Objective:To comparatively observe the effects of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on the Lewis lung cancer mice and to explore the mechanisms of Rg3 and PEG-PLGA-Rg3 nanoparticle anti-cancer in vivo.Methods:Lewis lung cancer mouse model was established and 60 mice were randomly divided into 5 groups with twelve in each group:PEG-PLGA-Rg3 nanoparticles group (Rg3-N),PEG-PLGA group (PEG),Rg3 group (Rg3 ),normal control group (C),saline control group(NS),and received intragastric administration for 1 4 days.The weights of the mice were measured every 2 days and the weight curves were obtained.At the same time,the color pattern,activity and men-tal status were observed.The mice were sacrificed when the administration was over,and the effects of 20 (R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on tumor weight,and the tumor:weight ratios were analysed.In addition,the tumor microvessel density (MVD)was measured by immunohistochemi-cal staining with anti-CD31 antibody to compare the effects of Rg3 and PEG-PLGA-Rg3 nanoparticles on the tumor angiogenesis in vivo.Furthermore,the levels of such angiogenesis and proliferation factors as MMP-9,HIF-1 α,VEGF,Ki-67 were examined by RT-PCR,Western blot and immunohistochemistry to explore the internal molecular mechanisms of anti-tumor effects in vivo.Results:The trends of variation of the mice weights in NS group and PEG group were rising early but declining later.In contrast,the trends of the other three groups were rising early and became stable later.In comparison with NS group, the mice of Rg3 group and Rg3-N group had better general status:brighter color,more active and better spirit.Compared with NS group,the tumor weight in PEG group,Rg3 group and Rg3-N group showed no significant difference but the tumor:weight ratio and MVD in Rg3 group and Rg3-N group declined signi-ficantly (P <0.01 ).Besides,there was no significant difference between Rg3 group and Rg3-N group. At the same time,the level of VEGF mRNA,the protein expression of MMP-9,HIF-1 α,VEGF in Rg3 group and Rg3-N group decreased compared with NS group.Furthermore,the level of each index above-mentioned in Rg3-N group was lower than that in Rg3 group.The expression of Ki-67 in PEG group,Rg3 group and Rg3-N group showed no significant difference compared with NS group.Conclusion:Rg3 and PEG-PLGA-Rg3 nanoparticle may suppress the expression of VEGF,MMP-9 and HIF-1 αin Lewis lung cancer mice,thereby indirectly contributing to their antitumor effects and alleviating the mice’s general status.In addition,PEG-PLGA nanoparticles embedding can promote Rg3 antitumor effect in vivo.

Objective The risk of current pancreaticojejunostomy is carefully considered from the perspective of the morphology of remnant pancreas,and we aimed to discuss the clinical outcomes of selecting different pancreaticojejunostomy techniques based on pancreatic morphology.Methods This was a prospective cohort study.The histopathology of remnant pancreatic tissues was categorized into four types based on preoperative radiological images and intraoperative palpation:Type Ⅰ:pancreas with hard texture in palpation,pancreatic atrophy,dilated pancreatic duct larger than 5 mm and remnant pancreatic surface ＜3 cm;Type Ⅱ:pancreas with hard texture in palpation,pancreatic atrophy and mild dilatation of pancreatic duct with the diameter of 3-5 mm and remnant pancreatic surface ＜3 cm;Type Ⅲ:pancreas with slightly hard texture,no atrophy,and normal or slightly dilated pancreatic duct with the diameter of 3-5 mm and remnant pancreatic surface ≥3 cm;Type Ⅳ:pancreas with soft texture,normal morphology and pancreatic duct.Results From January 2008 to August 2017,116 consecutive patients underwent pancreaticoduodenectomy in our center.Among them,10 patients with type Ⅰ underwent classic pancreatic ductal mucosa to mucosa anastomosis.19 patients with type Ⅱ underwent classic end to end invaginated pancreaticojejunostomy.45 patients with type Ⅲ underwent classic end to end invaginated pancreaticojejunostomy with overlapping U sutures;42 patients with type Ⅵ underwent total invaginated pancreaticojejunostomy.The post-operative pancreatic fistula occurred in 6 patients (5.2％) with one patient died.Postoperative bleeding occurred in 10 patients (8.6％),and gastroparesis occurred in 22 patients (19.0％).Overall complication rate was 33.6％.Conclusions Classification of pancreatic morphology based on preoperative radiological images and intraoperative palpation and the selection of corresponding pancreaticojejunostomy technique is theoretically rational and has the advantage of potentially reducing the risk of remnant pancreatic tissue.

Pancreatic ductal adenocarcinoma (PDA) organoids are 3D cultured from patient-derived stem cells or progenitor cells in vitro. PDA organoids have a variety of cell types, can realize structural self-organization through cell self-renewal, and are similar to the cells in the body of the original organ function in vivo biological bank. PDA organoids can be derived from surgical or biopsy tissue. The ability to build organoids from biopsy will facilitate the sampling of a larger population of PDA patients. Repeated sampling of patients can track the entire progression of the disease longitudinally. Compared with the traditional 2D cell culture and patient-derived xenotransplantation models, the three-dimensional culture of PDA organoids has the characteristics of short time and high success rate, and can be cryopreserved and maintain the stability of genetic traits. Organoids that can simulate diseases can be used as an alternative drug testing system. Using it for drug testing can not only better reflect the patient's response to drugs, but also can reduce the number of animal experiments. Moreover, when using organoids for testing, there is no need to understand the underlying molecular mechanism a priori, and chemical sensitivity testing can be performed directly, thereby shortening the testing time. In this paper, the advantages and disadvantages of different PDA organoids 3D culture methods and the verification methods for the stability and invasiveness of PDA organoids were reviewed. The mechanism of PDA organoids used for tumor chemotherapy drug sensitivity screening was discussed, and the application prospects and challenges of tumor biology in patient individualized treatment and precision medical treatment were discussed.

Objective : To investigate the effects of milk derived pentapeptide prolin⁃glycine⁃proline⁃isoleucine⁃pro⁃ line ( PGPIP) on chronic alcoholic liver injury in mice and its related molecular mechanism . Methods : Forty C57BL/6 mice were randomly divided into control group , model group , glutathione(GSH) group , PGPIPN group .The mice model of chronic alcoholic fatty liver was established by 10 d ad libitum oral feeding with the Lieber⁃DeCarli(LD) ethanol liquid diet plus one binge . Drug intervention was given at the same time . Based on the reported RNA sequencing data in gene expression omnibus (GEO) database , the differential expression of liver endoplasmic reticulum stress⁃related genes was analyzed by cluster heat map . Liver hematoxylin⁃eosin (HE) staining was used to analyze the pathological effects of each treatment group on alcoholic liver injury in mice . Oiled Red O staining was used to analyze the effects of each treatment group on the accumulation of liver lipid droplets in mice . Transtransduction protein expression was detected by Western blot . Results : The pathological examination of PGPIP group was similar to that of Control group , and the liver injury of mice was significantly reduced . The accumulation of lipid droplets in the liver of mice in the model group was manifested as mixed lipid droplets of different sizes , and PGPIP treatment significantly reduced the accumulation of liver lipid droplets induced by alcohol . PGPIP had significant effects on the PERK⁃eIF2α⁃ATF4 pathway and the expression of transcriptional activator 6 ( ATF6 ), Cleaved Caspase 3 protein . Conclusion Pentapeptide PGPIP can alleviate chronic alcoholic fatty liver and liver injury in mice . The mechanism may be attributed to reducing the accumulation of lipid droplets in hepatocytes , en⁃ doplasmic reticulum stress , and hepatocyte apoptosis .