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Background The tumor inflammatory microenvironment plays a vital role in the initiation and progression of pancreatic cancer (PC). Both the lymphocyte-to-monocyte ratio (LMR) and preoperative peripheral blood monocytes are related to the prognosis of PC patients. However, the direct effect of monocytes on PC cells is not fully understood. The current study aimed to assess the effect of monocytes on PC and explore its potential mechanism. Methods The cutoff value of peripheral blood monocytes was evaluated by the receiver operating characteristic (ROC) curve. Transwell migration and invasion assays were used to detect the mobility of PC cells. The cytokines derived from monocytes were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Western blotting was utilized to assess the expression of epithelial-mesenchymal transition (EMT) related markers. The expression level of Snail in PC tissue was determined by immunohistochemical (IHC) staining. Results A high monocyte count was inversely correlated with lymph node status and 5-year overall survival in PC. The PC cells underwent a cellular morphology change and increased cell motility after coculture with THP-1 monocytes. The THP-1 monocytes secreted various proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1α (IL-1α), which activated the nuclear factor-κB (NF-κB) signaling pathway leading to the upregulation of Snail and thereby promoting the EMT of PC cells. The expression level of Snail correlated significantly with the density of peripheral blood monocytes, and their level status was significantly associated with 5-year overall survival. Conclusions These findings indicated that elevated monocytes counts were a poor prognostic marker in PC, and monocytes could directly induce the EMT process of PC cells by upregulating Snail expression through the NF-κB signaling pathway.

BACKGROUND: The concept of precision medicine to treat cancer shows promise and a co-delivery carrier for chemotherapy drugs and target genes is the key tool for both basic research and clinical application. To address this, we developed a cancer-targeting nanoparticle vector to transfer gemcitabine (Gem) and small interfering RNA (siRNA) to pancreatic cancer. METHODS: Iron oxide nanoparticles (IONPs) resonant at 15 nm were conjugated with the single chain variable fragment (scFv) against CD44v6 (scFvCD44v6), which has proven pancreatic cancer-targeting specificity as reported in our previous study. Gem was then linked through a lysosomally cleavable tetrapeptide linker, resulting in a scFv-targeted nanoparticle construct, which was subsequently conjugated to siRNA targeting the Bmi-1 oncogene (siBmi-1) to obtain the multifunctional nanoparticle scFv-Gem-siBmi-1-NPs. A series of biological experiments were performed to test its biophysical characterization, gene silencing efficacy and anti-tumor effect in vitro and in vivo. RESULTS: The multifunctional nanoparticle not only possesses an ultra-small size of approximately 80 nm, excellent biocompatibility and biodegradability, but also exerts a synergistic anti-tumor effect both in vitro and in vivo, such as inhibition of tumor cell growth, invasion and migration, reduction of cell cycle progression and promotion of tumor apoptosis. Furthermore, this nanoparticle can efficiently target pancreatic cancer in vivo, resulting in the enhanced bioavailability and efficacy of Gem. CONCLUSION: scFv-Gem-siBmi-1-NPs provide an effective and targeted co-delivery of Gem and siBmi-1 to pancreatic cancer, and exert an efficient and corporate anti-tumor therapeutic effect. This prospective vector shows promise for precise treatment of pancreatic cancer.

This paper aims to introduce a new quantitative method for safety admittance of facilities based on G1-variation coefficient method in chemical industrial parks. As is known, at present mass incidents resisting the hazards of chemical facilities were happened in China frequently. In order to alleviate such prominent contradictions, from the perspective of safety admittance of facilities in chemical industrial parks, the judgement criteria and indexes were put forward. Then the subjective G1 method and the objective variation coefficient method were used to determine the weights of criteria and indexes. And the quantitative judgement model was established. At last, an empirical research was conducted. The results show that the judgement criteria and indexes proposed in this paper include four criteria and nine indexes. And the weight of environment bearing is higher based on subjective evaluation, complying with the people's risk perception of chemical facilities’ hazards. While the weights of economic effect and safety management are higher than others based on objective evaluation, in line with the current situation that how chemical industrial parks to choose the suit facilities for entering.

It's important for the safety planning of the chemical industrial park to calculate the safety capacity of the park as chemical industrial parks developed fast in recent decades in our country. This paper defined the safety capacity of chemical industrial park and improved the calculation methods which had been presented. The safety capacity of chemical industrial park could be calculated by using the indictors of the safety capacity (individual risk, social risk and potential risk), in the basic information of the park, such as the production scale of enterprises in the park, layout and the population distribution and so on. The new method presented the concepts of hazardous chemicals equivalent to research the impact of the hazardous chemicals species to the safety capacity. The effect of population distribution will also be considered when calculating the safety capacity. Besides, the domino effect should be discussed to fix the safety capacity of the chemical industrial park when the park is at full load condition. Then, the real safety capacity of the park could be calculated. Finally, the analysis process of the appropriate safety capacity is illustrated with an application example in a certain chemical industrial park.

Summary Background The Child-Pugh score, the model for end-stage liver disease (MELD) score, and the occurrence of cirrhosis-related complications are independent prognostic predictors used in the assessment of chronic liver diseases. Objectives The objectives of this study were to determine the best prognostic scoring system, and to create a combined method to predict the prognosis of liver cirrhosis more accurately. Methods We retrospectively reviewed 435 cirrhotic patients from January 2009 to June 2010 and evaluated their short- and medium-term survival. Child-Pugh, MELD and its advanced scoring systems were computed for each patient. The sensitivity and specificity of these scoring systems were analyzed and their validity was assessed using concordance (c)-statistics in predicting the prognosis of cirrhotic patients. Results Overall, 107 patients died within 6 months and 150 patients died within 1 year. The clinical and biochemical characteristics, cirrhosis-related complications, and the scores were significantly different among the survivors and patients who died. The largest area under the receiver operating characteristic curve was 0.741 for the integrated MELD (iMELD) at 6 months and 0.713 for iMELD at 12 months, indicating that iMELD was the best scoring system tested. Given this result, we created a new scoring system that combined iMELD and an index of cirrhosis-related complications, called iMELD-C. This novel system had c indexes of 0.758 for the 6-month survival and 0.746 for the 1-year survival. Conclusions The iMELD-C score is a better predictor of both short- and medium-term survival in patients with cirrhosis.