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.

Helicobacter pylori tumor necrosis factor-α inducing protein promotes cytokine expression via nuclear factor-κB

AIM:To study the effects of Helicobacter pylori(H. pylori)tumor necrosis factor-α(TNF)inducing protein (Tip-α)on cytokine expression and its mechanism. METHODS:We cloned Tip-αfrom the H.pylori strain 26695,transformed Escherichia coli with an expression plasmid,and then confirmed the expression product by Western blotting.Using different concentrations of Tip-αthat affected SGC7901 and GES-1 cells at different times,we assessed cytokine levels using enzyme-linked immunosorbent assay.We blocked SGC7901 cells with pyrrolidine dithiocarbamate(PDTC),a specific inhibitor of nuclear factorκB(NF-κB).We then detected interleukin(IL)-1βand TNF-αlevels in SGC7901 cells. RESULTS:Western blot analysis using an anti-Tip-α antibody revealed a 23-kDa protein,which indicated that recombinant Tip-αprotein was recombined successfully.The levels of IL-1β,IL-8 and TNF-αwere sig-nificantly higher following Tip-αinterference,whether GES-1 cells or SGC-7901 cells were used(P<0.05).However,the levels of cytokines(including IL-1β,IL-8 and TNF-α)secreted by SGC-7901 cells were greater than those secreted by GES-1 cells following treatment with Tip-αat the same concentration and for the same duration(P<0.05).After blocking NF-κB with PDTC, the cells(GES-1 cells and SGC-7901 cells)underwent interference with Tip-α.We found that IL-1βand TNF-αlevels were significantly decreased compared to cells that only underwent Tip-αinterference(P<0.05). CONCLUSION:Tip-αplays an important role in cyto-kine expression through NF-κB.

Hepatitis B virus X protein up-regulates tumor necrosis factor-α expression in cultured mesangial cells via ERKs and NF-κB pathways

Objective:To investigate the effects of hepatitis B virus(HBV)X protein(HBx)on the expression of tumor necrosis factor-α(TNF-α)in glomerular mesangial cells(GMCs)and the underlying intracellular signal pathways.Methods:The plasmid pCI-neo-X that carries the X gene of hepatitis B virus was transfected into cultured GMCs.HBx expression in the transfected GMCs was assessed by Western-blot.TNF-αprotein and mRNA were assessed by ELISA and semi-quantitative RT-PCR,respectively.Three kinase inhibitors-U0126,an inhibitor of extracellular signal-regulated kinases(ERKs);lactacvstin,an inhibitor of nuclear factor-κB(NF-κB);and SB203580,a selective inhibitor of p38 MAP kinase(p38 MAPK)were used to determine which intracellular signal pathways may underlie the action of HBx on TNF-αexpression in transfected GMCs.Results:A significant increase in HBx expression in pCI-neo-X transfected GMCs was detected at 36 h and 48 h,which was not affected by any of those kinase inhibitors mentioned above.A similar increase in the expression of both TNF-αprotein and mRNA was also observed at 36 h and 48 h,which was significantly decreased in the presence of U0126 or lactacytin,but not SB203580.Conclusions:HBx upregulates TNF-αexpression in cultured GMCs,possibly through ERKs and NF-κB pathway,but not p38 MAPK pathway.

Interleukin-1β,Tumor Necrosis Factor-α and Lipopolysaccharide Induce Expression of Monocyte Chemoattractant Protein-1 in Calf Aortic Smooth Muscle Cells

Summary: To investigate whether interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) induce expression of monocyte chemoattractant protein-1 (MCP-1 ) mRNA and protein in calf aortic smooth muscle cells(SMCs), calf aortic SMCs were cultured by a substrate-attached explant method. The cultured SMCs were used between the third to the fifth passage. After the cells became confluent, the SMCs were exposed to 2 ng/ml IL-1β, 20ng/ml TNF-1α and 100 ng/ml LPS respectively, and the total RNA of SMCs which were incubated for 4 h at 37℃ were extracted from the cells by using guanidinium isothiocyanate method. The expres- ion of MCP-1 mRNA in SMCs was detected by using dot blotting analysis using a probe of γ-32 P- end-labelled 35-mer oligonucleotide. After a 24-h incubation, the media conditioned by the cul- tured SMCs were collected. The MCP-1 protein content in the conditioned media was determined by using sandwich ELISA. The results were as follows: Dot blotting analysis showed that the cul- tured SMCs could express MCP-1 mRNA. After a 4-h exposure to IL-1β, TNF-α and LPS, the MCP-1 mRNA expression in SMCs was increased (3.6-fold, 2. 3-fold and 1. 6-fold, respectively). ELISA showed that the levels of MCP-1 protein in the conditioned media were also increased (2.9- fold, 1.7-fold and 1.1-fold, respectively). The results suggest that calf aortic SMCs could ex- press MCP-1 mRNA and protein. IL-1β and TNF-α can induce strong expression of MCP-1 mRNA and protein, and the former is more effective than the latter.

Xuebijing alters tumor necrosis factor-alpha, interleukin-1beta and p38 mitogen activated protein kinase content in a rat model of cardiac arrest following cardiopulmonary resuscitation

We established a rat model of cardiac arrest by clamping the endotracheal tube of adult rats at expiration. Twenty-four hours after cardiopulmonary resuscitation, nerve cell injury and expression of tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase content were increased. Rats injected with Xuebijing, a Chinese herb compound preparation, exhibited normal cellular structure and morphology, dense neuronal cytoplasm, and decreased tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase expression at 24 hours following cardiopulmonary resuscitation. These data suggest that Xuebijing can attenuate neuronal injury induced by hypoxia and reperfusion during cardiopulmonary resuscitation.

Responses of serum inflammatory factor high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha in elderly males with cerebral infarction Non-randomized concurrent control

BACKGROUND： Cerebral infarction is poorly treated due to neuronal necrosis and secondary pathophysiological changes; for example, free radical production and inflammatory reactions. OBJECTIVE： To detect the levels of high-sensitivity C-reactive protein （hs-CRP）, interleukin-6 （IL-6）, and tumor necrosis factor- a （TNF- α ） in elderly males with cerebral infarction. DESIGN： Non-randomized current control study. SETTING： Cadre Medical Department, Guizhou Provincial People＇s Hospital. PARTICIPANTS： Forty elderly males （65-89 years old） with cerebral infarction were selected from Cadre Medical Department, Guizhou Provincial People＇s Hospital from February 2004 to December 2006. All patients met the diagnostic criteria of cerebral infarction modified at the 4th National Cerebrovascular Disease Academic Meeting, and were diagnosed on the basis of CT or MRI tests. Furthermore, 35 elderly male inpatients （65-87 years old） without cerebral infarction were selected as the control group. Included subjects provided confirmed consent and did not have heart disease, diabetes mellitus, lipid disorder, acute trauma, infection, rheumatism, or other inflammatory diseases. The study was approved by the local ethics committee. There were no significant differences in age, blood pressure, and lipid levels between the cerebral infarction group and the control group （P 〉 0.05）, and this suggested that the baseline data of both groups were comparable. METHODS： Fasting venous blood was drawn from cerebral infarction patients 24 hours after cerebral infarction attack and from control subjects 24 hours after hospitalization. A latex-enhanced immunoturbidimetric assay and an enzyme-linked immunosorbent assay were used to detect the levels of hs-CRP, IL-6, and TNF- α in the serum. MAIN OUTCOME MEASURES： The levels of hs-CRP, 1L-6, and TNF- α in the serum in both groups. RESULTS： Forty cerebral infarction patients and thirty-five control subjects were included in the final analysis without any loss. Levels of hs-CRP, IL-6, and TNF-α in the cerebral infarction group were significantly higher than those in the control group （P 〈 0.01 ）. CONCLUSION： Levels of serum inflammatory reactive factors are increased in elderly males with cerebral infarction.

TUMOR NECROSIS FACTOR－α ALTERS PROTEINMETABOLISM AND CELL－CYCLE KINETICSIN MALIGNANT TUMOR

The effects of tumor necrosis factor-α(TNF) on protein metabolism and cell-cycle kinetics were investigated in malignant tumor. Sprague-Dawley rats, subcutaneously inoculated with Walker 256 carcinosarcoma,were injected intraperitoneally with recombinant human TNF at a dose of 4-75×106 U/kg for 3 consecutive days.Tumor protein metabolism and cell-cycle kinetics were analyzed. The results showed a significant decrease in tumor volume and weight in comparison with control.TNF resulted in significant decrease in tumor Protein fractional synthesis rate, Protein synthesis and fractional growth rate, but no change of tumor protein fractional degradation rate. TNF also resulted in remarkable decline in labelling index and GI phase increase of tumor cells, 6 hours after bromodeoxyuridine injection, by cytometry. The results indicated that TNF inhibits tumor growth as a result of decreases in tumor cell DNA and protein syntheses.

Inhibitory effect of matrine on tumor necrosis factor production and protein kinase C activity

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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.

Serum Concentrations of Angiotensin, C-Reactive Protein, Interleukin-8, and Tumor Necrosis Factor-α in Train Driver Population

Train drivers are engaged in high-stress job. It may induce sleep, fatigue, and alertness loss at work, and endanger public safety. It’s unclear that cytokines of train driver would be influenced by their job. The research considers the hypothesis that stressful professions, such as train driver, influence the body’s immune system through the long-time and high-pressure working, and change production of neuro-immune factors. Using enzyme linked immunosorbent assay (ELISA), several neuro-immune factors were assayed among train drivers (N = 82) and health blood donors (N = 80) enrolled in the Yunnan Collaborative Innovation Center for Public Health and Disease Control. The concentrations of angiotensin, C-reactive protein (CRP), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) were determined. Kruskal-Wallis test and Dunn’s multiple comparisons test were performed for overall comparison between groups and for pairwise comparison, respectively. Statistical significance level was set at P < 0.05. The profession of train driving was not associated with significant increases or decreases in the systemic levels of inflammatory (CRP, IL-8, and TNF-α), but it was associated with the high expression of angiotensin in vivo. These findings suggest that the job of train driving may not be associated with significant alterations in systemic immune condition, but arouse the level of angiotensin.

Effects of erythropoietin on the expression of tumor necrosis factor-alpha and Bax after facial nerve axotomy in rats

This study sought to evaluate the effect of high-dose erythropoietin （EPO; 5 000 IU/kg） on the expression of tumor necrosis factor-alpha （TNF-α） and Bax in the facial nucleus after facial nerve transection in rats. A total of 42 Wistar rats of both genders were used in this study, and 40 rats were randomly divided into 2 groups： EPO group and model group. The EPO group was treated with EPO once a day for 5 days at a dose of 5 000 IU/kg body weight. The model group was treated with saline of the same amount. At day 3 after EPO （or saline） treatment, the right facial nerves of the 40 rats were transected at the level of the stylomastoid foramen, with the left sides untreated. The remaining 2 rats that did not undergo axotomy served as the control group. The surviving motor neurons in operated rats were counted in coronal paraffin sections of the facial nucleus. The expression of TNF-a and Bax in the facial nucleus was detected by immunohistochemical staining at days 3, 7, 14, 21, and 28 after axotomy. At days 14, 21, and 28 after facial nerve axotomy, a significantly greater proportion of facial motor neurons survived in the EPO group than in the model group. After axotomy, the expression of TNF-a and Bax increased in motor neurons in both the EPO and the model groups. TNF-o expression reached its peak level at day 14 after axotomy, while Bax expression reached its peak level at day 21. TNF-α expression was much lower in the EPO group than in the model group at all time points. No significant difference in Bax expression was found between the EPO and the model groups. These results indicate that high-dose EPO treatment attenuates the increase in TNF-α expression in the facial nucleus and reduces the loss of motor neurons after facial nerve transection in rats. However, high-dose EPO treatment has little effect on Bax expression.

Altered pattern of tumor necrosis factor-alpha production in peripheral blood monocytes from Crohn's disease

AIM To evaluate the inflammatory state in Crohn's disease(CD) patients and correlate it with genetic background and microbial spreading.METHODS By means of flow cytometry, production of tumor necrosis factor-alpha(TNF-α) was measured in peripheral blood monocytes from patients suffering from CD, ulcerative colitis(UC) and in healthy subjects after stimulation of the NOD2 and TLR pathways. CD patients were genotyped for the three most common NOD2 variants(R702W, G908 R and L1007Pfs*2) and basal production of TNF-α was correlated to NOD2 genotype. Also, production of TNF-α was correlated to plasmatic levels of LPS Binding Protein(LBP), soluble(s) CD14 and to the activity state of the disease.RESULTS The patients with CD were characterized by a significantly higher monocyte basal expression of TNF-αcompared with healthy subjects and UC patients, and after stimulation with Pam3CSK4(ligand of TLR2/1) and MDP-L18(ligand of NOD2) this difference was maintained, while other microbial stimuli(LPS, ligand of TLR4 and Poly I:C, ligand of TLR3) induced massive activation in CD monocytes as well as in UC and in healthy control cells. There was no significant difference in the production of TNF- α between patients who carried CD-associated heterozygous or homozygous variants in NOD2 and patients with wild type NOD2 genotype. Although serum LBP levels have been shown to correlate positively with the state of activity of the disease, TNF-α production did not show a clear correlation with either LBP or s CD14 levels in plasma. Moreover, no clear correlation was seen between TNF-α production and activity indices in either CD or UC.CONCLUSION Peripheral monocytes from CD express higher basal and stimulated TNF-α than controls, regardless of NOD2 genotype and without a clear correlation with disease activity.

PEGylated PLGA Nanoparticles as Tumor Ecrosis Factor-α Receptor Blocking Peptide Carriers:Preparation,Characterization and Release in vitro

To assess the merits of PEGylated poly （lactic-co-glycolic acid） （PEG-PLGA） nanoparticles as drug carriers for tumor necrosis factor-α receptor blocking peptide （TNFR-BP）, PEG-PLGA copolymer, which could be used to prepare the stealth nanoparticles, was synthesized with methoxypolyethyleneglycol, DL-lactide and glycolide. The structure of PEG-PLGA was confirmed with ^1H-NMR and FT-IR spectroscopy, and the molecular weight （MW） was determined by gel permeation chromatography. Fluorescent FITC-TNFR- BP was chosen as model protein and encapsulated within PEG-PLGA nanoparticles using the double emulsion method. Atomic force microscopy and photon correlation spectroscopy were employed to characterize the stealth nanoparticles fabricated for morphology, size with polydispersity index and zeta potential. Encapsulation efficiency （EE） and the release of FITC-TNFR-BP in nanopartieles in vitro were measured by the fluorescence measurement. The stealth nanoparticles were found to have the mean diameter less than 270 nm and zeta potential less than -20 mV. In all nanoparticle formulations, more than 45% of EE were obtained. FITC-TNFR-BP release from the PEG-PLGA nanoparticles exhibited a biphasic pattern, initial burst release and consequently sustained release. The experimental results show that PEG-PLGA nanoparticles possess the potential to develop as drug carriers for controlled release applications of TNFR-BP.

Diagnostic and Predictive Levels of Calcium-binding Protein A8 and Tumor Necrosis Factor Receptor-associated Factor 6 in Sepsis-associated Encephalopathy： A Prospective Observational Study

Background： Despite its high prevalence, morbidity, and mortality, sepsis-associated encephalopathy （SAE） is still poorly understood. The aim of this prospective and observational study was to investigate the clinical significance of calcium-binding protein A8 （S 100AS） in serum and tumor necrosis factor receptor-associated factor 6 （TRAF6） in peripheral blood mononuclear cells （PBMCs） in diagnosing SAE and predicting its prognosis. Methods： Data of septic patients were collected within 24 h after Intensive Care Unit admission fi-om July 2014 to March 2015. Healthy medical personnel served as the control group. SAE was defined as cerebral dysfhnction in the presence of sepsis that fulfilled the exclusion criteria. The biochemical indicators, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation score II, TRAF6 in PBMC, serum S 100A8, S 10013, and neuron-specific enolase were evaluated in SAE patients afresh. TRAF6 and S 100A8 were also measured in the control group. Results： Of the 57 enrolled patients, 29 were diagnosed with SAE. The S 100A8 and TRAF6 concentrations in SAE patients were both significantly higher than that in no-encephalopathy （NE） patients, and higher in NE than that in controls （3.74 ± 3.13 vs. 1.08 ± 0.75 vs. 0.37 ± 0.14 ng/ml, P 〈 0.01 ; 3.18 ± 1.55 vs. 1.02 ± 0.63 vs. 0.47 ± 0.10, P 〈 0.01）. S 100A8 levels of 1.93 ng/ml were diagnostic of SAE with 92.90% specificity and 69.00% sensitivity in the receiver operating characteristic （ROC） curve, and the area under the curve was 0.86 （95% confidence interval [CI]： 0.76-0.95）. TRAF6-relative levels of 1.44 were diagnostic of SAE with 85.70% specificity and 86.20% sensitivity, and the area under the curve was 0.94 （95% CI： 0.88-0.99）. In addition, S 100A8 levels of 2.41 ng/ml predicted 28-day mortality of SAE with 90.00% specificity and 73.70% sensitivity in the ROC curve, and the area under the curve was 0.88. TRAF6 relative levels of 2.94 predicted 28-day mortality of SAE with 80.00% specificity and 68.40% sensitivity, and the area under the curve was 0.77. Compared with TRAF6, the specificity of serum S 100A8 in diagnosing SAE and predicting mortality was higher, although the sensitivity was low. In contrast, the TRAF6 had higher sensitivity for diagnosis. Conclusions： Peripheral blood levels of S 100A8 and TRAF6 in SAE patients were elevated and might be related to the severity of SAE and predict the outcome of SAE. The efficacy and specificity of S 100A8 for SAE diagnosis were superior, despite its weak sensitivity. S100A8 might be a better biomarker for diagnosis of SAE and predicting prognosis.

Tumor necrosis factor receptor-associated protein 1 regulates hypoxia-induced apoptosis through a mitochondria-dependent pathway mediated by cytochrome c oxidase subunit Ⅱ

Background:Tumor necrosis factor receptor-associated protein 1(TRAP1)plays a protective effect in hypoxic cardiomyocytes,but the precise mechanisms are not well clarified.The study is aimed to identify the mechanism of TRAP1 on hypoxic damage in cardiomyocytes.Methods:In this study,the effects of TRAP1 and cytochrome c oxidase subunit Ⅱ(COXⅡ)on apoptosis in hypoxia-induced cardiomyocytes were explored using overexpression and knockdown methods separately.Results:Hypoxia induced cardiomyocyte apoptosis,and TRAP1 overexpression notably inhibited apoptosis induced by hypoxia.Conversely,TRAP1 silencing promoted apoptosis in hypoxic cardiomyocytes.Further investigation revealed that the proapoptotic effects caused by the silencing of TRAP1 were prevented by COXⅡ overexpression,whereas COXⅡ knockdown reduced the antiapoptotic function induced by TRAP1 overexpression.Additionally,changes in the release of cytochrome c from mitochondria into the cytosol and the caspase-3 activity in the cytoplasm,as well as reactive oxygen species production,were found to be correlated with the changes in apoptosis.Conclusions:The current study uncovered that TRAP1 regulates hypoxia-induced cardiomyocyte apoptosis through a mitochondria-dependent apoptotic pathway mediated by COXⅡ,in which reactive oxygen species presents as an important component.

Simultaneous Cell Disruption and Aqueous Two-Phase Extraction for Isolation of Intracellular Recombinant Proteins

A new technique was developed for the integrated processing of cell disruption and aqueous two-phase extraction in a high-speed bead mill to separate intracellular proteins form microbial cells. The process was narned as simultanecus cell disruption and aqueous two-phase extraction (ADATE). Advantages, such as high cell disruption efficiency, biochemical activities proservation of proteins, cell debris elimination, and preliminary puriffcation of the target protein were being clairmed. When this technique was employed for isolating recombinant Tumor Necrois Factor (TNF) from E.coli, overall protein codcentration and TNF activity were found to have been increased. More than 85% of TNF was partitioned into the top phase and all cell debris were in the bottom phase. The partition coefficinet was greater than 3 and the TNF puriflcation fsctop was greater than 6. It is zhown that less separation steps were being utilized in the new techniqne, meaning a reduction in separation time and less process extractors required.

Membrane Proteins as Potential Colon Cancer Biomarkers: Verification of 4 Candidates from a Secretome Dataset

Colorectal cancer (CRC) is an important health issue in Taiwan. There were over ten thousand newly diagnosed CRC patients each year. The outcome of late stage CRC still remains to be improved, and tumor markers are expected to improve CRC detection and management. From a colorectal cancer cell secretome database, we chose four proteins as candidates for clinical verification, including tumor-associated calcium signal transducer 2 (TROP2, TACSTD2), transmembrane 9 superfamily member 2 (TM9SF2), and tetraspanin-6 (TSPAN6), and tumor necrosis factor receptor superfamily member 16 (NGFR). Different groups of 30 CRC patients’ tissue samples collected from Chang Gung Memorial Hospital were analyzed by immunohistochemistry (IHC) for the four proteins, and the results were scored by pathologist. For all the four candidate proteins, marked differences of IHC score existed between tumor and adjacent non-tumor counterpart. However, there were only trends between higher protein expression levels and worse outcome. Three proteins (TROP2, TM9SF2 and NGFR) had trends between higher tissue expression and tumor stage or lymph node metastasis. Our study revealed that tissue expression of four proteins (TROP2, TM9SF2, TSPAN6, and NGFR) was markedly different between tumor and adjacent non-tumor counterparts. Overexpression of all these four proteins showed some trends with poorer survival.

血清CysC和CTRP9水平对2型糖尿病视网膜病变的诊断价值

目的探讨血清胱抑素C(CysC)和C1q肿瘤坏死因子相关蛋白9(CTRP9)水平对2型糖尿病患者糖尿病视网膜病变(DR)及糖尿病黄斑水肿(DME)的诊断价值。方法采用横断面研究方法,纳入2021年4月至2022年4月在甘肃省人民医院就诊的135例2型糖尿病患者,年龄45~75岁,按照DR分级标准将患者分为无DR(NDR)组、非增生型DR(NPDR)组和增生型DR(PDR)组,每组45例。根据有无DME将NPDR组和PDR组患者分为DME组51例和非DME组39例。另选取45名健康体检者作为正常对照组。采集受检者空腹外周静脉血,检测血清中糖化血红蛋白、空腹血糖、三酰甘油、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、CysC和CTRP9水平。比较各组CysC和CTRP9表达差异。采用多因素Logistic回归分析模型评估DR及DME的独立影响因素,采用受试者工作特征(ROC)曲线评价血清CysC和CTRP9对DR及DME的诊断价值。结果正常对照组、NDR组、NPDR组和PDR组血清CysC水平分别为0.74(0.67,0.83)、1.03(0.85,1.22)、1.40(0.98,1.63)和1.66(1.31,1.85)mg/L,呈逐渐升高趋势;CTRP9水平分别为(136.90±14.95)、(120.23±16.31)、(109.50±14.71)和(90.99±13.88)pg/ml,呈逐渐降低趋势;组间总体比较差异均有统计学意义(Z=89.430,P<0.001;F=74.242,P<0.001),组间两两比较差异均有统计学意义(均P<0.05)。与非DME组相比,DME组血清CysC水平显著升高、CTRP9水平显著降低,差异均有统计学意义(均P<0.05)。多因素Logistic回归分析结果显示,血清CysC(OR=19.742,95%CI:4.515~86.316,P<0.001)是DR发生的独立危险因素,CTRP9水平(OR=0.937,95%CI:0.908~0.966,P<0.001)是DR发生的保护因素;血清CTRP9水平(OR=0.838,95%CI:0.778~0.903,P<0.001)为DME发生的保护因素。ROC曲线结果显示,血清CysC和CTRP9水平单独及联合诊断2型糖尿病患者并发DR的ROC曲线下面积(AUC)分别为0.798、0.802和0.870,血清CysC和CTRP9水平截断值分别取1.34 mg/L和110.12 pg/ml时可获得最佳诊断效能;其单独及联合诊断DR患者并发DME的AUC分别为0.682、0.923和0.923,血清CTRP9水平的截断值取104.68 pg/ml时可获得最佳诊断效能。结论血清CysC水平升高及CTRP9水平降低是2型糖尿病患者发生DR的危险因素,血清CTRP9水平降低为DR患者发生DME的危险因素之一。

ST段抬高型心肌梗死患者血清转化生长因子11、补体C1q/肿瘤坏死因子相关蛋白5的表达及临床意义

目的 探讨转化生长因子11(transforming growth factor 11,GDF11)、补体C1q/肿瘤坏死因子相关蛋白5(complement C1q/tumor necrosis factor-related protein 5,CTRP5)在ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者血清中的表达及诊断价值。方法 选取2019年3月到2021年2月石家庄市第三医院收治的60例STEMI患者为心肌梗死组,另选取同期健康体检者50名为对照组。检测两组受试者血清GDF11、CTRP5的表达水平。采用Pearson相关性分析对STEMI患者血清中GDF11和CTRP5表达水平及二者与高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)、血糖(blood glucose,GLU)、白细胞计数(white blood cell count,WBC)、中性粒细胞计数(neutrophil count,NEUT)、单核细胞计数(monocyte count,MONO)及超敏C反应蛋白(hypersensitive C reactive protein,hs-CRP)、高敏心肌肌钙蛋白T(high-sensitivity cardiac troponin T,hs-cTnT)、肌酸激酶同工酶(creatine kinase isoenzymes,CK-MB)浓度及预后不良事件的相关性进行分析。采用受试者工作特征曲线(receiver operating characteristic curve,ROC)分析血清中GDF11和CTRP5对STEMI患者的诊断价值。结果 心肌梗死组患者的血清GDF11(1.42±0.35 vs. 0.99±0.18,t=7.860,P<0.05)和CTRP5(1.49±0.43 vs. 1.01±0.22,t=7.148,P<0.05)表达水平高于对照组,差异有统计学意义。相关性分析结果显示,心肌梗死组血清GDF11和CTRP5表达水平呈正相关(r=0.550,P<0.05),GDF11和CTRP5表达水平与HDL-C呈负相关(r=-0.548,-0.592,P<0.05),与GLU(r=0.447,0.534,P<0.05)、WBC(r=0.653,0.502,P<0.05)、NEUT(r=0.562,0.578,P<0.05)、MONO(r=0.439,0.423,P<0.05)、hs-CRP(r=0.513,0.542,P<0.05)、hs-cTnT(r=0.513,0.524,P<0.05)、CK-MB(r=0.630,0.417,P<0.05)及预后不良事件(r=0.557,0.529,P<0.05)呈正相关。GDF11和CTRP5联合诊断STEMI的ROC曲线下面积大于GDF11、CTRP5单独诊断(Z=2.424、2.507,P<0.05)。结论 GDF11和CTRP5在STEMI患者血清中表达水平升高,两者联合对STEMI具有较高的诊断价值。