Rongchong Huang

Tumor necrosis factor-α and its role as a mediator in myocardial infarction: A brief review

Tumor necrosis factor-α (TNF-α) contributes to myocardial infarction (MI) injury. Polymorphism of TNF-α gene promoter region and secretion and release of TNF-α and its transformation by a series of signaling pathways are all changed at different points of pathophysiological process in MI. Researches also investigated TNF-α antagonists and their potential therapeutic role in the setting of MI and heart failure at both molecular and clinical level. This article briefly reviews TNF-α and its mechanism as a mediator in MI.

Shared decision-making in the People’s Republic of China: current status and future directions

Background Severe insufficiencies in the supply and inequities in the distribution of health care professionals, facilities, and services create conditions for limited quality of care and lack of trust – even violent conflict – between clinicians and patients in the People’s Republic of China. Alongside structural reform, shared decision-making (SDM) may help meet the needs and advance the goals of each patient. Little is known, however, about the realities and opportunities for SDM in the People’s Republic of China. Methods To identify reports of SDM in the People’s Republic of China, we used multiple sources, including: several databases, searched in English and Chinese, online journals, and clinical trial registries. In addition, we contacted experts in the field to identify any articles missed through our other search strategies. We included all trials and surveys reporting on SDM in Chinese patients. We summarized these studies by describing them with particular attention to reports of patient decisional preference and of the impact of SDM interventions on outcomes in Chinese patients. Results We identified five surveys examining patient preference for SDM and nine studies examining constructs related to SDM in Chinese patients, but none involving patients in Mainland China. We could not find any reports of development, testing, or implementation of SDM tools for patients in Mainland China. Conclusion The research on SDM in the People’s Republic of China is limited, with almost no direct evidence to inform clinical policies or implementation. Although multiple barriers are apparent, the value of implementing, testing, and disseminating effective SDM in the People’s Republic of China in terms of patient experience and outcomes demands urgent realization.

Assessing the feasibility and quality of shared decision making in China: evaluating a clinical encounter intervention for Chinese patients

Background The aim of this study was to evaluate the feasibility of using the Statin Choice decision aid to have discussions about starting a statin medication for cardiovascular risk reduction in Chinese patients with stable coronary artery diseases. Methods A prospective, pilot study of the Statin Choice decision aid in two teaching hospitals in Northern China was conducted. A total of seven clinicians were enrolled and underwent a 12-hour, group-based, in-person training on shared decision making (SDM) and the Statin Choice decision aid. Then, these clinicians used the Statin Choice decision aid in patients during a clinical encounter. A total of 86 patients aged 40−80 years, who had stable angina, were enrolled. All clinical encounters were video recorded. A team of three researchers viewed and scored all the encounter recordings to evaluate the SDM process and fidelity to the intervention using the OPTION scale and Fidelity scale, respectively. All the patients were followed up for 12 months to record adherence to statin and any major adverse cardiac events (MACEs). Results The average scores on the OPTION normalized score and Fidelity scale were 21 (range, 3–32; out of a possible, 48) and 10 (range, 6–10; out of a possible, 10), respectively. This suggested that Chinese clinicians who were using Statin Choice in their patients were able to exhibit behaviors consistent with SDM at a level that is similar to that reported in Western countries. After SDM, the statin adherence was 94.5% (69/73), and the proportion of MACEs was 2.9% (2/69). Conclusion Using an encounter decision aid developed in the US, it was feasible to implement SDM in a referral cardiology practice in Mainland China. Further work to ensure that the encounter aid is pertinent to the Chinese population and that SDM is tested in at-risk patients could contribute to the implementation of SDM across Mainland China.

Stem cell transplantation dose in patients with acute myocardial infarction: A meta-analysis

Objective To evaluate whether stem cell transplantation improves global left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction (AMI), and to determine the appropriate stem cell therapy dose as well as the effective period after stem cell transplantation for therapy. Methods A systematic literature search included Pubmed, MEDLINE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Cochrane Evidence-Based Medicine databases. The retrieval time limit ranged from January 1990 to June 2016. We also obtained full texts through manual retrieval, interlibrary loan and document delivery service, or by contacting the authors directly. According to our inclusion and exclusion criteria, data were extracted independently by two evaluators. In case of disagreement, a joint discussion occurred and a third researcher was utilized. Data were analyzed quantitatively using Revman 5.2. Summary results are presented as the weighted mean difference (WMD) with 95% confidence intervals (CIs). We collected individual trial data and conducted a meta-analysis to compare changes in global left ventricular ejection fraction (ΔLVEF) after stem cell therapy. In this study, four subgroups were based on stem cell dose (≤1 × 107 cells, ≤1 × 108 cells, ≤1 × 109 cells, and ≤1 × 1010 cells) and three subgroups were based on follow-up time (<6 months, 6–12 months, and ≥12 months). Results Thirty-four studies, which included 40 randomized controlled trials, were included in this meta-analysis, and 1927 patients were evaluated. Changes in global LVEF were significantly higher in the stem cell transplantation group than in the control group (95% CI: 2.35–4.26%, P < 0.01). We found no significant differences in ΔLVEF between the bone marrow stem cells (BMCs) group and control group when the dose of BMCs was ≤1 × 107 [ΔLVEF 95% CI: 0.12–3.96%, P = 0.04]. The ΔLVEF in the BMCs groups was significantly higher than in the control groups when the dose of BMCs was ≤1 × 108 [ΔLVEF 95% CI: 0.95–4.25%, P = 0.002] and ≤1 × 109 [ΔLVEF 95% CI: 2.31–4.20%, P < 0.01]. In addition, when the dose of BMCs was between 109 and 1010 cells, we did not observe any significant differences [ΔLVEF 95% CI: −0.99–11.82%, P = 0.10]. Our data suggest stem cell therapy improves cardiac function in AMI patients when treated with an appropriate dose of BMCs. Conclusion Stem cell transplantation after AMI could improve global LVEF. Stem cells may be effectively administered to patients with AMI doses between 108 and 109 cells.

Effects of different doses of granulocyte colony-stimulating factor mobilization therapy on ischemic cardiomyopathy

G-CSF mobilization might be beneficial to ICM, but the relationship between effect/safety and the dosage of G-CSF remains unclear. In this study, 24 pigs were used to build ICM models and were randomized into four groups. Four weeks later, different dosages of G-CSF were given daily by subcutaneous injection for 5 days. Another 4 weeks later, all the animals were sacrificed. Electrocardiography, coronary arteriography, left ventriculography, transthoracic echocardiography, cardiac MRI, and SPECT, histopathologic analysis, and immunohistochemistry techniques were used to evaluate left ventricular function and myocardial infarct size. Four weeks after G-CSF treatment, pigs in middle-dose G-CSF group exhibited obvious improvements of left ventricular remodeling and function. Moderate G-CSF mobilization ameliorated the regional contractility of ICM, preserved myocardial viability, and reduced myocardial infarct size. More neovascularization and fewer apoptotic myocardial cells were observed in the ischemic region of the heart in middle-dose group. Expression of vWF, VEGF and MCP-1 were up-regulated, and Akt1 was activated in high- and middle-dose groups. Moreover, CRP, TNF-α and S-100 were elevated after high-dose G-CSF mobilization. Middle-dose G-CSF mobilization therapy is an effective and safe treatment for ICM, and probably acts via a mechanism involving promoting neovascularization, inhibiting cardiac fibrosis and anti-apoptosis.

Tenascin‑C promotes the migration of bone marrow stem cells via toll‑like receptor 4‑mediated signaling pathways: MAPK, AKT and Wnt

There are currently limitations in stem cell therapy due to the low rate of homing and proliferation of cells following transplantation. The present study was designed to investigate the effects of Tenascin-C (TN-C) on bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. BMSCs were obtained from C57BL/6 mice. The survival and proliferation of BMSCs was analyzed by Cell Counting Kit-8 assay, migration was evaluated using the Transwell method, and differentiation was assessed by immunocytochemistry and immunofluorescence. In addition, the levels of proteins were detected by western blotting. High concentrations of TN-C promoted the migration of BMSCs. H2O2 at concentrations of 60–90 µmol/ml induced cell death in BMSCs, and thus, it was used to simulate oxidative stress in the microenvironment of acute myocardial infarction (AMI). High concentrations of TN-C were able to protect BMSCs from cell death, and promoted the migration of BMSCs (P<0.05). However, TAK-242 [the inhibitor of Toll-like receptor 4, (TLR4)] reduced the promoting effect of TN-C (P<0.05). By contrast, TN-C had no effect on the proliferation and differentiation of BMSCs. TN-C reduced the phosphorylation levels of p38 mitogen-activated protein kinase (MAPK), and increased the phosphorylation levels of Ser473 protein kinase B (AKT) and β-catenin, all of which were inhibited by TAK-242 (P<0.05). In the simulated AMI microenvironment, TN-C promoted the migration of BMSCs via TLR4-mediated signaling pathways, including MAPK, AKT and Wnt.

Downregulated caveolin‑1 expression serves a potential role in coronary artery spasm by inducing nitric oxide production in vitro

The present study aimed to investigate the effects of downregulated caveolin-1 (Cav-1) expression on nitric oxide (NO) production in lipopolysaccharide (LPS)-damaged primary human umbilical vein endothelial cells (HUVECs) in a model of coronary artery spasm (CAS) microenvironment induced by acetylcholine (ACh) treatment. Small interfering RNA (siRNA)-mediated Cav-1 downregulation in HUVECs was confirmed by western blotting. The cell viability and superoxide dismutase (SOD) inhibition in HUVECs incubated with LPS (0, 10, 25, 50, 75 and 100 µg/ml) were measured by cell counting kit-8 assay and a SOD kit, respectively. Intracellular Ca2+ [(Ca2+)i] in Fluo4-acetoxymethyl ester-loaded cells was detected by fluorescence microscopy. NO levels in the cell culture supernatants were measured by the nitrate reductase method. The results indicated that transfection with Cav-1 siRNA, in particular siCav-1 (2), downregulated the Cav-1 protein expression. LPS at a dose of 75 µg/ml induced a significant decrease in HUVECs/si-NC and HUVECs/siCav-1 viability compared with the other concentrations of LPS. Compared with the effects of untreated cells, SOD inhibition in HUVECs/si-NC and HUVECs/siCav-1 was significantly decreased by LPS (75 µg/ml). In addition, ACh stimulation caused a greater increase in [Ca2+]i in HUVECs/si-NC as compared with LPS-treated HUVECs/si-NC. ACh stimulation also induced significantly higher NO levels in LPS-treated HUVECs/siCav-1 compared with LPS-treated HUVECs/si-NC cells (P<0.05). In conclusion, the downregulated Cav-1 expression served a key role in NO production in the in vitro model of CAS induced by ACh stimulation of LPS-damaged HUVECs.

Selectins modify dendritic cells during atherosclerosis

Dendritic cells (DCs) are professional antigen-presenting cells (APC) that facilitate the development and progression of atherosclerosis. However, DCs also function as novel “switches” between immune activation and immune tolerance and represent a heterogeneous hematopoietic lineage, with cell subsets in different tissues that show a differential morphology, phenotype, and function. Regulatory DCs, depending on their immature state, can be induced by immunosuppressive modulation, which plays an important part in the maintenance of immunologic tolerance via suppression of the immune response. In this review, we describe the current understanding of the generation of regulatory DCs. The novel role of selectins in the modification of DCs in atherosclerosis is also discussed.