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OBJECTIVETo investigate the expression of metabotropic glutamate receptor 4 (mGluR4) in cardiomyocytes differentiated from mouse embryonic stem cells (ES cells).

METHODSES cells were differentiated into cardiomyocytes with hanging-drop cultures. Retinoic acid (RA) and dimethyl sulfoxide (DMSO) were used as positive and negative controls, respectively. The co-expression of cardiac sarcomeric protein (α-actinin or troponin-T) and mGluR4 were verified by immunocytochemistry and flow cytometry analysis. The mRNA and protein expressions of mGluR4 were verified by RT-PCR and Western blot analysis, respectively. Meanwhile, the expression of mGluR4 in prenatal mouse heart was also examined.

RESULTSmGluR4 was expressed in both mouse ES cells and ES cell-derived cardiomyocytes. The level of mGluR4 protein expression decreased during the maturation of the cardiomyocytes. The co-expression rate of mGluR4 and Troponin T in the beating embryoid bodies (EBs) was only (3.00 ±1.00)%. On the other hand, mGluR4 gene and protein expressions showed remarkable down-regulation in the development of mouse fetal heart, which was not detected in mouse adult heart.

CONCLUSIONThe expression of mGluR4 is down-regulated in the cardiomyocyte differentiation of ES cells. The trend of expression is consistent with that in the prenatal mouse heart development.

Animals ; Cell Differentiation ; physiology ; Cell Line ; Embryonic Stem Cells ; cytology ; metabolism ; Mice ; Mice, Inbred ICR ; Myocytes, Cardiac ; cytology ; metabolism ; RNA, Messenger ; genetics ; Receptors, Metabotropic Glutamate ; genetics ; metabolism

OBJECTIVETo study the morphologic and immunohistochemical features of gastrointestinal B-cell lymphomas.

METHODSOne hundred and ninety-four cases of gastrointestinal B-cell lymphoma were retrieved from the archival file. The clinical features and pathologic findings were reviewed. Immunohistochemical study for B-cell markers, T-cell markers, bcl-6, CD10, bcl-10, cyclin D1, TdT, MUM1 and Ki-67 was carried out.

RESULTSThe male-to-female ratio was 1.4:1. The age of patients ranged from 8 to 85 years. Amongst the 194 cases studied, 128 (66.0%) were diagnosed as diffuse large B-cell lymphoma, including 16 cases of large cell lymphoma associated with mucosa-associated lymphoid tissue (MALT) lymphoma component. There were also 40 cases (20.6%) of MALT lymphoma, 8 cases (4.1%) of follicular lymphoma, 5 cases of (2.6%) of lymphoplasmacytic lymphoma, 3 cases (1.6%) of mantle cell lymphoma, 1 case of (0.5%) of B-lymphoblastic lymphoma and 9 cases (4.6%) of indefinite type (including 5 biopsy cases). The site of involvement included stomach (100 cases, 51.5%), small intestine (43 cases, 22.2%), ileocecal junction (26 cases, 13.4%), appendix (1 case, 0.5%), colon (21 cases, 10.8%) and rectum (3 cases, 1.6%). Amongst the 163 cases which had undergone surgical resection, 20 cases (12.3%) cases had invasion down to the mucosa, 20 cases (12.3%) down to the superficial muscular layer, 19 cases (11.6%) down to the deep muscular layer and 104 cases (63.8%) with full-thickness involvement. Histologic examination showed lymphoepithelial lesions in 52 cases, residual lymphoid follicles in 29 cases, coagulative necrosis in 66 cases and nodular growth pattern in 30 cases. The lymphoma cells in all cases were immunoreactive for B-cell marker CD20. There was also various degrees of positivity for bcl-6, CD10, bcl-10, cyclin D1, TdT, MUM1 and Ki-67.

CONCLUSIONSGastrointestinal B-cell lymphomas can be subdivided into two main groups: large B-cell lymphomas and small B-cell lymphomas. The latter group often poses diagnostic pitfalls. Accurate pathologic typing requires correlation with histologic and immunohistochemical findings.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD20 ; metabolism ; Child ; DNA-Binding Proteins ; metabolism ; Female ; Gastrointestinal Neoplasms ; metabolism ; pathology ; surgery ; Humans ; Immunohistochemistry ; Lymphoma, B-Cell ; metabolism ; pathology ; surgery ; Lymphoma, B-Cell, Marginal Zone ; metabolism ; pathology ; surgery ; Lymphoma, Follicular ; metabolism ; pathology ; surgery ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neprilysin ; metabolism ; Proto-Oncogene Proteins c-bcl-6 ; Young Adult

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

OBJECTIVETo analyze the association between the EGFR protein level and the EGFR gene mutation status in advanced non-small cell lung cancer (NSCLC), and to explore whether the EGFR protein level is related to the efficacy and survival of the EGFR-TKI drug Gifitinib-treated patients with advanced NSCLC.

METHODSNinety-nine cases were enrolled in this study. Pathological tissue specimens and paired peripheral blood samples were collected. Exons 19 and 21 of the EGFR gene mutation were detected by direct sequencing. The concentration of plasma EGFR protein was detected by ELISA. Univariate and multivariate statistical analyses of the efficacy and survival were performed using SPSS 13.0 software.

RESULTSThe response rate (RR) and clinical benefit rate (CBR) of Gefitinib-treated patients were 51.5% and 79.8%, respectively. There were 35 (35.4%) with positive EGFR gene mutation of the 99 samples. The concentration limit of EGFR protein was 55.42 µg/L. The RR and CBR of patients with EGFR gene mutation was significantly higher than those without mutation (65.7% vs. 43.8%, P = 0.037; 94.3% vs. 71.9%, P = 0.008). The median PFS was prolonged (23 months vs. 10 months, P = 0.014). The CBR of patients with high EGFR protein expression (concentration ≥ 55.42 µg/L) was significantly higher than those with low expression (90.0% vs 64.1%, P = 0.004), and the median PFS was prolonged (21 months vs. 8 months, P = 0.016). EGFR protein level was an independent factor affecting the EGFR gene mutation status. The Correlation between EGFR gene mutation status and EGFR protein level was positive.

CONCLUSIONSGefitinib is effective in the treatment of advanced NSCLC patients with EGFR gene mutation and high EGFR protein expression. EGFR protein level in peripheral blood may be a molecular biomarker in prediction of efficacy and survival of the Gefitinib treatment in patients with advanced NSCLC.

Aged ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; genetics ; pathology ; Disease-Free Survival ; Exons ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; blood ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; blood ; genetics ; Remission Induction ; Survival Rate

The aim of the present study is to investigate how cytochrome P450 enzymes (CYP) 2C8-derived epoxyeicosatrienoic acids (EETs) regulate the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and protect against oxidative stress-induced endothelial injuries in the development and progression of atherosclerosis. In this study, cultured human umbilical vein endothelial cells (HUVECs) were transfected with CYP2C8 or pretreated with exogenous EETs (1 μmol/L) before TNF-α (20 ng/mL) stimulation. Apoptosis and intracellular ROS production were determined by flow cytometry. The expression levels of ROS-associated NAD(P)H subunits gp91 and p47, the anti-oxidative enzyme catalase (CAT), Nrf2, heme oxygenase-1 (HO-1) and endothelial nitric oxide synthase (eNOS) were detected by Western blotting. The results showed that CYP2C8-derived EETs decreased apoptosis of HUVECs treated with TNF-α. Pretreatment with 11, 12-EET also significantly blocked TNF-α-induced ROS production. In addition, 11, 12-EET decreased oxidative stress-induced apoptosis. Furthermore, the ability of 11, 12-EET to protect cells against TNF-α-induced apoptosis via oxidative stress was abrogated by transient transfection with Nrf2-specific small interfering RNA (siRNA). In conclusion, CYP2C8-derived EETs prevented TNF-α-induced HUVECs apoptosis via inhibition of oxidative stress associated with the Nrf2 signaling.
8,11,14-Eicosatrienoic Acid ; analogs & derivatives ; metabolism ; pharmacology ; Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Apoptosis ; drug effects ; Aryl Hydrocarbon Hydroxylases ; genetics ; metabolism ; Atherosclerosis ; genetics ; metabolism ; pathology ; Catalase ; genetics ; metabolism ; Cytochrome P-450 CYP2C8 ; genetics ; metabolism ; Gene Expression Regulation ; Heme Oxygenase-1 ; genetics ; metabolism ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Membrane Glycoproteins ; genetics ; metabolism ; Models, Biological ; NADPH Oxidase 2 ; NADPH Oxidases ; genetics ; metabolism ; NF-E2-Related Factor 2 ; antagonists & inhibitors ; genetics ; metabolism ; Nitric Oxide Synthase Type III ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; metabolism ; Reactive Oxygen Species ; antagonists & inhibitors ; metabolism ; Signal Transduction ; Tumor Necrosis Factor-alpha ; metabolism ; pharmacology

Aged ; Cognitive Dysfunction/epidemiology* ; Cross-Sectional Studies ; Geriatric Assessment ; Humans ; Independent Living ; Sarcopenia/epidemiology*