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Objective:To investigate the factors influencing the prognosis of hepatitis B-related hepatocellular carcinoma treated with programmed death receptor 1 (PD-1) inhibitors, and to construct a prognostic nomogram model for these patients and evaluate its clinical significances.Methods:The clinical data of 121 patients with hepatitis B-related hepatocellular carcinoma treated with PD-1 inhibitors at the First Affiliated Hospital of Xinxiang Medical College from July 2018 to July 2021 were retrospectively analyzed. Follow-up was performed from the beginning of PD-1 inhibitor use, and the Kaplan-Meier method was used to analyze the overall survival of patients. The variables screened by the univariate Cox proportional hazards model analysis and variables clinically believed to be related to the prognosis were included in the multivariate Cox proportional hazards model for overall survival, and the stepwise regression method was used to screen the independent factors influencing overall survival. Based on the independent influencing factors of overall survival, R 3.5.1 software was used to construct a prognostic nomogram model for overall survival of hepatitis B-related hepatocellular carcinoma treated with PD-1 inhibitors. Calibration curve was used to the consistency of model prediction and practice. The Harrell consistency index and receiver operating characteristic (ROC) curve (with imaging diagnosis as the gold standard) were used to analyze the efficacy of model in predicting the 1-year and 2-year overall survival rates.Results:The median follow-up time of 121 patients was 12.40 months, and the median overall survival time was 14.30 months, with overall survival rates of 82.60% and 62.30% at 6 and 12 months. Multivariate Cox regression analysis showed that albumin (ALB) ( HR = 0.946, 95% CI 0.901-0.992), international normalized ratio (INR) ( HR = 32.034, 95% CI 5.046-203.362), aspartate aminotransferase (AST) ( HR = 1.010, 95% CI 1.007-1.012) were independent influencing factors for overall survival of patients. According to the three factors, a prognostic nomogram model for hepatitis B-related hepatocellular carcinoma treated with PD-1 inhibitors was constructed. The slope of the calibration curve of the model predicting 1-year and 2-year overall survival rates was close to 1. The Harrell consistency index of the nomogram model was 0.809 (95% CI 0.760-0.858). ROC curve analysis showed that the area under the curve (AUC) of the nomogram model predicting 1-year and 2-year overall survival rates of patients was 0.794 (95% CI 0.744-0.887, P < 0.001) and 0.791 (95% CI 0.708-0.860, P = 0.002). Conclusions:ALB, INR and AST are the influencing factors of prognosis of hepatitis B-related hepatocellular carcinoma patients treated with PD-1 inhibitors, and the nomogram model constructed based on prognostic influencing factors has a good effect on predicting the 1-year and 2-year overall survival rates of patients, which can be used to screen the population suitable for immunotherapy and is conducive to the clinical formulation of individualized and precise treatment plans.
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Objective:To investigate the characteristics of natural killer (NK) cell subsets and function in methicillin-resistant staphylococcus aureus (MRSA) sepsis, and to assess the influence of matrix metalloproteinase (MMP) to NK cell function in MRSA sepsis patients.Methods:Twenty-one MRSA sepsis patients who were hospitalized in our department between January 2017 and June 2018 were enrolled. Eleven healthy individuals were served as healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated. NK cell subsets were investigated by flow cytometry. NK cell function was assessed by measuring CD107a, CD69, and CD16 expression in co-culture system between PBMCs and different target cells. MMP mRNA was semi-quantified by real-time PCR in purified NK cells. The influence of NK cell function was assessed by measuring CD107a expression in co-culture system between NK cells with MMP inhibitor stimulation and target cells.Results:There was no significant difference of total NK cell percentage between healthy controls and MRSA sepsis patients ( P>0.05). CD56brightCD16 -NK [(5.36±1.02)% vs (4.30±0.89)%] and CD56 -CD16 +NK [(24.04±2.92)% vs (9.70±1.54)%] percentage was elevated ( P<0.05), while CD56dimCD16 +NK percentage [(71.22±13.03)% vs (87.64±7.05)%, P<0.01] was reduced in MRSA sepsis. NK cells recognized and killed target cells via different receptors upon activation. CD107a [(33.55±3.84)% vs (25.34±6.20)%] and CD69 percentage [(14.96±1.47)% vs(18.80±1.49)%] was decreased ( P<0.0001), while CD16 MFI was increased [(247.1±50.31) vs (189.4±57.54), P<0.01] in MRSA sepsis patients in comparison with healthy controls. MMP-1/2/3/9 mRNA relative levels were elevated in purified NK cells from MRSA sepsis patients ( P<0.01). Inhibition of MMP in NK cells from MRSA sepsis patients promoted CD107a percentage [(33.67±8.03)% vs (25.87±6.23)%, P=0.018]. Conclusions:NK cell subsets imbalance and exhaustion is existed in MRSA sepsis, which might be due to the MMP-induced down-regulation of antibody-dependent cell-mediated cytotoxicity.
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With the discovery of exosomes,new pathways of intercellular information and material exchange mediated by exosomes are attracting more and more attention from researchers. The process of exo-some production overlaps with many viral assembly and outflow pathways,suggesting that exosomes may be related to viral infections. In vitro experiments also show that exosomes play a very important role in viral in-fections. On one hand,exosomes can transfer viral nucleic acids and proteins,and may change microenviron-ment to promote the spread of infection. On the other hand,exosomes can induce immune responses by activa-ting antiviral pathways or transferring antiviral molecules. Do they promote or suppress the spread of infec-tion? What are the factors that affect their functions? In this paper,we review the role of exosomes in viral in-fection in order to provide a reference for better understanding the process of viral infection and immune re-sponses,and to provide a new train of thoughts for the prevention,diagnosis and treatment of viral diseases.
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Objective To investigate the changes of serum transforming growth factor-β1 (TGF-β1),interleukin-10(IL-10) and interferon-γ(INF-γ) in elderly patients with hepatic fibrosis and their correlation with hepatic fibrosis.Methods One hundred and thirty-three patients diagnosed by pathological hepatic tissue were enrolled as case group who were in the first affiliated hospital of Xinxiang Medical University from 2007 to 2013.The enzyme-linked immunosorbent assay (ELISA) was applied to detect of serum levels of TGF-β1,IL-10and IFN-γ.Meanwhile 21 healthy people were recruited as control group.Results Comparison with the control group,the levels of TGF-β1 and IL-10 were significantly higher(TGF-β1:(217.4 ± 7.5) ng/L vs.(57.2±4.8) ng/L,t =15.61,P＜0.01;IL-10:(29.6 ±3.2) ng/L vs.(15.1 ±7.5) ng/L,t =11.44,P＜0.01),while IFN-γlevel was lower ((51.9 ± 3.5) ng/L vs.(75.8 ± 5.9) ng/L,P =0.03) in case group.The serum levels of TGF-β1,IL-10,IFN-γand stages of hepatic fibrosis was correlated and the correlation coefficients were 0.786,0.644 and-0.822 respectively (P ＜ 0.05).Conclusion Serum levels of TGF-β1,IL-10 and IFN-γ in patients with hepatic fibrosis are proved to be with ability of predicting the development of hepatic fibrosis and the post treatment.
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Objectives The purpose of this study is to observe the effects of valsartan on hepapetic fibrosis. Methods Thirty male Sprague-Dawley rats were randomly divided into three groups: valsartan -prevetive group (A), modle group of hepatic fibrosis (B)and valsar-tan-treating group (C). The model of hepatic fibrosis in rats was induced by intraperitoneai injection of dimethylnitrosamine (DMN) for 4 weeks(2ml/kg everyday, three times a week). Valsartan (10mg/kg everyday) was given together with injection of DMN per intrngastric (Ig) in group A for 8 weeks. After stop injection of DMN, the S valsartan(10mg/kg, everyday)was given per Ig in group C for 4 weeks. After modeling, normal saline were given per Ig everyday in group B. At the end of eighth week, the histomorphylogic structure of the liver was ob-served with light microscope. Immunohistoebemical staining was used to evaluate the expression of a-SMA. Results In group B, there was a large necrotic area and a number of pesudolobes appeared in the liver tissue. In group A, there were normal hepatic cords. In the group C, there was fibrosis interval formation and portal area expansion and fibrotie intervals extending to the lobule. The quantitative analysis of Mas-son staining showed that the collagen quantities in group B was higher than that of other group(P<0.01). The collagen quantities in group A was lower than that of group C(P<0.05). The results of immanohistochemical staining showed that the expression of a-SMA in group B was strong positive, middle positive in group C, and weak positive in group A (P<0.05). Conclusion The valsartan has preventive and treatment effects on hepatic fibrosis in rats of hepatic fibrosis model induced by DMN, and the preventive effect of valsartan is better than its treatment effect. The valsartan can ameliorate the hver cirrhosis by partly suppressing the activation of HSC.
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Objective To observe the effects of Sanjia Yigan Granule (S-JG) on hepatic fibrosis and explore its mechanism related to anti-lipid peroxidation in rats. Methods Forty male SD rats were randomly divided into four groups: normal group, model group, and compound Salviae Miltiorrhizae (Sm) group and S-JG group. Dimethylnitrosamine was injected intraperitoneally for 4 weeks to induce hepatic fobrosis. At the same time of modeling, Sm and S-JG were given in the corresponding groups. The rats were killed after four weeks. The histomorphylogic structure of the liver tissues was observed under optical microscope; the levels of MDA and SOD in serum were determined by radioimmunoassay. Results Compared with those in normal group, the collagen area in Masson staining and level of serum MDA were inreased obviously, and the level of serum SOD was dereased obviously in model group (P