Objective To investigate the immunological rejection after hepatocyte transplantation for acute liver failure （ALF） in mice．Methods The hepatocytes were isolated from pig，BALB/c and C57BL/6 mice livers were conducted and then transplanted into C57BL/6 mice．CCl4 was used to make ALF mice model．The experimental animals were randomly divided into three groups， including syngenic group，allogeneic group，and xenogenic group．The survival statuses of all the mice were recorded. The alteration of T lymphocyte subsets，immune globulin，and cytokine were determined．Results ①The survival ratio was 8/10，6/10， and 3/10 in the syngenic group， allogeneic group， and xenogenic group， respectively．The survival ratio in the syngenic group was significantly higher than that in the other two groups （P＜0.05）．②The CD4+ and CD8+ T cells of the peripheral blood in the syngenic group did not change significantly on week one after transplantation．The CD4+ T cells in the allogeneic group reached the peak on day 3 after hepatocyte transplantation （P＜0.05）， while CD8+ T cells did not change much in one week．The CD4+ and CD8+ T cells in the xenogenic group increased and reached the peak on day 3 after transplantation （P＜0.05）．③There were no significantly differences of IgM and IgG in the syngenic group among 0.5， 1， and 3 d after transplantation. IgM of the allogeneic group and xenogenic group reached the peak on day 1 （P＜0.05） and IgG reached the peak on day 3 （P＜0.05） after transplantation．④The concentrations of IFN-γ， TNF-ɑ， and IL-2 in the allogeneic group and xenogenic group were significantly higher than those in the syngenic group （P＜0.05）．The concentration of IL-6 of the xenogenic group was higher than that of the other two groups （P＜0.05）. Conclusions CD4+ and CD8+ T cells play an important role in immune response to both allogeneic and xenogenic hepatocyte transplantation， as well as induce humoral immune response early after hepatocyte transplantation．
ObjectiveTo investigate the efficacy, safety, and problems of immune checkpoint inhibitors (ICIs) and their combination with other therapies in treatment of patients with advanced hepatocellular carcinoma (HCC).MethodThe relevant literatures on the clinical trials of ICIs and their combination therapy in patients with advanced HCC in recent years were collected and reviewed.ResultsThe therapeutic effects of programmed death receptor 1 and its ligands and cytotoxic T lymphocyte associated antigen 4 monoclonal antibodies in clinical trials of patients with advanced HCC were better, but the therapeutic effect of single drug was limited. Double immunotherapy and its combination with anti-angiogenesis inhibitors, molecular targeted drugs, and local therapy might make patients achieve more remarkable therapeutic effects, especially in combination with anti-angiogenesis inhibitors.ConclusionICIs could remarkably improve survival prognosis of patients with advanced HCC, combined immunotherapy has better survival benefits.
Objective To summarize advances in the application of machine learning in the diagnosis and treatment of liver disease. Method The recent literatures on the progress of machine learning in the diagnosis, treatment and prognosis of liver diseases were reviewed. Results Machine learning could be used to diagnose and categorize substantial liver lesions, tumourous lesions and rare liver diseases at an early stage, which could facilitate clinicians to take timely and appropriate treatment measures. Machine learning was helpful in informing clinicians in choosing the best treatment decision, which was conducive to reducing medical risks. It could also help to determine the prognosis of patients in a comprehensive manner, and provide assistance in formulating early rehabilitation treatment plans, adjusting follow-up strategies and improving future prognosis. Conclusions Multiple types of machine learning algorithms have achieved positive results in the clinical application of liver diseases by constructing different prediction models, and have great potential and excellent prospects in multiple aspects such as diagnosis, treatment and prognosis of liver diseases.
Objective To investigate the changes of indocyanine green retention rate at 15 minutes (ICGR15) of autologous peripheral blood CD34+ hematopoietic stem cells transplantation in end-stage liver disease (end-stage liver, disease, ESLD) patients with different Child-Pugh grades during before and after transplantation of 3, 6, 12, 36, and 60 months. Methods The CD34+ hematopoietic stem cells transplantation were performed in 60 cases of advanced liver cirrhosis with different Child-Pugh grades who were ineffectively treated with strictly conservative treatment and complied with the criterion of liver transplantation. The ICGR15 were performed before transplantation and in 3, 6, 12, 36 and 60 months after transplantation. And the results of each time point in each Child-Pugh classification group were compared, and the rate of change of ICGR15 value were compared between each Child-Pugh classification group. Results The ICGR15 values of the Child-Pugh grading groups all decreased with time. In Child A group, there were respectively significant differences between the 6 months, 12 months, 36 months, and 60 months groups after transplantation and preoperative and 3 months groups after transplantation (P<0.05), but there was no significant difference between preoperative and 3 months group after transplantation (P>0.05), and there was significant difference between the 12 months and the 60 months group after transplantation (P<0.05). As same as Child A group, there were also significant differences between that time groups in the Child B group (P<0.05), but there were also significant differences between the 3 months group after transplantation and preoperative (P<0.05), and there were respectively significant differences between the 6 months and 12 months, 36 months, and 60 months group after transplantation in the Child B group (P<0.05). Also in the Child C group, there were significant differences between that time groups (P<0.05), but there was no significant difference between preoperative and 3 months group after transplantation (P>0.05), and there were respectively significant differences between the 6 months and 12 months, 36 months, and 60 months group after transplantation (P<0.05). There was no significant difference in the rate of ICGR15 between Child-Pugh classification groups. Conclusion Autologous peripheral blood CD34+ hematopoietic stem cells transplantation can effectively improve the liver function reserve capacity of ESLD patients and improve the safety of operation for a long time.
ObjectiveTo summarize mechanism of DNA methylation and histone methylation in liver fibrosis.MethodThe literatures on the DNA methylation and histone methylation during the liver fibrosis were reviewed and analyzed.ResultsThe DNA methylation and histone methylation were the important components of epigenetics. The up-regulation or down-regulation of genes during the liver fibrosis leaded to the activation or inactivation of the subsequent pathways. For example, the PTEN, SEPT9, Smad7, etc. were hypermethylated and the expressions were decreased in the liver fibrosis. The Spp1 was hypomethylated and the expression was increased in the liver fibrosis.ConclusionsMethylation affects expression of genes by altering epigenetics of genes. Systematic and in-depth study of role and mechanism of methylation in liver diseases provides a new direction and locations for some target treatments for liver disease.
Objective To investigate the appropriate indication about removing abdominal drainage after pancreaticoduodenectomy. Method The clinical data of 156 patients who underwent pancreaticoduodenectomy in our hospital from January 2014 to June 2016 were analyzed retrospectively. The patients were divided into two groups, with 76 patients in the enhanced recovery after surgery (ERAS) group and 80 patients in the control group according to the type of indications about removing abdominal drainage. The time of removing abdominal drainage, hospital stay, incidence of postoperative complications, and readmission rate during 30 days after surgery were compared between the2 groups. Results Compared with the control group, the time of removing abdominal drainage 〔(6.2±2.5) dvs. (10.8±2.2) d,P<0.001〕and hospital stay〔(11.8±3.4) dvs. (15.7±3.6) d,P<0.001〕 of the ERAS group were both shorter, incidence of abdominal infection was lower〔1.3% (1/76)vs. 10.0% (8/80), P=0.020〕 , but there was no significant difference in the incidence of postoperative pancreatic fistula 〔18.4% (14/76) vs. 21.3% (17/80)〕 , delayed gastric emptying〔1.4% (1/76) vs. 7.5% (6/80)〕 , and the readmission rate during 30 days after surgery〔5.3% (4/76) vs. 3.8% (3/80)〕 , P>0.05. Conclusions Indications about removing abdominal drainage after pancreaticoduodenectomy by authors are safe.
Objective To summarize the feasibility and safety of the islet cells co-transplantation with bone marrow mesenchymal stem cells (BMSCs) in the treatment of diabetes. Methods The latest progress and new achievements of islet cells transplantation and BMSCs transplantation in treatment of diabetes in the world were analyzed and reviewed. Results At present, the pancreas transplantation and the islet cells transplantation were mainly treatments for diabetes, the pancreas transplantation had disadvantages of large trauma and high mortality; the islet cells transplantation was safe, but had disadvantages of strong rejection, and the survival time of islets cells were short which affected the treatment effect of diabetes. The BMSCs co-transplanted with the islet cells could prolong the survival time of islet cells and could alleviate the rejection in body, so the co-transplantation can be more effective in treatment of diabetes. Conclusion The BMSCs co-transplant with the islet cells could reduce the rejection in vivo, reduce the inflammation in vivo, prolong the survival time of islet cells, extend the time of normal glucose, which may become the new treatment method for the diabetes.
ObjectiveTo evaluate the 3-year follow-up results of allogeneic islets combined with autologous peripheral blood stem cells (PBSC) transplantation in treatment of type 1 diabetes mellitus (T1MD). MethodsThe clinicopathologic data of recipients underwent allogeneic islet cells combined with (or without) PBSC transplantation in the Sichuan Provincial People’s Hospital from January 2017 to December 2019 were retrospectively analyzed. The allogeneic islet cells combined with (or without) PBSC were infused into the liver by percutaneous hepatic portal vein puncture. Then the modified Edmonton immunosuppressive regimen was used after the operation. The recipients were followed-up for 3 years, and the insulin usage, C-peptide, and glycosylated hemoglobin A1c (HbA1c) were analyzed. ResultsThere were 5 recipients of allogeneic islet cell transplantation alone (named as alone group) and 5 recipients of allogeneic islet cell combined with PBSC transplantation (named as combined group). The gender, age, body mass index, preoperative insulin dosage, and HbA1c concentration of the recipients in the two groups were similar. ① The numbers of islets transplanted in the alone group and combined group were (50.60±2.51)×104 islet equivalent quantity (IEQ) and (48.70±4.76)×104 IEQ, respectively, and the number of PBSC transplanted in the combined group was (9.2±2.6)×107. ② In the alone group and combined group, there were 3 cases and 3 cases of insulin withdrawal at the 12th month, as well as 2 cases and 3 cases of insulin withdrawal at the 36th month after operation, respectively. The postoperative insulin dosages of the two groups were decreased as compared with that before operation, and which of the combined group showed a lower trend as compared with the alone group within 12 months after operation. ③ The C-peptide level at the fasting in the alone group peaked at 24th month after operation and began to decline, and which at the fasting and postprandial 2 h peaked at 12th month after operation and began to decline, but that at postprandial 2 h began to increase slightly at 24th month in the combined group, and which showed a higher trend at 12th and 36th month after operation in the combined group as compared with the alone group. ④ Within 36 months after operation, the HbA1c concentrations of the two groups decreased at different times after operation as compared with those before operation, and basically maintained a normal and stable level at 6 months after operation, and the change trend of the two groups was basically similar. ⑤ There were no obvious immune rejection and adverse reactions in the two groups. ConclusionFrom the preliminary results of this study, PBSC has a certain protective effect on islet transplantation, which improves the clinical efficacy of allograft islet transplantation for 3 years, but the long-term efficacy still needs to be observed, and the mechanism still needs to be further explored.