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Intrahepatic cholangiocarcinoma (ICC) can invade and metastasize. EIF5A2 is involved in the invasive metastatic process of several digestive malignancies. However, its role in ICC is yet to be elucidated.Immunohistochemistry (IHC) and Western blot (WB) were used to detect the level of EIF5A2 in the tumor specimens of ICC patients and evaluate the correlation between its expression and clinicopathological characteristics. The significance of EIF5A2 in the prognosis of ICC patients was further evaluated by Kaplan-Meier and Cox regression analysis. In addition, CCK-8, EdU, Transwell invasion, and scratch assays were utilized to detect tumor cell proliferation, invasion, and metastasis. Furthermore, the role of EIF5A2 in ICC cells was evaluated after modification of EIF5A2 expression.The level of EIF5A2 protein was significantly higher in ICC than in adjacent tissues. This high expression in the tumor samples was significantly associated with malignant phenotypes, such as lymph node metastasis (LNM), microvascular or bile duct invasion, and poor differentiation. ICC patients with high expression of EIF5A2 had short overall survival and a high cumulative recurrence rate. The multifactorial analysis showed that EIF5A2 is an independent prognostic marker. Furthermore, high levels of EIF5A2 may activate the PI3K/AKT/mTOR signaling pathway and upregulate Cyclin D1, Cyclin D3, MMP2, and MMP9 to promote ICC cell proliferation, migration, and invasion.The current study found that EIF5A2 promotes ICC progression and is a prognostic biomarker and candidate therapeutic target for ICC patients.

Objective Although several statistical methods for adjusting for missing data have been developed and are widely applied in research, few studies have investigated these methods in adjusting for missingness in datasets that aim to estimate the prevalence of dementia. We attempted to develop a more feasible approach for handling missingness in a cross-sectional study among elderly. Methods Five methods of estimating prevalence, including stratified weighting (SW), inverse-probability weighting (IPW), hot deck imputation (HDI), ordinal logistic regression (OLR) and multiple imputation (MI), were applied to handle the missing data yielded by a dataset that include 2231 non-responders. Results Compared with the results of the complete case analysis, the differences in the prevalence rates of dementia and mild cognitive impairment (MCI) calculated by the prevalence-estimating methods after adjusting for non-responders were less than 7% and 6%, respectively. In contrast to the results of other methods, the estimated prevalence of dementia and MCI calculated by MI increased when more predictive factors were included, and the lowest rate of missing data was achieved using MI. Using the participants’ ages, the cognitive screening sores and activity of daily life sores as predictive variables when correcting for missingness induced relatively larger effects on the estimated dementia prevalence. Conclusions When adjusting for missingness while estimating the prevalence of dementia in cross-sectional studies, a simple method, such as SW, is recommended when limited information is available, whereas MI is the preferred method when additional information is available. Further simulation studies are needed to determine the optimal approach.

The immunoproteasome is a multicatalytic protease complex in all eukaryotic cells, which plays a key role in regulating essential cellular processes. However, the role of immunoproteasome subunit β2i in regulation of cardiac fibrosis and inflammation in deoxycorticosterone-acetate (DOCA)/salt mice remains unknown. Wild-type (WT) and β2i knockout (KO) mice were subjected to uninephrectomy and DOCA/salt treatment for 21 days. Blood pressure was measured by the tail-cuff system. Cardiac function and remodeling were examined by echocardiography, hematoxylin-eosin (H&E) and Masson's trichrome staining. The gene and protein expressions were detected by quantitative real-time PCR, and Western blot analysis. After 21 days, DOCA/salt treatment significantly up-regulated the expression of β2i mRNA and protein in the hearts. Moreover, systolic blood pressure and heart weight/body weight (HW/BW) ratio were significantly higher in DOCA/salt mice than in sham groups, and these effects were markedly reversed in β2i knockout mice. Importantly, DOCA/salt-induced cardiac fibrosis, inflammation and the expression of collagen I, collagen III, α-SMA, IL-1β, IL-6 and TNF-α in the wild-type hearts, which were markedly attenuated by β2i knockout. These beneficial effects were due, at least in part, to the inhibition of IκBα/NF-κB and TGF-β1/Smad2/3 signaling pathways. Collectively, these findings indicate that knockout of β2i ameliorates DOCA/salt-induced cardiac fibrosis and inflammation, and may be a novel potential therapeutic target for hypertensive heart diseases.

Aims Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), an intracellular pattern recognition receptor, which plays an important role in the innate immunity and inflammation. However, its role in myocardial ischemia/reperfusion (I/R) injury remains unknown. In this study, we sought to determine the role of NOD2 on cardiac I/R injury. Main methods Mice were induced 30 min ischemia followed by 24 h of reperfusion. Histological examinations were performed on heart sections with Evans blue and triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, immunohistochemistry and immunofluorescence staining. The messenger RNA (mRNA) expression and protein levels were detected by real-time polymerase chain reaction (RT-PCR) and western blot analysis respectively. Key findings I/R injury markedly upregulated NOD2 expression in heart tissue. Treatment of WT mice with NOD2 ligand (MDP) significantly increased infarct size, the number of apoptotic cells and inflammatory cells, as compared with wild-type mice after I/R injury. Furthermore, MDP enhanced I/R-induced cardiomyocyte apoptosis and inflammation in vitro, and these effects were attenuated by NOD2-siRNA. The mechanism of NOD2 on cardiac I/R injury is partly associated with JNK, p38MAPK and NF-κB signaling pathways. Significance NOD2 aggravates myocardial I/R injury by inducing cardiomyocyte apoptosis and inflammation through JNK, p38MAPK and NF-κB signaling pathways. This study provides insight into better understanding the molecular mechanism of NOD2, which may be served as a potential target for the treatment of myocardial I/R injury.

Chinese grasslands have undergone great changes in land use in recent decades. Approximately 18.2% of the present arable land in China originated from the cultivation of grassland, but its impact on the carbon cycle has not been fully understood. This study wasconducted insitu for3yearstoassessthecomprehensive effects ofcultivationof temperatesteppe onsoilorganiccarbon(SOC) and soil respiration rates as well as ecosystem respiration. As compared with those in the Stipa baicalensis steppe, the SOC concentrations at depths of 0‐10 and 10‐20 cm in the spring wheat field were found to have decreased by 38.3 and 17.4% respectively from 29.5 and 21.9 g kg � 1 to 18.2 and 18.1 g kg � 1 after a cultivation period of 30 years. Accordingly, the total amounts of soil respiration through the growing season (from April to September) in 2002, 2003 and 2004 were 265.2, 282.2 and 237.4 g C m � 2 respectivelyinthespringwheatfield,whichwereslightly lowerthanthevaluesof342.2,412.0and312.1 g C m � 2 in the S. baicalensis steppe, while ecosystem respiration of 690.9, 991.2 and 569.6 g C m � 2 respectively in the spring wheat field were markedly higher than those of 447.0, 470.9 and 429.7 g C m � 2 in the steppe plot. Similar seasonal variations of ecosystem respiration and soil respiration existed in both sample sites. Respiration rates were higher and greater differences existed in both ecosystem respiration and soil respiration during the exuberant growth stage of plants (from mid-June to mid-August). However, in the slower-growth period of the growing season (before late May and after late August), the CO2 effluxes of the two sample sites were similar and remained at a relatively low level. The results also showed that ecosystem respiration and soil respiration were under similar environmental controls in both sample sites. Soil water content at a depth of 0‐10 cm and soil temperatures at 5 and 10 cmwere themain factors affectingthevariations in ecosystemrespiration and soil respirationrates indroughty yearsof 2002and 2004 and in the rainy 2003, respectively. This study suggests that the conversion of the grassland to the spring wheat field has increased the carbon loss of the whole ecosystem due to the change of vegetation cover type and significantly reduced the carbon storage of surface soil. In addition, the tillage of grassland had different effects on ecosystem respiration and soil respiration. The effects were also dissimilar in different growthstages, which should be fully considered when assessing and predicting the effects of cultivation on the net CO2 balance of grassland ecosystems. # 2006 Elsevier B.V. All rights reserved.