Study of tumor necrosis factor receptor in the inflammatory bowel disease

Ulcerative colitis(UC)and Crohn’s disease(CD)are part of Inflammatory Bowel Diseases(IBD)and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells.In addition,the main inflammatory mediator is related to the tumor necrosis factor-alpha(TNF-α).TNF-αis a mediator of the intestinal inflammatory processes,thus being one of the main cytokines involved in the pathogenesis of IBD,however,its levels,when measured,are present in the serum of patients with IBD.In addition,TNF-αplays an important role in promoting inflammation,such as the production of interleukins(IL),for instance IL-1βand IL-6.There are two receptors for TNF as following:The tumor necrosis factor 1 receptor(TNFR1);and the tumor necrosis factor 2 receptor(TNFR2).They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity.The soluble TNF form binds to the TNFR1 receptor with,and its activation results in a signaling cascade effects such as apoptosis,cell proliferation and cytokine secretion.In contrast,the transmembrane TNF form can bind both to TNFR1 and TNFR2.Recent studies have suggested that TNF-αis one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD,since TNF levels are present in the serum of both patients with UC and CD.Intravenous and subcutaneous biologics targeting TNF-αhave revolutionized the treatment of IBD,thus becoming the best available agents to induce and maintain IBD remission.The application of antibodies aimed at neutralizing TNF-αin patients with IBD that induce a satisfactory clinical response in up to 60%of patients,and also induced long-term maintenance of disease remission in most patients.It has been suggested that anti-TNF-αagents inactivate the pro-inflammatory cytokine TNF-αby direct neutralization,i.e.,resulting in suppression of inflammation.However,anti-TNF-αantibodies perform more complex functions than a simple blockade.

Up-regulation of tumor necrosis factor-a pathway survival genes and of the receptor TNFR2 in gastric cancer

BACKGROUND Gastric carcinogenesis can be induced by chronic inflammation triggered by Helicobacter pylori(H. pylori) infection. Tumor necrosis factor(TNF)-α and its receptors(TNFR1 and TNFR2) regulate important cellular processes, such as apoptosis and cell survival, and the disruption of which can lead to cancer. This signaling pathway is also modulated by microRNAs(miRNAs), altering gene expression.AIM To evaluate the mRNA and miRNAs expression involved in the TNF-α signaling pathway in gastric cancer(GC) tissues and its relationship.METHODS Quantitative polymerase chain reaction(qPCR) by TaqMan? assay was used to quantify the RNA transcript levels of TNF-α signaling pathway(TNF, TNFR1,TNFR2, TRADD, TRAF2, CFLIP, NFKB1, NFKB2, CASP8, CASP3) and miRNAs that targets genes from this pathway(miR-19 a, miR-34 a, miR-103 a, miR-130 a,miR-181 c) in 30 GC fresh tissue samples. Molecular diagnosis of H. pylori was performed by nested PCR for gene HSP60. A miRNA:mRNA interaction network was construct using Cytoscape v3.1.1 from the in silico analysis performed using public databases.RESULTS Up-regulation of cellular survival genes as TNF, TNFR2, TRADD, TRAF2, CFLIP,and NFKB2, besides CASP8 and miR-34 a was observed in GC tissues, whereas mediators of apoptosis such as TNFR1 and CASP3 were down-regulated. When the samples were stratified by histological type, the expression of miR-103 a and miR-130 a was significantly increased in the diffuse-type of GC compared to the intestinal-type. However, no influence of H. pylori infection was observed on the expression levels of mRNA and miRNAs analyzed. Moreover, the miRNA:mRNA interaction network showed several interrelations between the miRNAs and their target genes, highlighting miR-19 a and miR-103 a, which has as predicted or validated target a large number of genes in the TNF-α pathway,including TNF, TNFR1, TNFR2, CFLIP, TRADD, CASP3 and CASP8.CONCLUSION Our findings show that cell survival genes mediated by TNF/TNFR2 binding is up-regulated in GC favoring its pro-tumoral effect, while pro-apoptotic genes as CASP3 and TNFR1 are down-regulated, indicating disbalance between apoptosis and cell proliferation processes in this neoplasm. This process can also be influenced by an intricate regulatory network of miRNA:mRNA.

Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas

AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-α and its receptors in 62 colorectal adenoma patients and 34 healthy controls. The protein expression of TNF-α, TNF-R1, TNF-R2 and downstream signals of the TNF receptors, such as c-Jun N-terminal kinase (JNK), nuclear factor-κ B and caspase-3, were also investigated in human colorectal adenomas and in normal colorectal mucosal tissues by immunohistochemistry. Immunofluorescence confocal microscopy was used to investigate the consistency of expression of TNF-R1 and phospho-JNK (p-JNK). RESULTS: The serum levels of soluble TNF-R1 (sTNF-R1) in adenoma patients were significantly higher than in the control group (3.67 ± 0.86 ng/mL vs 1.57 ± 0.72 ng/mL, P < 0.001). Receiver operating characteristic analysis revealed the high diagnostic sensitivity of TNF-R1 measurements (AUC was 0.928) for the diagnosis of adenoma, and the best cut-off level of TNF-R1 was 2.08 ng/mL, with a sensitivity of 93.4% and a specificity of 82.4%. There were no significant differences in the serum levels of TNF-α or sTNF-R2 between the two groups. Immunohistochemistry showed high levels of TNF-R1 and p-JNK expression in the epithelial cells of adenomas. Furthermore, a high incidence of co-localization of TNF-R1 and p-JNK was identified in adenoma tissue. CONCLUSION: TNF-R1 may be a promising biomarker of colorectal adenoma, and it may also play an important role in the very early stages of colorectal carcinogenesis.

Increase of tumor necrosis factor receptor 1 expression in women with unexplained early spontaneous abortion

Objective: To investigate membrane tumor necrosis factor receptor 1 protein expression level in decidua and concentration of soluble tumor necrosis factor receptor 1 in serum in women with unexplained early spontaneous abortion, threatened abortion, and compare the levels with healthy pregnant women. Methods: Thirty-seven women with unexplained early spontaneous abortion, 27 women with threatened abortion, and 34 healthy pregnant women undergoing artificial abortion of pregnancy at 6 - 10 weeks of gestation were selected. Decidual samples were collected when women were undergoing artificial abortion, and blood samples were collected at the same time. The level of membrane tumor necrosis factor receptor 1 in decidua was detected by flow cytometer, and the concentration of soluble tumor necrosis factor receptor 1 in sera was measured with an enzyme-linked immunosorbent assay. Results: The percentages of membrane tumor necrosis factor receptor 1 positive decidual cells were 16.42 ± 7.10 Mean ± SD for women with unexplained early spontaneous abortion and 13. 14 ± 6.30 for healthy pregnant women ( P < 0.05). Serum concentration of soluble tumor necrosis factor receptor 1 was significantly higher in women with unexplained early spontaneous abortion than in healthy pregnant women and in women with threatened abortion, and no difference was found between healthy pregnant women and women with threatened abortion. Conclusion: Women with unexplained early spontaneous abortion present significantly higher expression of tumor necrosis factor receptor 1 than healthy pregnant women, suggesting that over-expression of tumor necrosis factor receptor 1 may contribute to the development of early spontaneous abortion.

The interleukin-1 receptor antagonist (IL-1-Ra) and soluble tumor necrosis factor receptor I (sTNF RI) in periodontal disease

The course and severity of periodontitis can be significantly affected by bacterial virulence as well as host immunity dysfunction. Periodontal tissue destruction has been proved to result from cascade of cytokines synthesized by reactive cells upon stimulation by pathogenic bacteria and lipopolysaccharides within their cell membranes. The clinical use of genetically programmed cells, producing substances blocking IL-1, based on recombinant IL-1 antagonist, as well as cytokines activating fibroblasts and osteoblasts to regenerate the destroyed periodontal tissue could prove alternative to the conventional treatment. Another cytokine of interest in respect to periodontitis ethiopathogenesis is soluble tumor necrosis factor receptor I (sTNF RI). Observation of soluble TNF receptors as physiologic inhibitors of TNF led to its administration in therapeutic process as well as in therapy selected cases of aggressive periodontitis.

Tumor necrosis factor alpha receptor 1 deficiency in hepatocytes does not protect from non-alcoholic steatohepatitis, but attenuates insulin resistance in mice

BACKGROUND End-stage liver disease caused by non-alcoholic steatohepatitis(NASH)is the second leading indication for liver transplantation.To date,only moderately effective pharmacotherapies exist to treat NASH.Understanding the pathogenesis of NASH is therefore crucial for the development of new therapies.The inflammatory cytokine tumor necrosis factor alpha(TNF-α)is important for the progression of liver disease.TNF signaling via TNF receptor 1(TNFR1)has been hypothesized to be important for the development of NASH and hepatocellular carcinoma in whole-body knockout animal models.AIM To investigate the role of TNFR1 signaling in hepatocytes for steatohepatitis development in a mouse model of diet-induced NASH.METHODS NASH was induced by a western-style fast-food diet in mice deficient for TNFR1 in hepatocytes(TNFR1ΔHEP)and their wild-type littermates(TNFR1fl/fl).Glucose tolerance was assessed after 18 wk and insulin resistance after 19 wk of feeding.After 20 wk mice were assessed for features of NASH and the metabolic syndrome such as liver weight,liver steatosis,liver fibrosis and markers of liver inflammation.RESULTS Obesity,liver injury,inflammation,steatosis and fibrosis was not different between TNFR1ΔHEP and TNFR1fl/fl mice.However,Tnfr1 deficiency in hepatocytes protected against glucose intolerance and insulin resistance.CONCLUSION Our results indicate that deficiency of TNFR1 signaling in hepatocytes does not protect from diet-induced NASH.However,improved insulin resistance in this model strengthens the role of the liver in glucose homeostasis.

Effects of Irbesartan and Metformin on tumor necrosis factor receptor and monocyte chemotactic protein 1 in patients with early diabetic nephropathy

Objective: To explore the effect of Irbesartan and Metformin on tumor necrosis factor receptor 1 and monocyte chemoattractant protein-1 in patients with early diabetic nephropathy. Methods: A total of 162 patients with early diabetic nephropathy who had been admitted to the Hospital between February 2017 and February 2018 were randomly assigned into a Metformin group, an Irbesartan group, and a combination therapy group. The Metformin group were treated with oral Metformin, those in the Irbesartan group were given oral Irbesartan for treatment, and the combination therapy group was treated with Metformin combined with Irbesartan. After 3 months of continuous treatment, the levels of sTNFR1, high-sensitivity C-reactive protein, monocyte chemoattractant protein-1, glucose metabolism index, proteinuria, and serum creatinine levels in the two groups were compared. Results:After treatment, the levels of sTNFR1, sICAM-1, hs-CRP, and MCP-1 in the three groups decreased compared with those before treatment, and the levels in the combination therapy group were all shown to be lower than those of the Metformin group and the Irbesartan group, with statistically significant differences (P<0.05). The levels of glycosylated hemoglobin and fasting blood glucose in the three groups were significantly lower than before treatment, and those in the combination therapy group were lower than the Metformin group and Irbesartan group, where the difference was statistically significant (P<0.05). The 24-hour urinary protein quantification, urinary albumin excretion rate, and serum creatinine in the combination therapy group were lower than those in the Metformin group and in the Irbesartan group, where the differences were statistically significant (P<0.05). Conclusion: The effects of metformin combined with irbesartan on early diabetic nephropathy patients were significant, which can effectively reduce the levels of serum sTNFR1 and MCP-1, relieve inflammation and improve glucose metabolism and proteinuria level.

Effect of Llinagliptin on tumor necrosis factor receptor and monocyte chemoattractant protein-1 in patients with diabetic nephropathy

Objective:To explore the effect of Linagliptin on tumor necrosis factor receptor and monocyte chemoattractant protein-1 in patients with diabetic nephropathy.Methods: A total of 98 patients with diabetic nephropathy admitted to the Hospital from January 2017 to September 2018 were enrolled. The patients were divided into two groups according to the random double-blind method, with 49 cases in each group. The control group was treated with Metformin, whereas the experimental group was treated with Linagliptin plus Metformin. After 3 months of continuous treatment, the renal function [urinary albumin excretion rate, 24 h urine protein quantitation and serum creatinine], glycolipids metabolic levels [glycated hemoglobin, fasting blood glucose, total cholesterol and triglycerides], monocyte chemoattractant protein-1, tumor necrosis factor receptor, high-sensitivity C-reactive protein, and adverse reactions were compared between the two groups.Results:After 3 months of treatment, the levels of UAER, 24 h Upor and Scr in the experimental group were shown to be lower than those in the control group, and the difference was statistically significant. After 3 months of treatment, the levels of HbA1c, FPG, TC and TG in the experimental group were shown to be lower than the control group, and the difference was statistically significant. After 3 months of treatment, the levels of MCP-1, sTNFR1 and hs-CRP in the experimental group were lower than those in the control group, and the difference was statistically significant. There was no significant difference in incidence of adverse reactions between the two groups.Conclusion: For patients with diabetic nephropathy, Linagliptin is with higher safety, which can help improve their glycolipids metabolic levels and renal function, reduce the inflammatory response and the levels of MCP-1 and sTNFR1, and yet incur fewer adverse reactions.

肺癌组织中ERO1L、TNFRSF4的表达与患者免疫功能、炎症反应因子及预后的关系

目的探究肺癌组织中内质网氧化物蛋白(ERO1L)、肿瘤坏死因子受体4(TNFRSF4)的表达与肺癌患者免疫功能、炎症反应因子及其预后的关系。方法选取2018年7月~2020年7月于本院进行手术治疗的108例肺癌患者,收集术中留取的癌组织和癌旁组织标本。采用qRT-PCR检测ERO1L和TNFRSF4的mRNA相对表达量;使用免疫组织化学法检测ERO1L和TNFRSF4蛋白表达情况,分析二者表达水平与患者临床病理特征的关系,采用Kaplan-Meier法分析ERO1L、TNFRSF4蛋白表达水平与患者预后的关系。肺癌患者预后生存率的影响因素采用Cox多因素分析。结果肺癌患者癌组织中ERO1L mRNA表达水平显著高于癌旁组织,TNFRSF4 mRNA表达水平显著低于癌旁组织(P<0.05);肺癌组织中ERO1L蛋白高表达率显著高于癌旁组织,TNFRSF4蛋白高表达率显著低于癌旁组织(P<0.05)。ERO1L蛋白高表达组患者CD3^(+)、CD4^(+)显著低于低表达组(P<0.05),IL-1β、IL-6、TNF-α显著高于低表达组(P<0.05);TNFRSF4蛋白高表达组患者CD3^(+)、CD4^(+)显著高于低表达组,IL-1β、IL-6、TNF-α显著低于低表达组(P<0.05)。ERO1L高表达组患者3年累积生存率显著低于低表达组(Log rankχ^(2)=6.100,P=0.014),TNFRSF4高表达组患者3年累积生存率显著高于低表达组(Log rankχ^(2)=11.296,P=0.001)。肺癌组织的低分化、淋巴结转移、TNM分期为Ⅲ-Ⅳ期、ERO1L高表达、TNFRSF4低表达是影响患者生存率的危险因素。结论肺癌组织中ERO1L、TNFRSF4表达与患者免疫功能、炎症因子以及预后具有一定关系。

急性心肌梗死患者血清sTNFR1、CD137水平变化对MACE的影响及发生MACE的影响因素分析

目的探讨急性心肌梗死(AMI)患者血清可溶性肿瘤坏死因子受体1(sTNFR1)、白细胞分化抗原-137(CD137)水平变化对心血管不良事件(MACE)的影响及发生MACE的影响因素。方法前瞻性选取2019年10月至2022年3月商洛市中心医院收治的AMI患者120例作为观察组,并根据AMI患者MACE发生情况分为MACE组(n=25)及非MACE组(n=95),另选取同期来我院体检的健康者120名作为对照组。收集AMI患者一般资料与临床特征:性别、年龄、体重指数、合并糖尿病、高脂血症、高血压、Killip心功能分级、饮酒史、吸烟史、左心室射血分数、预后危险[心肌梗死溶栓(TIMI)评分]、脑钠肽、肌钙蛋白T水平。比较观察组与对照组、MACE组与非MACE组的血清sTNFR1、CD137水平。采用Pearson相关性分析法分析sTNFR1、CD137与AMI后MACE发生的相关性。采用单因素分析和多因素Logistics回归分析对影响AMI后MACE的因素进行分析。结果观察组sTNFR1、CD137水平分别为(372.53±65.26)μg/L、(125.75±23.67)pg/mL,均高于对照组[(231.56±46.80)μg/L、(71.43±11.57)pg/mL],差异均有统计学意义(P<0.05)。MACE组sTNFR1、CD137水平分别为(398.64±45.73)μg/L、(154.56±23.57)pg/mL,均高于非MACE组[(347.83±61.72)μg/L、(106.84±20.65)pg/mL],差异均有统计学意义(P<0.05)。Pearson相关分析结果显示,sTNFR1、CD137与AMI后MACE发生情况呈正相关(P<0.05)。非MACE组与MACE组患者性别、体重指数、饮酒史、左心室射血分数比较,差异均无统计学意义(P>0.05),非MACE组与MACE组患者年龄、合并糖尿病、高脂血症、高血压、Killip心功能分级、吸烟史、TIMI评分、脑钠肽、肌钙蛋白T水平比较,差异均有统计学意义(P<0.05)。以合并MACE为因变量,结果显示,心功能分级、吸烟史、TIMI、脑钠肽、sTNFR1、CD137为AMI后MACE的独立危险因素(P<0.05)。结论AMI患者MACE发生后会导致sTNFR1、CD137水平升高,且心功能分级、吸烟史、TIMI评分、脑钠肽、sTNFR1、CD137为AMI后MACE的独立危险因素。

Tumor necrosis family receptor superfamily member 9/tumor necrosis factor receptor-associated f

Hepatitis C virus(HCV)infection is an excellent immunological model for understanding the mechanisms developed by non-cytopathic viruses and tumors to evade the adaptative immune response.The antigen-specific cytotoxic T cell response is essential for keeping HCV under control,but during persistent infection,these cells become exhausted or even deleted.The exhaustion process is progressive and depends on the infection duration and level of antigenemia.During high antigenic load and long duration of infection,T cells become extremely exhausted and ultimately disappear due to apoptosis.The development of exhaustion involves the impairment of positive co-stimulation induced by regulatory cytokines,such as transforming growth factor beta 1.This cytokine downregulates tumor necrosis factor receptor(TNFR)-associated factor 1(TRAF1),the signal transducer of the T cell co-stimulatory molecule TNFR superfamily member 9(known as 4-1BB).This impairment correlates with the low reactivity of T cells and an exhaustion phenotype.Treatment with interleukin-7 in vitro restores TRAF1 expression and rescues T cell effector function.The process of TRAF1 loss and its in vitro recovery is hierarchical,and more affected by severe disease progression.In conclusion,TRAF1 dynamics on T cells define a new pathogenic model that describes some aspects of the natural history of HCV,and sheds light on novel immunotherapy strategies for chronic viral infections and cancer.

血清肿瘤坏死因子受体相关因子3和卵泡抑素样蛋白1检测对系统性红斑狼疮患者吗替麦考酚酯治疗无效的预测价值

目的:分析血清肿瘤坏死因子受体相关因子3(TRAF3)和卵泡抑素样蛋白1(FSTL1)水平检测对系统性红斑狼疮患者吗替麦考酚酯治疗无效的预测价值。方法:选择系统性红斑狼疮患者58例为研究对象,采用吗替麦考酚酯治疗,根据治疗效果分为有效组(45例)和无效组(13例)。检测血清TRAF3、FSTL1水平,分析TRAF3、FSTL1与系统性红斑狼疮患者吗替麦考酚酯治疗效果的关系,以及血清TRAF3、FSTL1对系统性红斑狼疮患者吗替麦考酚酯治疗无效的预测价值。结果:系统性红斑狼疮患者经吗替麦考酚酯治疗后,血清TRAF3、FSTL1水平降低(均P<0.05)。与无效组比较,有效组血清TRAF3、FSTL1水平降低(均P<0.05)。Logistic回归分析结果显示,TRAF3、FSTL1是系统性红斑狼疮患者吗替麦考酚酯治疗效果的影响因素(均P<0.05)。ROC曲线分析显示,血清TRAF3、FSTL1对系统性红斑狼疮患者吗替麦考酚酯治疗无效具有一定的预测价值,且联合检测预测价值更高(均P<0.05)。结论:血清TRAF3、FSTL1高表达与系统性红斑狼疮患者吗替麦考酚酯治疗无效相关,两者联合检测能提升系统性红斑狼疮患者治疗无效风险的预测价值。

基于Traf6/TAK1通路探讨维生素D对甲状腺功能减退肾损伤幼鼠肾小管上皮细胞间充质转化的影响

目的探讨维生素D(VD)对甲状腺功能减退(HT)肾损伤幼鼠肾小管上皮细胞间充质转化(EMT)的影响,以及其对肿瘤坏死因子受体相关因子6(Traf6)/转化生长因子-β活化激酶1(TAK1)通路的调控机制。方法通过丙基硫尿嘧啶(PTU)灌胃构建幼鼠HT模型,以过表达TAK1(pc DNA3.1-TAK1)作功能挽救实验;50只SPF级雄性SD大鼠分为正常组、HT组、VD低剂量(HT+VD-L)组、VD高剂量(HT+VD-H)组、HT+VD-H+pc DNA3.1-TAK1(HT+VD-H+pc)组,每组10只。全自动生化仪检测各组大鼠血清血肌酐(Scr)和血尿素氮(BUN)的含量;脱氧核糖核苷酸末端转移酶介导的缺口末端标记法试剂盒(TUNEL)检测肾组织中的细胞凋亡;免疫组化检测肾组织中转化生长因子β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)和上皮钙黏蛋白(E-cadherin)的表达;Western blot法检测肾组织中B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、Traf6、TAK1和磷酸化TAK1(p-TAK1)的表达。结果VD能明显降低HT幼鼠血清中Scr和BUN的含量,下调肾组织中的细胞凋亡率,降低肾组织中TGF-β1和α-SMA的表达,上调E-cadherin的表达;抑制肾组织中Traf6、p-TAK1和Bax的表达,升高肾组织中Bcl-2的表达,差异均具有统计学意义(均P<0.05)。结论维生素D能抑制HT幼鼠肾小管上皮细胞的EMT,降低肾组织中的细胞凋亡率,减轻肾组织的病理损伤,改善其肾功能,这与抑制Traf6/TAK1信号的激活有关。

血清NCAM sTNFR1水平与超时间窗后循环脑卒中患者接受替罗非班治疗后神经预后的关系分析

目的探讨血清神经细胞黏附分子(NCAM)、可溶性肿瘤坏死因子受体1(sTNF-R1)水平与超时间窗后循环脑卒中(APCIS)患者接受替罗非班治疗后神经预后的关系。方法选择2019-03—2022-01唐山中心医院收治的100例超时间窗APCIS患者(APCIS组)和63例健康体检志愿者(对照组),根据NIHSS评分将APCIS患者分为轻度损伤组(<6分,27例)、中度损伤组(6~13分,39例)、重度损伤组(≥14分,34例)。所有患者入组后均接受替罗非班经微导管动脉给药[0.4μg/(kg·min)]和静脉持续泵注[0.1μg/(kg·min)]治疗48 h,配合降脂以及双抗血小板治疗。检测血清NCAM、sTNF-R1水平,出院后定期随访90 d,统计随访期间不良神经预后发生情况。多因素Logistic回归分析APCIS患者接受替罗非班治疗后神经预后不良的危险因素,受试者工作特征曲线(ROC)分析NCAM、sTNF-R1预测APCIS患者接受替罗非班治疗后神经预后不良的价值。结果APCIS组血清NCAM、sTNF-R1水平高于对照组(P<0.05),重度损伤组血清NCAM、sTNF-R1水平高于中度损伤组和轻度损伤组(P<0.05),预后不良组血清NCAM、sTNF-R1水平高于预后良好组(P<0.05)。房颤、高NIHSS评分、高NCAM、高sTNF-R1是APCIS患者接受替罗非班治疗后神经预后不良的危险因素(P<0.05)。NCAM、sTNF-R1预测APCIS患者接受替罗非班治疗后神经预后不良的曲线下面积为0.698、0.770,联合预测曲线下面积为0.937,高于单独指标预测(P<0.05)。结论APCIS患者血清NCAM、sTNFR-1水平增高,且与APCIS神经缺损程度以及替罗非班治疗后神经预后不良有关。

雷公藤多苷联合他克莫司及激素治疗难治性肾病综合征的效果及对血清sTNF-R1、IGFBP-2、CFH水平的影响

目的 探讨雷公藤多苷联合他克莫司及激素治疗难治性肾病综合征(RNS)的疗效对血清可溶性肿瘤坏死因子受体1(s TNF-R1)、胰岛素样生长因子结合蛋白-2(IGFBP-2)、补体因子H(CFH)水平的影响。方法 研究对象为2018年8月至2021年8月于江南大学附属医院治疗的RNS患者102例,以随机数字表法分为对照组(n=51,采取甲泼尼龙片加他克莫司胶囊治疗)和观察组(n=51,在对照组基础上给予雷公藤多苷片治疗)。评估两组的治疗效果、血清相关指标,统计两组的不良反应。结果 观察组治疗总有效率(96.08%)高于对照组(80.39%)(χ^(2)=6.044,P=0.014);治疗后,观察组患者血清白蛋白、CFH水平[分别为(36.54±8.11) g·L^(-1)、(586.20±100.72)μg·m L^(-1)],高于对照组[分别为(32.58±6.12) g·L^(-1)、(540.11±100.47)μg·m L^(-1)],差异均有统计学意义(t=2.783,P=0.006;t=2.314,P=0.023);观察组患者24 h尿蛋白、肌酐、s TNF-R1、IGFBP-2水平[分别为(2.67±0.69) g、(82.25±16.13)μmol·L^(-1)、(1.56±0.45) ng·m L^(-1)、(51.34±10.44) ng·m L^(-1)],低于对照组[分别为(3.24±1.02) g、(92.68±17.35)μmol·L^(-1)、(1.91±0.58) ng·m L^(-1)、(57.79±12.58) ng·m L^(-1)],差异均有统计学意义(t=3.306,P=0.001;t=3.135,P=0.002;t=3.405,P=0.001;t=2.820,P=0.005);观察组复发率(1.96%)低于对照组(13.73%)(χ^(2)=4.883,P=0.027)。结论 公藤多苷联合他克莫司及激素治疗RNS效果佳,降低复发率,改善肾功能,减轻炎症,有望作为辅助治疗RNS的药物。

未足月胎膜早破患者血清和胎盘中可溶性髓系细胞触发受体-1与绒毛膜羊膜炎的相关性研究

目的探讨未足月胎膜早破(PPROM)患者血清和胎盘中可溶性髓系细胞触发受体-1(sTREM-1)及炎症介质TNF-α、IL-1β与绒毛膜羊膜炎(CA)的相关性,为疾病早期诊断提供敏感性标志物。方法收集2021年3月至2023年9月金华市中心医院收治的84例PPROM患者,平均孕周为(34.5±2.3)周。根据胎盘病理检查结果分为CA组40例和无CA组44例,并选择同期年龄和孕周匹配的正常妊娠者40例作为对照组。ELISA法检测产前孕妇血清sTREM-1、TNF-α和IL-1β水平,检查血液WBC、粒细胞百分比、CRP和降钙素原(PCT),Western blot法检测产后胎盘中sTREM-1、TNF-α和IL-1β蛋白相对表达量。分析血清和胎盘中各项检测指标的相关性。绘制ROC曲线,分析血清s TREM-1诊断PPROM和CA的效能。结果CA组血清sTREM-1、TNF-α、IL-1β、CRP和PCT水平均显著高于无CA组和对照组,无CA组sTREM-1、TNF-α和IL-1β水平均显著高于对照组(均P<0.05)。CA组胎盘sTREM-1、TNF-α和IL-1β蛋白相对表达量均显著高于无CA组(均P<0.05)。胎盘sTREM-1、TNF-α、IL-1β蛋白相对表达量与血清s TREM-1、TNF-α、IL-1β水平均两两呈正相关(均P<0.001)。血清sTREM-1、TNF-α和IL-1β诊断PPROM的AUC分别为0.916、0.785和0.815(均P<0.05);血清sTREM-1诊断CA的AUC为0.935(P<0.05)。结论PPROM患者血清s TREM-1升高可作为疾病诊断和CA评估的重要血清生化标志物。

感染性休克患者IRAK1和TRAF6的表达变化及临床意义研究

目的探讨感染性休克患者白细胞介素-1受体相关激酶1(IRAK1)、肿瘤坏死因子相关受体6(TRAF6)的表达变化及临床意义。方法以2020年11月至2022年11月该院收治的142例感染性休克患者(感染性休克组)为研究对象,并以同期来该院进行体检的体检者为对照组。根据感染性休克组患者住院观察治疗28 d后的生存状况分为生存组100例和死亡组42例,监测感染性休克患者入院时及治疗2、4、6 d后的IRAK1、TRAF6表达变化,并记录患者急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分和序贯器官功能衰竭评估(SOFA)评分动态变化;Spearman相关性分析评价感染性休克患者IRAK1、TRAF6与APACHEⅡ评分、SOFA评分的相关性;Pearson相关性分析IRAK1与TRAF6的相关性;Logistic回归分析感染性休克患者生存状况的影响因素。通过受试者工作特征曲线分析IRAK1、TRAF6对感染性休克患者生存状况的诊断价值。结果入院时感染性休克组IRAK1、TRAF6相对表达水平显著低于对照组,APACHEⅡ评分、SOFA评分显著高于对照组,差异有统计学意义(P<0.05)。与入院时比较,治疗2、4、6 d后两组IRAK1、TRAF6相对表达水平均显著升高,APACHEⅡ评分、SOFA评分均显著降低,差异有统计学意义(P<0.05);与死亡组比较,生存组在各个相应时间点IRAK1、TRAF6相对表达水平均较高,APACHEⅡ评分、SOFA评分均较低,差异有统计学意义(P<0.05)。相关性分析显示,感染性休克患者IRAK1、TRAF6与APACHEⅡ评分、SOFA评分均呈负相关,IRAK1与TRAF6呈正相关(r=0.688,P<0.05)。IRAK1、TRAF6及APACHEⅡ评分是影响感染性休克患者生存状况的独立危险因素(P<0.05)。IRAK1、TRAF6联合诊断的曲线下面积(AUC)显著大于IRAK1单独诊断的AUC(Z=2.044,P=0.041),以及TRAF6单独诊断的AUC(Z=2.442,P=0.015)。结论感染性休克患者IRAK1、TRAF6的表达可评估患者生存及预后状况。

血清SGK1、TRAP1、FOXQ1与晚期胃癌患者化疗疗效和 预后的关系研究

目的探讨晚期胃癌患者血清中血清和糖皮质激素调节蛋白激酶1(SGK1)、肿瘤坏死因子受体相关蛋白1(TRAP1)、叉头框蛋白Q1(FOXQ1)水平与化疗疗效和预后的关系。方法选择2017年10月至2020年10月该院收治的127例晚期胃癌患者(胃癌组),均接受SOX方案(奥沙利铂+替吉奥)化疗至少2个周期,根据化疗疗效分为有效组(52例)和无效组(75例)。另选择该院的62例体检健康的志愿者为对照组。检测并比较各组血清SGK1、TRAP1、FOXQ1水平。患者出院后随访2年。采用受试者工作特征(ROC)曲线分析SGK1、TRAP1、FOXQ1预测胃癌化疗疗效的价值,Kaplan-Meier生存曲线和Cox比例风险回归分析SGK1、TRAP1、FOXQ1与晚期胃癌化疗疗效及预后的关系。结果胃癌组血清SGK1、TRAP1、FOXQ1水平均高于对照组(P<0.05),无效组血清SGK1、TRAP1、FOXQ1水平均高于有效组(P<0.05)。SGK1、TRAP1、FOXQ1预测胃癌化疗疗效的曲线下面积(AUC)分别为0.836、0.833、0.778,联合预测的AUC为0.917,高于单独指标预测。SGK1高水平、TRAP1高水平、FOXQ1高水平的晚期胃癌患者总生存期(OS)生存率低于SGK1低水平、TRAP1低水平、FOXQ1低水平的晚期胃癌患者(Log-Rank χ^(2)=12.092、10.825、11.653,P<0.05)。多因素Cox比例风险回归结果显示,化疗耐药、SGK1高水平、TRAP1高水平、FOXQ1高水平是晚期胃癌患者预后不良的危险因素(P<0.05)。结论晚期胃癌患者血清SGK1、TRAP1、FOXQ1水平均升高,其与化疗疗效差及低OS生存率有关。

肿瘤坏死因子-α、可溶性血管内皮生长因子受体-1在妊娠期高血压疾病大鼠血清及胎盘中的表达水平及意义

目的:探讨肿瘤坏死因子-α(TNF-α)、可溶性血管内皮生长因子受体-1(sFlt-1)在妊娠期高血压疾病(HDCP)大鼠血清及胎盘中的表达水平及意义。方法:选择20只孕鼠,随机分为HDCP组和对照组,每组各10只,HDCP组于妊娠14 d时,皮下注射L-精氨酸甲酯,连续7 d,建立HDCP大鼠模型,对照组皮下注射等体积0.9%氯化钠溶液。妊娠21 d时,比较各组大鼠血压、24 h尿蛋白含量,记录胎盘重量、胎鼠重量、胎鼠身长,苏木精伊红(HE)染色观察各组胎盘组织结构,原位末端标记技术(Tunel)检测胎盘组织细胞凋亡情况,蛋白质免疫印迹(WB)法检测胎盘组织TNF-α、sFlt-1蛋白表达水平。结果:HDCP组胎鼠重量、胎盘重量、胎鼠身长低于对照组(均P<0.05)。HDCP组大鼠妊娠21 d血压及尿蛋白含量高于妊娠14 d,HDCP组大鼠妊娠14、21 d血糖及尿蛋白含量高于对照组(均P<0.05)。HDCP组大鼠血清TNF-α、sFlt-1水平高于对照组(均P<0.05)。对照组大鼠胎盘组织形态和结构正常,细胞完整。HDCP组大鼠胎盘组织细胞结构不完整,绒毛数目减少,且绒毛大部分不成熟。对照组胎盘组织凋亡细胞较少,HDCP组胎盘组织细胞凋亡率高于对照组(均P<0.05)。HDCP组大鼠胎盘组织中TNF-α、sFlt-1蛋白表达高于对照组(均P<0.05)。结论:TNF-α、sFlt-1高表达可能与妊娠期高血压疾病发生密切相关。

MCPIP1和TRAF6水平与肾细胞癌患者远端转移风险及预后的关系

目的探讨单核细胞趋化蛋白-1诱导蛋白-1(MCPIP1)和肿瘤坏死因子受体相关因子6(TRAF6)水平与肾细胞癌(RCC)患者远端转移风险及预后的关系。方法选取2017年3月至2020年4月河北省秦皇岛市第二医院收治的223例RCC患者作为研究对象,根据是否发生远端转移将患者分为远端转移组(69例)和无远端转移组(154例)。比较远端转移组和无远端转移组临床资料。以RCC患者血清MCPIP1和TRAF6平均值为临界值,将患者分为MCPIP1高表达组、MCPIP1低表达组和TRAF6高表达组、TRAF6低表达组。采用Pearson相关分析RCC患者血清MCPIP1、TRAF6水平之间及二者与碱性磷酸酶水平的相关性。采用多因素Logistic回归分析RCC患者发生远端转移的危险因素。绘制受试者工作特征(ROC)曲线分析血清MCPIP1、TRAF6对RCC患者发生远端转移的诊断价值。采用Kaplan-Meier分析血清MCPIP1和TRAF6水平与RCC患者预后的关系。结果远端转移组血清MCPIP1水平低于无远端转移组,TRAF6水平高于无远端转移组,差异均有统计学意义(P<0.05)。远端转移组和无远端转移组TNM分期、碱性磷酸酶水平比较,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,MCPIP1水平降低、TRAF6水平升高、TNM分期为Ⅲ+Ⅳ期、碱性磷酸酶水平升高为RCC患者发生远端转移的危险因素(P<0.05)。ROC曲线分析结果显示,2项指标联合诊断RCC患者发生远端转移的曲线下面积(AUC)为0.940,显著高于单项检测的AUC(Z_(MCPIP1-联合)=2.217,P=0.027;Z_(TRAF6-联合)=5.481,P<0.001)。Pearson相关分析结果显示,RCC患者血清MCPIP1水平和TRAF6水平呈显著负相关(r=-0.459,P<0.001),血清MCPIP1水平与碱性磷酸酶水平呈负相关(r=-0.443,P<0.001),TRAF6水平与碱性磷酸酶水平呈正相关(r=0.471,P<0.05)。Kaplan-Meier曲线分析结果表明,MCPIP1高表达组3年累积生存率显著高于MCPIP1低表达组(χ^(2)=12.625,P<0.001),TRAF6高表达组3年累积生存率显著低于TRAF6低表达组(χ^(2)=10.128,P=0.001)。结论RCC转移患者血清MCPIP1水平降低,TRAF6水平升高,与发生RCC转移和预后不良有关。