ObjectiveTo explore the combined application of neutrophil to lymphocyte ratio (NLR) and systemic immune inflammation index (SII) on the prognosis of hepatitis B-related hepatocellular carcinoma after resection.MethodsRetrospectively collected data of 180 patients with hepatitis B-related hepatocellular carcinoma who were hospitalized in the Department of Infectious Diseases and Hepatobiliary Surgery of the Affiliated Hospital of Southwest Medical University and received surgical treatment from January 2013 to December 2019, including general information, laboratory examination and abdominal CT or MRI results. NLR and SII values were measured at one week before operation, and their critical values of NLR and SII were determined by ROC curve analysis. Univariate and multivariate analysis were performed to determine the risk factors to predict the survival status of patients with hepatitis B-related hepatocellular carcinoma after hepatectomy.ResultsUnivariate analysis showed that AFP, platelets, TNM staging, portal vein tumor thrombus, tumor differentiation, NLR, SII, and NLR+SII combined score were significantly correlated with the prognosis of patients with hepatitis B-related hepatocellular carcinoma (P<0.05). Multivariate analysis showed that PLT [HR=1.791, 95%CI (1.124, 2.854), P=0.014], NLR [HR=4.289, 95%CI (2.571, 7.156), P<0.001], SII [HR=5.317, 95%CI (3.016, 9.374), P<0.001], and NLR+SII combined score [HR=7.901, 95%CI (4.124, 15.138), P<0.001] were independently correlated with the survival of patients with hepatitis B-related hepatocellular carcinoma.ConclusionsThe preoperative NLR+SII combined score can be used to evaluate the postoperative prognosis of patients with hepatitis B-related hepatocellular carcinoma. The higher the score, the lower the postoperative survival rate.
Objective To determine whether neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are important prognostic factors in patients with colorectal cancer, and to clarify relationship between NLR or PLR and TNM staging in colorectal cancer. Methods The clinical data of 304 patients with colorectal cancer who were admitted to the same medical group from January 2013 to December 2013 in the West China Hospital of Sichuan University were analyzed retrospectively. The relationship between NLR or PLR and the clinicopathologic characteristics and its effects on prognosis of patients with colorectal cancer were analyzed. Results The critical values of NLR (sensitivity=51.0%, specificity=75.4%, area under the receiver operating characteristic curve=0.66) and PLR (sensitivity=73.0%, specificity=46.4%, area under the receiver operating characteristic curve=0.60) was 2.27 and 155.92, respectively, with a 3-year cumulative survival rate as the end point. According to the critical values of NLR and PLR, there were 133 cases in a low NLR group (NLR≤2.27), 171 cases in a high NLR group (NLR>2.27), 207 cases in a low PLR group (PLR≤155.92), 97 cases in a high PLR group (PLR>155.92). ① The 3-year survival rate was 91.5% and 77.2% in the low NLR group and the high NLR group, respectively, which was 89.0% and 72.8% in the low PLR group and the high PLR group, respectively. The survival curves of NLR and PLR on prognosis prediction had significant differences (P=0.002, P=0.001). ② The results of multivariate analysis showed that the NLR was the independent risk factor for colorectal cancer (P=0.004), whereas PLR was not the independent risk factor for colorectal cancer (P=0.408). ③ The NLR and PLR were associated with the tumor TNM staging (P=0.002, P=0.000), which in the colorectal cancer with stage Ⅳ was significantly higher than those with stage Ⅰ–Ⅲ (P<0.05). ④ The NLR and PLR were associated with T stage (P=0.006, P=0.031). The NLR in the colorectal cancer with stage T4 was significantly higher than that with stage Ⅰ (P=0.015) or stage Ⅱ (P=0.032). The PLR in the colorectal cancer with stage T4 was significantly higher than that with stage Ⅱ (P=0.013). ⑤ The NLR was not associated with N staging (P=0.118). The PLR was associated with N staging (P=0.007), which in the colorectal cancer with N2 stage was significantly higher than that with N0 stage (P=0.008) or N1 stage (P=0.019). ⑥ The NLR and PLR in the colorectal cancer with stage M1/M2 were significantly higher than those with stage M0 (P=0.004, P=0.001). Conclusions Preliminary results of this study show that NLR is an important independent prognostic indicator for patient with colorectal cancer. While PLR is significantly increased when lymph node metastasis occurs, and platelet elevation might be related to lymph node metastasis.
In recent years, the incidence of primary liver cancer has been increasing, among which hepatocellular carcinoma (HCC) being the most common subtype. The treatment of early HCC is mainly surgery, but most patients are not diagnosed until the late stage of the disease. The treatment methods and effects are very limited and the prognosis is very poor. Although targeted therapy has prolonged the overall survival of patients with HCC, the overall efficacy is unsatisfactory. The emergence of immunotherapy has brought new therapeutic prospects for HCC. Immune checkpoint inhibitors, among which programmed death-1/programmed death ligand-1 and cytotoxic T-lymphocyte associated antigen-4 are the representative immunological checkpoints, have attracted more attention. This article will introduce the application of immune checkpoint inhibitors in the treatment of advanced HCC, in order to provide a theoretical basis for the use of immune checkpoint inhibitors in the treatment of advanced HCC.
Objective To explore the correlation and diagnostic value of neutrophil-to-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) in peripheral blood of patients with exacerbation of chronic obstructive pulmonary disease (COPD). Methods One hundred patients with acute exacerbation of COPD who were hospitalized in the hospital between January 2019 and October 2020 were selected as exacerbation group, and another 100 patients with stable COPD who received treatment during the same time period were enrolled as stable group. The general data of patients were collected, and blood samples were collected to detect hemoglobin (Hb), platelet count (PLT), white blood cell count (WBC), neutrophil count, lymphocyte count and RDW, and the NLR was calculated. The correlation between the detection indicators was analyzed and receiver operating characteristic (ROC) curve was drawn to analyze the detection significance of related indicators. Results There were no statistical differences in the levels of Hb and PLT between the exacerbation group and the stable group (P>0.05). The levels of WBC, NLR, RDW and high-sensitivity C-reactive protein (hs-CRP) in the exacerbation group were significantly higher than those in the stable group (all P<0.05). NLR in the patients with acute exacerbation of COPD was positively correlated with serological indicators of WBC and hs-CRP (all P<0.05). ROC curve showed that the sensitivity and specificity of NLR in the diagnosis of acute exacerbation of COPD were 92.0% and 68.0% respectively, those of RDW were 91.0% and 58.0% respectively, those of hs-CRP were 77.0% and 71.0% respectively, and those of NLR+RDW were 90.0% and 73.0% respectively. NLR had the highest diagnostic specificity, RDW had the highest diagnostic sensitivity, and NLR+RDW had the best diagnostic efficiency. Conclusions Serological indicators of WBC, hs-CRP, NLR and RDW in patients with acute exacerbation of COPD will be abnormally increased, and NLR has a positive correlation with WBC and hs-CRP. NLR and RDW have high specificity and high sensitivity respectively in the diagnosis of patients with exacerbation of COPD, and their detection can strengthen the diagnosis and mastery of disease in patients.
Objective To explore the possible anti-inflammatory mechanism of peroxisome proliferators-activated receptor（PPAR） gamma-agonists by investigating the effects of Rosiglitazone on the expression of phosphorylation of signal transducer and activator of transcription 6（p-STAT6） and the secretion of interleukin（IL）-4 in T-lymphocytes from patients with acute asthma.Methods Peripheral blood T-lymphocytes from 10 healthy volunteers（group A） and 10 patients with acute asthma were isolated，purificated and cultured.T-lymphocytes from the asthma patients were divided into a control group（group B） and a Rosiglitazone treated group（group C）.Rosiglitazone was added with a single dose of 10-4 mol/L at 0 hour of cultrue.After cultured for 48 hours，the concentration of IL-4 in supernatant of each groups were detected by ELISA.The express of p-STAT6 in the T-lymphocytes were determined by Western blot and immunohistochemical techniques.Results The levels of IL-4 were increased markedly in group B than those in group A and group C[（170.34±9.05）pg/mL vs（76.82±7.06）pg/mL and（123.59±8.70）pg/mL，both Plt;0.01]，and which in group C was significantly lower than group A（Plt;0.01）.The levels of p-STAT6 in T lymphocytes were increased markedly in group B than in group A and C[Western blot：（6.28±0.19 vs 3.07±0.18 and 4.12±0.16；immunohistochemistry：（36.58%±7.41）% vs（11.39±4.02）% and（23.92±5.8）%，all Plt;0.01），and which in group C were significantly higher than that in group B（both Plt;0.01）.There was a positive correlation between the level of p-STAT6 and IL-4（Plt;0.01）.Conclusion The levels of p-STAT6 and IL-4 in T-lymphocytes of patients with acute asthma were suppressed by Rosiglitazone in vitro.
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.
Twenty patients with chronic lymphedema had been treated by microwave heating. T-lympocyte subpopulation and HLA-DR phenotype of peripheral blood in patientswith lymphedema were examined by using dual colour flow cytometry before and after treatment. We found that CD4 (T helpe/inducer) in chronic lymphedema decreased significantly (Plt;0.01), HLA-DR increased significantly (P lt;0.05). After the microwave treatment, the CD4, CD4/CD8 ratio increased significantly; HLA-DR, HLA-DR+CD+8 lymphocyte reduced. It was clear that microwave could regulate the immunological disorder of lymphedema patients.
ObjectiveTo identify differences in blood routine indicators between lung cancer patients and healthy controls, and between different subgroups of lung cancer patients, so as to improve the early detection of lung cancer prognosis, and provide a basis for risk stratification and prognostic judgment for patients with lung cancer.MethodsThis study enrolled 1 227 patients pathologically diagnosed with lung cancer from December 2008 to December 2013 and 2 454 healthy controls 1∶2 matched by sex and age. The blood routine data of lung cancer patients were collected when they were first diagnosed with lung cancer. Gender and age stratified analysis of blood routine indicators between lung cancer patients and controls were conducted. Comparisons of blood routine indicators among lung cancer patients with different pathological types, stages, and prognosis were performed, followed by Cox regression survival analysis. Normally distributed quantitative variables were presented as mean ± standard deviation and non-normally distributed quantitative variables as medium (lower quartile, upper quartile).ResultsCompared to healthy controls, the counts of platelet [(206.84±80.47) vs. (175.27±55.74)×109/L], white blood cells [(7.04±2.29) vs. (6.08±1.40)×109/L], neutrophil [(4.90±2.08) vs. (3.61±1.07)×109/L], monocyte [0.42 (0.30, 0.54) vs. 0.33 (0.26, 0.42)×109/L], and eosinophil [0.14 (0.07, 0.24) vs. 0.12 (0.07, 0.19)×109/L], as the well as neutrophil-lymphocytes ratio (3.91±2.82 vs. 2.03±0.89) and platelet-lymphocyte ratio (160.35±96.06 vs. 96.93±38.02) in lung cancer patients increased significantly, while the counts of red blood cells [(4.41±0.58) vs. (4.85±0.51)×1012/L] and lymphocyte [(1.49±0.60) vs. (1.93±0.59)×109/L] in lung cancer patients decreased, and the differences were statistically significant (P<0.05). The counts of platelet, red blood cells, white blood cells, neutrophil, and monocyte differed among patients with different pathological types, tumor stages, and prognosis (P<0.05). Neutrophil-lymphocytes ratio and platelet-lymphocyte ratio were higher in squamous cell carcinoma patients than those in other pathological patients, higher in advanced lung cancer patients than those in early stage patients, and higher in dead lung cancer patients than those in survival patients (P<0.05). Neutrophil-lymphocyte ratio was an independent factor affecting the prognosis of lung cancer [hazard ratio=1.077, 95% confidence interval (1.051, 1.103), P<0.001].ConclusionsThe inflammatory index of blood routine indicators are higher in lung cancer patients than those in healthy controls, which indicates that lung cancer is closely related to chronic inflammation. There are significant differences in blood routine inflammation index among lung cancer patients with different pathological types, stages, and prognosis, which reflects the heterogeneity and complexity of lung cancer. Neutrophil-lymphocytes ratio inverse correlates with the prognosis of lung 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 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.