Fibulin-3 affects vascular endothelial function and is regulated by angiotensin II.

OBJECTIVE: The aim of the present study was to investigate the effect of fibulin-3 on vascular endothelial function, and to explore the relevant underlying mechanism with regard to the involvement of angiotensin II (AngII). METHODS: One hundred and eight patients with essential hypertension (EH) and 31 controls were included to measure the flow-mediated dilatation (FMD). Serum fibulin-3 and AngII were examined using enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay. Stable transfection of fibulin-3 was conducted on human umbilical vein endothelial cells (HUVECs) and SV40T-transformed HUVECs (PUMC-HUVEC-T1 cells). Cell counting kit-8 assay, cell cycle assay, wound healing assay, Transwell assay, apoptosis assay, and tube formation assay were subsequently performed. The expression of angiogenesis-associated genes [endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor A (VEGFA)] were measured by western blot analysis. HUVECs and PUMC-HUVEC-T1 cells were treated with AngII, and with or without an inhibitor of nuclear factor κB (NF-κB), BAY 11-7082. Pro-inflammatory cytokines [interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)] were detected by ELISA. The expression levels of fibulin-3 and p65 were then measured by western blotting. RESULTS: Lower levels of serum fibulin-3 were accompanied by poorer FMD and higher levels of serum AngII in patients with EH. Fibulin-3 overexpression promoted cell proliferation, migration, and angiogenesis, but led to an inhibition of apoptosis. By contrast, fibulin-3 downregulation inhibited cell proliferation, migration and angiogenesis, but promoted apoptosis. AngII induced inflammation and inhibited the expression of fibulin-3. BAY 11-7082 eliminated the inhibitory effect of AngII on fibulin-3. CONCLUSIONS: Taken together, the results of the present study have shown that serum fibulin-3 may be a predictor of vascular endothelial function in patients with EH. Fibulin-3 gene may also have a beneficial role in repairing the vascular endothelium. Furthermore, the results also suggested that fibulin-3 gene was suppressed by AngII via the NF-κB signaling pathway.

A community effort to assess and improve computerized interpretation of 12-lead resting electrocardiogram.

Computerized interpretation of electrocardiogram plays an important role in daily cardiovascular healthcare. However, inaccurate interpretations lead to misdiagnoses and delay proper treatments. In this work, we built a high-quality Chinese 12-lead resting electrocardiogram dataset with 15,357 records, and called for a community effort to improve the performances of CIE through the China ECG AI Contest 2019. This dataset covers most types of ECG interpretations, including the normal type, 8 common abnormal types, and the other type which includes both uncommon abnormal and noise signals. Based on the Contest, we systematically assessed and analyzed a set of top-performing methods, most of which are deep neural networks, with both their commonalities and characteristics. This study establishes the benchmarks for computerized interpretation of 12-lead resting electrocardiogram and provides insights for the development of new methods. Graphical Abstract A community effort to assess and improve computerized interpretation of 12-lead resting electrocardiogram.

Postoperative carcinoembryonic antigen (CEA) levels predict outcomes after resection of colorectal cancer in patients with normal preoperative CEA levels.

BACKGROUND: Carcinoembryonic antigen (CEA) is a cancer biomarker used in colorectal cancer (CRC) for tumor screening and outcome prediction. However it is still lack of sensitivity and specificity in general population. The present study aimed to investigate the clinical significance of CEA in patients with normal preoperative CEA levels. METHODS: Ninety-four patients were included who received surgery and developed an elevated CEA level postoperatively. They were divided into group A1 and A2 according to the peak CEA level (whether more than 10 ng/mL); group B1 and B2 according to CEA variation (whether reached a normal level at least once). The association between postoperative CEA and overall survival (OS), and disease-free survival (DFS) were analyzed using Kaplan-Meier method and Cox's proportional hazards regression model. RESULTS: The median follow-up time was 38 months. Patients in Group A2 and Group B2 had greater opportunities for recurrence and metastasis (P<0.05) compared to Group A1 and Group B1. Cox regression analysis revealed that high CEA levels and consistently elevated CEA levels were significantly associated with worse OS and DFS. Furthermore, patients with p-stage II in group A2 had worse OS than patients with p-stage III in group A1. The same result was detected when comparing group B2 and B1. CONCLUSIONS: Among patients with an initially normal CEA level, postoperative CEA level and variation could be effective markers for tumor progression assessment. TNM stage, combined with CEA level might be more accurate in prognostic prediction.

[The use of recombinant activated factor VII for blood loss after cardiovascular surgery].

OBJECTIVE: To describe the early experiences with rFVIIa in the management of bleeding after cardiovascular surgery. METHODS: From May 2006 through December 2007, 16 patients received rFVIIa during or after surgery despite conventional medical therapy and transfusion of blood products. There were 15 male patients and 1 female patients, aged from 36 to 77 years old with a mean of 52 years old. The surgical procedures include aortic procedures for 8 cases, valve replacement for 6 cases, pulmonary thromboendarterectomy for 1 case and atrial septal defect repair for 1 case. The data of these patients were reviewed and the safety and efficacy of rFVIIa after cardiovascular surgery were evaluated. RESULTS: rFVIIa was administered as a first dose of 27.6 to 54.5 microg/kg with a mean of 40.2 microg/kg. Six patients achieved hemostasis after the first dose. Nine patients received a second administration within 30 min, with a cumulative dose of 59.3 to 90.9 microg/kg, a mean of 80.3 microg/kg. Eight patients achieved hemostasis and 1 patient went to exploration. One patient received four doses of rFVIIa with a cumulative dose of 203.4 microg/kg and the bleeding stopped. Mean amount of chest drain loss and the amount of red blood cell, fresh frozen plasma, cryoprecipitate, and platelet transfusions decreased significantly after rFVIIa administration. The total amount of chest drain losses, transfusions of red blood cell and cryoprecipitate within 12 h postoperatively was positively correlated with the time from the end of bypass to administration of rFVIIa. No thromboembolic complications and other adverse reactions were noted. CONCLUSIONS: The use of rFVIIa is associated with reduced blood loss, rapid improvement of coagulation variables, and decreased need for blood products. rFVIIa is safe and efficacious in the management of refractory postcardiotomy bleeding.