Animals ; Cytoprotection ; Humans ; Ischemic Preconditioning ; Reperfusion Injury ; prevention & control ; therapy

Humans ; Myocardial Reperfusion Injury ; prevention & control ; Translational Medical Research

The quality and integrity of clinical trials and associated data are not only derived from accuracy of trial data analyses, but also closely embodied to the authenticity and integrity of those data and data documents as well as the compliant procedures obtaining those data and relevant files in the life cycle of clinical trials. The compliances of good clinical practices and standards suggest the reliability, complete and accuracy of data and data documents, which is constructing the convincible foundation of drug efficacy and safety validated via clinical trials. Therefore, the monitoring and auditing on clinical trials and associated data quality keep eyes on not only verifications of reliability and correctness on the data analytic outcomes, but also validation of science and compliance of the trial management procedure and documentations in the process of data collections.
Clinical Trials as Topic ; standards ; Data Accuracy ; Reproducibility of Results

BACKGROUNDCalreticulin (CRT) is major Ca 2+ -binding chaperone mainly resident in the endoplasmic reticulum (ER) lumen. Recently, it has been shown that non-ER CRT regulates a wide array of cellular responses. We previously found that CRT was up-regulated during hypoxia/reoxygenation (H/R) and this study was aimed to investigate whether CRT nuclear translocation aggravates ER stress (ERS)-associated apoptosis during H/R injury in neonatal rat cardiomyocytes.

METHODSApoptosis rate and lactate dehydrogenase (LDH) leakage in culture medium were measured as indices of cell injury. Immunofluorescence staining showed the morphological changes of ER and intracellular translocation of CRT. Western blotting or reverse transcription polymerase chain reaction was used to detect the expression of target molecules.

RESULTSCompared with control, H/R increased apoptosis rate and LDH activity. The ER became condensed and bubbled, and CRT translocated to the nucleus. Western blotting showed up-regulation of CRT, Nrf2, activating transcription factor 4 (ATF4), CHOP and caspase-12 expression after H/R. Exogenous CRT overexpression induced by plasmid transfection before H/R increased cell apoptosis, LDH leakage, ER disorder, CRT nuclear translocation and the expression of ERS-associated molecules. However, administration of the ERS inhibitor, taurine, or CRT siRNA alleviated cell injury, ER disorder, and inhibited ERS-associated apoptosis.

CONCLUSIONSOur results indicated that during H/R stress, CRT translocation increases cell apoptosis and LDH leakage, aggravates ER disorder, up-regulates expression of nuclear transcription factors, Nrf2 and ATF4, and activates ERS-associated apoptosis.

Animals ; Apoptosis ; genetics ; physiology ; Calreticulin ; genetics ; metabolism ; Cell Hypoxia ; genetics ; physiology ; Cell Survival ; genetics ; physiology ; Cells, Cultured ; Endoplasmic Reticulum Stress ; physiology ; Myocytes, Cardiac ; cytology ; metabolism ; RNA Interference ; Rats

Carcinoma, Renal Cell ; complications ; Humans ; Kidney Neoplasms ; complications ; Lymphoma, Non-Hodgkin ; complications ; Male ; Middle Aged

Cholesteatoma ; diagnosis ; Ear, Middle ; Humans ; Otitis Media ; diagnosis

Objective To evaluate the sleep characteristics of the Korean children,and explore the measurement of improving the sleep qua-lity of minority nationality children.Methods The sleep time of 1 183 from 3 to 12 years age Korean children were investigated with questionnaire The sleep time of korean children in different ages and cities were compared.Results The mean time of total sleep time in Korean children was(10.06?1.29) h,which was decreasing with the age′s increasing.The difference in different ages groups was remarkable(Pa

Objective To investigate the relationship of placental vascular anastomosis and physical development and morbidity of the disease in twin neonates.Methods Fourteen pairs of twin neonates deliveried from Sep.2005 to Aug.2009 were enrolled in Newborn Intensive Care Unit,the Third Affiliated Hospital of Zhengzhou University.These twins were divided into 2 groups according the conditions of placental vascular anastomosis:significant placental vascular anastomosis group(group A) and no significant vascula anastomosis group(group B).Birth weight,head circumference,length,the morbidity of disease were all investigated in 2 groups.Clinic follow-up included neonatal behavioral neurological assessment(NBNA) and children′s development center of China(CDCC).The correlation of neonates placental vascular anastomosis between twin neonates were compared.Results There were statistically significant differences between group A and group B in birth weight,head circumference and body length(t=6.070,5.237,5.784,Pa

Objective To study the effects of sample digestion conditions on measurement results of urinary iodine determined by As(Ⅲ)-Ce4+ catalytic spectrophotometry with ammonium persulfate digestion,and to promote the application of newly revised (the 2012 edition) national standard method for determination of urinary iodine.Methods According to the newly revised national standard method,various digestion conditions,such as ammonium persulfate concentration (0.8-1.3 mol/L,group interval 0.1),digestion instruments (heating block and drying oven) and standing time after digestion(0.5,1.0,2.0,4.0 and 22.0 h),were studied.The samples included 3 standard materials,which were GWB09108k,GWB09109f and GWB09110m containing iodine of (68.2 ± 9.0),(138.0 ± 10.0) and (221.0 ± 10.0) μg/L,and 5 urine samples with iodine concentration of 100-300 μg/L.Results Measurement results among the three groups of 0.9,1.0 and 1.1 mol/L ammonium persulfate digestion fluid showed no significant difference(P ＞ 0.05).The digestive effect showed no significant difference between heating block and drying oven (P ＞ 0.05) except one standard material in low concentration (GBW09108k).After digestion,samples were placed 0.5-22.0 h,the measurement results between groups showed no significant difference (P ＞ 0.05).Conclusions Appropriate concentrations of ammonium persulfate are from 0.9 mol/L to 1.1 mol/L.Heating block is recommended for the digestion,however,when absent,drying oven can be used alternatively.The standing times from 0.5 h to 22 h after digestion have not affected the measurement results.

Restoration of blood flow is the definitive therapy to salvage myocardium following ischemic injury. Sudden restoration of blood flow to the ischemic myocardium may, however, also cause reperfusion injury. Therefore, to prevent such ischemia/reperfusion (I/R) injury, one strategy could be to evoke endogenous myocardial protective mechanisms. Ischemic preconditioning (IPC) and postconditioning (I-postC) are endogenous protective mechanisms capable of protecting the myocardium from myocardial infarction, stunning, and ventricular arrhythmia induced by I/R injury. The mechanisms involve induction of triggers, activation of signaling pathways, and end-effectors, which attenuate generation of free radicals and calcium overload induced by I/R. The fact that I-postC can be applied after a prolonged period of ischemia offers a novel approach to myocardial protection. This article mainly reviews the cardioprotection, mechanisms, and application to clinical cardiology of I-postC.
Animals ; Arrhythmias, Cardiac ; Brugada Syndrome ; Cardiac Conduction System Disease ; Heart Conduction System ; abnormalities ; Humans ; Ischemic Postconditioning ; Myocardial Infarction ; Myocardial Reperfusion Injury ; Myocardium ; Reperfusion Injury ; Signal Transduction