Protective effect of curcumin on tumor necrosis factor-alpha-induced neuronal damage in the rat hippocampus A relationship to the inhibition of neuronal Ca^(2+) influx

BACKGROUND： Previous studies of curcumin have focused mainly on its cytotoxic properties for antitumor therapy. There are few studies addressing the application of curcumin in the prevention and treatment of nervous system diseases. OBJECTIVE： To observe the protective effect of curcumin against tumor necrosis factor-alpha （TNF-α）-induced neuronal damage in the rat hippocampus and to explore the intervention effect of curcumin on Ca^2＋ influx following neuronal damage. DESIGN, TIME AND SETTING： A cell morphological and physiological study was performed at the Institute of Brain Research, Medical College of Jinan University, China, from December 2006 to June 2007. MATERIALS： Curcumin （Sigma, USA） and TNF-α （Sigma, USA） were used in this study. METHODS： Hippocampal neurons were isolated from one-day neonatal rats and primarily cultured for 5 days. Following this they received 1 pmol/L curcumin and 100 ng/mL TNF-a pre-treatment. Dynamic morphological changes were observed for 1 hour by inverted microscopy. At 48 hours post-treatment, static morphological characteristics of the neurons were observed using inverted microscopy. Subsequently, hippocampal neurons were primarily cultured for 7 days, after receiving 1 pmol/L curcumJn and 4.5 ng/mL TNF-a pre-treatment. Intracellular free Ca^2＋ was measured using Fluo 3/acetoxymethyl ester. MAIN OUTCOME MEASURES： Effects of curcumin on TNF-a-induced neuronal damage and Ca^2＋ influx in the rat hippocampus were measured. RESULTS： Following curcumin treatment, TNF-a-induced neurons grew as normal. TNF-a induced a rapid Ca^2＋ influx into the neuronal cytoplasm; however, Ca2＋ fluorescence intensity only slightly increased when neurons were co-perfused with curcumin and TNF-α. CONCLUSION： Curcumin has a protective effect on rat hippocampal neurons possibly by reducing the TNF-α-induced rapid Ca^2＋ influx into neuronal cytoplasm and by maintaining the Ca^2＋ homeostasis.

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.

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.

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.

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.

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.

外周血TLR2、TIPE2、NLR联合检测对机械通气新生儿呼吸机相关性肺炎的预测价值

目的探讨外周血Toll样受体2(TLR2)、肿瘤坏死因子α诱导蛋白8样因子2(TIPE2)、中性粒细胞与淋巴细胞比值(NLR)联合检测对机械通气新生儿呼吸机相关性肺炎(VAP)的预测价值。方法选取2020年6月至2023年6月河北北方学院附属第一医院进行机械通气治疗的232例新生儿作为研究对象。将发生VAP的新生儿纳入VAP组,其余纳入非VAP组。检测并比较两组外周血TLR2、TIPE2表达水平和NLR。绘制受试者工作特征(ROC)曲线评估外周血TLR2、TIPE2、NLR单独及联合预测机械通气新生儿VAP发生的价值。采用多因素Logistic回归分析机械通气新生儿发生VAP的影响因素。结果232例机械通气新生儿中,60例发生VAP,发生率为25.86%,纳入VAP组;其余172例未发生VAP,纳入非VAP组。VAP组和非VAP组机械通气时间、置管次数和吸痰次数比较,差异均有统计学意义(P<0.05)。VAP组TLR2相对表达水平和NLR高于非VAP组,TIPE2相对表达水平低于非VAP组,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,机械通气时间≥3 d、置管次数≥2次、吸痰次数≥5次/天、TLR2相对表达水平升高、NLR升高是械通气新生儿发生VAP的危险因素(P<0.05),TIPE2相对表达水平升高是新生儿发生VAP的保护因素(P<0.05)。ROC曲线分析结果显示,TLR2、TIPE2和NLR单独预测机械通气新生儿发生VAP的曲线下面积(AUC)分别为0.783、0.754、0.745;且外周血TLR2、TIPE2、NLR联合检测预测机械通气新生儿发生VAP的AUC为0.823。结论外周血TLR2、TIPE2和NLR均是机械通气新生儿发生VAP的独立影响因素,且联合检测有助于预测VAP的发生。

2型糖尿病合并代谢综合征患者血清CTRP9、A-FABP水平变化及临床意义

目的研究2型糖尿病(T2DM)合并代谢综合征(MS)(T2DM~MS)患者血清补体C1q肿瘤坏死因子相关蛋白(CTRP9)、脂肪型脂肪酸结合蛋白(A-FABP)水平变化及临床意义。方法前瞻性选择2021年1月至2023年12月于广西医科大学第二附属医院治疗的90例T2DM患者纳入研究组,根据是否合并MS将其分为T2DM~MS组(n=71)、T2DM未合并MS组(n=19)。将同期于广西医科大学第二附属医院进行体检的90名健康者纳入对照组。检测并比较研究组与对照组、T2DM~MS组与T2DM未合并MS组的糖脂代谢指标[空腹血糖、高密度脂蛋白(HDL-C)、总胆固醇、低密度脂蛋白(LDL-C)、甘油三酯]及血清CTRP9、A-FABP水平。采用Pearson相关性分析CTRP9、A-FABP与各糖脂代谢指标的相关性;采用受试者操作特征(ROC)曲线评价CTRP9、A-FABP对T2DM~MS的诊断效能。结果研究组的空腹血糖、总胆固醇、LDL-C、甘油三酯及血清A-FABP水平分别为(9.37±0.95)mmol/L、(4.38±0.45)mmol/L、(2.83±0.29)mmol/L、(1.58±0.17)mmol/L、(15.48±1.72)ng/mL,均高于对照组,研究组HDL-C及血清CTRP9水平分别为(1.23±0.14)mmol/L、(8.38±0.85)ng/mL,均低于对照组,差异均有统计学意义(P<0.05)。T2DM~MS组空腹血糖、总胆固醇、LDL-C、甘油三酯及血清A-FABP水平分别为(10.26±1.32)mmol/L、(4.51±0.47)mmol/L、(3.15±0.33)mmol/L、(1.74±0.20)mmol/L、(18.21±2.06)ng/mL,均高于T2DM未合并MS组,T2DM~MS组HDL-C及血清CTRP9水平分别为(1.12±0.13)mmol/L、(7.26±0.75)ng/mL,均低于T2DM未合并MS组,差异均有统计学意义(P<0.05)。经Pearson相关分析,血清CTRP9水平与空腹血糖、总胆固醇、LDL-C、甘油三酯均呈负相关(r=-0.902、-0.780、-0.745、-0.753;均P<0.05),与HDL-C呈正相关(r=0.827,P<0.05);血清A-FABP水平与空腹血糖、总胆固醇、LDL-C、甘油三酯均呈正相关(r=0.843、0.812、0.839、0.722;均P<0.05),与HDL-C呈负相关(r=-0.768,P<0.05)。经ROC曲线分析,血清CTRP9联合A-FABP对T2DM~MS的诊断效能高于两者单独诊断。结论T2DM~MS患者血清CTRP9水平低表达,A-FABP水平高表达,血清CTRP9、A-FABP水平与糖脂代谢指标密切相关。血清CTRP9联合A-FABP可提高T2DM~MS的诊断效能,监测血清CTRP9、A-FABP水平有助于预测T2DM~MS的发生。

注意缺陷多动障碍患儿血清ACE2,TWEAK和CCL5水平检测及诊断价值研究

目的 探究血清血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2),细胞因子肿瘤坏死因子样细胞凋亡弱诱导因子(tumor necrosis factor-like weak inducer of apoptosis,TWEAK)和CC趋化因子配体5(CC motif chemokine ligand 5,CCL5)水平在注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)患儿诊断、病情严重程度评估中的价值。方法 选取2022年10月~2023年10月在河北省儿童医院就诊的125例ADHD患儿记为ADHD组,另选105例在河北省妇幼保健中心体检的健康儿童为对照组,根据临床总体印象严重程度量表(CGI-S)将患儿分为轻中度组(n=83)和重度组(n=42)。ELISA方法检测血清ACE2,TWEAK,CCL5,促黄体生成素(LH)和催乳素(PRL)水平,联合型瑞文测验(CRT)和Conners父母症状问卷(PSQ)对患儿认知和行为状况进行评分。Spearman相关性分析重度组血清ACE2,TWEAK,CCL5与CGI-S,CRT,PSQ评分的相关性;受试者工作特征(ROC)曲线分析ACE2,TWEAK,CCL5对ADHD及严重程度的诊断价值。结果 ADHD患儿血清ACE2(284.35±92.34 pg/ml),TWEAK(2.56±0.76 pg/ml)水平低于对照组(379.23±106.28 pg/ml,3.52±1.12 pg/ml),CCL5水平(7.36±2.37ng/ml)高于对照组(5.24±1.63 ng/ml),差异具有统计学意义(t=7.244,7.703,7.753,均P<0.05);重度组患儿CRT,血清ACE2,TWEAK水平低于轻中度组(t=5.318,6.686,6.490),而PSQ,CCL5水平较高于轻中度组(t=5.220,6.134),差异具有统计学意义(均P<0.05);Spearman相关性分析结果显示,重度组患儿血清ACE2,TWEAK水平与CGI-S,PSQ评分负相关(r=-0.432,-0.453;-0.421,-0.426,均P<0.001),与CRT评分呈正相关(r=0.427,0.418,均P<0.001);CCL5与CGI-S,PSQ评分呈正相关(r=0.421,0.433,均P<0.001),与CRT评分呈负相关(r=-0.446,P<0.001)。血清ACE2,TWEAK和CCL5诊断ADHD发生的AUC分别为0.814,0.803和0.807,三者联合诊断的AUC为0.945,优于各自单独诊断(Z=5.439,4.258,5.576,均P<0.001);血清ACE2,TWEAK,CCL5诊断重度ADHD的AUC分别为0.853,0.796和0.805,三者联合诊断的AUC为0.930,优于各自单独诊断(Z=2.604,3.851,3.567,均P<0.001)。结论 血清ACE2,TWEAK在ADHD患儿血清中低表达,而CCL5高表达,三者表达水平具有相关性,并且诊断ADHD发生和严重程度具有较高的价值。

CTRP3与T2DM骨代谢的关联及对骨折风险的预测效能

目的分析C1q肿瘤坏死因子相关蛋白3(CTRP3)与2型糖尿病(T2DM)骨代谢的关联及对骨折风险的预测效能。方法选取121例T2DM患者,根据CTRP3检测结果,将CTRP3<300 ng/mL的63例患者列为低水平组,将CTRP3≥300 ng/mL的58例患者列为高水平组,分析CTRP3与骨代谢指标的关联,分析T2DM骨折的危险因素,以及CTRP3对骨折风险的预测效能。结果低水平组的骨密度、骨保护素(OPG)、骨特异性碱性磷酸酶(BALP)均低于高水平组,1型胶原C端β特殊序列(β-CTX)高于高水平组,差异有统计学意义(P<0.05)。CTRP3表达与骨密度、OPG、BALP正相关,与β-CTX负相关。骨折组的CTRP3、骨密度、OPG、BALP均低于未骨折组,β-CTX高于未骨折组(P<0.05)。CTRP3、骨密度、OPG、BALP、β-CTX为导致T2DM骨折的危险因素。CTRP3对T2DM骨折风险有较高预测效能。结论CTRP3与T2DM患者的骨代谢水平密切相关,通过检测CTRP3表达能实现对其骨折风险的早期预测。

Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor-induced interleukin-6 expression via human antigen R

Background Human antigen R （HuR） is a ubiquitously expressed member of the ELAV family, and has relatively high cytoplasmic abundance in lung tissue regenerating after injury. In this study, we investigated whether mitogen-activated protein kinase （MAPK）-activated protein kinase 2 （MK2） and HuR participate in the tumor necrosis factor （TNF）-induced expression of interleukin-6 （IL-6）. Methods Human pulmonary microvascular endothelial cells were treated with TNF following short interfering RNAmediated knockdown of MK2 or HuR. Cell supernatants were collected to detect the mRNA and protein expression of IL-6 at different time points, The expression and half-life of IL-6 mRNA were then determined in cells that had been treated with actinomycin D. Finally, after knockdown of MK2, the cytoplasmic expression of HuR protein was analyzed using Western blotting. Results MK2 or HuR knockdown decreased both the mRNA and protein expression of IL-6 in TNF-stimulated cells. In MK2 knockdown cells, the half-life of IL-6 mRNA was reduced to 36 minutes, compared with 67 minutes in the control group. In HuR knockdown cells, the half-life of IL-6 mRNA decreased from 62 minutes to 24 minutes. Further analysis revealed that knockdown of MK2 resulted in reduced HuR protein expression in the cytoplasm. Conclusions MK2 regulates the TNF-induced expression of IL-6 by influencing the cytoplasmic levels of HuR.

Coronary microembolization induced myocardial contractile dysfunction and tumor necrosis factor-α mRNA expression partly inhibited by SB203580 through a p38 mitogen-activated protein kinase pathway

Background The microemboli produced during spontaneous plaque rupture and ulceration and during coronary intervention will reduce coronary reserve and cause cardiac dysfunction. It is though that inflammation caused by the microinfarction induced by the microembolization may play an essential role. It is known that the activation of p38 mitogen-activated protein kinases （MAPK） in both infected and non-infected inflammation in myocardium may cause a contractile dysfunction. But the relation between the activation of p38 MAPK and microembolization is still unknown. Methods Sprague-Dawley rats were randomly divided into three groups： Sham group, coronary microembolization （CME） group and SB203580 group （n=-10 per group）. CME rats were produced by injection of 42 pm microspheres into the left ventricle with occlusion of the ascending aorta. SB203580, a p38 MAPK inhibitor, was injected into the femoral vein after the injection of microspheres to make the SB203580 group. Left ventricular ejection fraction （LVEF） was determined by echocardiography. The protein concentration of P38 MAPK in the myocardium was assessed by Western blotting. The relative expression of mRNA for tumor necrosis factor （TNF）-a was assessed by the technique of semi-quantitative polymerase chain reaction amplification. Results LVEF was depressed at three hours up to 12 hours in the CME group. Increased p38 MAPK activity and TNF-a mRNA expression were observed in the CME group. The administration of SB203580 partly inhibited p38 MAPK activity, but did not fully depress the TNF-α expression, and partly preserved cardiac contractile function. Conclusions p38 MAPK is significantly activated by CME and the inhibition of p38 MAPK can partly depress the TNF-a expression and preserve cardiac contractile function.

Tumor Necrosis Factor-alpha Induced Protein 3 Interacting Protein I Gene Polymorphisms and Pustular Psoriasis in Chinese Han Population

Background： Psoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis （GPP） is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 （TNIP1） gene and psoriasis was confirmed in people with multiple ethnicities. This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Hart population. Methods： Seventy-three patients with GPP, 67 patients with palmoplantar pustulosis （PPP）, and 476 healthy controls were collected from Chinese Hart population. Six single nucleotide polymorphisms （SNPs） of the TNIP1 gene, namely rs3805435, rs3792798, rs3792797, rs869976, rs 17728338, and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction. Statistical analyses were performed using the PLINK 1.07 package. Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test, odd ratio （OR） （including 95% confidence interval） were calculated. The haplotype analysis was conducted by Haploview software. Results： The frequencies of alleles of five SNPs were significantly different between the GPP group and the control group （P ≤ 7.22 × 10^-3）, especially in the GPP patients without psoriasis vulgaris （PsV）. In the haplotype analysis, the most significantly different haplotype was H4： ACGAAC, with 13.1% frequency in the GPP group but only 3.4% in the control group （OR = 4.16, P = 4.459 × 10^-7）. However, no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs （P 〉 0.05）. Conclusions： Polymorphisms in TNIP1 are associated with GPP in Chinese Han population. However, no association with PPP was found. These findings suggest that TNIPI might be a susceptibility gene for GPE

Fibrinogen-like protein 2 expression correlates with microthrombosis in rats with type 2 diabetic nephropathy

Fibrinogen-like protein 2 （fgl2）, a novel prothrombinase, is involved in microthrombosis. We examined fgl2 expression in the glomerular and tubulointerstitial capillaries and its correlation with microthromsis in rats with streptozocin-induced type 2 diabetic nephropathy. Our RT-PCR and immunoblotting analysis showed that fgl2 mRNA and protein levels were increased in microvascular endothelial cells of the glomeruli and renal interstitia at week 19 and became significantly elevated with the development of diabetic nephropathy （P 〈 0.01）. Fgl2 was not or only weakly expressed in the renal tissues of normal rats. Furthermore, a direct significant correlation （r = 0.543, P 〈 0.01） was found between fgl2 expression and microthrombotic capillaries in the renal tissues. Enzyme linked immunosorbent assays （ELISA） additionally showed that circulating TNF-α levels in rats with type 2 diabetes were significantly elevated and closely correlated with fgl2 expression （r = 0.871, P 〈 0.01）. Our results suggest that fgl2 may activate renal microthrombosis, thus contributing to glomerular hypertension and renal ischemia.

TNF-α抑制剂注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白/注射用依那西普致葡萄膜炎2例分析

目的探讨TNF-α抑制剂与葡萄膜炎发病的关系并分析TNF-α抑制剂诱发性葡萄膜炎的临床特点。方法回顾性分析2021年7月至2023年2月某院收治的2例使用TNF-α抑制剂注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白注射用依那西普后出现葡萄膜炎患者的临床特征并复习相关文献。结果2例患者葡萄膜炎发生时间分别在用药后2周和6周,其中前葡萄膜炎1例,前、中间葡萄膜炎1例,经对症治疗后均有好转。在持续生物制剂治疗过程中2例患者均有反复发作倾向。查阅文献发现目前引起葡萄膜炎的TNF-α抑制剂主要包括英夫利昔单抗、阿达木单抗等,多用于治疗类风湿性关节炎、肿瘤、强直性脊柱炎、眼内葡萄膜炎患者等。患者年龄区间在5~77岁,发病时间为用药后1周~4年。经系统治疗,停止免疫抑制剂后,绝大多数诱发性葡萄膜炎患者视力可恢复。结论TNF-α抑制剂可以诱发葡萄膜炎的发生,发病类型以前葡萄膜炎为主,且有复发倾向。及时诊疗后患者的视力预后较好。

嗜酸粒细胞型哮喘患儿外周血单个核细胞肿瘤坏死因子α诱导蛋白8样分子2 mRNA和M2巨噬细胞检测及意义

目的:检测嗜酸粒细胞型哮喘(EA)患儿外周血单个核细胞(PBMC)肿瘤坏死因子α诱导蛋白8样分子2(TIPE2)mRNA和M2巨噬细胞,并分析其意义。方法:回顾性收集EA患儿100例,根据糖皮质激素(ICS)治疗后2周内症状缓解情况,分为完全缓解组(78例)和部分缓解组(22例)。另选取体检健康儿童52例,设为对照组。比较三组临床资料[肺功能、血常规、呼出气一氧化氮(FeNO)]、TIPE2 mRNA、M2巨噬细胞占比、治疗前后免疫细胞[辅助性T细胞1(Th1)、辅助性T细胞2(Th2)]以及细胞因子[白细胞介素-2(IL-2)、γ-干扰素(IFN-γ)、IL-4、IL-13、精氨酸酶1(Arg-1)]。分析EA患儿预后的影响因素,并进行相关性分析。结果:完全缓解组和部分缓解组用力肺活量(FVC)、呼吸流量峰值(PEF)、第1秒用力呼气容积(FEV1)、嗜酸性粒细胞(EOS)、淋巴细胞(LYM)、白细胞(WBC)、FeNO与对照组比较差异有统计学意义(均P<0.05),但两组间上述指标比较差异无统计学意义(均P>0.05)。治疗前,完全缓解组与部分缓解组TIPE2 mRNA、M2巨噬细胞占比、M2/M1、IL-4、IL-13、IL-2、Arg-1高于对照组,Th1、Th1/Th2、IFN-γ低于对照组,且完全缓解组TIPE2 mRNA、M2巨噬细胞、Th1、IL-4、IL-13、Arg-1与部分缓解组比较差异有统计学意义(均P<0.05)。治疗后,完全缓解组和部分缓解组TIPE2 mRNA、M2巨噬细胞占比、M2/M1、IL-4、IL-13、IL-2、Arg-1降低,Th1、Th1/Th2、IFN-γ升高,且完全缓解组与部分缓解组比较差异有统计学意义(均P<0.05)。Logistic回归分析结果显示,TIPE2 mRNA、M2巨噬细胞、IL-4、IL-13、Arg-1为EA患儿预后的影响因素(均P<0.05)。Pearson分析结果显示,M2巨噬细胞与IL-4、IL-13呈负相关,与TIPE2 mRNA、Arg-1呈正相关;TIPE2 mRNA与IL-4、IL-13的水平呈负相关(均P<0.05)。结论:EA患儿PBMC中TIPE2 mRNA与M2巨噬细胞呈高表达,均为影响预后的因素。

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。

2型糖尿病患者血清C1q肿瘤坏死因子相关蛋白5、脂联素水平与颈动脉粥样硬化关系研究

目的:探讨2型糖尿病(T2DM)患者血清C1q肿瘤坏死因子相关蛋白5(CTRP5)、脂联素(APN)水平与颈动脉粥样硬化(CAS)的关系。方法:选择T2DM患者96例为观察组,选择体检健康者108例为对照组。采用酶联免疫吸附(ELISA)法检测血清CTRP5、APN水平。根据超声检查将T2DM患者分为CAS组和无CAS组,并比较两组一般资料及血清生化指标。分析T2DM患者发生CAS的影响因素,并进行相关性分析。结果:观察组血清CTRP5水平高于对照组,APN水平低于对照组(均P<0.05)。T2DM患者中,40例出现CAS,56例无CAS。CAS组患者年龄、空腹血糖(FPG)、糖化血红蛋白(HbA1c)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、CTRP5水平较无CAS组升高,APN水平较无CAS组下降(均P<0.05)。HbA1c、TG、LDL-C、CTRP5为CAS发生的独立危险因素,APN是CAS的独立保护因素(均P<0.05)。血清CTRP5与HbA1c、TG、LDL-C水平呈正相关,血清APN与HbA1c、TG、LDL-C水平呈负相关(均P<0.05)。结论:T2DM患者发生CAS后CTRP5水平升高,APN水平下降,CTRP5为CAS发生的独立危险因素,APN为CAS发生的独立保护因素。

丁苯酞软胶囊联合瑞舒伐他汀治疗急性脑梗死患者的临床观察及对血清HIF-1α、Lp-PLA、Sestrin2水平的影响

目的探究丁苯酞软胶囊联合瑞舒伐他汀治疗急性脑梗死患者的疗效及对血清缺氧诱导因子-1α(HIF-1α)、脂蛋白相关磷脂酶A2(Lp-PLA)、应激诱导蛋白2(Sestrin2)水平的影响。方法前瞻性选取2021年1月至2022年12月在秦皇岛市第一医院治疗的急性脑梗死患者101例作为研究对象,按照信封法将患者分为对照组(n=50)和研究组(n=51)。对照组行常规治疗并瑞舒伐他汀治疗,研究组在对照组基础上联合丁苯酞软胶囊治疗。统计分析两组患者治疗前及治疗14 d后的美国国立卫生研究院脑卒中量表(NIHSS)评分、FuglMeyer评测法(FMA)评分、改良Rankin量表(mRS)评分、血流动力学指标(血浆黏度、全血高切黏度、低切黏度、红细胞压积、红细胞变形指数)、血清HIF-1α、Lp-PLA、Sestrin2水平并比较临床疗效的组间差异。结果治疗14 d后,两组患者的NIHSS评分和mRS评分均较治疗前降低,FMA较治疗前升高,且研究组患者的NIHSS评分和mRS评分分别为(4.03±0.38)、(3.01±0.45)分,均低于对照组,FMA为(80.64±9.16)分,高于对照组,差异均有统计学意义(P<0.05)。治疗14 d后,两组患者的血浆黏度、全血高切黏度、低切黏度、红细胞压积均较治疗前降低,红细胞变形指数均较治疗前升高,且研究组的血浆黏度、全血高切黏度、低切黏度、红细胞压积分别为(1.56±0.33)mPa·s、(4.78±0.31)mPa·s、(9.81±0.64)mPa·s、(0.37±0.05)%,均低于对照组,红细胞变形指数为0.78±0.11,高于对照组,差异均有统计学意义(P<0.05)。治疗14 d后,两组患者的血清HIF-1α、Lp-PLA、Sestrin2水平均降低,且研究组患者血清HIF-1α、Lp-PLA、Sestrin2水平分别为(690.56±65.12)ng/mL、(13.65±2.13)μg/L、(11.33±1.45)ng/mL,均显著低于对照组,差异均有统计学意义(P<0.05)。两组近期疗效比较,差异有统计学意义(P<0.05);研究组总有效率为90.20%,高于对照组(64.00%),差异有统计学意义(P<0.05)。结论采用丁苯酞软胶囊联合瑞舒伐他汀治疗急性脑梗死患者可显著提高患者临床治疗效果,提高肢体活动能力,缓解神经功能损伤,降低血清HIF-1α、Lp-PLA、Sestrin2水平,具有较高的临床应用潜力。

CTRP2与主动脉夹层发生的相关性研究

目的检测C1q肿瘤坏死因子相关蛋白2(CTRP2)在患者主动脉、小鼠主动脉以及小鼠主动脉血管平滑肌细胞中的表达水平,分析其与主动脉夹层(AD)发病之间的相关性。方法利用GEO数据库分析CTRP2在AD患者和非AD患者中的表达差异。选择2021年6月—2022年12月在武汉大学人民医院的6例确诊为急性Stanford A型AD患者的主动脉标本作为夹层组,6例心脏移植患者的主动脉作为对照组,通过Western blot法检测夹层组与对照组的CTRP2表达差异。将24只C57BL/6雄性3周龄野生型小鼠随机分为对照组和夹层组,夹层组用含有0.25%β-氨基丙腈的饲料喂养4周,取主动脉组织用石蜡包埋,标本切片后用免疫组织化学法检测CTRP2表达差异。细胞实验分为对照组和夹层组,分别用磷酸盐缓冲溶液和不同浓度的血管紧张素Ⅱ处理小鼠主动脉血管平滑肌细胞后提取细胞,用Western blot法检测CTRP2表达水平。结果免疫组织化学和Western blot法检测结果显示CTRP2在夹层组的患者主动脉、小鼠主动脉以及小鼠主动脉血管平滑肌细胞中的表达均显著升高。结论CTRP2蛋白表达水平在对照组和夹层组中的表达存在差异,与AD的发生具有相关性,有望成为治疗AD的新靶点。