Retracted: Osteoprotegerin (OPG) Promotes Recruitment of Endothelial Progenitor Cells (EPCs) via CXCR4 Signaling Pathway to Improve Bone Defect Repair.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Rongfeng Zhang, Jianwei Liu, Shengpeng Yu, Dong Sun, Xiaohua Wang, Jingshu Fu, Jie Shen, Zhao Xie. Osteoprotegerin (OPG) Promotes Recruitment of Endothelial Progenitor Cells (EPCs) via CXCR4 Signaling Pathway to Improve Bone Defect Repair. Med Sci Monit, 2019; 25: 5572-5579. DOI: 10.12659/MSM.916838.

Risk Stratification for Atrial Fibrillation and Outcomes in Tachycardia-Bradycardia Syndrome: Ablation vs. Pacing.

Background: Catheter ablation of atrial fibrillation is an alternative treatment for patients with tachycardia-bradycardia syndrome (TBS) to avoid pacemaker implantation. The risk stratification for atrial fibrillation and outcomes between ablation and pacing has not been fully evaluated. Methods: This retrospective study involved 306 TBS patients, including 141 patients who received catheter ablation (Ablation group, age: 62.2 ± 9.0 months, mean longest pauses: 5.2 ± 2.2 s) and 165 patients who received pacemaker implement (Pacing group, age: 62.3 ± 9.1 months, mean longest pauses: 6.0 ± 2.3 s). The primary endpoint was a composite of call cause mortality, cardiovascular-related hospitalization or thrombosis events (stroke, or peripheral thrombosis). The second endpoint was progress of atrial fibrillation and heart failure. Results: After a median follow-up of 75.4 months, the primary endpoint occurred in significantly higher patients in the pacing group than in the ablation group (59.4 vs.15.6%, OR 6.05, 95% CI: 3.73-9.80, P < 0.001). None of deaths was occurred in ablation group, and 1 death occurred due to cancer. Cardiovascular-related hospitalization occurred in 50.9% of the pacing group compared with 14.2% in the ablation group (OR: 4.87, 95% CI: 2.99-7.95, P < 0.001). More thrombosis events occurred in the pacing group than in the ablation group (12.7 vs. 2.1%, OR 6.06, 95% CI: 1.81-20.35, P = 0.004). Significant more patients progressed to persistent atrial fibrillation in pacing group than in ablation group (23.6 vs. 2.1%, P < 0.001). The NYHA classification of the pacing group was significantly higher than that of the ablation group (2.11 ± 0.83 vs. 1.50 ± 0.74, P < 0.001). The proportion of antiarrhythmic drugs and anticoagulants used in the pacing group was significantly higher than that in the ablation group (41.2 vs. 7.1%, P < 0.001; 16.4 vs. 2.1%, P = 0.009). Conclusion: Catheter ablation for patients with TBS was associated with a significantly lower rate of a composite end point of cardiovascular related hospitalization and thromboembolic events. Furthermore, catheter ablation reduced the progression of atrial fibrillation and heart failure.

Osteoprotegerin (OPG) Promotes Recruitment of Endothelial Progenitor Cells (EPCs) via CXCR4 Signaling Pathway to Improve Bone Defect Repair.

BACKGROUND The aim of this study was to investigate the effect of using osteoprotegerin (OPG) to treat bone defects mediated by endothelial progenitor cell (EPC) recruitment and migration through the CXCR4 signaling pathway. MATERIAL AND METHODS The EPCs extracted from human peripheral blood were cultured in vitro and the expression of CXCR4 and its downstream p-AKT was monitored by the Western blot analysis after OPG treatment. Using the scratch wound healing test and Transwell assay, we assessed the variables influencing the effect of OPG on EPCs after pre-treatment with CXCR4 blocker (AMD3100) and PI3K blocker (Ly294002). After 4 weeks, the bone defect repair condition was estimated via micro-CT and staining with HE and Masson trichrome. Then, immunofluorescence staining was performed to assess angiogenesis in bone defects, while the expression of EPC marker and vascular endothelial growth factor receptor 2 (VEGFR2) was detected by immunohistochemical staining. RESULTS The EPCs treated with OPG had increased levels of CXCR4 and p-AKT. Moreover, the difference in EPC levels among groups in the scratch wound healing experiment and migration experiment indicated that the OPG treatment promoted cell migration and AMD3100 and LY294002 inhibited the function of OPG. In addition, OPG promoted angiogenesis and repair of bone defect in rats, and these effects were abolished by AMD3100 and LY294002 administration. CONCLUSIONS OPG enhanced the proliferation and migration of EPCs through the CXCR4 pathway and promoted angiogenesis and bone formation at bone defect sites.

Comparison of cryoballoon ablation for atrial fibrillation guided by real-time three-dimensional transesophageal echocardiography vs. contrast agent injection.

BACKGROUND: Pulmonary vein (PV) occlusion generally depends on repetitive contrast agent injection when cryoballoon ablation for atrial fibrillation (AF). The present study was to compare the effect of cryoballoon ablation for AF guided by transesophageal echocardiography (TEE) vs. contrast agent injection. METHODS: Eighty patients with paroxysmal AF (PAF) were enrolled in the study. About 40 patients underwent cryoballoon ablation without TEE (non-TEE group) and the other 40 underwent cryoballoon ablation with TEE for PV occlusion (TEE group). In the TEE group during the procedure, PVs were displayed in 3-dimensional images to guide the balloon to achieve PV occlusion. The patients were followed up at regularly scheduled visits every 2 months. RESULTS: No differences were identified between the groups in regard to the procedure time and cryoablation time for each PV. The fluoroscopy time (6.7 ±â€Š4.2 min vs. 17.9 ±â€Š5.9 min, P < 0.05) and the amount of contrast agent (3.0 ±â€Š5.1 mL vs.18.1 ±â€Š3.4 mL, P < 0.05) in the TEE group were both less than the non-TEE group. At a mean of 13.0 ±â€Š3.3 mon follow-up, success rates were similar between the TEE group and non-TEE group (77.5% vs. 80.0%, P = 0.88). CONCLUSIONS: Cryoballoon ablation with TEE for occlusion of the PV is both safe and effective. Less fluoroscopy time and a lower contrast agent load can be achieved with the help of TEE for PV occlusion during procedure.

Atrial fibrillation is related to lower incidence of deep venous thrombosis in patients with pulmonary embolism.

BACKGROUND: Atrial fibrillation (AF) is an established risk factor of left atrial thrombosis and systemic embolism. Traditionally pulmonary embolism (PE) is a recognized complication of deep vein thrombosis (DVT). However, whether AF is responsible for right atrial thrombosis and leads to PE has not been examined. METHODS: We retrospectively analyzed medical records of patients with confirmed diagnosis of PE with AF (study group) from 2002-2015. Patients with PE without AF, matched by age and sex, served as controls (control group). The CHA2DS2-VASc and CHADS2 scores were classified into two categories, low-intermediate (<2 points) and high-risk (≥2 points). RESULTS: A total of 330 patients (110 in study group and 220 in control group). The study group had significantly lower incidence of newly diagnosed DVT (21% vs. 44%, P<0.001), previous history of DVT (6% vs. 17%, P=0.006) and recent surgery or trauma (10% vs. 23%, P=0.004) compared to the control group. When stratified by the CHADS2 score, 49 patients (44.5%) were considered low-intermediate risk. This proportion significantly differed when stratified using CHA2DS2-VASc, in which 13 patients (13.6%) were considered low-intermediate risk, P<0.001. CONCLUSIONS: The incidence of DVT was much lower in the study group, suggesting the possibility of clots originated from the right heart that may increase the risk of PE. The CHA2DS2-VASc scoring system might be more sensitive for prediction and stratification of the PE in AF patients than the CHADS2 score.

Activated platelets inhibit hepatocellular carcinoma cell differentiation and promote tumor progression via platelet-tumor cell binding.

Lack of differentiation in hepatocellular carcinoma (HCC) is associated with increased circulating platelet size. We measured platelet activation and plasma adenosine diphosphate (ADP) levels in HCC patients based on differentiation status. Local platelet accumulation and platelet-hepatoma cell binding were measured using immunohistochemistry (IHC) or flow cytometry. Using a xenograft assay in NON/SCID mice, we tested the effects of the anti-platelet drug clopidogrel on platelet activation, platelet infiltration, platelet-tumor cell binding and tumor cell differentiation. HCC patients with poor differentiation status displayed elevated platelet activation and higher ADP levels. Platelets accumulated within poorly differentiated tissues and localized at hepatoma cell membranes. Platelet-tumor cell binding was existed in carcinoma tissues, largely mediated by P-selectin on platelets. NOD/SCID mice with xenograft tumors also exhibited increased platelet activation and platelet-tumor cell binding. Clopidogrel therapy triggered hepatoma cell differentiation by attenuating platelet activation and platelet-tumor cell binding. TCF4 knockdown promoted HepG-2 cell differentiation and inhibited tumor formation, and TCF4 could be the potential downstream target for clopidogrel therapy.

[In vitro studies on tissue engineered intervertebral disc].

OBJECTIVE: To investigate the feasibility of tissue engineered intervertebral disc for regeneration of discs. METHODS: A three-dimensional porous poly (L-lactic-co-glycolic acid) (PLGA) scaffold was fabricated by temperature induced phase separation method. Human fetal disc cells were isolated and cultured in vitro. The disc cells labeled with a PKH-26 fluorescent dye were seeded into a three-dimensional porous scaffold. The proliferation of disc cells with PKH-26 fluorescent labels was assessed by using MTT uptake, laser fluorescence microscopy and SEM. RESULTS: Human fetal disc cells displayed a polygonal shape in primary monolayer culture. A regular arrangement and microtubules orientation-structure scaffold with 50-300 microm in diameter was fabricated by thermal-induced phase separation technique. MTT uptake and fluorescent microscopy examination indicated that the seeded disc cells were viable and showed proliferation activity within a porous scaffold. CONCLUSION: The above findings support potential applications of tissue engineered disc in treatment of disc degenerative diseases.

Effects of TGF-beta1 and IGF-1 on proliferation of human nucleus pulposus cells in medium with different serum concentrations.

BACKGROUND: The low proliferative viability of human nucleus pulposus(NP) cells is considered as a cause of intervertebral discs degeneration. Growth factors, such as TGF-beta1 and IGF-1, have been implicated in cell proliferation and matrix synthesis. OBJECTIVE: To investigate the dose-response and time-course effect of transforming growth factorbeta1(TGF-beta1) and insulin-like growth factor-1(IGF-1) on proliferation of NP cells. STUDY DESIGN: 3-(4,5-dimethylthiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) is reduced by dehydrogenase in mitochondria of live cells. The proliferative viability of cells corresponds to the amount of MTT reduced, which is measured with an enzyme-linked immunosorbent assay plate reader. In this study, we assessed dose- and time-dependent effects of NP cells to TGF-beta1 and IGF-1 in medium with different serum concentrations by MTT assay. METHODS: After release of informed consent, tissue samples of NP were obtained from anterior surgical procedures performed on five donors with idiopathic scoliosis. Isolated cells were cultured in F12 medium supplemented with 10% fetal bovine serum(FBS). Cells were seeded in 96-well plates at 1 x 103 cells/well. After synchronization, medium was replaced by F12 containing 1% or 10% FBS with either single or combination of TGF-beta1 and IGF-1. Dose-response and time-course effect were examined by MTT assay. RESULTS: In the presence of 1% FBS, the response to IGF-1 was less striking, whereas TGF-beta1 had a remarkably stimulating effect on cell proliferation. In 10% FBS, both of the two growth factors had statistical significant mitogenic effects, especially TGF-beta1. The dose-dependent effect of TGF and IGF on cell proliferation was found within different concentrations of each growth factor(TGF-beta1 1-10 microg/L, IGF-1 10-100 microg/L). The time-course effect showed a significant elevation three days later. CONCLUSION: TGF-beta1 and IGF-1 were efficient to stimulate cell proliferation of human NP cells in vitro with a dose- and time-dependent manner. These results support the therapeutic potentials of the two growth factors in the treatment of disc degeneration.