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.
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 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.
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 analyze effects of histone demethylase Jumonji-domaincontaining protein 3 (JMJD3) in macrophages in order to provide a new target for treatment of macrophage-related inflammatory reactions, autoimmune diseases, and organ transplantation rejection.MethodThe related literatures of researches on the effects of JMJD3 in the macrophages in recent years were searched and reviewed.ResultsThe macrophages played the important roles in maintaining tissue homeostasis and host response, clearing pathogens and apoptotic cells, and promoting tissue repair and wound healing. The JMJD3 could regulate the balance of M1 and M2 types of macrophages through the different ways and had different effects on the polarization of M2 macrophages when it was stimulated by the different extracellular substances. In some immune diseases and wound repairing, the JMJD3 could not only promote the inflammatory responses, but also polarize the M2 macrophages so as to inhibit the inflammation and promote the tissue repair. Clinically, the JMJD3 expression might be different in the different diseases and its low or high expression both might be involved in the occurrence of diseases.ConclusionHistone demethylase enzyme JMJD3 is involved in macrophage polarization and expression of inflammatory genes, but there are still many problems that require further to be investigated.
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 Analyze the relationship between Kupffer cells (KCs) and ischemia-reperfusion injury (IRI) during liver transplantation.MethodThe relevant studies in recent years on the KCs in the hepatic IRI during the liver transplantation were collected and summarized.ResultsSome recent studies had shown that both the congenital immunity and adaptive immunity were closely related to the occurrence and development of hepatic IRI and the activation of KCs. The KCs were the resident macrophage of the liver and played the key role in the aseptic inflammatory injury. The KCs could secrete various pro-inflammatory factors to aggravate the liver cell injury. On the other hand, the KCs could also improve the hepatic IRI by upregulating anti-inflammatory factors.ConclusionsHepatic IRI can activate the innate immune system and the adaptive immune system to cause the sterile inflammatory response of damaged liver cells. During hepatic IRI, the activated KCs can secrete pro-inflammatory factors and anti-inflammatory factors to play the dual roles of injury and protection.
ObjectiveTo summarize the individualized diagnosis and treatment experience in a patient with primary pancreatic diffuse large B-cell lymphoma.MethodsBy muti-disciplinary term (MDT) model, a patient with primary pancreatic diffuse large B-cell lymphoma admitted in the People’s Hospital of Chishui in Dec. 2016 was discussed. The diagnosis, perioperative period management, and operation scheme were carried out by the MDT.ResultsThe patient’s general condition was good. After multidisciplinary discussion in the Department of Radiology, Oncology, Interventional, and Hepatobiliary and Pancreatic Surgery, the patient was considered to have surgical indications. After thorough communication with the patient and family, the patient was selected for surgical resection. The whole operation lasted for 5 hours, and the intraoperative blood loss was about 300 mL. The operation was successfully completed and no complications such as pancreatic fistula occurred after operation. Liquid drainage tube was drawn out at 10 days after opertion, and pancreatic tube stent and T tube were retained. The patient discharged on 13 days after surgery. Subsequently, the patient underwent adjuvant chemotherapy. At present, the patient has been followed up for 1 year, no signs of tumor recurrence and metastasis, and continued follow-up.ConclusionsPrimary pancreatic diffuse large B-cell lymphoma is rare and has a poor prognosis. The main treatment is mutli-mode treatment based on surgical resection combined with chemotherapy.
ObjectiveTo summarize the experience of combined treatment of conventional transcatheter arterial chemoembolization (cTACE) and drug-eluting-bead chemoembolization(D-TACE) in a case of advanced hepatocellular carcinoma with intrahepatic metastasis.MethodsA patient with advanced hepatocellular carcinoma who was admitted to The Second Affiliated Hospital of Chongqing Medical University in October 2018 was treated with TACE for three times.ResultsAfter MDT discussion, three interventional operations were performed on this patient in The Second Affiliated Hospital of Chongqing Medical University. CT examination after the first treatment with cTACE showed that lipiodol deposited in liver lesions and the lesions were more stable than before; after the second treatment with cTACE and D-TACE, CT examination showed more lipiodol deposited in the tumors, and the tumors were more limited and significantly reduced; after the third treatment with cTACE, CT examination showed that the tumors were effectively controlled and no progress was made. This patient was followed-up for 2 months after the fourth cTACE, tumors were effectively controlled and no progress occurred.ConclusionsIn advanced hepatocellular carcinoma with intrahepatic metastasis, TACE is the best treatment. Combination of D-TACE and cTACE can achieve better clinical efficacy.
ObjectiveTo elucidate the metabolic characteristics of mitochondria in sepsis and review its cellular mechanism, so as to provide new ideas for the treatment of sepsis. MethodThe previous literatures and latest research results about mitochondrial metabolism during sepsis were reviewed. ResultsAt present, the researchers were not only concerned about the inflammatory response of sepsis, but also concerned about the systemic metabolic disorder caused by sepsis. It was believed that the damage of mitochondria caused by sepsis was one of the main reasons for the disorder of cell metabolism. During the sepsis, the patient’s metabolism had changed, for example, enhancement of aerobic glycolysis, lactic acid accumulation, elevated levels of fatty acids and triglycerides in blood, and so on. ConclusionMetabolic change during sepsis is related to mitochondria, which can provide some new methods for treatment of sepsis.