups., Results: 1). Expression of twenty-one genes encoding complement components was detected. In PE patients, expression of the genes encoding C1qα, C1qβ, C4b, C5 and Factor P was significantly greater (P<0.05) than controls, while C6, C7, C9, mannose-binding lectin (MBL) and mannan-binding lectin serine peptidase 1 (MASP1) mRNAs were lower (P<0.05) than controls. 2). Expression of seven genes encoding complement receptors was examined. In PE patients, CR1, integrin αM, integrin αX and C5aR mRNAs were significantly up-regulated (P<0.01) compared with controls. 3). Seven genes encoding complement regulators were examined. The mRNA expression of CD59 and CD55 was significantly up-regulated (P<0.05), whereas Factor I mRNA was significantly down-regulated (P<0.05) in PE patients than controls., Conclusions: In PE patients, the mRNA expressions of complement components, receptors and regulators were unbalanced, suggesting dysfunction and/or deficiency of the complement system, which leads to decreased function of MAC-induced cell lysis in PE patients finally., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Few studies have investigated the changes of Th1- and Th2-type cytokines in pulmonary embolism (PE) patients. In this study, the gene expression of interleukins and the balance of Th1- and Th2-type cytokines in the peripheral blood mononuclear cells (PBMCs) of PE patients and controls were investigated. A total of 20 PE patients and 20 gender- and age-matched controls were included in the study. Human cDNA microarray analysis was used to detect the differences in cytokine gene expression between the two groups and a random variance model corrected t-test was used to analyze the statistical data. In comparison with the controls, 12 genes were found to be downregulated, specifically IL1A, IL9, IL17B, IL19, IL23A, IL25 (p<0.05), IL2, IL3, IL13, IL22, IL24 and IL31 (p<0.01), and 2 genes were found to be upregulated, specifically IL10 and IL28A, in the PE patients. The expression levels of IFN-γ and IL2 mRNA in the PE patients were significantly lower than those in the control group (p<0.01), while the IL20 mRNA expression levels were significantly upregulated (p<0.01). We conclude that there are significant differences in interleukin gene expression between the PE patients and the control group. A shift of the Th1/Th2 balance comprising enhanced Th2 activity and reduced Th1 activity in the PE patients is also demonstrated.

The aim of this study was to identify the differences in the expression of cell adhesion molecule-related mRNAs between symptomatic pulmonary embolism (PE) and a control group, and to investigate the interactions among activated leukocytes, platelets and endothelial cells. Whole human gene chip was applied to detect the expression of cell adhesion molecule-related mRNAs in symptomatic PE and in the control group, and statistical analysis was performed. In patients with PE, the expression of the majority of integrin mRNAs located on leukocytes and platelets was significantly upregulated. The expression of mRNAs related to L-selectin and P-selectin glycoprotein ligand was significantly upregulated, while the expression of mRNA related to E-selectin was significantly downregulated. The expression of mRNAs related to classic cadherins and protocadherins was downregulated, and the expression of mRNAs related to vascular endothelial cadherin was significantly downregulated; the expression of mRNAs related to the immunoglobulin superfamily had no obvious difference between the 2 groups. In conclusion, we demonstrated that, in symptomatic PE patients, the adhesion of leukocytes and platelets was enhanced; the activation of endothelial cells was obviously weakened; the adherens junctions among endothelial cells were weakened, with the endothelium becoming more permeable.

Background: In the present study, the whole human genome oligo microarray was employed to investigate the gene expression profile in symptomatic pulmonary embolism (PE)., Methods: Twenty patients with PE and 20 age and gender matched patients without PE as controls were enrolled into the present study in the same period. The diagnosis of PE was based on the clinical manifestations and findings on imaging examinations. Acute arterial and/or venous thrombosis was excluded in controls. The whole human genome oligo microarray was employed for detection. Statistical analysis was performed with t test following analysis of very small samples of repeated measurements and Gene Ontology (GO) analysis., Results: Genomic data showed no damage to vascular endothelial cells in PE patients. Genomic data only found increased mRNA expression of a small amount of coagulation factors in PE patients. In the PE group, anticoagulant proteins, Fibrinolytic system and proteins related to platelet functions only played partial roles in the pathogenesis of PE. In addition, the mRNA expressions of a fraction of adhesion molecules were markedly up-regulated. Gene Ontology analysis showed the genes with down-regulated expressions mainly explain the compromised T cell immunity. Symptomatic VTE patients have compromised T cell immunity., Conclusion: The damage to vascular endothelial cells is not necessary in the pathogenesis of VTE, and only a fraction of factors involved in the shared coagulation cascade are activated. Genomic results may provide a new clue for clinical diagnosis, treatment and prevention of VTE.

The characteristics of human genomics and cellular immune function between clinically symptomatic venous thromboembolism (VTE) and controls were systematically compared to explore the immunologic pathogenesis of VTE. Microarray assay showed the mRNA expressions of genes related to non-specific cellarer immune and cytokines were significantly down-regulated. Abnormal expressions of CD3+, CD4+, CD8+, NK marker CD16+56+, CD19 and aberrant CD4+/CD8+ ratio were detected in 54 among 56 patients. In PE patients, microarray assay revealed the imbalance in the expressions of genes related to the immune system. The expressions of genes related to non-specific immune cells and cytokines were markedly up-regulated and those associated with cellular immune were dramatically down-regulated. In VTE patients, cytological examination indicated the functions of NK cells were significantly compromised, and the antigen recognition and killing function of T cells markedly decreased. The consistence between genomic and cytological examination suggests the symptomatic VTE is closely associated with the infection and immune dysfunction.