DUSP4 inhibits autophagic cell death in PTC by inhibiting JNK-BCL2-Beclin1 signaling.

Dual specificity phosphatase 4 (DUSP4) is a prognostic marker and potential target of papillary thyroid carcinoma (PTC); however, the molecular mechanism underlying DUSP4-regulated PTC carcinogenesis is unknown. DUSP4 is a negative regulator of the autophagy promoter, JNK. This study explored the relationship between DUSP4 and JNK-mediated autophagic cell death in PTC, and the roles of DUSP4 in PTC using gain-of-function and loss-of-function assays. In addition, we further identified the significance of the JNK-BCL2-Beclin1-autophagy signaling pathway on DUSP4-regulated PTC carcinogenesis by combining knockdown of DUSP4 with a JNK-specific inhibitor (SP600125). We found that knockdown of DUSP4 promoted the phosphorylation of JNK and BCL2 in PTC cells, and enhanced the release of Beclin1 from the BCL2-Beclin1 complex. Knockdown of DUSP4 promoted autophagy and the death of PTC cells. The death and autophagy enhanced by knockdown of DUSP4 was reversed by the JNK inhibitor. We further extended the in-vitro experiments by subcutaneously injecting nude mice with K1 cells transfected with DUSP4-silencing vector. In-vivo assays showed that knockdown of DUSP4 not only inhibited tumor growth, but also promoted the phosphorylation of JNK and BCL2 and the expression of LC3II. In conclusion, DUSP4 inhibits BCL2-Beclin1-autophagy signaling by negatively regulating JNK activity, thus inhibiting PTC oncogenesis. The data from this study contribute to the prevention and cure of PTC.

Warm ischemia may damage peribiliary vascular plexus during DCD liver transplantation.

Biliary complications cause significant morbidity and mortality in liver transplantation. Warm ischemia can induce biliary duct injury. This study aimed to investigate the effects of warm ischemia on the peribiliary vascular plexus in rat liver transplantation. A total of 102 Sprague-Dawley rats were divided into three groups: sham-operation group, non-ischemic group, and ischemic group. Liver transplantation was performed in both the non-ischemic group and the ischemic group. The animals were sacrificed on day 1, 3, 7, and 14 to collect the blood and liver samples. Serum levels of bile duct obstruction, viz, alkaline phosphatase and gamma-glutamyl transpeptidase, as well as direct and indirect bilirubin were measured. Liver biopsy samples were examined with hematoxylin-eosin staining and transmission electron microscopy. The levels of enzymes and bilirubin were significantly higher in the ischemic group than the non-ischemic group and sham-operated animals (P<0.05), with return to normal levels in the ischemic group after two weeks. Morphological examination showed microthrombi and endothelial damage in the bile ducts and the peribiliary vascular plexus of the ischemic group. Warm ischemia/reperfusion injury can damage the endothelium of the peribiliary vascular plexus, which might compromise the bile duct microcirculation and lead to ischemic cholangiopathy after liver transplantation.

Comparison of stroke volume variation with pulse pressure variation as a diagnostic indicator of fluid responsiveness in mechanically ventilated critically ill patients.

OBJECTIVE: To compare the diagnostic accuracy of stroke volume variation (SVV) and pulse pressure variation (PPV) in studies that examined both parameters in the same patient population. METHODS: Literature search was conducted in PubMed, EMBASE, CINAHL, and Google Scholar. Receiver operator characteristic (ROC) curves were examined, and summary ROC curves were plotted. RESULTS: The study was conducted from January to July 2013 in The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China. The meta-analysis of 19 studies published during the years 2005 and 2013 revealed a high degree of diagnostic accuracy of both SVV and PPV in predicting fluid responsiveness. The sensitivity and specificity of both the parameters were observed above 80% in a heterogeneous group of over 850 patients of which 55% responded to fluid challenge. The following values along with 95% confidence interval were noticed: SVV - sensitivity 82 (59-93%) and specificity 84 (62-95%), PPV - sensitivity 84 (62-95%) and specificity 83 (58-94%). Area under the curve values obtained in the pooled analysis were 0.84 (0.79-0.89) for SVV, and 0.88 (0.84-0.92) for PPV. CONCLUSION: Both SVV and PPV exhibit a high degree of diagnostic accuracy in predicting the success or failure of a fluid challenge in hemodynamically unstable critically ill patients under controlled mechanical ventilation.

Comparison of the accuracy of transpulmonary thermodilution measurement using indicators of different temperatures.

Transpulmonary thermodilution measurement is a convenient method for hemodynamic monitoring. However, the previously reported indicator temperature was not consistent. This study aimed to compare the accuracy of Pulse index Continuous Cardiac Output (PiCCO) monitoring using indicators of different temperatures. A total of 104 critically ill patients received PiCCO monitoring using indicators of either 0°C or 8°C. The PiCCO measurements, including general ejection fraction, global end-diastolic index, and cardiac index, were compared between the two temperatures, and were also correlated with that of transesophageal echocardiography (TEE). The two indicator temperatures differed significantly in hemodynamic measurements (P<0.01). PiCCO measurements with either indicator temperatures showed positive correlation with TEE results (P<0.05). The 0°C indicator had universally higher correlation coefficients than the 8°C indicator. So, PiCCO monitoring with the 0°C indicator might have better accuracy than the 8°C indicator.