Chemotherapy response rates in patients with cholangiocarcinoma remain low, primarily due to the development of drug resistance. Epithelial-mesenchymal transition (EMT) of cancer cells is widely accepted to be important for metastasis and progression, but it has also been linked to the development of chemoresistance. Salinomycin (an antibiotic) has shown some potential as a chemotherapeutic agent as it selectively kills cancer stem cells, and has been hypothesized to block the EMT process. In this study, we investigated whether salinomycin could reverse the chemoresistance of cholangiocarcinoma cells to the chemotherapy drug doxorubicin. We found that combined salinomycin with doxorubicin treatment resulted in a significant decrease in cell viability compared with doxorubicin or salinomycin treatment alone in two cholangiocarcinoma cell lines (RBE and Huh-28). The dosages of both drugs that were required to produce a cytotoxic effect decreased, indicating that these two drugs have a synergistic effect. In terms of mechanism, salinomycin reversed doxorubicin-induced EMT of cholangiocarcinoma cells, as shown morphologically and through the detection of EMT markers. Moreover, we showed that salinomycin treatment downregulated the AMP-activated protein kinase family member 5 (ARK5) expression, which regulates the EMT process of cholangiocarcinoma. Our results indicated that salinomycin reversed the EMT process in cholangiocarcinoma cells by inhibiting ARK5 expression and enhanced the chemosensitivity of cholangiocarcinoma cells to doxorubicin. Therefore, a combined treatment of salinomycin with doxorubicin could be used to enhance doxorubicin sensitivity in patients with cholangiocarcinoma.

ABSTRACT This study aimed to investigate the effect of chronic kidney dysfunction (CKD) on the clinical characteristics of patients with acute coronary syndrome (ACS) and the degree of coronary arterial stenosis. The study enrolled 368 patients with ACS who underwent coronary angiography. Blood glucose, glycated haemoglobin (HbA1c), total cholesterol, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), uric acid (UA), and serum creatinine were examined randomly, and the severity of coronary artery lesions was assessed using the Gensini score. Patients were divided into three groups according to estimated glomerular filtration rate: normal renal function (n = 102), mild renal insufficiency (n = 198), and moderate to severe renal dysfunction (n = 68). The characteristics of patients with coronary artery lesions in the three groups were analysed. Of all patients, 27.7% had normal renal function. In the moderate to severe renal dysfunction group, the majority of patients were women whose average age was older. The ratio of patients with history of hypertension and diabetes mellitus was higher, blood glucose, HbA1c, TG, UA and Gensini score were obviously increased, while HDL-C was significantly decreased; all differences had statistical significance (p < 0.05). Different degrees of CKD occur in patients with ACS. In patients with ACS and CKD, metabolism of glucose and fat are significantly abnormal, and coronary arterial lesions are more serious.

RESUMEN Este estudio se propuso investigar el efecto de la disfunción renal crónica (DRC) sobre las características clínicas de los pacientes con síndrome coronario agudo (SCA), y el grado de estenosis arterial coronaria. El estudio comprendió 368 pacientes con SCA sometidos a angiografía coronaria. La glucosa en sangre, la hemoglobina glicosilada (HbA1c), el colesterol total, los triglicéridos (TG), el colesterol de lipoproteína de baja densidad (LDL-C), el colesterol de lipoproteínas de alta densidad (HDL-C), el ácido úrico (AU), y la creatinina sérica fueron examinados de manera aleatoria, evaluándose la grave-dad de las lesiones de la arteria coronaria mediante la puntuación de Gensini. Los pacientes fueron divididos en tres grupos según el índice de filtración glomerular estimado: función renal normal (n = 102), insuficiencia renal leve (n = 198), y disfunción renal moderada a severa (n = 68). Se analizaron las características de los pacientes con lesiones de la arteria coronaria en los tres grupos. De todos los pacientes, 27.7% tenían función renal normal. En el grupo de disfunción renal moderada a severa, la mayoría de los pacientes eran mujeres cuya edad promedio era mayor. La proporción de pacientes con historia de hipertensión y la diabetes mellitus era mayor; la glucosa en sangre, HbA1c, TG, AU y la puntuación Gensini estaban obviamente aumentados, mientras que el C-HDL estaba significativamente disminuido; todas las diferencias tuvieron significación estadística (p < 0.05). Diferentes grados de DRC ocurren en pacientes con SCA. En pacientes con SCA y DRC, el metabolismo de la glucosa y la grasa son significativamente anormales, y las lesiones arteriales coronarias son más graves.

A 9-year field micro-plot experiment was conducted to investigate the use efficiency, residual effect, and fate of 15N-labelled ryegrass green manure in soil-crop system, so as to offer useful information for reasonable application of green manures on meadow burozem. Results showed that high application rate (600g per plot) of 15N-labelled ryegrass green manure resulted in reduction of percent recovery (PR)15Nplant and PR15Nsoil by 25.0% and 12.8%, respectively, and elevation of percent loss (PL)15N by 31.2%, as compared with low application rate. The 15N utilization and loss could be divided into three phases, i.e., high uptake and fast loss in the first and second growth seasons, low uptake and slow loss in the following four growth seasons, and little change in the last three growth seasons. This suggested that the green manure N had a long residual effect but its loss was faster at early phase, and thus, rational application of green manure was of considerable importance to reduce its N loss while improve its N use efficiency.

We report a previously healthy 29 years old man, presenting with a sudden episode of abdominal pain, mild jaundice, hepatomegaly and ascites. Magnetic resonance imaging study and liver biopsy were compatible with veno-occlusive disease. Incidentally, an ulcerative colitis and portal vein thrombosis were diagnosed. Anticoagulant treatment was started, with good clinical and radiological response. Veno-occlusive disease of the liver must be suspected in cases of liver failure and ascites associated to procoagulant conditions (Rev Méd Chile 2004; 132: 1091-5)