Increased MCL-1 synthesis promotes irradiation-induced nasopharyngeal carcinoma radioresistance via regulation of the ROS/AKT loop.

Worldwide, nasopharyngeal carcinoma (NPC) is a rare head and neck cancer; however, it is a common malignancy in southern China. Radiotherapy is the most important treatment strategy for NPC. However, although radiotherapy is a strong tool to kill cancer cells, paradoxically it also promotes aggressive phenotypes. Therefore, we mimicked the treatment process in NPC cells in vitro. Upon exposure to radiation, a subpopulation of NPC cells gradually developed resistance to radiation and displayed cancer stem-cell characteristics. Radiation-induced stemness largely depends on the accumulation of the antiapoptotic myeloid cell leukemia 1 (MCL-1) protein. Upregulated MCL-1 levels were caused by increased stability and more importantly, enhanced protein synthesis. We showed that repeated ionizing radiation resulted in persistently enhanced reactive oxygen species (ROS) production at a higher basal level, further promoting protein kinase B (AKT) signaling activation. Intracellular ROS and AKT activation form a positive feedback loop in the process of MCL-1 protein synthesis, which in turn induces stemness and radioresistance. AKT/MCL-1 axis inhibition attenuated radiation-induced resistance, providing a potential target to reverse radiation therapy-induced radioresistance.

[The Diagnostic Value of Peripheral Blood Cell Parameters for Early Recognition of Myelodysplastic Syndrome].

OBJECTIVE: To evaluate the diagnostic value of peripheral blood cell parameters for early recognition of myelodysplastic syndrome (MDS) patients. METHODS: The clinical and laboratory data of 86 patients with MDS and 72 patients with non-malignant clonal anemia treated in first diagnosed in the Second Hospital of Hebei Medical University from January 1, 2015 to December 31, 2017 was retrospectively analyzed. The peripheral blood cell parameters of the patients in two groups were analyzed, generated the receiver operator characteristic curve (ROC curve) from the statistically significant parameters, the binary logistic model was build to calculate and compare the area under the ROC curve (AUC) combined with multiple indicators and individual indicators, sensitivity, specificity, positive and negative likelihood ratio, and diagnostic accuracy, the diagnostic efficacy of the patients was analyzed. RESULTS: Compared with patients in the non-malignant clonal anemia group ,white blood cell count (WBC), neutrophil percentage (NE%), eosinophil percentage (E%), eosinophil absolute value (E#), platelet count (PLT), platelet specific volume (PCT%) in the MDS patients were significantly reduced; while percentage of lymphocytes (LY%), basophilic percentage (B%), and the width of platelet distribution (PDW) significantly increased. The several ROC curves with the above indicators were established, which showed that AUCLY%%=0.718 (P=0.040); AUCPDW=0.674 (P=0.044); AUCB%=0.650 (P=0.044) were >0.5. After established a binary logistic regression model, the AUCPRE-4 obtained by combining the three indicators of LY%, PDW and B% was 0.777 (P=0.037), which was significantly higher than the AUC of any indicator alone. When the sensitivity was 77.91% and the specificity was 61.11%, the corresponding threshold value was 0.47, the positive likelihood ratio was 2.00, the negative likelihood ratio was 0.36, and the case ratio of correct classification was 54.40%. CONCLUSION: PDW, B% and LY% in peripheral blood cell parameters have certain diagnostic value for early recognition of MDS.

[Clinical significance of intermittent sinusoidal fetal heart rate at third trimester].

OBJECTIVE: To investigate clinical significance of intermittent sinusoidal fetal heart rate at third trimester. METHODS: From Jan 2002 to Dec 2010, 48 pregnant women at 33 to 41 gestational weeks undergoing electronic fetal heart rate (FHR) monitoring presented with intermittent sinusoidal FHR in Department of Obstetrics and Gynecology, Second School of Clinical Medicine, Jinan University were enrolled in this retrospective study. Twenty-one cases were categorized into continuous group (i.e. with sinusoidal feature and a constant duration ≥ 10 minutes), while the other 27 cases were categorized into intermittent group (i.e. with a duration < 10 minutes). In the mean time, 76 normal cases were chosen randomly matched as control group. Blood gas and hemoglobin were measured in umbilical artery after fetal head delivery. General neurological system examination were performed in those fetus in hospitalization. The outcome of those fetuses was compared. RESULTS: (1) Neonatal complications: the rate of asphyxia, meconium-stained amniotic fluid and fetal anemia were 63% (17/27), 33% (9/27) and 63% (17/27) in group of intermittent sinusoidal FHR, which were significantly higher than 1% (1/76), 4% (3/76), 3% (2/76) in control group (P < 0.05). When compared with 67% (14/21), 52% (11/21), 76% (16/21) in group of continuous sinusoidal, the statistical difference were not observed (P > 0.05). (2) Blood gas in neonate: the rates of pH less than 7 were 18% (5/27) in intermittent group, 52% (11/21) in continuous group and 0 in control group, which all reached statistical difference among those three groups (P < 0.05). (3) Brain damage and death: the rates of brain damage and death were 48% (13/27) and 11% (3/27) in intermittent group, 81% (17/21) and 43% (9/21) in continuous group, and 0 in control group, which all showed significant difference between them (P < 0.05). CONCLUSION: Intermittent and continuous sinusoidal FHR are typical graphics of severe fetal anemia at third trimester. Intermittent sinusoidal FHR is indicative of serious fetal hypoxia.