Objective.This study was performed to explore the clinical manifestations and longterm prognosis in patients with Takayasu arteritis (TA) with pulmonary artery involvement (PAI).Methods.The medical records of 194 patients with TA who underwent traditional catheter angiography or computed tomography of pulmonary artery from 2009 to 2016 were retrospectively reviewed. The clinical manifestations, angiographic features, and mortality of 128 patients with TA with PAI were further analyzed.Results.Patients with TA with PAI had a higher risk of pulmonary hypertension (PH) than patients with TA alone (61.7% vs 7.6%, p < 0.001). Patients with PAI and PH more frequently developed dyspnea, hemoptysis, and lower limbs edema (all p < 0.05) than those without PH. Patients with PH also had a higher incidence of bilateral PAI (84.8% vs 34.7%, p < 0.001) and a higher pulmonary artery obstruction index [23 (interquartile range 20–27) vs 10 (6–15), p < 0.001]. Left heart disease was presented in 39 (30.5%) patients with TA with PAI. During the median followup of 38 (21–58) months, 19 and 2 deaths occurred among patients with and without PH, respectively. Among patients with PAI, the mortality rate was 7 times higher in patients with than without PH (p = 0.009). Independent predictors of mortality were the disease duration (p = 0.047), New York Heart Association class III/IV (p = 0.019), right ventricular systolic dysfunction (p = 0.019), and respiratory failure (p = 0.007).Conclusion.Patients with TA with PAI have a higher risk of developing PH than patients with TA alone. The presence of PH in patients with PAI increases the risk of early mortality.

Background Coronavirus disease 2019 (COVID-19) is still ongoing throughout the world and has resulted in considerable fatality. Inflammation and cardiac injury are commonly observed in these cases. However, the association between the hyper-inflammatory response and cardiac injury among patients with COVID-19 remains unknown. Methods The study was designed based on severe and critically ill patients with COVID-19. Information on demographics and baseline clinical characteristics as well as laboratory examinations were collected from the electronic medical records and analyzed. Results There were 32.4% (n = 107) of patients presenting with cardiac injury. The median age was 67 years, and 48.8% (n = 161) of patients were men. Hypertension was the most common in 161 (48.8%) patients, followed by diabetes (16.7%, n = 55) and coronary heart disease (13.3%, n = 44). Moreover, compared to cases without cardiac injury, those with cardiac injury were older, had higher proportions of coronary heart disease, had significantly elevated leukocyte counts and concentrations of N-terminal pro-B-Type natriuretic peptide, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, interleukin-2 receptor (IL-2R), IL-6, and IL-8, but lower lymphocyte counts. A significant positive correlation was observed between high-sensitivity troponin I and hs-CRP, TNF-α, IL-2R, IL-6 and IL-8. Stepwise logistic regression analysis showed that hs-CRP, TNF-α and IL-6 were independent risk factors for cardiac injury. Conclusions Pro-inflammatory cytokines were associated with cardiac injury among severe and critically ill patients with COVID-19, suggesting that hyper-inflammatory response may involve in cardiac injury.

Pancreatic cancer patients are asymptomatic at early stages and leading to late diagnoses. Additionally, pancreatic cancer easily metastasizes and is resistant to radiotherapy and chemotherapy. Therefore, it is critical to understand the underlying molecular mechanisms involved in pancreatic cancer to develop more efficient diagnostic and treatment strategies. In this study, we demonstrated that circRHOT1 was overexpressed in pancreatic cancer tissues and cell lines, and it was found to directly bind to miR‐125a‐3p, acting as an endogenous sponge to inhibit its activity. Knockdown of circRHOT1 expression significantly inhibited proliferation as well as invasion, and it promoted apoptosis of pancreatic cancer cells via the regulation of E2F3 through the targeting of miR‐125a‐3p. Taken together, our results showed that circRHOT1 plays critical roles in regulating the biological functions of pancreatic cancer cells, suggesting that circRHOT1 may serve as a potential diagnostic marker and therapeutic target for patients with pancreatic cancer.

Background High-dose intravenous vitamin C (HIVC) is a major concern on treating coronavirus disease 2019 (COVID-19). Objective To assess the clinical efficacy of HIVC on hyperinflammation among patients with severe COVID-19. Methods The retrospective cohort study included inpatients with severe COVID-19, a subset of whom was treated with HIVC. The medical records were screened for demographic data, laboratory findings, medications, as well as initial and repeated values of multiple inflammatory markers for analysis. Results The percentages of patients presented hyperinflammation based on inflammatory markers levels above upper limit of normal (hs-CRP, 80.1%; IL-6, 91.5%; TNF-a, 67.4%). A total of 85 (36.0%) patients received HIVC therapy. After treatment with HIVC, the levels of inflammatory markers displayed significant decrease related to those among patients without HIVC. Furthermore, the percentages of reduction in inflammatory markers levels were higher in patients receiving HIVC compared with those in patients treated without HIVC. Stepwise multiple linear regression analysis revealed that HIVC was independently associated with percentages of reduction in inflammatory markers levels. Conclusions HIVC has potential benefit in attenuating hyperinflammation through reducing inflammatory markers levels in patients with severe COVID-19.

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Background Ischemic heart disease (IHD) is the major cause of death in patients with cardiovascular disease. Cardiac remodeling is a common pathological change following myocardial infarction (MI), and cardiomyocyte apoptosis plays a key role in this change. Transcription factor recombination signal-binding protein-J (RBP-J)-mediated Notch signaling pathway has been implicated in several inherited cardiovascular diseases, including aortic valve diseases, but whether the RBP-J-mediated Notch signaling pathway plays a role in cardiomyocyte apoptosis after MI is unclear. Method We crossed RBP-Jfl/fl mice and Myh6-Cre/Esr1 transgenic mice to delete RBP-J in vivo and to partly inhibit the canonical Notch signaling pathway. MI was induced in mice by permanent ligation of the left anterior descending coronary artery followed by the knockout of RBP-J. Cardiac function and morphology were assessed by echocardiography and histological analysis 4 weeks after infarction. In addition, the expression and regulation of apoptosis-related molecules were examined by real time PCR and western blot. Results RBP-J knockout decreased the survival rate and deteriorated post-MI remodeling and function in mice, and this effect was associated with increased cardiomyocyte apoptosis. The potential mechanisms might be related to the downregulated expression of bcl-2, upregulated expression of bax, and cleaved-caspase 3 to exacerbate cardiomyocyte apoptosis. Conclusion These findings show that the RBP-J-mediated Notch signaling pathway in cardiomyocytes limits ventricular remodeling and improves cardiac function after MI. The RBP-J-mediated Notch signaling pathway has a protective role in cardiomyocyte apoptosis following cardiac injury.

Acute myocardial infarction (AMI) remains one of the leading causes of mortality worldwide; however, endothelial progenitor cell (EPC) transplantation has been proposed as a promising treatment strategy for EPC. High levels of tumor necrosis factor-related weak inducer of apoptosis (TWEAK) have been reported in AMI, although its effect on EPCs has not been reported. In the present study, immunofluorescence and flow cytometry were performed to assess the effect of TWEAK in isolated mouse EPCs. Echocardiography was used to evaluate the cardiac function of murine hearts following EPC treatment in the AMI model, while collagen synthesis within the heart tissue was assessed using Masson's trichrome staining. A tube formation assay and Transwell migration assay were performed to investigate the effects of TWEAK on vessel formation and EPC migration in vitro. Angiogenesis and arteriogenesis were assessed in vivo using immunohistochemistry and western blotting was performed to determine the effect of TWEAK-mediated nuclear factor (NF)-κB pathway activation in EPCs. The results revealed that TWEAK promotes EPC migration, tube formation and viability in vitro. Furthermore, TWEAK treatment resulted in improved cardiac function, decreased heart collagen and vasculogenesis in mice with AMI, which was mediated by the TWEAK- fibroblast growth factor-inducible 14 (Fn14)-NF-κB signaling pathway, as determined using Fn14 small interfering (si)RNA and Bay 11–7082 (an NF-κB inhibitor). In summary, the results of the present study suggest that activation of the TWEAK-Fn14-NF-κB signaling pathway exerts a beneficial effect on EPCs for the treatment of AMI.

Cardiac fibroblast (CF) differentiation to myofibroblasts expressing α-smooth muscle actin (α-SMA) plays a key role in cardiac fibrosis. Therefore, a study of the mechanism regulating α-SMA expression is a means to understanding the mechanism of fibroblast differentiation and cardiac fibrosis. Previous studies have shown that DNA methylation is associated with gene expression and is related to the development of tissue fibrosis. However, the mechanisms by which CF differentiation is regulated by DNA methylation remain unclear. Here, we explored the epigenetic regulation of α-SMA expression and its relevance in CF differentiation. In this study, we demonstrated that α-SMA was overexpressed and DNMT1 expression was downregulated in the infarct area after myocardial infarction. Treatment of CFs with transforming growth factor-β 1 (TGF-β 1 ) in vitro upregulated α-SMA expression via epigenetic modifications. TGF-β 1 also inhibited DNMT1 expression and activity during CF differentiation. In addition, α-SMA expression was regulated by DNMT1. Conversely, increasing DNMT1 expression levels rescued the TGF-β 1 -induced upregulation of α-SMA expression. Finally, TGF-β 1 regulated α-SMA expression by inhibiting the DNMT1-mediated DNA methylation of the α-SMA promoter. Taken together, our research showed that inhibition of the DNMT1-mediated DNA methylation of the α-SMA promoter plays an essential role in CF differentiation. In addition, DNMT1 may be a new target for the prevention and treatment of myocardial fibrosis.