Efficacy and safety of nicorandil monotherapy and nicorandil-clopidogrel combination therapy on cardiac function in patients with coronary heart disease.

OBJECTIVES: To compare the efficacy and safety of nicorandil monotherapy and nicorandil-clopidogrel combination therapy on cardiac function in patients with coronary heart disease (CHD). METHODS: The clinical data of 200 patients with CHD were retrospectively analyzed. The patients were divided into two groups according to different treatment methods. Group A (n = 100) received nicorandil-clopidogrel combination therapy (intravenously injected with 25 mg of nicorandil and orally administered 300 mg of clopidogrel for 3 months), and Group B (n = 100) received nicorandil monotherapy (intravenously injected with 25 mg of nicorandil for 3 months). The primary endpoints included cardiac function indices and ST-segment behavior on electrocardiogram (ECG) before and after treatment. The secondary endpoints included adverse reactions, clinical efficacy, platelet aggregation, activated partial thromboplastin time (APTT), high-sensitivity cardiac troponin T (hs-cTnT), and creatine kinase isoenzyme MB (CK-MB) levels after treatment. Multivariate regression analyses were used to assess the contribution of a single drug to the ultimate outcome. RESULTS: After treatment, both groups exhibited significant decreases in brain natriuretic peptide (BNP) and N-terminal pro-hormone BNP levels compared with before treatment, with the levels significantly lower in Group A than in Group B (P < 0.05). After treatment, left ventricular ejection fraction was significantly increased in both groups compared with before treatment, and that was much higher in Group A than in Group B (P < 0.05). After treatment, the frequency and duration of ST-segment depression were decreased in both groups compared with before treatment, and they were much lower in Group A than in Group B (all P < 0.05). The total incidence of adverse reactions in Group A (4.00%) was slightly lower than that in Group B (7.00%), with no significant difference (P > 0.05). Group A (92.00%) had a higher overall response rate than Group B (81.00%) (P < 0.05). CONCLUSION: Nicorandil-clopidogrel combination therapy exhibited enhanced clinical efficacy in patients with CHD. In addition, the combination therapy regulated hs-cTnT and CK-MB levels, which may suggest a better patient prognosis.

GATA3 Exerts Distinct Transcriptional Functions to Regulate Radiation Resistance in A549 and H1299 Cells.

Background: Radiation resistance of lung cancer cells is a vital factor affecting the curative effect of lung cancer. Transcription factor GATA3 is involved in cell proliferation, invasion, and migration and is significantly expressed in a variety of malignancies. However, the molecular mechanism governing GATA3 regulation in lung cancer cells' radiation resistance is unknown. Methods: Radiation-resistant cell models (A549-RR and H1299-RR) were made using fractionated high-dose irradiation. Use clone formation, CCK-8, F-actin staining, cell cycle detection, and other experiments to verify whether the model is successfully constructed. Cells were transiently transfected with knockdown or overexpression plasmid. To explore the relationship between GATA3/H3K4me3 and target genes, we used ChIP-qPCR, ChIP-seq, and dual luciferase reporter gene experiments. Xenograft tumor models were used to evaluate the effect of GATA3 depletion on the tumorigenic behavior of lung cancer cells. Results: We report that transcription factors GATA3 and H3K4me3 coactivate NRP1 gene transcription when A549 cells develop radiation resistance. However, the mechanism of radiation resistance in H1299 cells is that GATA3 acts as a transcription inhibitor. The decrease of GATA3 will promote the increase of NRP1 transcription, in which H3K4me3 does not play a leading role. Conclusions: GATA3, an upstream transcriptional regulator of NRP1 gene, regulates the radioresistance of A549 and H1299 cells by opposite mechanisms, which provides a new target for radiotherapy of lung cancer.

[Phenotype analysis and mutant gene location of ventral yellow mouse (VY(Slac))].

The ventri-yellow pigmentation mouse (temporarily named VY(Slac)) arose spontaneously in the C57BL/6J inbred mouse strain, found and bred by Shanghai SLAC Laboratory Animal Co., Ltd. VY(Slac) presented a special phenotype marked by yellow coat on the ventral surface of neck and trunk that was without melanin deposition but maintained a normal structure. The number of melanocytes in epidermis and melanin in hair follicle of the abdominal skin of the mutant mouse were less than that of their background strain, while there was no significant difference between the dorsal skins of the two strains. This mutant phenotype was inherited as single-gene dominant inheritance, confirmed by genetic experiment, and there was no significant difference between VY(Slac) and B(6) for other biological parameters such as weight, anatomic and histological structures of major organs and blood physiology. When the linkage relationship between the genomic DNA samples of F(2) 48 mice (VY(Slac)D(2)F(1)×D(2)) and mutant phenotype were evaluated, the mutant gene was confirmed on chromosome 2 near D2Mit229. New microsatellite and SNP markers were selected to amplify genomic DNA samples of 196 F(2) mice and the mutant gene was narrowed down to 5.3 Mb region between rs13476833 and rs27310903 on chromosome 2. The preliminary results of our phenotype analysis and gene location provides a solid basis for further identification of this mutant gene.