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.
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 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 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.
Objective To summarize and evaluate the significance of tumor necrosis factor (TNF) tolerance, and to understand the general characteristics and known molecular mechanisms of different forms of tolerance, including the roles of transcription factors, signaling systems and receptors. Method The relevant literatures at home and abroad in recent years were collected and readed, and the content related to TNF tolerance was summarized. ResultsTNF tolerance could be produced after TNF pretreatment, and be divided into absolute tolerance and induced tolerance. TNF tolerance was related to a variety of interrelated and interdependent intracellular signal transduction. There was cross tolerance between TNF and lipopolysaccharide. Conclusions TNF tolerance may represent a protective mechanism, participating in the termination of inflammation and preventing excessive or persistent inflammation. TNF tolerance may also trigger immune paralysis, leading to severe inflammatory diseases, such as sepsis. The understanding of TNF tolerance can promote the diagnosis of inflammation related diseases or the implementation of treatment methods, so as to achieve more accurate evaluation and treatment.
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide. Although surgery remains the key approach for achieving long-term survival, the majority of patients are ineligible for surgery at the time of initial diagnosis, resulting in suboptimal overall treatment outcomes. This paper reviews the current treatment strategies for HCC, with a particular focus on comprehensive treatment plans centered around surgery. It explores the status and advancements in multidisciplinary treatment approaches, including preoperative conversion therapy, minimally invasive surgery, and postoperative adjuvant therapies. Through the adoption of rational comprehensive treatment strategies, it is anticipated that the therapeutic outcomes and quality of life for HCC patients can be improved.
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 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.
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.