Objective To compare the effectiveness and safety of different concentrations of elastin-like polypeptides (ELP) as novel submucosal injection material for endoscopic submucosal dissection.Methods Forty healthy New Zealand white rabbits were randomly divided into two groups (n=20).The first group by submucosal injection of different drugs were randomly divide into five groups (n=4).Four concentrations of 50 ku ELP (0.05,0.025,0.012 5,0.005 g/ml) were used separately in each group,while glycerin fructose was used for control group.Each solution (2 ml) was injected into the submucosa through the resected margin,the increase of mucosal thickness and surface changes were observed and recorded at 0,5,10,and 30 min.The subgroup by submucosal injection of different drugs were randomly divide into five groups (n=4).The injection pressure of each solution (2 ml) with the 25-gauge needle was calculated by a manometer,which was connected between the needle and syringe.Results The submucosal uplift heights in groups using the 0.05 g/ml ELP and 0.025 g/ml ELP injection were significantly thicker than that of glycerin fructose (P＜0.05),the 0.012 5 g/ml ELP and glycerin fructose injection showed no significant difference (P＞0.05),whereas the uplift height in glycerin fructose group was thicker than that of the 0.005 g/ml ELP (P＜0.05).The injection pressure correlated with the ELP concentration.The injection pressures of 0.05,0.025,0.012 5,0.005 g/ml ELP solutions were (332±36) kPa,(223±24) kPa,(174±22) kPa and (142±19) kPa,respectively,and that of glycerin fructose was (269±17) kPa.The 0.025 g/ml ELP solution was easily injected into the porcine stomach to create submucosal uplift.The injection pressure of the 0.025 g/ml ELP solution showed significantly lower value compared with that of glycerin fructose (P＜0.05).Conclusions ELP might be a promising agent for submucosal injection for endoscopic submucosal dissection (ESD),and 0.025 g/ml ELP might be efficient concentration for maintaining mucosal elevation,injection pressure and safety.

Objective To explore the mechanisms of mesenchymal stem cells (MSC) in the treatment of concanavalin A (ConA)-induced acute immune liver injury in mice.Methods MSC were isolated and cultured from bone of the four limbs of three-week-old C57BL/6 mice.The specific surface markers were identified and osteogenic,adipogenic differentiation ability were tested.A total of 15 six to seven-week old C57BL/6 mice were divided into control group,MSC treatment group and phosphate buffer saline (PBS) treatment group,five mice in each group.The mice of MSC treatment group was injected through tail firstly with ConA and then MSC,PBS treatment group was injected through tail firstly with ConA and then PBS,control group was injected through tail with PBS twice.The mice were sacrificed in 14 to 16 hours after injection.The level of alanine aminotransferase (ALT),aspartate transaminase (AST) in peripheral blood were detected and the pathological change in liver tissue was scored by Knodell score system.Activation rate of splenic CD4+ T cells and the proportion changes of T hepler cell (Th)1,Th2,Th17 and regulatory T cells (Treg) were detected by flow cytometry and the ratio of Th17/Treg was calculated.The levels of tumor necrosis factor α (TNF-α),interferon (IFN)-γ and interleukin (IL)-4 in peripheral blood were detected by enzyme linked immunosorbent assay (ELISA).Independent-sample t test was used for comparison between groups of measurement data.Results ALT,AST and Knodell score of MSC treatment group was (174.2± 46.9) U/L,(185.6± 71.6) U/L and 3.4±1.3,respectively,which were better than those of PBS treatment group ((647.0± 118.0) U/L,(749.0± 104.0) U/L and 5.2 ±0.8,respectively),and the differences were statically significant (t =8.33,9.98 and 2.55,all P＜0.05).The activation rate of splenic CD4+ T cell of PBS treatment group was (26.10±2.17) ％,the proportion of Th1 and Th2 in CD4+ T cell was (5.81±0.79) ％ and (5.98± 1.22)％,the ratio of Th17/Treg was 0.29±0.03,the levels of TNF-α,IFN-γ and IL4 in peripheral blood were (1 281.95±88.61) U/L,(1 838.66±196.91) U/L and (1 192.36±163.94) U/L,which were higher than those of control group ((13.74±1.59)％,(1.35±0.17)％,(2.13±0.17)％,0.15± 0.05,(21.71±2.50) U/L,(11.84±1.28) U/L and (24.46±3.96) U/L),and the differences were statistically significant (t=10.26,12.37,7.02,5.30,31.79,15.93 and 20.75,all P＜0.01).There was no statistically significant difference in the activation rate of splenic CD4+T cell between MSC treatment group and PBS treatment group ((26.20±3.09)％ vs (26.10±2.17)％,P＞0.05).However,in MSC treatment group,the proportion of Th1 and Th2 in CD4+ T cell ((1.83±0.52) ％ and (2.75±1.06％)),the ratio of Th17/Treg (0.18±0.02) and the levels of TNF-α,IFN-γ and IL-4 in peripheral blood ((760.71± 73.19) U/L,(742.49±76.46) U/L and (825.76±101.74) U/L) significantly decreased compared with those of PBS treatment group,and the differences were statistically significant (t=9.45,4.48,6.41,10.14,5.56 and 10.22,all P＜0.01).There was no significant difference in the ratio of Th17/Treg between MSC treatment group and control group (P＞0.05).Conclusions The therapeutic effects of MSC on ConA induced acute immune liver injury were through influence splenic CD4+ T cell subsets by decreasing the proportion of Th1 and Th2 and then declining the levels of secreted cytokines such as TNF,IFN-γ and IL-4 in peripheral blood,increasing the proportion of Treg and decreasing the proportion of Th17 and keeping the balance of Th17/Treg.

Prostate cancer is the most common cancer among men and the fifth leading cause of cancer-related death among men worldwide. Gastrin-releasing peptide receptor (GRPR) is an important complementary target of prostate specific membrane antigen (PSMA) and a key target for prostate cancer diagnosis and treatment. Radionuclide labeled bombesin (BBN) analogues can accurately target overexpressed GRPR in tumor cells, thus providing early diagnosis and treatment of prostate cancer. In this review, we focus on the studies of 99Tc m, 111In, 68Ga, 64Cu, 18F, and 177Lu nuclide-labeled BBN analogues for diagnosis and peptide receptor radionuclide therapy.

Objective This study aimed to explore the expression trends of innate immune cells and immune-checkpoint molecules validated by data calculation in the process of oral mucosal carcinogenesis,as well as to explore methods of suppressing oral mucosal carcinogenesis based on immunotherapy by predicting their interactions.Me-thods 1)The cancer genome atlas(TCGA)database comprehensively scores immune cells and immune-checkpoint molecules in the process of oral mucosal carcinogenesis and screens out intrinsic immune cells and immune-check-point molecules that interfere with tumor immune escape.2)Clinical patient blood routine data were collected for the statistical analysis of peripheral blood immune cells during the progression of oral mucosal carcinogenesis.Immune cells in peripheral blood that may affect the progression of oral mucosal carcinogenesis were screened.3)Immunohis-tochemical staining was performed on intrinsic immune cells and immune-checkpoint molecules validated based on da-ta calculation in various stages of oral mucosal carcinogenesis.4)Special staining was used to identify innate immune cells in various stages of oral mucosal carcinogenesis based on data-calculation verification.5)Survival analysis was conducted on intrinsic immune cells and immune-checkpoint molecules validated based on data calculation during the process of oral mucosal carcinogenesis.The association of intrinsic immune cells and immune-checkpoint molecules with the prognosis of oral squamous cell carcinoma was verified.Results The expression of monocytes and neutro-phils increased during the process of oral mucosal carcinogenesis.The expression of eosinophils showed a single peak trend of up and down.The expression of mast cells decreased.In the process of oral mucosal carcinogenesis,the ex-pression of the immune-checkpoint molecules cytotoxic T-lymphocyte-associated protein 4(CTLA4)and programmed cell death-ligand(PD-L1)increased.The expression trends of monocytes,neutrophils,and eosinophils were positively correlated with those of CTLA4 and PD-L1 immune-checkpoint molecules.The expression trend of mast cells was negatively correlated with the expression of CTLA4 and PD-L1.Monocytes,neutrophils,and eosinophils may pro-mote tumor immune escape mediated by CTLA4 and/or PD-L1,thereby accelerating the progression of oral mucosal carcinogenesis.Mast cells may inhibit tumor immune escape mediated by CTLA4 and/or PD-L1,delaying the progres-sion of oral mucosal carcinogenesis.Conclusion Therefore,interference with specific immune cells in innate immu-nity can regulate the expression of CTLA4 and/or PD-L1 to a certain extent,inhibit tumor immune escape,and delay the progression of oral mucosal carcinogenesis.