Triple versus dual oral antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: The efficacy and safety of dual therapy (dual antiplatelet therapy [DAPT] and warfarin plus single antiplatelet [WS]) versus triple therapy (TT, DAPT plus warfarin) are still debated in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). The purpose of this study was to determine the optimal antithrombotic strategy. METHODS: Electronic databases (PubMed, Embase, Cochrane Library, CNKI and WanFang Data) were searched to retrieve studies on the efficacy and safety of TT vs. dual therapy in patients with AF undergoing PCI until August 2017. A meta-analysis was conducted using a random-effects model. The primary efficacy and safety endpoints were major adverse cardiac events (MACEs) and major bleeding events. RESULTS: Twenty-four studies involving 21,167 patients were included. The TT group had a significantly lower risk of MACEs (P=0.024) but a higher risk of major bleeding (P<0.001). In TT vs. DAPT subgroup, TT was associated with a lower risk of MI and stent thrombosis in Asian patients and a lower risk of stroke in non-Asian patients. Furthermore, TT did not decrease MACEs incidence (P=0.458) but increased the risk of major bleeding (P=0.008) relative to WS. The same trends were observed in Asian and non-Asian patients. CONCLUSION: Patients with AF undergoing PCI who received TT had significant reduction in MACEs but increased the risk of major bleeding compared with DAPT. However, WS had a similar efficacy but reduced the risk of major bleeding compared with TT. Current evidence suggests that TT might not be required and might be replaced by WS.

The Expression of LDL-R in CD8+ T Cells Serves as an Early Assessment Parameter for the Production of TCR-T Cells.

BACKGROUND/AIM: The quantity and the phenotypes of desired T cell receptor engineered T (TCR-T) cells in the final cell product determine their in vivo anti-tumor efficacy. Optimization of key steps in the TCR-T cell production process, such as T cell activation, has been shown to improve cell quality. MATERIALS AND METHODS: Using a modified TCR (mTCR) derived from mice transducing PBMCs, we assessed the proportions of low-density lipoprotein receptor (LDL-R) and mTCR expressing cells under the various activation conditions of CD3/CD28-Dynabeads or OKT3 via flow cytometry. RESULTS: We demonstrate that the proportion of T cells expressing LDL-R post activation is positively correlated with the percentage of mTCR+CD8+ T cells with their less differentiated subtypes in the final product. In addition, we show that shifting the CD3/CD28-Dynabeads activation duration from a typical 48 h to 24 h can significantly increase the production of the desired mTCR+CD8+ T cells. Importantly, the percentages of TCR-T cells with less-differentiated phenotypes, namely mTCR central memory T cells (TCM), were found to be preserved with markedly higher efficiency when T cell activation was optimized. CONCLUSION: Our findings suggest that the proportion of LDL-R+ T cells may serve as an early assessment parameter for evaluating TCR-T cell quality, possibly facilitating the functional and economical improvement of current adoptive therapy.

The expression of von Willebrand factor, soluble thrombomodulin, and soluble p-selectin during orthotopic liver transplantation.

BACKGROUND: We evaluated von Willebrand factor (vWF), soluble thrombomodulin (sTM), and soluble P-selectin (sP-selectin) levels in ischemia/reperfusion injury during orthotopic liver transplantation (OLT). METHODS: The vWF, sTM, and sP-selectin were analyzed in 20 patients who underwent liver transplantation. Blood samples were drawn from the radial artery at serial times during surgery. Plasma levels of sTM and sP-selectin were detected by enzyme-linked immunosorbent assay (ELISA). The wWF activity was measured using the immuno-turbidimetric method. Plasma aspartate transaminase (AST) and alanine transaminase (ALT) were assayed by routine clinical chemistry testing. RESULTS: Marked elevation levels of plasma AST and ALT were released during the 15 minutes after reperfusion phase, with a peak on the first postoperative day (P < .01). The sTM level remained unchanged from preoperative to anhepatic phase (P > .05). In contrast, a mean 2.5-fold increase of sTM was observed during the 15-minute reperfusion stage compared with the preoperative value (P < .01). The vWF activity only showed significant increase during the 60-minute reperfusion stage compared with the preoperative value (P < .05). No significant increase occurred in sP-seletin levels during the reperfusion phase. Platelet count showed significant decrease during the entire observation period compared with the preoperative value (P < .01). CONCLUSION: The endothelial reperfusion injury after OLT is characterized by increased vWF and sTM but not by sP-selectin in peripheral blood.

Hypolipidemic effects of flavonoids extracted from Lomatogonium rotatum.

Contained in the Mongolian volumes of Chinese Materia Medica, Lomatogonium rotatum Fries ex Nym. may reduce blood lipid levels and prevent obesity; however, its exact mechanism of action remains unclear. The present study investigated the hypolipidemic and obesity-inhibiting effects of four similarly structured flavonoids extracted from L. rotatum. According to a well-established method, flavonoids such as decussatin were extracted from the whole herb of L. rotatum, and male Wistar rats were subsequently fed a high-fructose diet supplemented with flavonoids (20 mg/kg) for 12 weeks. The levels of total cholesterol, triglyceride (TG), low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol (HDL-C) were detected. In addition, hepatic and epididymal adipose tissues were weighed, and levels of blood glucose, alanine aminotransferase, aspartate aminotransferase, non-esterified fatty acid, insulin and leptin were determined. The mRNA expression levels of fatty acid synthase (FAS) were analyzed using a reverse transcription polymerase chain reaction; whereas FAS, adenosine monophosphate-activated protein kinase (AMPK) and threonine-172 phosphorylated AMPK protein levels were detected by western blotting. The epididymal adipose tissues of rats fed with flavonoids were lighter, as compared with those fed with fructose in the model group. Following a 12-week administration of flavonoids, the serum levels of fasting blood glucose, feeding blood glucose and leptin were decreased. Furthermore, flavonoid treatment reduced TG and cholesterol levels in the blood and increased serum HDL-C levels, as compared with the model group. High-fructose diet administration significantly increased FAS mRNA and protein expression levels, whereas the FAS protein levels of flavonoid-treated rats were markedly reduced. The flavonoid compounds also enhanced threonine-172 phosphorylation of AMPK in the liver lysate, and all flavonoids successfully downregulated leptin levels and the majority decreased the relative weights of epididymal adipose tissue. Therefore, flavonoids may function in a similar way to epigallocatechin gallate, which has previously been shown to inhibit FAS activity by stimulating AMPK in hepatocyte cells via the liver kinase B1 pathway.

Metformin use and young age lung cancer: A case series report.

Metformin, a widely-prescribed antihyperglycemic drug for the treatment of diabetes mellitus type 2 (DM-II), has been demonstrated to be antineoplastic in vivo and in vitro. However, various preclinical and epidemiological studies investigating the effects of metformin on lung cancer have obtained inconclusive results. The aim of the present study was to retrospectively investigate the effects of metformin, for the treatment of diabetes mellitus type 2 (DM-II), on the onset of lung cancer. In the present study, the pathological features of ten consecutive young age lung cancer cases, aged between 15 and 45 years old at the time of diagnosis and exhibiting existing primary DM, were investigated using the Mayo Clinic Lung Cancer Cohort database. Amongst this cohort, there were 2 cases of DM type 1 (DM-I) and 8 cases of DM-II. Of these patients, two exhibiting adenocarcinoma and DM-II had not been administered metformin; however, 1 patient exhibiting lymphoma and 4 patients with pulmonary neuroendocrine tumors (NETs) had been administered metformin at least 12 months prior to lung cancer diagnosis. The remaining 3 patients exhibiting NETs and DM-II had been treated with insulin therapy. The present study hypothesized that the high proportion of NETs observed in the cases of metformin-treated DM-II was unlikely to be a random event. It was suggested that metformin treatment was not effective in the prevention of pulmonary NETs, and that metformin may instead induce the occurrence of NETs via as yet unknown signaling pathways. The present hypothesis may potentially serve as a novel indicator for the requirement to monitor young patients with diabetes, who are being treated with metformin, for the occurrence of pulmonary NETs.

Immunogenicity of varicella zoster virus glycoprotein E DNA vaccine.

In the present study a eukaryotic expression vector of varicella zoster virus (VZV) glycoprotein E (gE) was constructed and enabled to express in COS7 cells. Furthermore, a specific immune response against the VZV gE eukaryotic expression plasmid was induced in BALB/c mice. The VZV gE gene was amplified using polymerase chain reaction (PCR) and cloned into a eukaryotic expression vector, pcDNA3.1. The recombinant vector was subsequently transfected into COS7 cells using a liposome transfection reagent. The recombinant protein was instantaneously expressed by the transfected cells, as detected by immunohistochemistry, and the recombinant pcDNA-VZV gE plasmid was subsequently used to immunize mice. Tissue expression levels were analyzed by reverse transcription-PCR. In addition, the levels of serum antibodies and spleen lymphocyte proliferation activity were investigated. The amplified target gene included the full-length gE gene (~2.7 kb), and the recombinant expression vector induced gE expression in COS7 cells. In addition, the expression plasmid induced sustained expression in vivo following immunization of mice. Furthermore, the plasmid was capable of inducing specific antibody production and effectively stimulating T cell proliferation. Effective humoral and cellular immunity was triggered in the mice immunized with the VZV gE eukaryotic expression vector. The results of the present study laid the foundation for future research into a VZV DNA vaccine.

Neuroprotective effect of interleukin-6 in a rat model of cerebral ischemia.

Interleukin (IL)-6 is known to be a key cytokine in immune regulation in addition to serving crucial functions in various autoimmune diseases; however, the neuroprotective potential of IL-6 has not been fully investigated. The aim of the present study was to investigate the neuroprotective effects of the inflammatory cytokine IL-6 in a rat model of cerebral ischemia. Rat cerebral ischemia was induced by intraluminal middle cerebral artery occlusion. Following treatment with 500 or 50 ng IL-6, the infarct volumes and symptoms of neurological deficit were ameliorated. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining suggested that the IL-6 treatment reduced neuronal apoptosis in vivo, which was consistent with a lower percentage of annexin V- and caspase-3-positive cortical neurons. In addition, IL-6 in vitro induced the phosphorylation of signal transducer and activator of transcription (STAT) 3 and the expression of induced myeloid leukemia cell differentiation protein Mcl-1, but not the expression of B-cell lymphoma 2, suggesting the activation of the Janus kinase/STAT pathway by IL-6. IL-6 also appeared to be involved in the regulation of cytokine secretion and blood-brain barrier (BBB) integrity in cerebral ischemia. IL-6 downregulated a number of inflammatory cytokines, including tumor necrosis factor-α and IL-1ß, as well as myeloperoxidase activity, indicating the accumulation of granulocytes in the ischemic brain tissue. IL-6 was also observed to support the integrity of the BBB by reducing Evans blue leakage in vivo and suppressing the expression of matrix metalloproteinase-9 in ischemic brain tissue. In conclusion, the results of the present study indicate that the neuroprotective effects of IL-6 in cerebral ischemia are the result of a range of processes, including the modulation of cell apoptosis, cytokine secretion and the integrity of the BBB. IL-6 could therefore be used as a therapeutic agent in clinical practice.

Enhanced antitumor effect of combining chemotherapy with Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes in mice with EBV-related non-Hodgkin's lymphoma.

Epstein-Barr virus (EBV)-related non-Hodgkin's lymphoma (NHL) represents a major problem in hematological clinical studies due to its drug tolerance and refractoriness. EBV infection is a key factor driving the process of tumor growth. Immune therapy is an important biotherapeutic method of treating cancer, which is attracting increasing attention. We hypothesized that combining conventional chemotherapy with immune therapy in the treatment of EBV-related NHL may achieve better outcomes. First, we successfully cloned large numbers of EBV-specific T cells by immune stimulation ex vivo. Subsequently, the combined therapy was applied in a murine model of human EBV-related NHL. As expected, combined therapy inhibited tumor growth more effectively compared with monotherapy. In addition, we continuously tested the tumor-associated immune microenvironment and observed that the numbers of tumor-infiltrating cytotoxic T lymphocytes (CTLs) and macrophages were elevated following combined therapy. These effects suggest that EBV-specific CTLs may indirectly promote an innate immune reaction in lymphoma by activating tumor-infiltrating macrophage proliferation. Our findings may provide a guide for the prospective treatment of EBV-related NHL.

Subcapsular intratesticular assay: a preliminary screening method for putative male antifertility drugs.

The subcapsular intratesticular assay was developed for the preliminary screening of male antifertility agents. In the assay, small amounts of the test sample are injected twice, 1 week apart just beneath the tunica albuginea of the testes of rats. The rats were killed within 3 weeks of treatment to examine epididymal spermatozoa and the histology of the testis and epididymis. There is an excellent agreement between this method and the modified MB-50 assay developed by the World Health Organization. To date, more than 300 samples have been assayed, of which the results of 10 plant-derived compounds are reported here. Not one active sample has been missed as confirmed by the modified MB-50 method, although one compound which was positive in the subcapsular assay did not show antifertility action in the in-vivo assay. Compared with the latter assay, the advantages of this method are: simplicity, time-saving, rat-saving and the need for far smaller amounts of test sample. The absence of false-negative results makes the subcapsular intratesticular assay applicable as a preliminary screening method to test potential male fertility regulating agents.