Objective To investigate the prognostic value of serum gamma-glutamyltransferase-to-lymphocyte ratio (GLR) in patients with chronic hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) after radical resection. Methods The clinical data of HBV-HCC patients diagnosed and treated with radical hepatectomy in the Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital) from January 2012 to December 2022 were retrospectively collected and analyzed. Log-rank and multivariate Cox proportional hazard model were performed to analyze the risk factors affecting overall postoperative survival (OS) and relapse-free survival (RFS) of HBV-HCC patients, and receiver operating characteristic (ROC) curve was used to evaluate the predictive value of GLR for OS and RFS of HBV-HCC patients. Results A total of 196 eligible HBV-HCC patients underwent radical hepatectomy were included. The optimal cutoff value of GLR was 182.31 through ROC curve, and 144 cases were in low GLR group and 52 cases in high GLR group. Compared with the low GLR group, ratios of preoperative portal vein tumor thrombus, China liver cancer staging (CNLC) stage Ⅲ, preoperative AFP level ≥400 ng/mL and low tumor differentiation were higher in the high GLR group (χ2=10.071, P=0.002; χ2=32.552, P<0.001). Cox proportional hazard model showed that higher maximum tumor diameter (HR=1.099, P=0.009), GLR>182.31 (≤182.31 vs. >182.31, HR=0.211, P<0.001) and low tumor differentiation grade (high+moderate vs. low, HR=0.182, P<0.001) were risk factors for postoperative OS of HBV-HCC patients, and the area under curve (AUC) of these risk factor for predicting OS of HBV-HCC patients was 0.930 [95%CI (0.884, 0.977)]. Preoperative portal vein tumor thrombus (No vs. Yes, HR=0.404, P=0.002) and GLR>182.31 (≤182.31 vs. >182.31, HR=0.435, P=0.001) were risk factors for postoperative RFS of HBV-HCC patients, and the AUC of these risk factor for predicting RFS was 0.729 [95%CI (0.654, 0.805)]. Conclusion This study preliminarily indicates that GLR is associated with postoperative prognosis of HBV-HCC patients, and GLR combined with maximum tumor diameter and tumor differentiation degree has a certain value in predicting OS.
ObjectiveTo study the contents of CD44 that shared exon variant 5 (CD44v5) in peripheral blood lymphocytes (PBL) of patients with gastric carcinoma and the expression of CD44v5 in tumor tissue and their clinical significance. MethodsThe contents of CD44v5 were determined by FlowCytometry in PBL of 31 patients with gastric carcinoma before surgery and 10 normal controls. Tissue expression of CD44v5 in 33 patients with gastric carcinoma was investigated by immunohistochemistry. ResultsThe contents of CD44v5 were significantly higher in PBL of patients with gastric carcinoma before surgery than those of controls (P＜0.01). Nodepositive gastric cancer patients showed significantly elevated contents of CD44v5 in PBL in comparison with nodenegative gastric cancer (P＜0.01）. Significant correlations were noted between the contents of CD44v5 in PBL of patients with gastric carcinoma before surgery and tumor size, depth of invasion, lymph node metastasis and different the Vnion International Centre Le Cancer (VICC) stages of tumor (P＜0.05). The expression of CD44v5 could be detected in 69.7% of tumor tissue,but was not detected in adjacent normal gastric mucosa. Significant correlations were noted between CD44v5 expression and depth of invasion,and lymph node metastasis.The presence of CD44v5 protein was correlated with the lymph node involvement rate. Conclusion CD44v5 in PBL or tumor tissue may be useful as a metastatic marker. It may be of important clinical value in the diagnosis of metastasis and judgement of development for the patients with gastric cancer.
Objective To explore the changes and interrelationship of serum interleukin-12 (IL-12) and T lymphocyte subset in patients with primary hepatic carcinoma (PHC). Methods Serum IL-12 level was determined by ELISA in 36 patients with PHC. The peripheral blood T lymphocyte subset was assessed with flow cytometry. The distribution and changes of T lymphocyte subset in the tumor tissue were detected by immunohistochemistry analysis. Results The numbers of the CD＋4 T cell were reduced and of the CD＋8 T cell increased either in peripheral blood or tumor tissue, and showed the trend of the ratio (T4/T8) declined progressively with the aggravation of the state with PHC. IL-12 and T4/T8 had significant interrelationship.Conclusion IL-12 is an important antitumor factor of the patients with PHC. T lymphocyte subset plays a great role in the process of antitumor.
ObjectiveTo investigate the method for generating anchor chemric T lymphocytes that can target tumor associated glycoprotein-72 (TAG72) antigen and analyze their repressive effects on proliferation of TAG72 positive hepatocarcinoma cells. MethodsFirstly, peripheral blood mononuclear cells (PBMCs) from healthy volunteers were isolated. And then, CD8+ T cells were isolated from PBMCs via magnetic activated cell sorting (MACS). These lymphocytes were transfected with recombinant vector, anti-TAG72-scFv-CD28-pcDNA3, through Lipofectamine2000 to gernerate anchor chimeric TAG72-specific CD8+ T cells. SMMC7721 (TAG72 positive) hepatocarcinoma cells were co-cultured with chimeric T lymphocytes and their cell cycles were analyzed by flow cytometry (FCM). ResultsAnchor chmeric T lymphcytes targetting TAG72 recognized TAG72 positive SMM7721 cells and repressive effects on their proliferation were observed by flow cytometry. ConclusionAnchor chmeric T lymphcytes targetting TAG72 on tumor surface can specifically recognize TAG72 positive hepatocarcinoma cells and may exert repressive effect on their proliferation.
Objective To observe the effects of Thymosin α1 （Tα1） on acute rejection after liver transplantation and immune function of T cells. Methods Twenty recipients of liver transplantation due to primary hepatic carcinoma were divided into two groups: Tα1 group (n=10) and control group (n=10). Tα1 group received subcutaneous injection of Tα1 1.6 mg on the first day after liver transplantation and then twice a week for at least one month. Both Tα1 group and control group took same immunodepressants. Core biopsies were carried to compare the incidence rate of acute rejection between Tα1 group and control group. Peripheral T cellular immune function in these two groups was detected on 1 d before, 1 week, 2 weeks and 1 month after transplantation. Results There was not significant difference of incidence rate of acute rejection between Tα1 group and control group (Pgt;0.05). In the Tα1 group, CD4+, CD8+ lymphocyte cell counts and the CD4+/CD8+ ratio were significantly higher than those in the control group in 2 weeks and 1 month after transplantation (P＜0.05). Conclusion Use of Tα1 in recipients who also takes rountine immunosuppressants dose not increase the risk of occurring acute rejection after liver transplantation. Tα1 can significantly increase CD4+, CD8+ counts and CD4+/CD8+ ratio, which shows that Tα1 may improve recipients’ cellular immune function.
Objective To investigate the relationship between preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) score, and clinicopathologic features of colon cancer, and to analyze the predictive value of HALP score for postoperative liver metastasis. Methods The clinical data of 163 patients with colon cancer admitted to the 909th Hospital of Joint Logistic Support Force (Dongnan Hospital of Xiamen University) from January 2018 to December 2019 were retrospectively analyzed. According to the occurrence of postoperative liver metastasis, the patients were divided into metastatic group (n=35) and non-metastatic group (n=128). The correlation between preoperative HAPL score and clinicopathologic features of colon cancer was analyzed. The predictive value of HALP score for postoperative liver metastasis of colon cancer was analyzed by using receiver operating characteristic (ROC) curve. The risk factors of liver metastasis after colon cancer surgery were analyzed by using univariate and multivariate logistic analysis. Kaplan-Meier risk curve was drawn, and log-rank test was used to analyze the predictive value of different HALP score for postoperative liver metastasis. Results HALP score were decreased in patients with maximum tumor diameter ≥5 cm, preoperative carcinoembryonic antigen (CEA) ≥5 μg/L, serous membrane and extrasserous infiltration, lymph node metastasis and vascular invasion, and the difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that HALP score [OR=1.467, 95%CI (1.253, 1.718), P<0.001], maximum tumor diameter [OR=3.476, 95%CI (1.475, 5.358), P=0.013], preoperative CEA level [OR= 6.197, 95%CI (2.436, 6.248), P=0.005], and lymph node metastasis [OR=2.593, 95%CI (1.667, 6.759) , P=0.003] were risk factors for postoperative liver metastasis of colon cancer. ROC curve analysis showed that the area under the curve of HALP score for predicting liver metastasis after colon cancer surgery was 0.908 (0.841, 0.974), the maximum value of the Youden index was 0.738, the optimal cut-off value of the HALP score was 35.5, the sensitivity was 0.852, the specificity was 0.886. Kaplan-Meier risk curve showed that the risk of early postoperative liver metastasis in the low HALP score group was higher than that in the high HALP score group (χ2=8.126, P=0.004). Conclusion Low HALP score in patients with colon cancer is associated with adverse prognosisi related pathological features, and is an influential factor for postoperative liver metastasis of colon cancer, and has predictive value for patients with postoperative liver metastasis of colon cancer.
ObjectiveTo investigate the factors that affect the occurrence of postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP).MethodsThe clinical data of 114 patients underwent DP who were performed in the First Affiliated Hospital of Xinjiang Medical University from Jan. 2014 to Jun. 2019, were retrospectively analyzed.ResultsIn this group of 114 patients, 43 cases (37.7%) of POPF occurred after DP, including 19 cases of grade A (biochemical fistula), 21 cases of grade B, and 3 cases of grade C. The univariate analysis results showed that: BMI value, drinking history, preoperative plasma albumin level, postoperative plasma albumin level, postoperative neutrophil/lymphocyte ratio (NLR), preoperative and postoperative prognostic nutrition index (PNI) levels were significant different between the POPF group and non-POPF group (P<0.05). Multivariate analysis results showed that: preoperative plasma albumin>35 g/L [OR=0.115, 95%CI was (0.038, 0.348)], postoperative plasma albumin>35 g/L [OR=0.126, 95%CI was (0.031, 0.516)], and postoperative NLR value≤6.65 [OR=0.149, 95%CI was (0.048, 0.461)] were the influencing factors of POPF after DP. The area under curve of postoperative NLR was 0.731 [95%CI was (0.639, 0.824)]. ConclusionPreoperative and postoperative plasma albumin>35 g/L, as well as postoperative NLR ≤6.65 are protective factors for POPF after DP, and postoperative NLR can be used as a predictor of POPF.
After escaping from the hyperacute rejection (HAR), the xenograft has to be faced the challenge of acute vascular, acute cellular and even chronic rejection. Endothelial cells have been confirmed as a kind of antigen processing cell (APC) in allo-rejection. The porcine aortic endothelial cell (PAEC) expressed SLA-II and B7 which are the characteristics of professional APC. PAEC also has plenty of alpha-Gal residues, whether the antigen play any role in the post-HAR is still unknown. Human and porcine peripheral blood lymphocyte (PBLC) were isolated and divided into two parts, one for the effectors and the another were incubated with mitomycin C (MMC) as stimulators. The two kinds of PBLC were mixed-cultured within five days. Cultured PAEC from NJZ Pig was incubated with MMC and divided into two: One digested with alpha-galactosidase. The two kinds of PAEC were taken as stimulators to mixed-culture with human PBLC for five days. All the proliferation was detected with 3H-TdR intermingled in the system. The results showed that allo-MLR was ber than xeno-MLR in the cases. The proliferation was much ber when PAEC was used as the stimulator than that of porcine PBLC. However, the response was remarkably decreased after the digestion of alpha-Gal with alpha-galactosidase. The conclusion was that the low response of porcine-to-human MLR in vitro might be related to the predominant indirect pathway of antigen recognition in this system. While PAEC was used as the stimulator the proliferation in MLR was ber which might be concerned that PAEC itself was an APC as well as xeno-antigen sources, thus the direct pathway was predominant and worked more efficiently. The alpha-Gal might induce T cell proliferation through the linkage with the biological big molecules working as a complete antigen. The other post-HAR antigen might also exist in PAEC such as SLA-II, etc.
ObjectiveTo investigate the inhibitory effect of the inhibition of antigen-presentation attenuators (iAPA)-based dendritic cells (DC) and cytotoxic T lymphocytes (CTL)-iAPA-DC/CTL on SMMC-7721 xenograft in nude mice. MethodsUsing the human hepatic carcinoma cell line SMMC-7721 on nude mice to establish a transplanted tumor model of human hepatocellular carcinoma (HCC).Twelve nude mice were divided into two groups randomly: normal saline control group (control group) and iAPA-DC/CTL group (n=6, each).After four times treatment with iAPA-DC/CTL (once a week), all mice were sacrificed.Tumor growth was calculated by measuring the long/short diameters and the tumor growth curve was delineated.The tumors were weighed and the tumor inhibition rate was calculated.In addition, the histopathological examination was conducted. ResultsThe SMMC-7721 xenograft model was successfully established in 85.71% (12/14) of all mice.The tumor volume was (3 661.48±322.59) mm3 and (2 725.36±252.65) mm3 in control group and iAPA-DC/CTL group, respectively.The tumor growth was significantly inhibited in iAPA-DC/CTL group (t=5.62, P < 0.05).The tumor weight was (1.97±0.21) g and (1.38±0.14) g in control group and iAPA-DC/CTL group, respectively.The tumor weight in iAPA-DC/CTL group was significantly reduced (t=5.73, P < 0.05), and the tumor inhibition rate was 29.95%.After immunohistochemical staining T lymphocyte counts was 0 cell/HPF and (54.24±4.31) cells/HPF in control group and iAPA-DC/CTL group, respectively.The number of T lymphocytes in iAPA-DC/CTL group was significantly increased (t=25.02, P < 0.05). ConclusioniAPA-DC/CTL could effectively inhibit the growth of subcutaneously implanted HCC.
ObjectiveTo investigate the effect of interleukin (IL)-23 receptor (IL-23R) overexpression on the balance of T helper 17 (Th17 cells)/regulatory T cells (Treg cells) in experimental autoimmune uveitis (EAU) mice. MethodsTwelve 8-week-old female C57BL/6J mice were randomly divided into LV-Ctrl group and LV-IL-23R group, with 6 mice in each group. Two groups of mice were injected with LV-Ctrl and LV-IL-23Rlentiviruses through the tail vein, respectively; 7 days after injection, the EAU mouse model was established by active immunization with vitamin A-binding protein 1-20 between photoreceptors. Starting from 13 days after immunization, the fundus of the mice was observed by indirect ophthalmoscopy every 2 days and clinical scores were performed; 30 days after immunization, hematoxylin-eosin staining was used to observe the histopathological changes of mouse retina. The levels of IL-17 in serum of the two groups of mice were detected by enzyme-linked immunosorbent assay; the proportion of Th17 cells and Treg cells was detected by flow cytometry. The relative mRNA expression of IL-23R, IL-17, retinoic acid-related orphan receptor γt (RORγt), IL-10 and forkhead transcripyion factor p3 (Foxp3) were detected by real-time quantitative polymerase chain reaction. Comparisons between groups were performed using repeated measures analysis of variance, independent samples Mann-Whitney U test, and independent samples t test. ResultsCompared with the LV-Ctrlgroup, the retinal inflammatory reaction of the LV-IL-23R group was more severe. At 13 days after immunization, there was no significant difference in fundus inflammation scores between LV-IL-23R group and LV-Ctrl group (t=－2.001, P=0.058); 15-29 days after immunization. The fundus inflammation scores of LV-IL-23Rgroup were higher than those of LV-Ctrl group, and the difference was statistically significant (t=－4.429, －6.578, －7.768, －10.183, －6.325, －7.304, －4.841, －6.872; P＜0.001). Histopathological examination showed that the infiltration of inflammatory cells in the fundus increased, the retinal structure was damaged more seriously, and the histopathological score was significantly increased, and the difference was statistically significant (t=－4.339, P=0.001). Compared with the LV-Ctrl group, the relative expression of IL-23RmRNA in the spleen of the LV-IL-23R group was significantly increased, and the difference was statistically significant (Z=2.087, P=0.037). The relative expression of IL-17 and RORγt mRNA increased, while the relative expression of IL-10 and Foxp3 mRNA decreased, and the differences were statistically significant (t=－6.313,－5.922, 4.844, 7.572; P=0.003, 0.004, 0.008, 0.002). Compared with the LV-Ctrl group, the level of IL-17 in the serum of the mice in the LV-IL-23R group was significantly increased, and the difference was statistically significant (t=－5.423, P=0.002); the proportion of Th17 cells in the spleen and lymph nodes was significantly increased, whereas, the proportion of Treg cells was significantly reduced, and the difference was statistically significant (t=－4.290, 3.700; P=0.002, 0.006). ConclusionIL-23R overexpression can promote Th17/Treg imbalance in EAU mice, and aggravate the clinical and pathological manifestations of EAU.