Preclinical and clinical studies have shown that statins, the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors with cholesterol-lowering properties, exhibited anticancer effects. However, the underlying mechanisms remain ill defined. In this study, we showed that atorvastatin could inhibit the growth of hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) cells via induction of apoptosis. Atorvastatin also induced autophagy that is a physiologic process involved in the turnover of intracellular organelles. Atorvastatin-induced autophagy was found to be inhibited by AMP-activated protein kinase (AMPK) small interfering RNA. Examination of HCC patients showed the positive correlation between AMPK activity and autophagic marker (beclin-1). Atorvastatin-induced AMPK activation could induce p21 expression, which was also positively correlated with beclin-1 expression in CRC patients. AMPK/p21 signaling caused endoplasmic reticulum (ER) stress response leading to the induction of autophagy. Inhibition of autophagy by an autophagic inhibitor bafilomycin A1 or genetic knockout of autophagy-related gene 5 enhanced atorvastatin-induced cytotoxicity and apoptosis. In summary, activation of AMPK by atorvastatin enhances p21 expression and ER stress response, leading to autophagy, which promotes survival of cancer cells. Combinations of atorvastatin with bafilomycin A1 provide a novel and promising strategy to improve the treatment of digestive malignancies.

These data identify specific factors that are determinants of patients' perception of privacy. It was found that patients' perception of privacy strongly predicts satisfaction. ED improvement efforts should focus on improving ED environmental design and continuing education of healthcare providers to protect patient privacy during their stay in the ED.

Peroxiredoxin (Prdx) 2 is an antioxidant protein that utilizes its redox-sensitive cysteine groups to reduce hydrogen peroxide molecules and protect cells against oxidative damage from reactive oxygen species (ROS). However, its function in trophoblasts at the maternal–fetal interface has not been clarified yet. In this study, significantly lower Prdx2 expression was found in the first-trimester villous cytotrophoblasts of patients with recurrent miscarriage (RM) than in cytotrophoblasts from healthy controls. Further, Prdx2 knockdown inhibited proliferation and increased apoptosis of trophoblast cells. The reason for this may be an increase in the level of cellular ROS after knockdown of Prdx2, which may subsequently lead to an increase in the expression of phosphorylated p53 (p-p53) and p38-MAPK/p21. Prdx2 knockdown also impaired the fusion of BeWo cells induced by forskolin. Bioinformatics analysis identified a c-Myc-binding site in the Prdx2 promoter region, and chromatin immunoprecipitation verified that c-Myc directly bound to a site in this locus. Suppression and overexpression of c-Myc resulted in reduction and increase of Prdx2 expression respectively. Furthermore, we demonstrated that c-Myc was downregulated in the first-trimester cytotrophoblasts of patients with RM, and its downregulation is also related with inhibited cell proliferation, increased apoptosis, as well as upregulated p21 expression and p-p53/p53 ratio. Our findings indicate that Prdx2 might have an important role in the regulation of trophoblast proliferation and apoptosis during early pregnancy, and that its expression is mediated by c-Myc. Thus, these two proteins may be involved in the pathogenesis of RM and may represent potential therapeutic targets.

On the basis of our result, we recommend that type II and type III fractures be treated with open reduction and internal fixation. Despite the results of type IV fractures being significantly worse than that of type II and type III fractures, we recommend open reduction and internal fixation for type IV fractures to restore the hindfoot architecture and the subtalar joint, if possible. When the disrupted subtalar joint is so comminuted that it is beyond the surgeon's ability to reconstruct, primary subtalar arthrodesis should be performed in addition to open reduction and internal fixation.

No abstract

The prognosis of type II floating knee injuries was not as good as that of type I. Our purpose is to clarify the factors affecting the outcome of type II floating knee injuries. Thirty-five patients (36 limbs) with type II floating knee injury were studied with a mean follow-up of 52 months (26-96). Blake and McBryde had classified these injuries into type I for pure diaphyseal (true type) fracture and type II if the intra-articular involvements are one or more including hip, knee and ankle joints (variant type). According to this classification, we divided these patients into two groups depending on whether their knees were involved or not. Those cases with intra-articular knee involvement were classified as type IIA, while those without intra-articular knee involvement were classified as type IIB. Of the 36 cases, 21 were classified as type IIA and 15 were type IIB. The functional outcomes of these injuries were evaluated by using the criteria of Karlström and Olerud and analyzed with multivariate analysis. After multivariate analysis with logistic regression, we show the following results: first, the poor functional outcome of type II floating knee is contributed by type IIA. Second, the type IIA group has severer femoral open fracture grading (P = 0.027) and poorer functional outcome (P = 0.009) than type IIB. Third, the significant contributing factors to final outcome are the group (P = 0.013) and the fixation time after injury in femur (P = 0.015). Intra-articular knee involvement is the most important factor contributing to poor outcome of type II floating knee. The treatment of floating knee injuries with intra-articular knee involvement is still difficult. Further efforts to search better methods of treatment are required for these complex injuries in the future.

No abstract

Elevated levels of NF-κB are frequently detected in many inflammatory diseases and cancers. Blocking the IKK–NF-κB pathway has been seen as a promising approach for new therapies. By employing the dominant-negative mutant of IKKβ, our data revealed that loss of IKKβ activity reduces not only the proliferation and invasion of lung adenocarcinoma A549 cells in vitro but also the tumour formation, metastasis and angiogenesis in mouse xenograft model. Treatment of IKKβ inhibitors (CYL-19s and CYL-26z) leads to the arrest of cell cycle progression at G1 and G2/M, followed by apoptosis. IKKβ inhibitors can increase the protein stability, nuclear accumulation and promoter-binding activity of p53, leading to the p21 gene transcription. Furthermore, knockdown of IKKβ by siRNA increased the stability and expression of p53 and p21 promoter activity. In addition, IKKβ inhibitor–induced p53 and p21 expressions were augmented in the presence of IKKβ siRNA. Correlation between p53 acetylation and its protein stabilization was also seen after treatment with IKKβ inhibitors. These results suggest that loss of IKKβ activation is important for the enhancement of p53 stability, leading to p21 expression and cell cycle arrest and apoptosis of tumour cells.