Yanting Wen

Effects of Omega-3 fatty acid on major cardiovascular events and mortality in patients with coronary heart disease: A meta-analysis of randomized controlled trials

AIM There is considerable discrepancy regarding the protective effects of Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) in patients with coronary heart disease (CHD) from the early-phase clinical randomized controlled trials (RCTs). We conducted a meta-analysis of RCTs to address this issue. DATA SYNTHESIS Pubmed, the Cochrane Central Register of Controlled Trials, and EMBASE databases (∼ May 2013) were systematically searched. Odds ratios (OR) and associated 95% CI were retrieved by using random-effect model according to heterogeneity. A total of 14 RCTs involving 16,338 individuals in the Omega-3 PUFAs group and 16,318 in the control group were identified. Patients assigned to Omega-3 PUFAs did not demonstrate satisfactory improvements on major cardiovascular events (OR, 0.93; 95% CI, 0.86 to 1.01; P = 0.08; I(2) = 46%). By contrast, the reduced risks of death from cardiac causes, sudden cardiac death and death from all causes (OR, 0.88; 95% CI, 0.80 to 0.96; P = 0.003; I(2) = 0%; OR, 0.86; 95% CI, 0.76 to 0.98; P = 0.03; I(2) = 29%; and OR, 0.92; 95% CI, 0.85 to 0.99; P = 0.02; I(2) = 6%; respectively) were shown. CONCLUSIONS Supplement of Omega-3 PUFAs in patients with CHD is not associated with a protective effect on major cardiovascular events, while it does exert beneficial effects in reducing death from cardiac causes, sudden cardiac death and death from all causes. However, with currently available cardio-protective therapies, whether dietary supplementation with Omega-3 PUFAs should be still considered in patients with CHD is currently debated.

Direct autologous bone marrow-derived stem cell transplantation for ischemic heart disease: a meta-analysis

Objective: Previous evaluation of intracoronary autologous bone marrow-derived stem cell (BMSCs) therapy following ischemic heart disease (IHD) suggested improvement of cardiac functional parameters. We performed a meta-analysis to provide systematic assessment of the safety and efficacy of direct (intramyocardial or endomyocardial) BMSCs transplantation in patients with IHD. Research design and methods: Randomized controlled Trials (RCTs) were identified in the MEDLINE (∼ Oct. 2010), the Cochrane Central Register of Controlled Trials (Central) (∼ Oct. 2010), EMBASE (∼ Oct. 2010), and EBSCO (∼ Oct. 2010), reviews, and reference lists of relevant articles. Weighted mean difference (WMD) was calculated for changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV) by using a fixed effects model. Results: Eight RCTs with 307 participants were eligible. Compared with controls, direct BMSCs transplantation improved LVEF (8.4%, 95% CI, 6.49 to 10.31%; p < 0.01), reduced LVESV and LVEDV (–14.85 ml, 95%CI, –27.29 to –2.41 ml, p = 0.02 and –12.79 ml, 95% CI, –24.94 to –0.65 ml, p = 0.04, respectively). Conclusions: This meta-analysis suggests that direct BMSCs transplantation is associated with moderate but significant improvements over regular therapy in cardiac functional parameters in patients with IHD, and supports conducting further RCTs of a higher quality.

Association between telomere length and survival in patients with idiopathic pulmonary fibrosis

Short telomere is a crucial risk factor for idiopathic pulmonary fibrosis (IPF). However, little is known about the association between baseline telomere length and survival in IPF. We aimed to determine whether telomere length is associated with survival of IPF.

Autologous bone marrow cell therapy for patients with peripheral arterial disease: a meta-analysis of randomized controlled trials.

Objective: Early-phase clinical trials suggest that autologous bone-marrow-derived cells (BMCs) may have a positive effect on patients with severe peripheral arterial disease (PAD). However, the therapeutic effects of BMCs treatment in various aspects remain controversial. Research design and methods: We conducted a meta-analysis using data from randomized controlled trials (RCTs) by comparing autologous BMCs therapy with controls in patients with severe PAD. Pubmed, EMBASE, EBSCO and the Cochrane Central Register of Controlled Trials ( to approximately April 2011) were searched. Results: Seven RCTs with 276 patients were included. Pooled comparisons of studies found that BMCs therapy significantly improved ankle-brachial index (ABI) by 0.10 (95% CI, 0.07 to 0.14; p < 0.00001), transcutaneous oxygen tension (TcO2) by 13.39 mmHg (95% CI, 6.69 to 20.1 mmHg; p < 0.0001) and pain-free walking distance by 119.91 m (95% CI, 90.71 to 149.11 m; p < 0.00001). BMCs therapy significantly decreased scale of rest pain by 1.13 (95% CI, -1.71 to -0.54, p = 0.0002) and helped heal ulcers (OR, 7.17; 95% CI, 2.66 to 19.32; p < 0.0001). Conclusions: Our analysis based on seven RCTs suggests that autologous BMCs therapy, has a beneficial effect on physiologic and anatomic parameters in patients with severe PAD.

Autologous transplantation of blood-derived stem/progenitor cells for ischaemic heart disease.

Aims:  Early clinical trials suggest that blood‐derived stem/progenitor cells (including peripheral blood‐derived stem cells and circulating progenitor cells) may have a positive impact on patients with ischaemic heart disease (IHD). The therapeutic effects of these cells remain unclear, considering the inconsistent results of several clinical trials. The objective of this meta‐analysis was to evaluate the effects of autologous blood‐derived stem/progenitor cells on improvement of cardiac functional parameters on the basis of a synthesis of the data generated by randomised controlled clinical trials (RCTs) of patients with IHD.

Bone marrow-derived mononuclear cell therapy for patients with ischemic heart disease and ischemic heart failure.

Objective: This meta-analysis aimed to assess whether bone marrow-derived mononuclear cells (BMMNCs) therapy may improve cardiac functional parameters in patients with ischemic heart disease (IHD) or ischemic heart failure (IHF). Methods: Relevant randomized controlled trials (RCTs) were searched from web databases. Weighted mean difference was calculated for changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volumes by using a random effects model. Results: 13 RCTs met inclusion criteria. Compared with controls, BMMNCs therapy improved LVEF by 3.83% (95% confidence interval (CI): 2.10 – 5.56%; p < 0.0001) in patients with ischemic heart conditions. Notably, in patients with IHF, a more severe clinical condition when compared with IHD, BMMNCs therapy appeared more effective in LVEF improvement. While LVEF increased by 5.67% (95% CI: 3.65 – 7.69%; p < 0.00001) in IHF patients, it only increased by 2.19% (95% CI: 0.37 – 4.00%; p = 0.02) in patients with IHD. Conclusions: BMMNCs therapy is associated with moderate but significant improvement over regular therapy in LVEF in patients with IHD and IHF. This observation, therefore, supports further RCTs conducting safety and efficiency of BMMNCs therapy with longer-term follow-up.

Ouabain induces apoptosis and autophagy in Burkitt's lymphoma Raji cells.

The steroid Na+/K+-ATPase blocker ouabain has been shown to exhibit cytotoxic effects in various tumor cell systems. This study aimed to determine the effects of ouabain on Burkitts lymphoma Raji cells. Ouabain treatment of Raji cells significantly inhibited cell proliferation in a dose-dependent manner and increased the morphological changes associated with apoptosis. Additionally, increased numbers of both early and late apoptotic cells were observed by annexin V-FITC/PI flow cytometry assay. Increased levels of caspase-3 and cleaved-caspase-3, higher Bax activity and decreased expression of the anti-apoptotic protein Bcl-2 were detected in ouabain-treated Raji cells. Vacuole accumulation was also observed in transmission electron microscope (TEM) images of ouabain-treated Raji cells, indicating that these cells were undergoing autophagy. Expression of the autophagy-related proteins LC3-II and Beclin-1 was upregulated in ouabain-treated Raji cells. These results suggest that ouabain may promote cell death in Raji cells by inducing pathways associated with apoptosis and autophagy. Our study also provides novel evidence that ouabain may be an effective agent for treating Burkitts lymphoma.

Protective role of low-dose TGF-β1 in early diabetic nephropathy induced by streptozotocin.

OBJECTIVE To determine whether low-dose TGF-β1 and/or IL-6-receptorα monoclonal antibody (anti-IL-6Rα) can be used to delay renal damage and preserve renal function by rebalancing regulatory T (Treg)/Th17 cells during the course of early diabetic nephropathy (DN) induced by streptozotocin (STZ). METHODS Diabetes was induced in C57BL/6 mice by multiple STZ injection. Low-dose TGF-β1 (0.1 μg/mouse/week) and/or anti-IL-6Rα (10 μg/mouse/week) were administered 6 dozes after STZ injection. After 40 days of diabetes onset, metabolic indices, renal structure, activated Akt and Stat3, Treg/Th17 balance, markers and inflammatory cytokines, and oxidative stress in glomeruli were assessed. RESULTS Low-dose TGF-β1, instead of causing renal damage, decreased blood glucose, ameliorated kidney hypertrophy, attenuated oxidative stress, maintained activated Stat3, and induced Treg/Th17 balance in early DN. Interestingly, low-dose TGF-β1+anti-IL-6Rα or anti-IL-6Rα alone did not attenuate DN. CONCLUSIONS This study provides convincing experimental evidence of the protective effects of low-dose TGF-β1 in improving metabolic disorder and slowing renal damage in early DN.

Combinatorial Treatment of Bone Marrow Transplantation and Regulatory T Cells Improves Glycemia in Streptozotocin-diabetic Mice.

Autologous hematopoietic stem cell transplantation (HSCT) has limited benefits in patients with a long-duration of diabetes. To test whether a T regulatory cells (Tregs) and syngeneic bone marrow transplantation (syn-BMT) co-transplantation regimen will be effective, BMT±Tregs infusion was performed in streptozotocin-diabetic mice with a long-duaration of diabetes. Diabetic status, pancreata morphometry and Tregs/Th17 balancing were tested on day 100 after transplantation. While hyperglycemia relapsed in mice receiving BMT monotherapy about 6 weeks after transplantation, combined therapy with BMT+Tregs improved hyperglycemia and C-peptides, preserved islet cell mass within 100 days after BMT. Although both groups BMT and BMT+Tregs induced Tregs/Th17 rebalancing, combined treatment of BMT+Tregs synergistically elevated TGF-β1 and FoxP3 expression compared with BMT monotherapy. The sustained rebalance of Tregs/Th17 may be one possible explanation for the longer benefits of the combined treatment of BMT+Tregs over BMT monotherapy to mice with a long-duaration of diabetes. This observation of the therapeutic potential of BMCs+Tregs treatment may have important implications for clinical therapy for patients with a long-duration of diabetes.

Bone marrow-derived mononuclear cell therapy for nonischaemic dilated cardiomyopathy-A meta-analysis

The therapeutic effects of bone marrow‐derived mononuclear cells (BMMNCs) transplantation in patients with nonischaemic dilated cardiomyopathy (DCM) are still under debate. Current randomized controlled trials (RCTs) reported conflicting results. The aim of this study was to assess the effects of BMMNCs transplantation on left ventricular ejection fraction (LVEF) in patients with nonischaemic DCM.