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.
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 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.
Objective To explore the predictive value of neutrophil-to-lymphocyte ratio (NLR) in peripheral blood for postoperative complications of elective endovascular repair for abdominal aortic aneurysm (AAA). Methods From August 2016 to November 2021, the clinical data of patients with AAA who received endovascular isolation repair for the first time in the Department of Vascular Surgery of Beijing Hospital were retrospectively analyzed, including the basic information of the patients, comorbid diseases, and the largest diameter of AAA, preoperative blood labotry test, postoperative complications, long-term survival rate and other indicators. The optimal NLR in peripheral blood was determined, and the differences in postoperative complications and long-term survival rates between the high NLR group and the low NLR group were analysed. Results A total of 120 patients with AAA underwent endovascular isolation for the first time were included in this study, including 105 males and 15 females. The age ranged from 52 to 94 years, with an average of (73.3 ± 8.26) years. The largest diameter of abdominal aortic aneurysm was 35 to 100 mm, with an average of (58.5 ± 12.48) mm. The best cut-off value of NLR for predicting postoperative complications of AAA was 2.45 by using Yoden index screening. Those with NLR ≥2.45 were in the high NLR group (n=66), and those with NLR <2.45 were in the low NLR group (n=54). There was no statistically significant difference between the two groups in the incidence of overall complications and the incidence of sub-complications (P>0.05). The results of logistic regression analysis suggested that NLR was an independent risk factor for complications after endovascular repair of AAA (P<0.05). The median survival time of patients in the high NLR group and the low NLR group was 31.47 months and 35.28 months, respectively, and there was no statistically significant difference between the two groups (P>0.05). Conclusion NLR can be used as a reference predictor of complications after elective endovascular repair of AAA, but more research results are still needed to confirm.
Objective To investigate the pleural effusion lymphocyte subsets in patients with pneumonia complicated with pleural effusion and its relationship with the occurrence of critical illness. MethodsPatients with pneumonia complicated with pleural effusion (246 cases) admitted to our hospital from January 2020 to June 2022 were selected as the research subjects. According to the severity of pneumonia, they were divided into a critical group (n=150) and a non-critical group (n=96). After 1:1 matching by propensity score matching method, there were 60 cases in each group. The general data of the two groups were compared. CD3+, CD4+, CD8+, CD4+/CD8+ ratio were detected by flow cytometry. Multivariate logistic regression was used to analyze the risk factors of critical pneumonia, and a nomogram prediction model was constructed and evaluated. The relationship between PSI score and lymphocyte subsets in pleural effusion was analyzed by local weighted regression scatter smoothing (LOWESS). Results After matching, the differences between the two groups of patients in the course of disease, heat peak, heat course, atelectasis, peripheral white blood cell count (WBC), C-reactive protein (CRP), D-dimer (D-D), procalcitonin (PCT) and hemoglobin were statistically significant (P<0.05). Compared with the non-critical group, the proportion of CD3+, CD4+, CD4+/CD8+ cells in critical group was lower (P<0.05), and the proportion of CD8+ cells was higher (P<0.05). Combined atelectasis, increased course of disease, fever peak and fever course, increased WBC, CRP, D-D, CD8+ and PCT levels, and decreased CD3+, CD4+, CD4+/CD8+ and Hb levels were independent risk factors for the occurrence of critical pneumonia (P<0.05). The nomogram prediction model based on independent influencing factors had high discrimination, accuracy and clinical applicability. There was a certain nonlinear relationship between pneomonia severity index and CD3+, CD4+, CD8+ and CD4+/CD8+. Conclusions Lymphocyte subsets in pleural effusion are closely related to the severity of pneumonia complicated with pleural effusion. If CD3+, CD4+, CD8+ and CD4+/CD8+ are abnormal, attention should be paid to the occurrence of severe pneumonia.
Objective To investigate the prognostic value of preoperative plasma fibrinogen (FIB) combined with lymphocyte-to-monocyte ratio (LMR) in predicting the prognosis of patients with esophageal squamous cell carcinoma. Methods A retrospective analysis was conducted on patients who underwent esophagectomy in our hospital from January 2015 to December 2018. Based on the cut-off values of preoperative FIB and LMR, The F-LMR scoring system was constructed, and patients were divided into three groups. Kaplan-Meier analysis was used to assess 5-year overall survival and 5-year progression free survival, and univariate and multivariate Cox regression analyses were performed to identify prognostic factors. Results Finally 260 patients were collected, including 237 males and 23 females, with a median age of 64 years (ranging from 59 to 70 years). The 5-year OS rates for patients with F-LMR score of 0, 1, and 2 were 24.44%, 51.69%, and 67.31%, respectively, and the 5-year PFS rates were 15.56%, 42.37%, and 57.62%, respectively. Lower preoperative F-LMR scores were associated with worse prognosis. Multivariate analysis showed that deeper tumor invasion, presence of lymph node metastasis, larger tumor maximum diameter, and lower preoperative F-LMR score were independent prognostic factors for OS. Conclusion The F-LMR score system based on the preoperative FIB and LMR can serve as an effective tool for predicting the prognosis of patients with esophageal squamous cell carcinoma.
Objective To investigate the correlation between the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune inflammation index (SII) and clinicopathological characteristics and prognosis in patients with gastrointestinal stromal tumor (GIST). Methods The clinicopathological data and blood routine results of 101 patients with GIST who were treated surgically in the General Hospital Western Theater Command PLA from December 2014 to December 2018 were collected retrospectively, samples were obtained to calculate NLR, PLR and SII. The optimal cutoff value of NLR, PLR and SII were evaluated by receiver operating characteristic (ROC) curve. The Chi-square test and t-test were used to analyze the relationship between NLR, PLR, SII and clinicopathological characteristics of GIST. The Kaplan-Meier plots and the log-rank test were used to analyze the influence factors affecting the recurrence-free survival (RFS) of patients with GIST. Multivariate Cox regression analyses was used to identify the independent influence factors affecting the RFS of patients with GIST. Results The preoperative peripheral blood NLR, PLR and SII of patients with GIST were correlated with the tumor site, tumor diameter and modified NIH risk stratification (P<0.05), but not with the mitotic count of tumor cells (P>0.05). Kaplan-Meier plots and log-rank test showed that NLR, PLR, SII, surgical method, tumor site, tumor diameter, mitosis rate and modified NIH risk stratification were the influential factors of RFS in with GIST. The multivariate Cox regression analysis revealed that postoperative whether to accept regular imatinib adjuvant therapy (HR=32.876, P<0.001), modified NIH risk stratification (HR=129.182, P<0.001), and PLR (HR=5.719, P=0.028) were independent influence factors affecting the RFS of patients with GIST. Conclusions Preoperative peripheral blood PLR, NLR, and SII are correlated with clinicopathological characteristics such as the tumor location, tumor diameter and modified NIH risk stratification, and are the influencing factors of postoperative RFS in patients with GIST. PLR is an independent predictor of RFS in patients with GIST.
ObjectiveTo investigate the prognostic value of preoperative serum albumin-to-globulin ratio (AGR) and neutrophil-lymphocyte ratio (NLR) in the overall survival (OS) of patients with esophageal squamous cell carcinoma (ESCC), and to establish an individualized nomogram model and evaluate its efficacy, in order to provide a possible evaluation basis for the clinical treatment and postoperative follow-up of ESCC patients. MethodsAGR, NLR, clinicopathological and follow-up data of ESCC patients diagnosed via pathology in the Department of Thoracic Surgery, The First Affiliated Hospital of Xinjiang Medical University from 2010 to 2017 were collected. The correlation between NLR/AGR and clinicopathological data were analyzed. Kaplan-Meier analysis and log-rank test were used for survival analysis. The optimal cut-off values of AGR and NLR were determined by X-tile software, and the patients were accordingly divided into a high-level group and a low-level group. At the same time, univariate and multivariate Cox regression analyses were used to identify independent risk factors affecting OS in the ESCC patients, and a nomogram prediction model was constructed and internally verified. The diagnostic efficacy of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve, and the clinical application value was evaluated by decision curve analysis. ResultsA total of 150 patients were included in this study, including 105 males and 45 females with a mean age of 62.3±9.3 years, and the follow-up time was 1-5 years. The 5-year OS rate of patients in the high-level AGR group was significantly higher than that in the low-level group (χ2=6.339, P=0.012), and the median OS of the two groups was 25 months and 12.5 months, respectively. The 5-year OS rate of patients in the high-level NLR group was significantly lower than that in the low-level NLR group (χ2=5.603, P=0.018), and the median OS of the two groups was 18 months and 39 months, respectively. Multivariate Cox analysis showed that AGR, NLR, T stage, lymph node metastasis, N stage, and differentiation were independent risk factors for the OS of ESCC patients. The C-index of the nomogram model was 0.689 [95%CI (0.640, 0.740)] after internal validation. The area under the ROC curve of predicting 1-, 3-, and 5-year OS rate was 0.773, 0.724 and 0.725, respectively. At the same time, the calibration curve and the decision curve suggest that the model had certain efficacy in predicting survival and prognosis. ConclusionPreoperative AGR and NLR are independent risk factors for ESCC patients. High level of AGR and low level of NLR may be associated with longer OS in the patients; the nomogram model based on AGR, NLR and clinicopathological features may be used as a method to predict the survival and prognosis of ESCC patients, which is expected to provide a reference for the development of personalized treatment for patients.
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.
Diabetic retinopathy (DR) isacommon cause of blindness, its occurrence and development are the synergic results of multiple factors. Current studies suggest that inflammation and inflammatory factor has an important role in the pathogenesis of DR. The occurrence and development of DR are closely related with interleukins, intercellular adhesion molecules, hasten factors, tumor necrosis factor, C-reactive protein etc. Mesenchymal stem cells (MSCs) are pluripotent cells derived from the mesoderm and have multiple differentiation potentials, and anti-inflammatory and immunosuppressive function. Recent studies shown that MSCs transplantation can protect damaged retina by inflammatory regulation, which becomeanew research direction for DR treatment.