Objective To explore the effect of cytotoxic T lymphocyte-associated antigen 4 (CTLA4-Ig) fusion protein on the function of orthotopic liver allograft. Methods Orthotopic liver allograft models of rhesus monkeys were established in this study. The survival time, liver function and morphologic changes of graft were observed, respectively. The levels of IL-2 and IL-10 were detected by ELISA. Apoptosis was monitored by TUNEL.Results The average survival of control group was 6.57 d, while the average survival of CTLA4-Ig group was 14.92 d, which was statistically prolonged (Plt;0.05). Serum ALT level was highly increased, and Alb level decreased obviously in control group. While the levels of ALT and Alb kept in normal in CTLA4-Ig group. After day 3-7, the expressions of IL-2 were highly expressed in control group, while the expressions of IL-10 in CTLA4-Ig group were higher than those of control group. The severity of rejection reaction after day 3 was weaker in CTLA4-Ig group than that of control group by histological assessment. The apoptosis index after day 3 in the liver cells was highly increased in control group as compared with the CTLA4-Ig group. Conclusions CTLA4-Ig fusion protein therapy can induce immunotolerance and prolong the survival of recipients. The increasing of cytokines IL-2 or the decreasing of cytokines IL-10 may be one of the laboratory indexes in monitoring immunotolerance of transplantation.
【Abstract】Objective The effects of tumor infiltrating lymphocytes (TIL) on cellular immunologic function of patients with breast cancer were studied. Methods Twenty five patients with breast cancer were treated by the TIL that were isolated from tissue of tumor. T cell subgroups and natural killer cell (NK cell) activity of peripheral blood, the levels of serum soluble interleukin-2 receptor (sIL-2R) were assayed before and after treatment. Results CD3, CD4, CD4/CD8 and NK cell activity were ascended obviously, and CD8, sIL-2R were descended obviously after the treatment of TIL. Conclusion TIL can enhance the cellular immunologic function of patients with breast cancer.
【Abstract】Objective This study was conducted to build experimental model of orthotopic liver transplantation in rat (ROLT) with the character of acute rejection; and to study the effect of cytotoxic T lymphocyte antigen 4 immunoglobulin G (CTLA4Ig) on prevention of rejection and the induction of immune tolerance of ROLT. Methods Build model of Wistar→SD ROLT(performed by the two cuff method) with character of acute rejection.Recipients were injected with CTLA4Ig 75 μg per ROLT into abdominal cavity after 2 days of operation. Contrast was made with no treatment group, the clinical characters, the liver function, the transplantated liver pathologic character and the concentrations of TNFα in serum were observed and measured on postoperative day 7. In treatment group, all above observation were done on postoperative month 4. Above all, determination of the effect of CTLA4Ig on preventing acute rejection and inducing tolerance in ROLT was observed.Results ①Recipients (no treatment group) died one by one within 6th～14th days; pathologic character of rejection in transplantation liver could be found; ② In treatment group, on postoperative day 7 and month 4, no clinical rejection character and no pathologic character of rejection in transplantation liver were found and serum concentration of cytokins related to TNFα found lower than that of contrast group(P＜0.05), and serum concentration of ALT、AST、TBIL、DBIL found lower too(P＜0.05); But serum concentration of TP and Alb was found higher than that of contrast group(P＜0.05). Conclusion ① CTLA4Ig treatment alone inhibits the rejection responce in ROLT. ② CTLA4Ig treatment can Prevent rejection and induce immune tolerance in ROLT model with characters of acute rejection; the serum concentration of cytokins related to TNFα can probably be used as evaluation standard of rejection in ROLT rejection.
To search for the relationship between immune state and tumor metastases, CD3,CD4,CD8 and CD44 contents in 13 speciments of fine needle aspiration (FNA) from thyroid cancer patients were detected by the flowcytometry (FCM) and comparison between thyroid cancer and benign tumor was made. The result showed :in thyroid cancer group, CD＋3，CD＋4 cells and the ratio of CD＋4/CD＋8 reduced significantly (Ｐ＜0.01),and CD＋8 cell increased significantly (Ｐ＜0.01), in metastases group,this change was much significantly. CD44 expressed significantly higher in cancer group than that of the benign thyroid neoplasms, and the change was related to the tumor metastases. The results indicate that CD44 can be as a marker of tumor and indicator of metastases. The disturbance of immune system results in active expression of CD44 by tumor cells, so, lead to metastases. It is helpful to the diagnosis of thyroid cancer, assessment of metastases and management in surgery.
ObjectiveTo compare the clinical recovery and immune response between laparoscopic-assisted and open D2 gastrectomy for advanced gastric cancer. MethodsThe clinical data of 53 patients with advanced gastric cancer from January 2012 to October 2013 were studied prospectively. According to random number table, patients were randomly divided into laparoscopic-assisted group(LA group, n=27) and open operation group(OO group, n=26). Operative time, blood loss, time to passage of flatus, time to resume soft diet, after bed time, postoperative hospital stay, and number of retrieved lymph nodes were compared respectively between the two groups. The changes in CD3, CD4+, CD8+, IgG, IgA, IgM, and CRP were examined respectively by using flow cytometry and immunoturbidimetric assays on the preoperative day 1, and on the postoperative day 1 and 7. ResultsThe operative time was longer significantly in LA group than that in OO group(P < 0.05). The mean blood loss, the first flatus time, after bed time, and postoperative hospital stay in the two groups were all different statistically(P < 0.05), and all were better in LA group. However, the mean number of retrieved lymph nodes and the time to resume soft diet were not significantly different in the two groups(P > 0.05). On the day 1 and 7 after operation, the CD3, CD4+, and CD8+ significantly decreased as compared with those preoperatively in two groups(P < 0.01, P < 0.05). On the day 1 after operation, the levels of IgG, IgA, and IgM significantly decreased as compared with those preoperatively in two groups(P < 0.05). Those immunoglobulin in LA group recovered to close to the level before surgery, but in OO group sustained lower level(P < 0.05). On the day 1 and 7 after operation, CRP level significantly increased as compared with those preoperatively in two groups(P < 0.01, P < 0.05). Those changes of above index were not significantly different between the LA group and OO group on the day 1 after operation(P > 0.05). All index recovered gradually in the two groups on the day 7 after operation and were better in LA group(P < 0.05, except IgA). ConclusionLaparoscopic radical gastrectomy for advanced gastric cancer resulted in a quicker clinical recovery and a lesser depression to the perioperative cellular and humoral immune function.
Acute cerebral infarction is characterized by high incidence rate, high recurrence rate, high disability rate and multiple complications. Early evaluation and treatment of acute cerebral infarction is particularly important to improve the survival rate and prognosis of patients. As an easily available clinical laboratory indicator, blood routine test can reflect the pathological changes in the body to a certain extent. In recent years, many studies have shown that the indicators such as red cell volume distribution width, mean platelet volume, neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in blood routine examination have important values in the onset, severity and prognosis of acute cerebral infarction. This article reviews the correlations of the above parameters and ratio parameters with acute cerebral infarction, in order to provide some reference and basis for clinical diagnosis, treatment and prognosis evaluation of acute cerebral infarction.
Objective To asses the clinical effectiveness and safety of combined treatment with antilymphocyte globulin (ATG) and cyclosporine A (CSA) versus antilymphocyte globulin alone in patients with aplastic anemia (AA). Methods Randomized controlled trials (RCTs) were identified from MEDLINE (1966 to September 2007), EMBASE (1984 to September 2007), The Cochrane Library (issue 4, 2007) and CBM-disc (1978 to September 2007). The references of eligible studies were hand searched. RCTs involving ATG and CSA in the treatment of AA were included. Data were evaluated and extracted by two reviewers independently with designed extraction form. The Cochrane Collaboration’ s RevMan 4.2.10 software was used for data analyses. Results Two RCTs involving 160 patients were included. Two studies showed that the effective rate in the ATG+CSA group was significantly higher than that in the ATG group (Plt;0.0001). Two studies indicated that the survival rate in the ATG+CSA group was improved compared with the ATG group (P=0.0002). One study reported adverse effect. The ATG group caused more fever and serum diseases compared with the ATG+CSA group, but the ATG+CSA group had a higher incidence of hepatotoxicity. Conclusion Treatment with ATG+CSA for aplastic anemia has higher effective rate and survival rate than ATG alone. More trials of high quality are required.
ObjectiveTo summarize the blood routine indexes and predictive systems that can predict the severity of acute pancreatitis (AP). MethodThe recent domestic and foreign literatures on the predictive value of blood routine indexes for the severity of AP were reviewed.ResultsFrom the current research results at domestic and foreign, independent blood routine indexes such as red blood cell distribution width, average platelet volume, hematocrit (TCT), platelet (PLT) count, platelet distribution width, percentage of immature granulocytes (IG%), and some blood routine calculation indexes such as neutrophil to lymphocyte ratio (NLR), PLT to lymphocyte ratio (PLR), red blood cell distribution width to PLT ratio (RPR), neutrophil-monocyte product, and so on, all had different predictive value for the severity of AP. In addition, multiple prediction modes such as blood routine indexes combined with some serological indexes or other scoring systems could also be used to predict the severity of AP. In general, the predictive value of the NLR, IG%, and HCT on the severity of AP had been unanimously recognized by researchers. However, the conclusions of related studies on the predictive values of PLT, PLR, and RPR on the severity of AP were still controversial. ConclusionsAt present, there are a variety of blood routine indexes can be used to predict severity of AP, but their predictive values are different. Further researches are still needed.
ObjectiveTo evaluate the effects and mechanism of indoleamine 2, 3-dioxygenase (IDO) modified rat bone marrow mesenchymal stem cells (BMSCs) in composite tissue allograft rejection. MethodsBMSCs isolated from Brown Norway (BN) rats (aged, 4-6 weeks) were infected by IDO[green fluorescent protein (GFP)]-lentivirus. The high expression target gene and biological activity cell line (IDO-BMSCs) were screened. IDO mRNA and protein expressions were detected by RT-PCR and Western blot. The biological activity of IDO in supernatant was detected by measuring the amount of kynurenine generation. In mixed lymphocyte reaction system, different numbers of IDO-BMSCs mixed with responding cells (peripheral blood mononuclear cell isolated from 4-6-week-old LEWIS rats, as recipient) and stimulating cells (peripheral blood mononuclear cell isolated from BN rats, as donor), with the cells ratios of 1:5:5, 1:10:10, 1:50:50, and 1:100:100 (as experimental groups 1, 2, 3, and 4, respectively). Each reaction system was blocked by 1 mmol/L 1-methyl-tryptophan (1-MT) (IDO specific inhibitor). IDO-BMSCs mixed with responding cells (1:5) as the negative control group, responding cells mixed with stimulating cells (1:1) as positive control group; and IDO-BMSCs were cultured in RPMI 1640 medium alone as blank control group. MTT assay was used to detect the T lymphocytes proliferation at 5 days. Furthermore, GFP-BMSCs (group A), IDO-BMSCs (group B), and normal saline (group C) were infused via the tail vein of allogeneic limb transplantation rats, and graft survival time and rejection were observed in each group. ResultsThe IDO expression of BMSCs after genetic modification was higher than that before genetic modification. IDO-BMSCs could significantly improved kynurenine concentration in culture medium supernatant when compared with GFP-BMSCs (P<0.05). Before adding 1-MT, with the ratio of IDO-BMSCs to responding cells decreased, T lymphocytes proliferation rate increased in experimental groups 1, 2, and 3, showing significant differences between groups (P<0.05); there was no significant difference between experimental group 4 and the positive control group (P>0.05). After adding 1-MT, T lymphocytes proliferation rate was significantly higher than that before adding 1-MT in the other experimental groups (P<0.05) except experimental group 4 (P>0.05). In vivo, IDO-BMSCs could promote colonization in allograft, inhibit transplantation rejection, and prolong survival time of composite tissue allograft; the survival time of composite tissue allograft was (11.5±0.6) days in group A, (14.5±0.8) days in group B, and (9.0±0.3) days in group C, and it was significantly longer in group B than in groups A and C, and in group A than in group C (P<0.05). ConclusionIDO-BMSCs can promote the survival of allogeneic composite tissue grafts in rats, and its mechanism may involve in inhibition of T lymphocytes proliferation and promotion their own colonization in allograft.
ObjectiveTo evaluate prognostic value of change of immune status in locally advanced gastric cancer (LAGC) patients. Methods We retrospective collected 210 LAGC patients who underwent treatment in our department from January 2013 to December 2018, then we collected lymphocyte-to-monocyte ratio (LMR) and cLMR (change of lymphocyte-to-monocyte ratio, cLMR) before operation and after three cycles of adjuvant chemotherapy. We had developed a new immune state change score (ICS) based on preoperative LMR (pLMR) and cLMR, and explored its prognostic value. The definition of ICS in this study was: ICS=1, pLMR≤4.53 and cLMR≤1; ICS=2, pLMR≤4.53 and cLMR>1, or pLMR>4.53 and cLMR≤1; ICS=3, pLMR>4.53 and cLMR>1. Results The results of multivariate Cox proportional hazard regression model showed that ICS was an influencing factor for overall survival [ICS=2, RR=0.397, 95%CI (0.260, 0.608), P<0.001; ICS=3, RR=0.080, 95%CI (0.040, 0.162), P<0.001), patients with ICS scores of 2 and 3 had better overall survival. In addition, the prognostic accuracy of ICS was superior to pLMR and Clmr, and the C-index of ICS [0.806, 95%CI (0.746, 0.865)] was higher than that of pLMR [0.717, 95%CI (0.635, 0.799), P=0.003)] and cLMR [0.723, 95%CI (0.641, 0.806), P=0.005)]. Based on this, a Nomogram model included ICS, CEA, and pTNM staging was constructed to predict the 3-year and 5-year survival rates of patients. The calibration curve and C-index [0.821, 95%CI (0.783, 0.859)] showed high discrimination and accuracy of Nomogram, and decision curve analysis confirmed that the model had good clinical application value. Conclusions The dynamic changes in the patient’s immune status before and after adjuvant therapy are related to the overall survival of LAGC patients. As an evaluating system which combined the cLMR and pLMR, ICS can better predict the prognosis of LAGC patients.