ABSTRACT
Postoperative pancreatic fistula (POPF) is the most common and critical complication after pancreatic body and tail resection. How to effectively reduce the occurrence of pancreatic fistula and conduct timely treatment thereafter is an urgent clinical issue to be solved. Recent research standardized the definition of pancreatic fistula and stressed the correlation between POPF classification and patient prognosis. According to the literature, identification of the risk factors for pancreatic fistula contributed to lowering the rate of the complication. Appropriate management of the pancreatic stump and perioperative treatment are of great significance to reduce the rate of POPF in clinical practice. After the occurrence of POPF, the treatment of choice should be determined according to the classification of the pancreatic fistula. However, despite the progress and promising treatment approaches, POPF remains to be a clinical issue that warrants further studies in the future.
ABSTRACT
Objective:To investigate the role of interleukin-13(IL-13), interleukin-13 receptor α2(IL-13Rα2) and 11 β -hydroxysteroid dehydrogenase 2(11βHSD2) signaling pathway in liver metastasis of colon cancer and its mechanism.Methods:A retrospective case-control study was conducted to analyze the clinical data of 80 patients with colorectal cancer who were operated in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 2015 to December 2018.All patients were followed up by clinic or telephone until August 30, 2019.According to the occurrence of liver metastasis, the patients were divided into metastasis group ( n=22) and non metastasis group ( n=58). Real-time fluorescence quantitative Polymerase Chain Reaction(PCR) and Western blotting were used to detect and compare the mRNA relative expression and protein expression of IL-13, IL-13Rα2, 11βHSD2, cyclooxygenase 2(COX 2) and protein kinase B in cancer tissues and cancer adjacent tissues. Glycyrrhetinic acid, an inhibitor of 11 β HSD2, was used to inhibit the activity of 11hsd2 in human colon cancer cell line HCT-8.The mRNA relative expression and protein expression of IL-13, IL-13Rα2, 11βHSD2, COX 2 and protein kinase B were detected by real-time fluorescence quantitative PCR and Western blotting before and 24 hours after glycyrrhetinic acid addition. Results:The mRNA relative expression of IL-13(0.79±0.11, 0.40±0.10), IL-13Rα2(0.72±0.13, 0.46±0.11), 11βHSD2(0.84±0.26, 0.60±0.08), COX 2(0.70±0.25, 0.37±0.04), protein kinase B (0.76±0.13, 0.42±0.06) in colon cancer tissues of metastatic and non metastatic groups were higher than those in cancer adjacent tissues(0.09±0.01, 0.10±0.06, 0.09±0.02, 0.09±0.03, 0.09±0.01, 0.09±0.02, 0.13±0.02, 0.12±0.07, 0.05±0.02, 0.05±0.03). The difference was statistically significant (t value was 28.36, 23.20, 22.07, 24.88, 16.47, 16.47, 47.86, 18.55, 24.55, 26.20, 44.40, all P<0.001). The protein expression of IL-13(0.48±0.11, 0.32±0.07), IL-13Rα2(0.52±0.11, 0.36±0.11), 11βHSD2(0.63±0.12, 0.48±0.11), COX2(0.45±0.15, 0.27±0.09), protein kinase B(0.50±0.12, 0.29±0.08) in colon cancer tissues of metastatic and non metastatic groups were higher than those in cancer adjacent tissues(0.12±0.02, 0.13±0.01, 0.10±0.02, 0.10±0.02, 0.14±0.06, 0.13±0.05, 0.10±0.03, 0.10±0.04, 0.10±0.03, 0.10±0.02). The difference was statistically significant ( t value were 15.63, 21.15, 17.71, 17.28, 11.01, 18.14, 10.55, 13.12, 15.76 and 18.90 respectively, all P<0.001). The relative expression of mRNA and protein in metastasis group was higher than that in non metastasis group ( t=15.15, 3.01, 8.97, 2.52, 6.34, 2.26, 9.82, 2.52, 16.02, 3.57, respectively, all P< 0.05). Compared with that those of before glycyrrhetinic acid addition, after 24 hours of glycyrrhetinic acid addition, the mRNA relative expression and protein expression of IL-13, IL-13Rα2 had no significant change (all P>0.05), while the mRNA relative expression and protein expression of COX 2 and protein kinase B(before adding: 0.725±0.159, 0.639±0.162, 0.741±0.178, 0.668±0.145, after adding: 0.108±0.085, 0.116±0.048, 0.122±0.063, 0.119±0.066) were decreased( t value were 18.744, 16.954, 17.956, 18.875 respectively , all P<0.01). Conclusion:The activation of IL-13/IL-13α2/11βHSD2 signaling pathway can promote liver metastasis of colon cancer.The mechanism may be that 11βHSD2 over expression promotes cancer cells invasion and migration-related COX2 expression and PI3K/protein kinase B pathway, and promotes liver metastasis of colon cancer.
ABSTRACT
Polyelectrolyte layer-by-layer assembled lipid nanoparticles (NPs) were prepared to improve their stability against lipolysis in gastrointestinal tract, and efficiency of oral absorption of doxorubicin (DOX). The lipid NPs were prepared by hot melt-probe sonication method. The polyelectrolyte layer-by-layer assembled lipid NPs (DOX-NPs/CS/γ-PGA) was prepared by layer-by-layer self-assembling polyelectrolytes cationic chitosan (CS) and anionic poly (γ-glutamic acid) (γ-PGA) on the surface of lipid NPs based on electrostatic interaction. The particle size, polydispersity index (PDI) and zeta potential of lipid NPs and DOX-NPs/CS/γ-PGA were determined by dynamic light scattering (DLS). The in vitro drug release was determined in pH 1.2 HCl solution and pH 6.8 phosphate buffer solution (PBS). The stability of lipid NPs against lipolysis was evaluated in simulated gastrointestinal medium containing lipase. The cellular uptake of lipid NPs and DOX-NPs/CS/γ-PGA was evaluated in Caco-2 cell model. The pharmacokinetic of DOX after oral absorption was studied in SD rats. Results showed that the average particle size and zeta potential of DOX-NPs/CS/γ-PGA were 180.6±5.4 nm and -38.53±0.29 mV, respectively. The DOX-NPs/CS/γ-PGA effectively slowed down the release of DOX from nanoparticles, and decreased the lipolysis of lipid NPs in simulated gastrointestinal medium. The cell study showed that DOX-loaded lipid NPs and DOX-NPs/CS/γ-PGA remarkably enhanced the cell uptake in comparison with DOX solution. The DOX-NPs/CS/γ-PGA significantly improved oral absorption of DOX compared with DOX-loaded lipid NPs. The Cmax, tmax were 0.76±0.25 μg·mL-1 and 0.5 h, respectively; AUC0-24h was 3.02 folds and the relative bioavailability was 302.46% with DOX solution as reference. The stability of lipid NPs against lipolysis and drug release were significantly improved by layer-by-layer assembling, leading to an improved oral absorption.
ABSTRACT
The improvement of the electroosmotic pump properties and the effects of the bi-directional electrostacking system on the pre-concentration factor were investigated.A portable electrokinetic flow analysis system with electroosmotic driving and bi-directional electrostacking unit was introduced.The improved system with graphite furnace atomic absorption spectrometry was employed to separate,pre-concentrate and determine Cr(Ⅵ) and Cd(Ⅱ)in mineral water.The detection limit of Cr(Ⅵ)and Cd(Ⅱ)was 9 ng/L and 10 ng/L(3б of blank,n=11),respectively.Their recoveries of 200ng/L Cr(Ⅵ) and 100ng/L Cd(Ⅱ) added to samples were(105～107)±2% and (104～106)±2%(n=3).