Objective To summarize the role of costimulatory molecules in inducing immune tolerance of organ transplantation. Methods Domestic and international publications online involving costimulatory molecules and immune tolerance in recent years were collected and reviewed. Results The relationship between costimulatory pathways and transplantation immunity has already been clarified in recent years. The main costimulatory molecules alreadly found mainly include B7-CD28/CTLA4, CD40-CD154, 4-1BB/4-1BBL, and ICOS-B7h, etc. Costimulatory pathways com-inhibition or combining with other immunosuppression methods could obtain stable and long lasting immune tolerance. Conclusions With the development of immunology and molecular biology, costimulatory pathways of T lymphocyte activation will be further interpreted. Other new costimulatory molecules will be discovered in the future, which will afford theory evidence for inducing immune tolerance.
ObjectiveTo explore the effect of La-related protein 6 (LARP6) gene on the survival of postoperative patients with gastric cancer, and to explore its relationship with immune cell infiltration.MethodsThe clinical survival information and gene expression information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. The relationship between LARP6 gene expression and clinical characteristics of patients were analyzed. Cox proportion hazard regression model was used to find out the prognostic risk factors of gastric cancer patients, and then Kaplan-Meier plotter database was used to verify. Then the correlation between LARP6 gene expression and immunity was proved by Tumor IMmune Estimation Resource (TIMER) immune database.ResultsIn gastric cancer patients, the expression of LARP6 gene was related to pathological stage, T stage, and N stage (P<0.05), but not related to M stage and sex (P>0.05). Multivariate Cox proportion hazard regression analysis showed that age [HR=2.022, 95%CI was (1.287, 3.176), P=0.002] and LARP6 gene expression [HR=1.176, 95%CI was (1.070, 1.293), P<0.001] were prognostic factors. Further verified by Kaplan Meier plotter database, the results also showed that the overall survival (OS) and progression-free survival (PFS) of gastric cancer patients with high expression of LAPR6 gene were worse than those with low expression of LARP6 gene (P<0.001). TIMER database was used to explore the correlation between the expression level of LARP6 gene and immune cell infiltration in patients with gastric cancer, and the results showed that the expression level of LARP6 gene in gastric cancer patients was positively correlated with the infiltration number of CD4+ T cells and macrophage cell (P<0.001). Log-rank results showed that infiltration number of macrophage cell and LARP6 gene expression were risk factors for clinical prognosis of gastric cancer patients (P<0.05).ConclusionsMacrophage cell andcell and LARP6 gene expression are risk factors for gastric cancer patients. LARP6 may be a new target for the treatment of gastric cancer.
ObjectiveCombined with long non-coding RNA (lncRNA) to find a regression model that can be used to predict the survival rate of patients with colon cancer before operation.MethodsThe clinical information and gene expression information of patients with colon cancer were downloaded by using TCGA database. The differentially expressed lncRNAs in tumor and paracancerous tissues were screened out, and then combined with the clinical information of patients to construct Cox proportional hazard regression model.ResultsA total of 26 kinds of lncRNAs with statistical difference in gene expression between paracancerous tissues and tumor tissues were selected (P<0.05). Through repeated screening and comparison of prediction efficiency, the prediction model was finally selected, which was constructed by patients’ age, M stage, N stage, and three kinds of lncRNAs (ZFAS1, SNHG25, and SNHG7) gene expression level: age [HR=4.00, 95%CI: (1.48, 10.84), P=0.006], M stage [HR=3.96, 95%CI: (2.23, 7.04), P<0.001], N stage [HR=1.87, 95%CI: (1.24, 2.84), P=0.003], ZFAS1 gene expression level [HR=0.60, 95%CI: (0.41, 0.86), P=0.006], SNHG25 gene expression level [HR=0.85, 95%CI: (0.73, 1.00), P=0.045], and SNHG7 gene expression level [HR=2.32, 95%CI: (1.53, 3.52), P<0.001] were all independent risk factors for postoperative survival of patients with colon cancer. The area under the ROC curves for predicting 1, 3, and 5-year overall survival were 0.802, 0.828, and 0.771, respectiely, which had a good prediction ability.ConclusionThe predictive model constructed by the combination of ZFAS1, SNHG25, SNHG7 genes expression level with M stage, N stage, and age can better predict the overall survival rate of patients before operation, which can effectively guide clinical decision-making and choose the most suitable treatment method for patients.
ObjectiveTo construct a new model for predicting the overall survival rate of gastric cancer and to guide the clinical work.MethodsThe clinical information and gene expression information of patients with gastric cancer were downloaded through The Cancer Genome Atlas (TCGA) database. The clinicopathologic characteristics and gene expression information affecting the overall survival rate of gastric cancer patients were screened by univariate COX regression and Lasson regression, then the predictive model was constructed by multiple COX regression model, and the predictive model was tested by receiver operating characteristic curve, calibration curve and decision curve analysis curve. The effect of genes included in the predictive model on the overall survival rate of patients with gastric cancer was discussed, and the predictive model diagram was drawn.ResultsThrough repeated screening and comparison of the model, the patient’s age, T stage, N stage, M stage and 12 genes (INCENP, IGHD3-16, ITFG1-AS1, NEK5, MATN3, YWHABP2, SYT12, LINC01210, ZNF385C, LINC01980, CYMP-AS1 and FAT3) were included in the predictive model. The prediction ability of this model was close to or more than 80%, which was significantly higher than that of the traditional TNM staging prediction system. All the indexes included in the model were significantly different by univariate and multivariate COX regression analysis（P<0.05）, and the 12 genes included were the risk factors affecting the overall survival rate of gastric cancer.ConclusionThe gastric cancer prediction model constructed by combining clinical characteristics and genomics has good predictive ability and can guide clinical work.
ObjectiveTo elucidate the mechanism of multiple organs dysfunction (MOD) during acute obstructive cholangitis (AOC). MethodsThe reports about MOD and AOC in recent 10 years were collected and reviewed.ResultsApplicable animal models of AOC were established. During AOC, the decrease of Kupffer cells (KCs) phagocytic function and clearance function, hepatocyte mitochondrion damage, the effect of KCs on protein synthesis of hepatocytes and activation of KCs by endotoxin played an important role in the pathogenesis of MOD. ConclusionThe mechanism of pathogenesis of MOD during AOC is complicated and the changes of KCs functions is one of major factors.
ObjectiveThe present study was to investigate the value of multi-disciplinary team (MDT) model in patient with primary giant liver cancer.MethodsThe MDT model was carried out for a BCLC B stage patient who admitted in the Second Affiliated Hospital of Chongqing Medical University in July 2018. The associated references were reviewed and the treatment methods were discussed about primary giant liver cancer.ResultsAn elder man who was diagnosed as primary hepatocellular carcinoma (minor cancer) in right lobe of the liver in three years ago and took Chinese medicine orally. When the patient subsequent visited this time, the liver cancer increased about 10 cm. After discussed by MDT, the treatment method was draw up to transarterial chemoembolization (TACE) plus surgery. After received twice TACE therapies in the later 14 weeks, the tumor in right lobe had significantly shrinked and left lobe enlarged. The patient underwent laparoscopic right liver hepatectomy after the second MDT discussion in 5 months later. The patient underwent operation successfully. The operation lasted for 270 minutes, and the intraoperative blood loss was about 500 mL. The suspended red blood cells (400 mL) was infused. The patient underwent transient liver failure and recovered through hepatoprotective and symptomatic supportive treatment, and discharged on 12 days after operation. A retrospective examination of abdominal CT at 4 months postoperatively revealed a significant hyperplasia of the left lobe of the liver, and there was no sign of recurrent tumor. The patient was continue to followed up.ConclusionsThepatient with primary giant hepatocellular carcinoma who cannot underwent surgery at the first time can received TACE, and a few patients could be underwent radical operation later. MDT should be applied flexibly in the treatment of patients with huge hepatocellular carcinoma from beginning to end, so the best treatment plan should be carried out for patients.
ObjectiveTo summarize the related researches of pancreatic portal hypertension (PPH) in recent years in order to diagnose and treat the disease more timely and effectively. MethodThe literatures relevant to etiology, mechanism, clinical features, diagnostic criteria, and treatment of PPH were searched and reviewed. ResultsThe occurrence of PPH was related to its anatomical structure. Its clinical manifestations were not characteristic, but it was not difficult to diagnose by the assistance of auxiliary examinations. The treatment of PPH was mainly targeted at pancreatic diseases and portal hypertension, and the treatment targeted at portal hypertension was performed according to the situation with or without gastrointestinal bleeding. So, in clinical practice, different treatment measures should be taken according to different situations. ConclusionAt present, the clinical diagnosis and treatment of PPH is relatively mature, but its preventive treatment is still controversial, which will be the focus of future research.
ObjectiveTo understand the interplay between tumor-associated macrophages (TAMs) and T lymphocytes, as well as the effect on the pathogenesis of hepatocellular carcinoma (HCC) again, so that providing new ideas and methods for the immunotherapy of HCC.MethodSearched the literatures about the interplay between TAMs and T lymphocytes in HCC to analyze and summarize the relationship between TAMs and T lymphocytes in HCC.ResultsWhile TAMs and T lymphocytes themselves regulate the process of tumorigenesis and development, they also had a mutual regulatory mechanism to further promote the development of HCC.ConclusionsThere is an interaction between TAMs and T lymphocytes, and this interaction forms a vicious circle to a large extent and promotes the development of HCC. Recognizing and making rational use of this interaction can provide new ideas and methods for the future immunotherapy of HCC.
ObjectiveTo investigate activation of phosphatidylinositol 3 hydroxykinase (PI3K)/AKT pathway and sphingosine 1-phosphate receptor 2 (S1PR2) in peripheral blood mononuclear cells (PBMCs) of acute obstructive cholangitis (AOC) rats and their effects on systemic inflammation in rats.Methods① In vitro experiment: The isolated PBMCs from the rats were divided into 4 groups: a control group, LY294002 treatment group, lipopolysaccharide (LPS) treatment group, and LPS+LY294002 treatment group. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the supernatant were detected and the phosphorylation levels of PI3K and AKT and protein level of S1PR2 in the PBMCs were detected. ② In vivo experiment: The rats were randomly divided into four groups: a control group, LY294002 treatment group, AOC model group, and AOC+LY294002 treatment group. The survival rate of rats was recorded, the liver function (ALT, AST, and TBIL), TNF-α, and IL-6 levels in the serum were detected. The phosphorylation levels of PI3K and AKT and protein level of S1PR2 in the PBMCs of the rats were detected. Results① The results of in vitro experiment: The levels of TNF-α and IL-6 in the LPS+LY294002 treatment group were significantly lower than those in the LPS treatment group (P<0.050). The phosphorylation levels of PI3K and AKT and protein level of S1PR2 in the LPS+LY294002 treatment group were significantly lower than those in the LPS treatment group (P<0.050). ② The results of in vivo experiment: The survival rate of rats in the AOC+LY294002 treatment group was higher than those in the AOC group. The serum levels of ALT, AST, TBIL, TNF-α, and IL-6 in the AOC+LY294002 treatment group were significantly lower than those in the AOC model group (P<0.050). The phosphorylation levels of PI3K and AKT and protein level of S1PR2 in the AOC+LY294002 treatment group were significantly lower than those in the AOC model group (P<0.050).ConclusionInhibition of activation of PI3K/AKT pathway in PBMCs can inhibit expression of S1PR2, then alleviate systemic inflammatory response induced by AOC in rats.
ObjectiveTo summarize the relationship between integrins, tumor metabolism, and tumor cells with pancreatic stellate cells in the tumor microenvironment, in order to provide targets and ideas for the treatment of pancreatic ductal adenocarcinoma.MethodTo review the literatures on pancreatic stellate cells, integrins, and amino acid metabolism as therapeutic targets for pancreatic ductal adenocarcinoma in the domestic and overseas.ResultsThe drug research for pancreatic ductal adenocarcinoma was currently under vigorous development, but remain in the animal and clinical test stage. As a new therapeutic protein, ProAgio could inhibit the expression of integrin αvβ3, activation and secretion of pancreatic stellate cells, and alanine metabolism in the microenvironment of pancreatic ductal adenocarcinoma, so as to achieve the dual effects of anti-fibrosis and anti-tumor.ConclusionsThe roles of activated pancreatic stellate cells, ProAgio, integrin αvβ3, and alanine metabolism in pancreatic ductal adenocarcinoma have been partially elucidated, but the specific mechanism still needs further investigation and may become a completely new therapeutic target someday.
