Five-year follow-up on two revascularization methods used on patients with left main artery disease and/or multivessel coronary artery disease.

BACKGROUND: Coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) are the main treatment methods for left main artery disease (LMAD) and triple-vessel coronary artery disease (TVCAD). OBJECTIVE: This study aimed to evaluate the five-year post-treatment effects of CABG and PCI in patients with severe coronary vasculopathy. METHODS: A total of 430 patients with LMAD and/or triple-vessel coronary artery disease from November 2014 to July 2015 were enrolled retrospectively in the affiliated cardiovascular hospital of Shanxi Medical University and divided into the CABG group and PCI group. The living conditions of the patients were obtained through medical records and telephonic follow-ups five years after the surgery date. The independent risk factors for major adverse cardiovascular and cerebrovascular events (MACCE) were analyzed using logistic regression analysis. The effects of the two treatment methods were followed up and evaluated to measure the predictive ability of the Global Risk Classification (GRC) scoring system for MACCE after five years. RESULTS: There were 212 cases in the CABG group and 218 cases in the PCI group. Smoking (P= 0.047), diabetes (P= 0.031), LVEF (P= 0.020), LMAD (P= 0.008), and anterior descending branch lesions (P= 0.038) were significantly correlated with MACCE. The prevalence of MACCE in the CABG group and PCI group had no significant difference (P= 0.549). The GRC scoring system received an AUC of 0.701 for predicting MACCE. CONCLUSION: For patients with severe coronary artery disease, there was no significant difference in the prevalence of MACCE between the CABG and the PCI groups. Several independent risk factors for MACCE were found. The GRC scoring system showed a strong predictive ability for MACCE after five years of revascularization.

A novel miRNA-762/NFIX pathway modulates LPS-induced acute lung injury.

Severe acute lung injury (ALI) cause significant morbidity and mortality worldwide. MicroRNAs (miRNAs) are possible biomarkers and therapeutic targets for ALI. We aimed to explore the role of miR-762, a known oncogenic factor, in the pathogenesis of ALI. Levels of miR-762 in lung tissues of LPS-treated ALI mice and blood cells of patients with lung injury were measured. Injury of human lung epithelial cell line A549 was induced by LPS stimulation. A downstream target of miR-762, NFIX, was predicted using online tools. Their interactions were validated by luciferase reporter assay. Effects of targeted regulation of the miR-762/NFIX axis on cell proliferation, apoptosis, and inflammatory responses were tested in vitro in A549 cells in vivo with an ALI mouse model. We found that upregulation of miR-762 expression and downregulation of NFIX expression were associated with lung injury. Either miR-762 inhibition or NFIX overexpression in A549 lung cells significantly attenuated LPS-mediated impairment of cell proliferation and viability. Notably, increasing expressions of miR-762 inhibitor or NFIX in vivo via airway lentivirus infection alleviated the LPS-induced ALI in mice. Further, targeted downregulation of miR-762 expression or upregulation of NFIX expression in A549 cells markedly down-regulates NF-κB/IRF3 activation, and substantially reduces the production of inflammatory factors, including TNF-α, IL-6, and IL-8. This study reveals a novel role for the miR-762/NFIX pathway in ALI pathogenesis and sheds new light on targeting this pathway for diagnosis, prevention, and therapy.

Surgical management of Boerhaave's syndrome with early and delayed diagnosis in adults: a retrospective study of 88 patients.

BACKGROUND: spontaneous esophageal rupture (Boerhaave's syndrome) is a rare and challenging clinical condition. OBJECTIVE: to evaluate the outcome of different surgical treatments for patients with Boerhaave's syndrome with an early diagnosis (< 24 h) and delayed diagnosis (> 24 h), using a retrospective cohort study in a tertiary referral center. PATIENTS AND METHODS: eighty-eight patients with Boerhaave's syndrome who underwent surgical treatment were identified from March 1994 to March 2019 in the First Hospital of Shanxi Medical University. Subsequently, they were retrospectively divided into two groups according to time from symptom onset to diagnosis (group 1, < 24 h, n = 16; group 2, > 24 h, n = 72). Primary suture repair was used in group 1 and reinforcement with a vascular muscle flap was used in group 2, in order to reduce the incidence of fistula. Patients in group 2 were further divided into two subgroups according to reinforcement using diaphragmatic flaps (subgroup 1) or intercostal muscle flaps (subgroup 2). RESULTS: the duration of hospitalization and stay in Intensive Care Unit (ICU) was significantly shorter in group 1 (p = 0.027 and p = 0.001). Group 1 had fewer postoperative esophageal leaks (p = 0.037) compared to group 2. Various aspects were compared in the two subgroups and the differences were not statistically significant (p > 0.05). CONCLUSIONS: it is very important to establish an early diagnosis for patients with Boerhaave's syndrome. Early (< 24 h) and primary suture repair is superior to delayed (> 24 h) primary repair, even for those reinforced with vascular muscle flaps. Furthermore, repair reinforcement with different muscle flaps appears to render similar results for patients with delayed diagnosis.

The role of endogenous reactive oxygen species in cardiac myocyte autophagy.

Autophagy is implicated in the maintenance of cardiac homeostasis. Autophagy is activated in heart failure, in which reactive oxygen species (ROS) are increased. Exogenous ROS have been shown to induce cardiomyocyte autophagy alterations. However, little is known about the influences of physiological levels of endogenous ROS on cardiomyocyte autophagy. In the present study, we tested the hypothesis that endogenous ROS in cardiomyocytes play an important role in inducing autophagy. Cultured H9C2 cardiomyocytes or Sprague-Dawley rats were treated with the antioxidant N-acetyl-cysteine (NAC) or the superoxide dismutase mimic tempol under the basal or nutrient deprivation conditions. The autophagic flux was assessed by the lysosomal inhibitor chloroquine. In H9C2 cardiomyocytes, under a basal condition, NAC or tempol increased the ratio of LC3 II/I proteins and reduced LC3 II autophagic flux. Under nutrient deprivation, NAC increased the LC3 II/I ratio and reduced LC3 II autophagic flux. In vivo studies in rats, NAC treatment increased the LC3 II/I ratio and p-Akt protein expression in myocardium. We concluded that the antioxidants reduced autophagic flux in cardiomyocytes under the basal or nutrient deprivation conditions, suggesting that endogenous ROS promote autophagy flux under physiological conditions, and this effect is mediated, at least in part, through Akt inhibition.

Resistin-induced cardiomyocyte hypertrophy is inhibited by apelin through the inactivation of extracellular signal-regulated kinase signaling pathway in H9c2 embryonic rat cardiomyocytes.

It has been reported that resistin induces, whereas apelin inhibits cardiac hypertrophy. However, the underlying molecular mechanisms of apelin inhibiting resistin-induced cardiac hypertrophy remain unclear. The aim of the current study is to investigate the effects of apelin on resistin-induced cardiomyocyte hypertrophy and elucidate the underlying molecular mechanism. H9c2 cells were used in the present study, and cell surface area and protein synthesis were evaluated. Reverse transcription-quantitative polymerase chain reaction was performed to analyze the expression levels of hypertrophic markers, brain natriuretic peptide (BNP) and ß-myosin heavy chain (ß-MHC). In addition, western blotting was conducted to examine phosphorylation of extracellular signal-regulated kinase (ERK)1/2. Following treatment of H9c2 cells with resistin, cell surface area, protein synthesis, and BNP and ß-MHC mRNA expression levels were increased. Subsequent to co-treatment of H9c2 cells with apelin and resistin, lead to the inhibition of resistin-induced hypertrophic effects by apelin. In addition, treatment with resistin increased phosphorylation of ERK1/2, whereas pretreatment with apelin decreased phosphorylation of ERK1/2, which was increased by resistin. These results indicate that resistin-induced cardiac hypertrophy is inhibited by apelin via inactivation of ERK1/2 cell signaling.

LKB1/AMPK pathway mediates resistin-induced cardiomyocyte hypertrophy in H9c2 embryonic rat cardiomyocytes.

Resistin has been previously demonstrated to induce cardiac hypertrophy, however, the underlying molecular mechanisms of resistin-induced cardiac hypertrophy remain unclear. Using H9c2 cells, the present study investigated the liver kinase B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway for a potential role in mediating resistin-induced cardiomyocyte hypertrophy. Treatment of H9c2 cells with resistin increased cell surface area, protein synthesis, and expression of hypertrophic marker brain natriuretic peptide and ß-myosin heavy chain. Treatment with metformine attenuated these effects of resistin. Furthermore, treatment with resistin decreased phosphorylation of LKB1 and AMPK, whereas pretreatment with metformin increased phosphorylation of LKB1 and AMPK that is reduced by resistin. These results suggest that resistin induces cardiac hypertrophy through the inactivation of the LKB1/AMPK cell signaling pathway.

Expression profile and kinetics of cytokines and chemokines in patients with chronic hepatitis C.

Cytokines and chemokines play an important role in defense against viral infection and modulating immune response. However, expression prolife of serum cytokines and chemokines, which were associated with the outcome of patients in response to anti-HCV treatment have not been fully elucidated. The current study aimed to determine the expression pattern of cytokines and chemokines in chronic HCV infection and their association with outcome in response to therapy. Seventy-two patients with HCV infection were enrolled, and fifty-one received peg-interferon α-2a and ribavirin therapy for 48 weeks. Thirty-nine cytokines and chemokines were analyzed by Luminex 200 and ELISA. In comparison to healthy individuals, production of IL-8 and IL-10 were increased in chronic hepatitis C patients. In contrast, IFN-γ, IL-7, and IL-15 were remarkably decreased, especially in HCV genotype 1b infection. HCV RNA load is closely associated with IL-10 and IL-15 expressions, and inhibition of HCV replication was accompanied by reduction in IL-10 and elevation in IL-7 and IL-15. Skewed cytokines and chemokines expression existed in chronic HCV infection, and might play an important role in persistent HCV infection. Exploiting the expression pattern of cytokines and chemokines may help to develop a better understanding of the pathogenesis of chronic HCV infection.

[Effects of H2-Bl gene transfection on biological behaviour of mouse vascular smooth muscle cell].

AIM: To investigate the effects of H2-Bl gene on biological behaviour of mouse vascular smooth muscle cells (VSMCs) including apoptosis, proliferation and anti-cytolysis to peripheral blood mononuclear cells (PBMCs), then speculate the possible mechanism of immunological rejection after heart transplantation in maternal-fetal immune tolerance. METHODS: The mouse VSMC were transfected with 0.5 mg/L of pEGFP-N1 plasmid vector, 0.5 mg/L of pEGFP-N1-H2B1 plasmid vector and 1.0 mg/L of pEGFP-N1-H2B1 plasmid vector, respectively. The efficiency of transfection was detected, and the H2-Bl mRNA level, the apoptosis, the proliferation and cytotoxicity of VSMCs were also investigated at 24 h, 48 h and 72 h, respectively. RESULTS: Expression of the H2-Bl gene was determined by real time quantitative PCR. Expressions of the H2-Bl in experimental groups were higher than that of the control group (P<0.001). VSMC apoptosis was observed after 24 h in the 0.5 mg/L and 1.0 mg/L H2-Bl experimental groups compared with control group (P<0.05, P<0.001, respectively). VSMC proliferation was also inhibited in the 0.5 mg/L and 1.0 mg/L H2-Bl gene groups at 24 h and 72 h (P<0.05, P<0.01, respectively). The cytotoxicity of PBMC in the 0.5 mg/L and 1.0 mg/L H2-Bl gene groups at 24 h was lower than the control group (P<0.005, P<0.001, respectively). CONCLUSION: Transfection of pEGFP-N1-H2B1 plasmid to mouse VSMC causes the over expression of H2-Bl mRNA, induces the apoptosis, inhibits the proliferation and attenuates the cytotoxicity of PBMC, leading to immune tolerance.

[Local shRNA modulation of phosphatidylinositol 3-kinase signaling pathway reduces intimal hyperplasia in vein grafts: experiment with rats].

OBJECTIVE: To investigate whether knockdown Pik3cb p110beta subunit by shRNA in autologous vein grafts can reduce intimal hyperplasia. METHODS: 180 adult SD rats underwent carotid artery bypass graft surgery by using the autologous branch of jugular vein, and they were randomly divided into 6 equal groups: Group A (with the jugular vein grafts treated with 25% Pluronic F-127 only), Group B (with the graft treated with the plasmid encoding shRNA targeting Pik3cb p110beta subunit, pU6-Pik3cb-shRNA-1), Group C (with the graft treated with the plasmid encoding shRNA targeting Pik3cb p110beta subunit, pU6-Pik3cb-shRNA-2), Group D (with the graft treated with the half pU6-Pik3cb-shRNA-1 and pU6-Pik3cb-shRNA-2), and Group E (with the graft treated with the pGenesil-1 scramble shRNA), and Group F (with the jugular vein grafts treated with wortmannin). Specimens of jugular vein graft were harvested 1, 3, 7, 14, and 28 days after surgery to assess the neointimal hyperplasia. Another 18 rats were randomly divided into 6 equal groups as mentioned above to be used in a parallel experiment: 72 h after surgery specimens of jugular vein graft were harvested to undergo fluorescence quantitative real-time PCR and Western blotting to detect the mRNA expression of P13K p110beta subunit and the protein expression of phosphorylated Akt - phospho-Akt (Thr 308) and phospho-Akt (Ser473)-, and mTOR (Ser 2448). And another 9 rats received jugular vein grafts treated with the pGenesil-1 scramble shRNA, and on the postoperative days 1, 2, and 3 respectively 3 rats were killed to undergo fluorescence staining to detect the transfection efficacy. RESULTS: The transfection rate of the plasmid pGenesil-1 was 60% in the vascular smooth muscle cells and 90% in the endothelial cells. The thickness of tunica intima 28 days after the surgery of the pU6-Pik3cb-shRNA-1, pU6-Pik3cb-shRNA-2, 1/2 (shRNA1 + shRNA2), and wortmannin groups were (34.6 +/- 2.7) microm, (39.4 +/- 2.5) microm, (36.7 +/- 2.9) microm, and (40.6 +/- 3.1) microm respectively, all significantly lower than that of the control group (61.8 +/- 4.3 microm, P < 0.05). The expression levels of phospho-Akt (Thr 308), phospho-Akt (Ser 473), and mTOR of the shRNA intervention and wortmannin groups were all down-regulated. CONCLUSION: Knockdown of Pik3cb in interposition carotid artery branch of jugular vein grafts reduces intimal hyperplasia with the possible mechanism of downregulation of phosphatidylinositol 3-kinase signaling through Akt, with resultant decreases in VASC growth and survival. Modulation of the phosphatidylinositol 3-kinase pathway through knockdown Pik3cb may represent a novel therapy to prevent vein graft intimal hyperplasia after bypass grafting.

[Inhibitory effects of RNA interference on MyD88 expression and biological activity in murine myeloid dendritic cells].

AIM: To investigate inhibitory effects of RNA interference on MyD88 expression in murine myeloid dendritic cells(DCs) and detect the biological activity of DCs. METHODS: Three pairs of myeloid differentiation factor 88(MyD88) siRNA were synthesized and transfected into DCs by RNAi-mate. The mRNA and protein expression of MyD88 were analyzed by semi-quantified RT-PCR and Western blot. Mouse DCs were divided into control group and RNA interference group. One of the highest effective siRNA was transfected into RNA interference group. 12 hours later, LPS of the final concentrations of 1.0 mg/L was added in two groups and continued to culture for 3 days. The phenotype and functional properties of DCs were detected by flow cytometry and mixed lymphocyte reaction (MLR). The concentration of TNF-alpha, IFN-gamma and IL-12 in the supernatant was detected by ELISA, and the concentration of NF-kappaB was detected by immunochemistry. RESULTS: mRNA and protein expression were reduced 90% and 85% in sequence2 siRNA, 92% and 88% in sequence3 siRNA respectively but no change was found in other groups. LPS stimulation increased the expression of CD80, CD86 and MHC-II in the cytomembrane of DCs, the concentration of TNF-alpha, IFN-gamma and IL-12 in the supernatant in control group. Besides, LPS stimulation promoted the shift of NF-kappaB to karyon and the proliferation of allogeneic T cells in control group. RNA interference inhibited these effects induced by LPS. CONCLUSION: RNA interference can reduce MyD88 expression in murine myeloid dendritic cells and inhibit the maturation of DCs, which may provide a new strategy of gene therapy for related diseases.

[Origin of neointimal cells in autologous vein graft in rat model].

OBJECTIVE: To investigate the potential cell sources of neointimal cells in autologous vein graft in rat model. METHODS: Vein graft neointimal cell origins were investigated using a model of vein-to-artery interposition modal. Slides were stained with hematoxylin and eosin, immunohistochemical staining was also performed with primary antibodies alpha-smooth actin or CD34. RESULTS: Neointimal thickening was greater at the proximal ends (65.2 +/- 4.6) microm and, to a lesser extent, distal ends (64.7 +/- 5.3) microm, in comparison to the middle of the graft (63.5 +/- 5.6) microm. Vein-originating cells survived and make a contribution to neointimal formation within the vein graft, mostly adjacent to the lumen, suggesting an intimate association with endothelial cells, donor arterial smooth muscle cells or circulating progenitor cells. CONCLUSIONS: Vein graft neointimal cells arise predominantly from vein-derived endothelial cells, donor arteria smooth muscle cells or circulating progenitor cells. It suggests clinical relevance of stenosis-inhibiting therapies directed at the vein graft or early system pharmacologic administration.