Giant Solitary Fibrous Tumor of the Ascending Aortic Wall Causing Reversible Heart Failure: A Case Report and Review of the Literature.

A 56-year-old woman was admitted to our hospital with a 2-week history of chest tightness and fatigue, and an echocardiogram revealed a massive polyserous cavity effusion. A massive (13.5 cm maximum diameter) intrapericardial mass was discovered using computed tomography (CT) and cardiovascular magnetic resonance imaging (MRI) in the ascending aortic wall. A pericardial biopsy was performed and diagnosed as a solitary fibrous tumor (SFT). After successful mass resection, an immunohistochemical test was positive for CD34, STAT-6, CD34, and Bcl2, which indicates a giant benign solitary fibrous tumor of the ascending aortic wall. After three years of follow-up, the patient is symptom-free, and histological indications of malignancy were absent. A giant benign solitary fibrous tumor is extremely rare in the heart, especially from the ascending aorta wall, and experience with this tumor location is limited, so close follow-up at regular intervals is considered necessary. We present this case, followed by a literature review on SFTs involving the heart and management approaches.

Clinical assessment of VSR site and size and its relation to the severity of heart failure in post-myocardial infarction ventricular septal rupture patients.

BACKGROUND: Ventricular septal rupture (VSR) is a rare but well-known mechanical consequence of an acute myocardial infarction (AMI). Even in the later stages of re-perfusion therapy, the result of VSR remains poor. Our aim is to assess the site and size of VSR in relation to the severity of cardiac failure. METHODS: From January 2016 to December 2022, a total of 71 patients with a diagnosis of post-myocardial infarction VSR were admitted to the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Data records were retrospectively included in this registry. In all patients, clinical and echocardiographic data were gathered, and statistical analyses were performed. RESULTS: A total of 71 consecutive patients (mean age: 66.27 ± 8.88 years); 50.7% male, 49.3% female, with (M:F) ratio of almost (1:1). Left ventricular ejection fraction (LVEF) was (48.55 ± 10.44%) on echocardiography, and apical VSR was the most common site (69.0%). Overall, the VSD site was strongly related to the VSD size (p = .016), LVEF (p = .012), AMI site (p = .001), and affected coronary vessel (p = .004). Prodromal angina (p = .041), intra-aortic balloon pump (p = .002), affected coronary vessels (p = .020), pro-BNP (p = .000), and LVEF (p = .017) were predictors of the severity of heart failure. CONCLUSIONS: Diabetes mellitus is a common risk factor for post-myocardial infarction VSR. VSR site and size had no relation to the severity of heart failure. A presentation with prodromal angina predicted severe heart failure and a worse prognosis.

Prediction of no reflow phenomenon in percutaneous coronary intervention with optical coherence tomography and analysis of risk factors.

Objective :To investigate the predictive value of no reflow phenomenon in interventional therapy by measuring plaque quantitatively with optical coherence tomography (OCT).  Methods:196 patients with acute ST segment elevation myocardial infarction who visited the Department of Cardiology of the Second Affiliated Hospital of Zhengzhou University from January 2020 to January 2022 were selected as the study objects. According to whether there was no reflow during the operation, they were divided into no reflow group (46 cases) and normal flow group (150 cases). Systematically collect general clinical data and coronary angiography related data of patients through inpatient cases, measure fiber cap thickness and lipid core angle of diseased vascular plaque through optical coherence tomography, and analyze the relationship between fiber cap thickness and no reflow phenomenon   Results:BMI, LDL, phospholipase A, the proportion of family history of coronary heart disease, and the thrombus load in the no reflow group were higher than those in the normal flow group (P<0.05), while the thickness of the fibrous cap was lower than that in the normal flow group (P<0.05); Further multivariate logistic regression analysis showed that fiber cap thickness, phospholipase A and severe thrombosis load were independent risk factors for non reflow phenomenon (P<0.05); Further ROC curve analysis found that the thickness of fiber cap had a high predictive value for no reflow phenomenon, and the best cutoff value for no reflow was 95, AUC: 0.926 (95% CI: 0.891-0.961, P<0.001). Conclusions: Optical coherence tomography can predict the occurrence of no reflow phenomenon by measuring the fiber cap thickness quantitatively. The prediction effect is the best when the fiber cap thickness is 95.

Establishment of a PPP2CA homozygous knockout human embryonic stem cell line via CRISPR/Cas9 system.

Protein phosphatase 2A (PPP2CA) is one of the four main Ser/Thr phosphatase enzymes, which involved in the negative control of cell growth and division. PPP2CA is the main protein phosphatase in the heart, which regulates Ca (2+) through a series of ion channels and transporters. In this study, we generated a PPP2CA homozygous knockout human embryonic stem cell line WAe009-A-25 based on the transient expression CRISPR/Cas9 system to investigate functional effect of PP1 deficiency. This cell line has multidirectional differentiation potential, normal karyotypic and trilineage differentiation potential in vivo.

Reprogramming of a human induced pluripotent stem cell line (ZZUSAHi004-A) from a long QT syndrome patient with a heterozygous AKAP9 (c. 4021C > A) mutant.

Long QT syndrome is one of the most common hereditary arrhythmias in clinic. Mutations in AKAP9 gene can lead to long QT syndrome type 11 (LQT11). In this study, a human induced pluripotent stem cell line ZZUSAHi004-A from a 3-year-old male patient with long QT syndrome carrying a heterozygous mutation in AKAP9 gene using non-integrative Sendai viral reprogramming technology. ZZUSAHi004-A showed normal male karyotype (46, XY), expressed pluripotency markers and could differentiate into all three germ layers in vitro. ZZUSAHi004-A can serve as a cell disease model in the understanding of LQT11 pathogenesis.

Dynamics of binding ability prediction between spike protein and human ACE2 reveals the adaptive strategy of SARS-CoV-2 in humans.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus causing the COVID-19 pandemic in 2020. High adaptive plasticity on the spike protein of SASR-CoV-2 enables it to transmit across different host species. In the present study, we collected 2092 high-quality genome sequences of SARS-CoV-2 from 160 regions in over 50 countries and reconstructed their phylogeny. We also analyzed the polymorphic interaction between spike protein and human ACE2 (hACE2). Phylogenetic analysis of SARS-CoV-2 suggests that SARS-CoV-2 is probably originated from a recombination event on the spike protein between a bat coronavirus and a pangolin coronavirus that endows it humans infectivity. Compared with other regions in the S gene of SARS-CoV-2, the direct-binding sites of the receptor-binding domain (RBD) is more conserved. We focused on 3,860 amino acid mutations in spike protein RBD (T333-C525) of SARS-CoV-2 and simulated their differential stability and binding affinity to hACE2 (S19-D615). The results indicate no preference for SARS-CoV-2 infectivity on people of different ethnic groups. The variants in the spike protein of SARS-CoV-2 may also be a good indicator demonstrating the transmission route of SARS-CoV-2 from its natural reservoir to human hosts.

Impact of peroxisome proliferator-activated receptor-α on diabetic cardiomyopathy.

The prevalence of cardiomyopathy is higher in diabetic patients than those without diabetes. Diabetic cardiomyopathy (DCM) is defined as a clinical condition of abnormal myocardial structure and performance in diabetic patients without other cardiac risk factors, such as coronary artery disease, hypertension, and significant valvular disease. Multiple molecular events contribute to the development of DCM, which include the alterations in energy metabolism (fatty acid, glucose, ketone and branched chain amino acids) and the abnormalities of subcellular components in the heart, such as impaired insulin signaling, increased oxidative stress, calcium mishandling and inflammation. There are no specific drugs in treating DCM despite of decades of basic and clinical investigations. This is, in part, due to the lack of our understanding as to how heart failure initiates and develops, especially in diabetic patients without an underlying ischemic cause. Some of the traditional anti-diabetic or lipid-lowering agents aimed at shifting the balance of cardiac metabolism from utilizing fat to glucose have been shown inadequately targeting multiple aspects of the conditions. Peroxisome proliferator-activated receptor α (PPARα), a transcription factor, plays an important role in mediating DCM-related molecular events. Pharmacological targeting of PPARα activation has been demonstrated to be one of the important strategies for patients with diabetes, metabolic syndrome, and atherosclerotic cardiovascular diseases. The aim of this review is to provide a contemporary view of PPARα in association with the underlying pathophysiological changes in DCM. We discuss the PPARα-related drugs in clinical applications and facts related to the drugs that may be considered as risky (such as fenofibrate, bezafibrate, clofibrate) or safe (pemafibrate, metformin and glucagon-like peptide 1-receptor agonists) or having the potential (sodium-glucose co-transporter 2 inhibitor) in treating DCM.

CRISPR/Cas9 mediated establishment of a human CSRP3 compound heterozygous knockout hESC line to model cardiomyopathy and heart failure.

The role of muscle LIM protein (MLP), encoded by CSRP3, is not well understood in humans. CSRP3 knockout mice developed dilated cardiomyopathy with hypertrophy and heart failure after birth. Using CRISPR/Cas9, we generated an MLP deficient human ESC line WAe009-A-41 carrying a compound heterozygous 13 bp deletion/1 bp insertion in the CSRP3 gene. The WAe009-A-41 line exhibited a normal female karyotype (46, XX), expressed pluripotency markers and exhibited capability to differentiate into the three germ layers in vitro. MLP expression was not detectable in WAe009-A-41 line. This cell line can be a useful tool for studying the role of CSRP3 in cardiomyopathy and heart failure.

Establishment of an induced pluripotent stem cell line (ZZUSAHi002-A) derived from peripheral blood mononuclear cells of a healthy individual.

Peripheral blood mononuclear cells (PBMCs) were isolated from a 32-year-old female and were reprogrammed to human induced pluripotent stem cells (iPSCs) using non-integrative Sendai viral vectors containing reprogramming factors OCT4, SOX2, KLF4 and cMYC. The ZZUSAHi002-A iPSC line expresses pluripotency markers, exhibits a normal female karyotype (46, XX) and has the capacity to differentiate into three germ layers in vivo. This iPSC line may be used for cell transplantations, drug testing and biological tissue engineering.

METTL14 aggravates endothelial inflammation and atherosclerosis by increasing FOXO1 N6-methyladeosine modifications.

Aims: The N6-methyladenosine (m6A) modification plays an important role in various biological processes, but its role in atherosclerosis remains unknown. The aim of this study was to investigate the role and mechanism of m6A modification in endothelial cell inflammation and its influence on atherosclerosis development. Methods: We constructed a stable TNF-α-induced endothelial cell inflammation model and assessed the changes in the expression of m6A modification-related proteins to identify the major factors involved in this process. The m6A-modified mRNAs were identified by methylated RNA immunoprecipitation (RIP) sequencing and forkhead box O1 (FOXO1) was selected as a potential target. Through cytological experiments, we verified whether methyltransferase-like 14 (METTL14) regulates FOXO1 expression by regulating m6A-dependent mRNA and protein interaction. The effect of METTL14 on atherosclerosis development in vivo was verified using METTL14 knockout mice. Results: These findings confirmed that METTL14 plays major roles in TNF-α-induced endothelial cell inflammation. During endothelial inflammation, m6A modification of FOXO1, an important transcription factor, was remarkably increased. Moreover, METTL14 knockdown significantly decreased TNF-α-induced FOXO1 expression. RIP assay confirmed that METTL14 directly binds to FOXO1 mRNA, increases its m6A modification, and enhances its translation through subsequent YTH N6-methyladenosine RNA binding protein 1 recognition. Furthermore, METTL14 was shown to interact with FOXO1 and act directly on the promoter regions of VCAM-1 and ICAM-1 to promote their transcription, thus mediating endothelial cell inflammatory response. In vivo experiments showed that METTL14 gene knockout significantly reduced the development of atherosclerotic plaques. Conclusion: METTL14 promotes FOXO1 expression by enhancing its m6A modification and inducing endothelial cell inflammatory response as well as atherosclerotic plaque formation. Decreased expression of METTL14 can inhibit endothelial inflammation and atherosclerosis development. Therefore, METTL14 may serve as a potential target for the clinical treatment of atherosclerosis.

GPER was Associated with Hypertension in Post-Menopausal Women.

OBJECTIVE: To explore the relationship between G protein-coupled estrogen receptor (GPER) and hypertension in post-menopausal women. METHODS: Using a matched case-control design, clinical and laboratory data were collected. Conditional logistic regression with stratified analysis was conducted to identify the association between GPER and hypertension. RESULTS: The GPER level was significantly lower in the case group than in the control group (126.3 ± 21.6 vs. 133.6 ± 27.3, P=0.000). The GPER levels of the hypertension cases with and those without menopause were significant (120.5 ± 11.8 and 127.2 ± 12.1, P=0.000). No significant difference in the GPER level between the controls with and those without menopause was observed (P=0.241). Logistic regression revealed that the GPER quartile was related to hypertension (odds ratio [OR]: 0.63, 95% confidence interval [CI]: 0.13-0.93, P=0.018) after adjusting for potential confounding factors. Stratified analysis revealed that the GPER quartile was not associated with hypertension in premenopausal women, and the fourth GPER quartile showed a predictive association with hypertension (OR: 0.43, 95% CI: 0.29-0.90) in menopausal women. CONCLUSIONS: GPER level is associated with hypertension and is a protective factor for hypertension in menopausal women but not premenopausal women. Further research is required due to study limitations.

Relationship between red cell distribution width and early renal injury in patients with gestational diabetes mellitus.

Previous studies found that red cell distribution width was related to adverse cardiovascular events. However, few studies reported the relationship between red cell distribution width and early-stage renal injury in pregnant women with gestational diabetes mellitus. Using a cross-sectional design, 334 pregnant women with gestational diabetes mellitus were enrolled according to the criterion of inclusion and exclusion. Demographic and clinical examination data were collected. Depended on the urine albumin, study population were divided into case group (n = 118) and control group (n = 216). Compared with control group, the case group tend to be higher red cell distribution width level (13.6 ± 0.9 vs.12.5 ± 0.6, p < 0.001). The red cell distribution width was positively associated with albuminuria creatinine ratio (r = 0.567, p < 0.001). Multiple logistic regressions showed that red cell distribution width was still associated with early-stage renal injury after adjusting for many other potential cofounders. Compared with the first quartile, the risk ratio of the second, the third and the fourth quartile were 1.38 (95%CI: 1.06-1.80), 1.57 (95%CI: 1.21-2.97), 2.71 (95%CI: 2.08-3.54), respectively. Besides, systolic blood pressure, estimated glomerular filtration rate, uric acid and blood urea nitrogen were also significantly associated with renal injury in gestational diabetes mellitus patients. The elevated red cell distribution width level might be a predictor of early-stage renal injury in pregnant women with gestational diabetes mellitus. As an easy and routine examination index, red cell distribution width may provide better clinical guidance when combined with other important indices.

Knockdown of SCARA5 inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration through suppression of the PDGF signaling pathway.

Vascular smooth muscle cell (VSMC) proliferation and migration are critical in the progression of atherosclerosis and can be induced by platelet-derived growth factor (PDGF). Several studies have demonstrated that scavenger receptor class A, member 5 (SCARA5) is important in cancer cell migration and invasion. However, the role of SCARA5 in VSMCs remains to be elucidated in the development of atherosclerosis. Therefore, the role of SCARA5 was investigated in PDGF­BB­stimulated VSMC proliferation and migration. In the present study, it was shown that SCARA5 expression was enhanced by PDGF­BB in human aortic smooth muscle cells (HASMCs). Knockdown of SCARA5 by small interfering (si)RNA significantly inhibited PDGF­BB­induced HASMC proliferation and migration. Furthermore, siRNA­SCARA5 significantly inhibited the phosphorylation of PDGF receptor (PDGFR) ß, AKT and extracellular signal­regulated kinase 1/2 in PDGF­BB­stimulated HASMCs. In conclusion, this study demonstrated that knockdown of SCARA5 inhibits PDGF­BB­induced HASMC proliferation and migration through suppression of the PDGF signaling pathway. Thus, SCARA5 may be a novel therapeutic target for preventing or treating vascular diseases involving VSMC proliferation and migration.

Long Noncoding RNAs in Atherosclerosis.

Long noncoding RNAs (lncRNAs) were a group of non-protein-coding RNAs ＞200 nucleotides and participated in biological processes and pathophysiological conditions in vivo or in vitro. Recently, more and more lncRNAs interfering with the progress of atherosclerosis were identified and characterized in the atherogenic cells such as vascular smooth muscle cells (VSMCs), endothelial cells (ECs), and monocytes/macrophages showing that lncRNAs play an important role in the occurrence of atherosclerosis. In this review, we summarized and highlighted the lncRNAs that play a role in the process of atherosclerosis. This study may provide helpful insights regarding further study of lncRNAs associated with atherosclerosis.

Functional analysis of UMOD gene and its effect on inflammatory cytokines in serum of essential hypertension patients.

OBJECTIVE: The study aimed to investigate the function of uromodulin (UMOD) gene and its effect on inflammatory cytokines in serum of essential hypertension patients. METHODS: The online database and software of computer were used for bioinformatics analysis on UMOD gene as well as the structure and function of its encoding proteins. Moreover, radioimmunoassay and enzyme linked immunosorbent assay was adopted to validate the content of urine UMOD protein of essential hypertension patients and their serum inflammatory cytokines. RESULTS: As an alkaline and hydrophilic protein, UMOD has no transmembrane region, but it does have a signal peptide sequence. It is mainly located extracellularly, belonging to a secreted protein, whose secondary structure was based mainly on Random coil which account for 58.44%. According to function prediction, it is found that the UMOD protein has stress response which may be participate in the inflammatory reaction. It has been observed from the experiment which was designed on the basis of the correlation between inflammation reaction and essential hypertension that the content of urine UMOD protein of essential hypertension patients who is in stage I was (28.71 ± 10.53) mg/24 h and when compared with the control group's content (30.15 ± 14.10 mg/24 h), the difference was not obviously; The content of urine UMOD protein of essential hypertension patients who's in stage II and III was (18.24 ± 6.12) mg/24 h and (9.43 ± 3.16) mg/24 h, respectively, which were obviously lower than that of the control group (P<0.01). Additionally, the serum inflammatory cytokines, such as TNF-α, IL-6 and IL1-α content of essential hypertension patients were all markedly higher than that of control group (P<0.05). CONCLUSION: For essential hypertension patients, there's a close relationship between the expression level of UMOD gene and inflammatory cytokines, which were manifested as the negative correlation between the level of the gene's expression and inflammatory cytokines. That has certain reference value to realize the targeted treatment for essential hypertension through regulated blood pressure conversely in the view of expression level of inflammatory cytokines.

Curative effect of amlodipine combined with enalapril in curing hypertension of the aged.

This paper aims to research the clinical effect and security of using amlodipine and enalapril together to cure hypertension of aged people. Random number table was used to divide clinical data of 114 aged hypertensives into two groups: control group (treat with only amlodipine) and observation group (treat with both amlodipine and enalapril). We formulated evaluation standard and compared the effects in pretherapy and post-treatment of two groups. Results showed that the total effective rate of control group was 59.6% and the total effective rate of observation group was 87.5% and blood pressure was lower. These findings suggest that amlodipine together, with enalapril has outstanding curative effect in hypertension treatment of the aged, they can effectively control the blood pressure, the security is fine and it deserves the popularization and application clinically.