Tumor necrosis factor-α and interleukin-6 in cirrhotic patients with spontaneous bacterial peritonitis

AIM:To evaluate the role of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis(SBP).METHODS:We prospectively studied 120 cirrhotic patients with SBP and 80 cirrhotic patients with sterile ascitic fluid.They included 144 males and 56 females with ages ranging between 34 and 62 years.The diagnosis of cirrhosis was established by clinical and laboratory criteria that did not require histological confirmation.The severity of underlying liver disease was evaluated using Pugh's modification of Child's criteria(Child-Pugh scores).Ascitic fluid was sent to the laboratory for cell count,culture,sensitivity testing,and measurement of chemical elements(i.e.,albumin,glucose).Specimens were inoculated into aerobic and anaerobic blood culture bottles.Serum and ascitic fluid were also collected in sterile tubes at study entry(before the initiation of antibiotic treatment) and 48 h later.Assays for TNF-α and IL-6 in the serum and ascitic fluid were performed with an immunoenzymometric assay using manufacture's instructions.RESULTS:Cytokine levels in serum and ascitic fluid were significantly higher in the patients with SBP.(plasma TNF-α:135.35 ng/mL ± 11.21 ng/mL vs 92.86 ng/mL ± 17.56 ng/mL,P < 0.001;plasma IL-6:32.30 pg/mL ± 7.07 pg/mL vs 12.11 pg/mL ± 6.53 pg/mL,P < 0.001;ascitic fluid TNF-α:647.54 ± 107.11 ng/mL vs 238.43 ng/mL ± 65.42 ng/mL,P < 0.001);ascitic fluid IL-6:132.84 ng/mL ± 34.13 vs 40.41 ± 12.85 pg/mL,P < 0.001).About 48(40%) cirrhotic patients with SBP developed renal and hepatic impairment and showed significantly higher plasma and ascitic fluid cytokine levels at diagnosis of infection.[(plasma TNF-α:176.58 ± 17.84 vs 135.35 ± 11.21 ng/mL)(P < 0.001) and(IL-6:57.83 ± 7.85 vs 32.30 ± 7.07 pg/mL)(P < 0.001);ascitic fluid TNF-α:958.39 ± 135.72 vs 647.54 ± 107.11 ng/mL,(P < 0.001),ascitic fluid IL-6:654.74 ± 97.43 vs 132.84 ± 34.13 pg/mL,(P < 0.001)].Twenty nine patients(60.4%) with SBP and renal impairment died whereas,only four patients(5.55%) with SBP but without renal impairment died from gastrointestinal hemorrhage(P < 0.0005).CONCLUSION:It appears that TNF-α production may enhance liver cell injury and lead to renal impairment.This correlated well with the poor prognosis and significantly increased mortality associated with SBP in cirrhotic patients.

Elevated levels of interleukin-1β, interleukin-6, tumor necrosis factor-α and vascular endothelial growth factor in patients with knee articular cartilage injury

BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor (VEGF) are involved in the pathogenesis of keen articular cartilage injury remains poorly understood. AIM To measure the levels of inflammatory factors [IL-1β, IL-6, TNF-α and VEGF] in patients with knee articular cartilage injury. METHODS Fifty-five patients with knee articular cartilage injury were selected as patient groups, who were divided into three grades [mild (n = 20), moderate (n = 19) and severe (n = 16)] according to disease severity and X-ray examinations. Meanwhile, 30 healthy individuals who underwent physical examination were selected as the control group. The levels of IL-1β, IL-6, TNF-α and VEGF were measured by ELISA and immunohistochemical staining. RESULTS Compared with the control group, patient groups displayed significantly higher levels of IL-1β, IL-6, TNF-α and VEGF, and the extent of increase was directly proportional to the severity of injury (P < 0.05). In addition, the number of cells with positive staining of IL-1β, IL-6, TNF-α and VEGF in the synovial membrane were significantly increased, along with increased disease severity (P < 0.05). After treatment, the scores of visual analogue scale and the Western Ontario and McMaster University of Orthopaedic Index in patient groups were 2.26 ± 1.13 and 15.56 ± 7.12 points, respectively, which were significantly lower than those before treatment (6.98 ± 1.32 and 49.48 ± 8.96). Correlation analysis suggested that IL-1β and TNF-α were positively correlated with VEGF. CONCLUSION IL-1β, IL-6, TNF-α and VEGF levels are increased in patients with knee articular cartilage injury, and are associated with the disease severity, indicating they might play an important role in the occurrence and development of knee articular cartilage injury. Furthermore, therapeutically targeting them might be a novel approach for the treatment of keen articular cartilage injury.

Clinical Implications of Tumor Necrosis Factor-Alpha, Interleukin-6 and Resistin in Coronary Artery Disease

Tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) are involved in the progression of coronary artery disease (CAD). The cytokines’ levels are associated with the severity of CAD. We have recently reported on the association of resistin, a relatively novel cytokine with the pathogenesis of cardiovascular disease (CVD). Although the inflammatory cytokines’ impact on atherosclerosis is widely accepted, yet some controversy exists regarding the involvement of these factors in atherogenesis. The current review highlights the potential association of TNF-alpha, IL-6 and resistin SNPs (single nucleotide polymorphisms) with CAD. Molecular genetics data along with the intracellular signaling cascade mechanisms may have important clinical implications in the treatment of CAD.

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.

The Change of Interleukin-6 and Tumor Necrosis Factor in Patients with Obstructive Sleep Apnea Syndrome

The levels of lipopolysaccharide (LPS) induced interleukin 6 (IL 6) and tumor necrosis factor α (TNF α) expression in culture of peripheral blood mononuclear cells (PBMC) and the plasma levels of IL 6 and TNF α in the patients with obstructive sleep apnea syndrome (OSAS) were measured and the relationship between OSAS and IL 6 or TNF α expression studied. Both IL 6 and TNF α were detected by using ELISA in 22 patients with OSAS and 16 normal controls. The levels of LPS induced IL 6 (787.82±151.97 pg/ml) and TNF α (4165.45±1501.43 pg/ml) expression in the supernatant of the culture of PBMC and plasma level of IL 6 (50.67±4.70 pg/ml) and TNF α (299.09±43.57 pg/ml) in the patients with OSAS were significantly higher than those in the normal controls (in the supernatant of the culture of PBMC: 562.69±197.54 pg/ml and 1596.25±403.08 pg/ml respectively; in the plasma: 12.69±2.75 pg/ml and 101.88±21.27 pg/ml respectively). There were significantly positive correlation between the levels of IL 6 and TNF α and the percentage of time of apnea and hyponea, as well as the percentage of time spending at SaO 2 below 90 % in the total sleep time. It was concluded that LPS induced IL 6 and TNF α levels as well as plasma IL 6 and TNF α levels in the patients with OSAS were up regulated, which may be associated with the pathogenesis of OSAS.

Effect of oxymatrine on interferon-gamma and tumor necrosis factor-alpha serum levels in an experimental rat model of autoimmune encephalomyelitis

BACKGROUND： Studies have demonstrated that experimental autoimmune encephalomyelitis （EAE） onset correlates with increased interferon-v （IFN-γ） and tumor necrosis factor-α （TNF-α） expression. Oxymatrine （OM） has been shown to inhibit autoimmune responses, but there are no reports showing that it could prevent the development of EAE. OBJECTIVE： To observe the effect of OM on serum levels of IFN-γ and TNF-α in a rat model of EAE.DESIGN, TIME AND SETTING： A randomized, controlled, animal study was performed at the Experimental Animal Center of Henan Academy of Chinese Medicine and at the Key Disciplines Laboratory Clinical Medicine of Henan Province between July and December 2008. MATERIALS： OM was purchased from Chia-tai Tianqing Pharmaceutical, China; complete Freund＇s adjuvant was purchased from Sigma, USA. METHODS： Forty female Wistar rats were randomly assigned to four groups： EAE model （M）, low-dose OM treatment （OM-L）, high-dose OM treatment （OM-H）, and normal control （N, no immunization）, with 10 rats in each group. EAE was established in the M, OM-L, and OM-H groups following immunization with Guinea pig spinal cord homogenate and complete Freund＇s adjuvant. The M and N groups were intraperitoneally injected with normal saline （6.7 mL/kg per day）, the OM-L group received an intraperitoneal injection of OM （100 mg/kg per day）, and the OM-H group received OM （150 mg/kg per day）. MAIN OUTCOME MEASURES： At 16 days after immunization, the degree of histopathological changes in the spinal cord was assessed by hematoxylin-eosin stanining. Enzyme-linked immunosorbent assay was used to detect serum levels of IFN-γ, and radioimmunoassay was utilized to determine serum TNF-α level. Neurological scores were measured on a daily basis according to a 0-5 scale. RESULTS： Daily injections of OM, both high and low doses, resulted in decreased neurological scores in EAE rats （P〈0.01）, as well as reduced cellular infiltration in the spinal cord and decreased levels of serum IFN-γ and TNF-α （P〈 0.01）. CONCLUSION： OM reduced the onset and severity of EAE, which correlated with decreased IFN-γ and TNF-α expression.

Dual neuronal response to tumor necrosis factor-alpha following spinal cord injury

BACKGROUND： Numerous studies have shown that tumor necrosis factor α （TNF-α） is closely correlated with spinal cord injury （SCI）, but the mechanisms of TNF-α and therapeutic treatments for SCI are still poorly understood. OBJECTIVE： To determine the role of TNF-α in the pathogenesis of SCI. DESIGN, TIME AND SETTING： An in vivo experiment based on genetically engineered animals was performed at the Medical University of South Carolina, Charleston, South Carolina, USA, between June 2007 and October 2008. MATERIALS： TNF-α transgenic rats （Xenogen Biosciences in Cranbury, New Jersey, USA） were utilized in this study. METHODS： TNF-α transgenic （tg） and wild-type （WT） rats underwent a complete single-level laminectomy at the 10^th thoracic vertebra （T10）. MAIN OUTCOME MEASURES： Motor function of rat hindlimb was assessed using the Basso, Beattie, and Bresnahan hindlimb locomotor rating scale. Histological evaluation of spinal cord tissue loss was conducted. Immunohistochemistry for astrocytes, microglia/macrophages, and TNF receptors （TNFRs） was performed on spinal cord tissue sections. TNF-α mRNA expression was detected by real-time polymerase chain reaction. The concentrations of nerve growth factor （NGF） and brain-derived neurotrophic factor （BDNF） in the supernatant were determined using an enzyme-linked immunosorbent assay kit for rat NGF or BDNF, respectively. The rats were injected subcutaneously with etanercept to verify that TNF-α was the direct effect of the modulation of behavioral and neurodegenerative outcomes in the TNF-α tg rats. RESULTS： TNF-α tg rats showed higher expression of TNF-α mRNA in the spinal cord prior to SCI. TNF-α tg rats showed worse motor deficits than WT rats in the acute period （〈 3 days） after SCI （P 〈 0.01）, while in the chronic period, TNF-α tg rats exhibited persistent elevated baseline levels of TNF-α mRNA and improved recovery in motor function and tissue healing compared to WT rats （P 〈 0.01 ）. Following SCI, the number of microglia/macrophages in TNF-α tg rat was always greater than in WT rat （P 〈 0.01）. There were no significant differences in NGF and BDNF levels in the supernatant of spinal cord homogenates. TNFR1 expression was significantly greater in the TNF-α tg rats compared to the WT rats （P 〈 0.01）. However, TNFR2 expression did not reveal a significant increase in the TNF-α tg rats compared to the WT rats. Finally, treatment with etanercept reduced injury acutely, but exacerbated the injury chronically. CONCLUSION： Overexpression of TNF-α is deleterious in the acute phase, but beneficial in the chronic phase in the response to SCI. The role of TNF-α post-injury may depend on TNF-α expression in the spinal cord and its differential binding to TNFRI. Our observations may have clinical relevance that antagonists or inhibitors of TNF-α could be administered within the early time window post-injury, and appropriate amounts of TNF-α could be administered during the chronic stage, in order to improve the final neurological recovery in patients with SCI.

Dynamic Expression of Tumor Necrosis Factor-α and Vascular Endothelial Growth Factor in Rat Model of Pulmonary Emphysema Induced by Smoke Exposure

In order to explore the roles of tumor necrosis factor-α （TNF-α） and vascular endothelial growth factor （VEGF） in the pathogenesis of pulmonary emphysema, male Wistar rats were randomized into group At, group A2.5 and group A4, each with smoke exposure for 1 month, 2.5 months or 4 months, respectively. Group B t, group B2.5 and group B4 were used as non smoking controls at corresponding time points. TNF-α in bronchoalveolar lavage fluid （BALF） and expression of VEGF in lung tissue was determined by ELISA or by SABC immunohistochemistry assay either. Lung slices were stained with hematoxylin and eosin （HE）. Results showed that in animal with smoke exposure the mean linear interceptor （Lm）, an index of pulmonary emphysema and the content of TNF-α in BALF increased gradually, on contrary, the expression of VEGF in lung tissue decreased （P〈0.05）. This phenomenon was not obvious in animals without smoke exposure. Lm was negatively correlated to the VEGF expression （7=--0.81, P〈0.01） and positively correlated to TNF-α concentration （7 = 0.52, P〈0.004）, which implies that smoke exposure decreased the expression of VEGF and increased the expression of TNF-α. It is plausible to speculate that the imbalance of TNF-α and VEGF may play an important role in the pathogenesis of smoke-induced pulmonary emphysema.

Upregulation of stromal cell-derived factor-1 alpha/CXCR4 axis-induced migration of human neural progenitors by tumor necrosis factor-alpha and interleukin-8

BACKGROUND： Studies of several animal models of central nervous system diseases have shown that neural progenitor cells （NPCs） can migrate to injured tissues. Stromal cell-derived factor 1 alpha （SDF-la）, and its primary physiological receptor CXCR4, have been shown to contribute to this process. OBJECTIVE： To investigate migration efficacy of human NPCs toward a SDF-1α gradient, and the regulatory roles of tumor necrosis factor-α （TNF-α） and interleukin-8 （IL-8） in SDF-1α/CXCR4 axis-induced migration of NPCs. DESIGN, TIME AND SETTING： An in vitro, randomized, controlled, cellular and molecular biology study was performed at the Laboratory of Department of Cell Biology, Medical College of Soochow University between October 2005 and November 2007. MATERIALS： SDF-1α and mouse anti-human CXCR4 fusion antibody were purchased from R＆D Systems, USA. TNF-αwas purchased from Biomyx Technology, USA and IL-8 was kindly provided by the Biotechnology Research Institute of Soochow University. METHODS： NPCs isolated from forebrain tissue of 9 to 10-week-old human fetuses were cultured in vitro. The cells were incubated with 0, 20, and 40 ng/mL TNF-α, or 0, 20, and 40 ng/mL IL-8, for 48 hours prior to migration assay. For antibody-blocking experiments, cells were further pretreated with 0, 20, and 40 μg/mL mouse anti-human CXCR4 fusion antibody for 2 hours. Subsequently, the transwell assay and CXCR4 blockade experiments were performed to evaluate migration of human NPCs toward a SDF-1α gradient. Serum-free culture medium without SDF-1α served as the negative control. MAIN OUTCOME MEASURES： The transwell assay was performed to evaluate migration of human NPCs toward a SDF-1α gradient, which was blocked by fusion antibody against CXCR4. In addition, CXCR4 expression in human NPCs stimulated by TNF-α and IL-8 was measured by flow cytometry. RESULTS： Results from the transwell assay demonstrated that SDF-1α was a strong chemoattractant for human NPCs （P 〈 0.01）, and 20 ng/mL produced the highest levels of migration. Anti-human CXCR4 fusion antibody significantly blocked the chemotactic effect （P 〈 0.05）. Flow cytometry results showed that treatment with TNF-α and IL-8 resulted in increased CXCR4 expression and greater chemotaxis efficiency of NPCs towards SDF-1α（P 〈 0.01）. CONCLUSION： These results demonstrated that SDF-la significantly attracted NPCs in vitro, and neutralizing anti-CXCR4 antibody could block part of this chemotactic function. TNF-α and IL-8 increased chemotaxis efficiency of NPCs towards the SDF-1αgradient by upregulating CXCR4 expression in NPCs.

齐刺环跳穴干预坐骨神经损伤大鼠海马IL-1β、IL-6、TNF-α及GFAP表达影响的实验研究

目的 通过观察齐刺环跳穴对坐骨神经损伤大鼠海马白细胞介素-1β(Interleukin-1β,IL-1β)、白细胞介素-6(Interleukin-6,IL-6)、肿瘤坏死因子-α(Tumor Necrosis Factor-alpha, TNF-α)及胶质纤维酸性蛋白(Glial Fibrillary Acidic Protein, GFAP)表达的影响,探讨齐刺环跳穴治疗坐骨神经痛的中枢镇痛机制。方法 60只SD大鼠随机分为假手术组、模型组、齐刺组、单刺组及药物组,每组12只,采用钳夹法制备大鼠坐骨神经损伤模型。造模第2天开始进行针刺及药物干预,连续14 d。观察各组大鼠干预前后坐骨神经功能指数(Sciatic nerve Function Index, SFI)、热缩足反射潜伏期(Paw Withdrawal Latency, PWL)的变化,ELISA法检测海马组织IL-1β、IL-6、TNF-α蛋白表达水平,实时定量PCR法及免疫组化法检测海马组织GFAP表达水平。结果 干预前,与假手术组比较,其余各组大鼠PWL值、SPI值显著降低(P<0.01),与模型组比较,齐刺组干预后大鼠PWL值、SPI值显著改善(P<0.01)。ELISA法、RT-PCR法及免疫组化检测结果显示,模型组、齐刺组、单刺组、药物组IL-1β、IL-6、TNF-α、GFAP表达较假手术组显著升高(P<0.01);与模型组相比,齐刺组、单刺组、药物组IL-1β、IL-6、TNF-α、GFAP表达显著下降,齐刺组表达低于单刺组及药物组(P<0.01)。结论 齐刺环跳穴缓解坐骨神经痛的镇痛机制可能与下调海马炎症因子表达,抑制星形胶质细胞活化,从而降低中枢痛觉敏化程度有关。

血清TRAF6、activin-A、SFMC水平与子痫前期患者病情及妊娠结局的相关性

目的分析血清肿瘤坏死因子受体相关因子6(TRAF6)、糖蛋白激素-激活素A(activin-A)、可溶性纤维蛋白复合物(SFMC)水平与子痫前期患者病情及妊娠结局的相关性。方法回顾性选取2020年7月至2023年1月郑州大学第二附属医院收治的134例子痫前期患者为研究组,另选取同期健康孕检女性为对照组,根据子痫前期患者病情程度分为轻度、重度患者,所有患者均随访至分娩结束后30 d,根据本次妊娠结局是否发生不良妊娠情况将研究组分为发生、未发生患者。对比对照组和研究组、不同病情程度及不同妊娠结局患者入院时血清TRAF6、activin-A、SFMC水平,并分析其相关性,分析入院时血清各指标水平检测对子痫前期患者妊娠结局的预测价值。结果研究组入院时血清TRAF6、activin-A、SFMC水平高于对照组(P<0.05);重度患者血清TRAF6、activin-A、SFMC水平高于轻度患者(P<0.05);入院时血清TRAF6、activin-A、SFMC均与患者病情程度呈正相关(P<0.05);妊娠不良患者入院时血清TRAF6、activin-A、SFMC水平高于妊娠良好患者(P<0.05);入院时血清TRAF6、activin-A、SFMC水平联合预测子痫前期患者妊娠不良的曲线下面积(AUC)为0.748。结论血清TRAF6、activin-A、SFMC表达与子痫前期患者病情程度及预后密切相关,其三者联合检测对预测子痫前期患者妊娠不良具有较高的应用价值,可辅助临床诊疗。

脊柱结核术后TLR-4、TNF-α、IL-6、IL-17的变化及与预后的相关性研究

目的分析脊柱结核术后Toll样受体(TLR)-4、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-17的变化及与预后的相关性。方法选择2021年1月—2022年12月收治的60例接受手术治疗的脊柱结核患者作为观察组,另选60例非脊柱结核且行脊柱手术的患者作为对照组(部分病例由基金项目中合作医院提供)。检测两组患者血清及病灶组织TLR-4、TNF-α、IL-6、IL-17表达水平。根据观察组患者术后6个月的预后情况,分为预后良好组和预后不良组,比较两组术前及术后6个月的血清TLR-4、TNF-α、IL-6、IL-17表达水平,使用Pearson相关性分析评价脊柱结核患者术前血清TLR-4、TNF-α、IL-6、IL-17表达水平与术后6个月改良巴氏指数(MBI)量表评分的关系,受试者工作特征(ROC)曲线分析术后血清TLR-4、TNF-α、IL-6联合IL-17对脊柱结核术后预后不良的预测效能。结果观察组术前血清及病灶组织的TLR-4、TNF-α、IL-6、IL-17表达水平均高于对照组,差异均有统计学意义(P<0.05);预后不良组术前血清TLR-4、TNF-α、IL-6、IL-17表达水平均高于预后良好组,差异均有统计学意义(P<0.05);术后6个月,预后良好组血清TLR-4、TNF-α、IL-6、IL-17表达水平较术前明显降低,与预后不良组比较,差异均有统计学意义(P<0.05);经Pearson相关性分析,脊柱结核患者术前血清TLR-4、TNF-α、IL-6、IL-17表达水平与术后6个月MBI量表评分呈负相关(P<0.05);经ROC曲线分析,术前血清TLR-4、TNF-α、IL-6联合IL-17预测脊柱结核术后预后不良的ROC曲线下面积为0.921。结论脊柱结核术后血清TLR-4、TNF-α、IL-6、IL-17较术前明显降低,与预后密切相关,术前血清TLR-4、TNF-α、IL-6联合IL-17预测预后不良的效能较好,值得临床予以重视。

TNF-α和IL-6对胎儿生长受限胎儿骨骼肌的影响

胎儿生长受限(fetal growth restriction,FGR)是一种常见的产科疾病,其可导致新生儿低出生体质量和出生后肌肉量减少。这可能与肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-6(interleukin-6,IL-6)的调控密切相关。研究发现,这两种炎症因子在FGR胎儿中表达水平异常,可通过影响成肌细胞的增殖和分化,干扰正常骨骼肌的发育。此外,TNF-α与IL-6还可以激活特定的信号通路,如核因子κB(nuclear factor-κB,NF-κB)、Janus激酶/信号转导及转录活化因子(Janus kinase/signal transducer and activator of transcription,JAK/STAT)、丝裂原激活的蛋白激酶(mitogen-activated protein kinase,MAPK)等信号通路,调节肌细胞的代谢和功能。如使用特定的抗炎药物或生物制剂来降低TNF-α和IL-6的活性,可能有助于改善FGR胎儿的骨骼肌发育。总的来说,TNF-α和IL-6在FGR胎儿骨骼肌发育中的作用是一个多层面、复杂的过程,需要进一步的深入研究来阐明其具体机制,帮助理解FGR的病理生理学,并为治疗FGR胎儿提供新的思路。

血清MyD88和TRAF-6联合检测在儿童重度急性呼吸道感染诊断和预后评估中的价值

目的探讨血清髓系分化初级反应蛋白88(MyD88)、肿瘤坏死因子受体相关因子6(TRAF-6)在儿童重度急性呼吸道感染辅助诊断和预后评估中的价值。方法选取2020年1月—2022年6月南阳市中心医院儿童急性呼吸道感染患儿80例(急性呼吸道感染组)。根据病原学检测结果分为非细菌感染组(42例)和细菌感染组(38例)。根据患儿病情严重程度分为轻度组(28例)、中度组(20例)、重度组(32例)。根据患儿预后情况分为预后良好组(58例)和预后不良组(22例)。以同期80名体检健康儿童为正常对照组。采用多因素Logistic回归分析评估急性呼吸道感染患儿预后的影响因素。采用受试者工作特征(ROC)曲线评价各项指标诊断儿童重度急性呼吸道感染和评估预后的效能。结果急性呼吸道感染组血清MyD88、TRAF-6水平显著高于正常对照组(P<0.001)。细菌感染组血清MyD88、TRAF-6水平显著高于非细菌感染组(P<0.001)。轻度组、中度组、重度组血清MyD88、TRAF-6水平依次升高(P<0.001)。ROC曲线分析结果显示,血清MyD88、TRAF-6单项检测和联合检测诊断重度急性呼吸道感染的曲线下面积(AUC)分别为0.762、0.734、0.876。预后不良组细菌感染、下呼吸道感染、重度病情所占比例和白细胞(WBC)计数、反应蛋白(CRP)、MyD88、TRAF-6水平均显著高于预后良好组(P<0.05)。多因素Logistic回归分析结果显示,重度病情、CRP升高、MyD88升高、TRAF-6升高均是儿童急性呼吸道感染预后不良的危险因素[比值比(OR)值分别为1.693、1.864、3.218、2.869,95%可信区间(CI)分别为1.142~2.510、1.228~2.830、1.561~6.633、1.511~5.446,P<0.05]。ROC曲线分析结果显示,血清MyD88、TRAF-6、CRP单项检测和联合检测判断急性呼吸道感染患儿预后的AUC分别为0.848、0.900、0.817、0.951。结论急性呼吸道感染患儿血清MyD88、TRAF-6水平显著升高,联合检测对儿童重度急性呼吸道感染的辅助诊断和预后评估均有较高的临床价值。

孕早期血清脂肪因子CTRP6与妊娠糖尿病的关系

目的研究孕早期妇女血清补体C1q/肿瘤坏死因子相关蛋白6(C1q/tumor necrosis factor-related protein 6,CTRP6)的表达水平,探讨其与妊娠糖尿病(gestational diabetes mellitus,GDM)的关系。方法前瞻性连续选取2021年3月至2022年3月在郑州大学第二附属医院门诊产检的孕10~13周孕妇,收集孕妇的年龄、身高、体质量、末次月经时间,检测孕早期总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、高密度脂蛋白(high density lipoprotein,HDL)、低密度脂蛋白(low density lipoprotein,LDL)、空腹血糖(fasting plasma glucose,FPG)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、空腹胰岛素(fasting insulin,FINS)、CTRP6水平,计算孕前体质量指数(body mass index,BMI)、基线BMI、产前BMI和胰岛素抵抗指数(亦称胰岛素抵抗的稳态模型评估,homeostatic model assessment of insulin resistance,HOMA-IR)。所有孕妇均于孕24~28周行75g口服葡萄糖耐量试验,根据试验结果分为GDM组和糖耐量正常(normal glucose tolerance,NGT)组。比较两组孕妇孕早期的临床资料及实验室指标,分析孕早期血清CTRP6与各指标的相关性及其与GDM的关系。结果共纳入孕妇213例,完整随访203例,其中52例孕妇被诊断为GDM,GDM发病率25.62%。GDM组孕妇的孕早期血清CTRP6、年龄、孕前BMI、基线BMI、产前BMI、TC、LDL、FPG、HbA1c、FINS、HOMA-IR均较NGT组升高,差异有统计学意义(P<0.05)。孕早期CTRP6与年龄、孕前BMI、基线BMI、产前BMI、TG、LDL、FPG、HbA1c、FINS、HOMA-IR呈正相关,与HDL呈负相关(P<0.05)。校正年龄、BMI、糖脂代谢指标及HOMA-IR后,孕早期CTRP6为GDM发病的独立影响因素。结论孕早期血清CTRP6升高与GDM相关,是GDM的独立危险因素。

养精种玉汤对薄型子宫内膜大鼠血清TNF-α、IL-6的影响

目的:探讨养精种玉汤对薄型子宫内膜大鼠血清肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)的调节作用。方法:21只雌性大鼠分为三组,每组7只,于造模结束观察三个动情周期后连续灌胃12 d,对照组、模型组予等量0.9%氯化钠溶液灌胃,中药组予1.68 g/kg养精种玉汤(免煎颗粒)灌胃。测量各组大鼠子宫湿重和子宫脏器系数;HE染色观察各组大鼠子宫内膜组织形态学变化;RT-qPCR法检测子宫内膜TNF-αmRNA、IL-6 mRNA的表达;ELISA法检测血清TNF-α、IL-6水平。结果:与对照组比较,模型组子宫湿重、子宫脏器系数均降低,子宫内膜明显变薄,腺体数目减少(P<0.001),TNF-αmRNA、IL-6 mRNA表达升高(P<0.05),TNF-α、IL-6水平明显升高(P<0.01或P<0.05);与模型组比较,中药组子宫湿重、子宫脏器系数均升高,子宫内膜增厚(P<0.05),腺体数目增多(P<0.001),TNF-αmRNA、IL-6 mRNA表达降低(P<0.05),TNF-α、IL-6水平降低(P<0.01或P<0.05)。结论:调节血清TNF-α、IL-6的异常表达可能是养精种玉汤治疗薄型子宫内膜大鼠的机制之一。

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。

先兆流产保胎治疗孕妇血清PCSK9和CTRP6水平对妊娠结局的预测价值研究

目的探究先兆流产保胎治疗孕妇血清前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9),C1q肿瘤坏死因子相关蛋白6(complement-C1q/tumor necrosis factor-related protein 6,CTRP6)水平对妊娠结局的预测价值。方法选取2021年08月~2022年05月在陕西中医药大学第二附属医院行保胎治疗的80例先兆流产孕妇为研究对象,根据妊娠结局将其分为良好妊娠结局组(n=62)、不良妊娠结局组(n=18);另选取同期在该院孕检正常的孕妇60例作为对照组。采用酶联免疫吸附法(ELISA)检测研究对象血清PCSK9,CTRP6,孕酮和β-人绒毛膜促性腺激素(β-HCG)水平;采用Pearson法分析血清PCSK9,CTRP6水平与孕酮,β-HCG水平的相关性;采用多因素Logistic回归分析影响先兆流产保胎治疗孕妇妊娠结局的因素;采用受试者工作特征(ROC)曲线分析先兆流产保胎治疗孕妇血清PCSK9和CTRP6对妊娠结局的预测价值。结果对照组、良好妊娠结局组和不良妊娠结局组的孕酮(45.65±3.48,38.29±3.54和31.56±4.11 nmol/L),β-HCG(32056.56±4244.54,23642.32±3897.67和11375.56±3454.35 mIU/L),CTRP6(436.53±36.23,328.44±31.06和277.86±25.56 ng/ml)水平均呈逐渐降低趋势,PCSK9(64.22±10.35,82.24±13.33和114.56±17.67 ng/ml)表达水平呈逐渐升高趋势,差异具有统计学意义(F=129.231,199.334,244.007,111.297,均P<0.05)。Pearson法分析显示,血清PCSK9与孕酮、β-HCG水平呈负相关(r=-0.545,-0.514,均P<0.05),血清CTRP6与孕酮、β-HCG水平呈正相关(r=0.567,0.496,均P<0.05)。多因素Logistic回归分析显示,PCSK9水平升高为先兆流产保胎治疗孕妇妊娠结局的独立危险因素,CTRP6,孕酮、β-HCG水平升高为先兆流产保胎治疗孕妇妊娠结局的独立保护因素(P<0.05)。ROC结果显示,先兆流产保胎治疗孕妇血清PCSK9,CTRP6预测患者发生不良妊娠结局的曲线下面积(AUC)分别为0.843,0.849,两者联合预测的AUC为0.941,优于两者各自单独预测(Z=1.725,1.882,P<0.05),且特异度和敏感度分别为85.48%,94.44%。结论先兆流产保胎治疗孕妇血清PCSK9水平显著上调,CTRP6水平显著下调,两者在预测先兆流产保胎治疗孕妇的妊娠结局中具有重要价值。

学龄前龋病儿童龈沟液IL⁃6、TNF⁃α、MCP⁃1与CAT分度相关性及对慢性根尖周炎的预测价值研究

目的探讨学龄前龋病儿童龈沟液白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白-1(MCP-1)与龋病活跃性试验(CAT)分度相关性及对慢性根尖周炎的预测价值。方法选取2020年1月—2021年6月480例3~6岁接受口腔检查儿童,根据龋齿发生情况分为发生组、未发生组,比较2组及不同龋病危险度患儿龈沟液IL-6、TNF-α、MCP-1水平,比较发生慢性根尖周炎(有慢性根尖周炎亚组)、未发生慢性根尖周炎(无慢性根尖周炎亚组)患儿入院时龈沟液IL-6、TNF-α、MCP-1水平,应用Spearman相关性分析患儿龈沟液IL-6、TNF-α、MCP-1与龋病危险度的相关性,采用受试者工作特征(ROC)曲线分析患儿龈沟液IL-6、TNF-α、MCP-1及CAT分度预测慢性根尖周炎的价值。结果发生组龈沟液IL-6、TNF-α、MCP-1高于未发生组(P<0.01);随着龋病危险度增加,患儿龈沟液IL-6、TNF-α、MCP-1呈递增趋势(P<0.05);患儿龈沟液IL-6、TNF-α、MCP-1与龋病危险度呈正相关(P<0.01);有慢性根尖周炎亚组龈沟液IL-6、TNF-α、MCP-1高于无慢性根尖周炎亚组(P<0.01);患儿龈沟液IL-6、TNF-α、MCP-1及CAT分度预测慢性根尖周炎的ROC曲线显示,其曲线下面积(AUC)依次为0.732、0.774、0.743、0.745,其中TNF-α预测敏感度最高,CAT分度预测特异度最高;患儿龈沟液IL-6、TNF-α、MCP-1联合CAT分度预测慢性根尖周炎的AUC为0.924,敏感度为0.919,特异度为0.806,高于各指标单独预测。结论学龄前龋病患儿龈沟液IL-6、TNF-α、MCP-1与儿童龋活性及慢性根尖周炎发生密切相关,三者联合CAT分度或可作为预测学龄前龋病患儿并发慢性根尖周炎的有效方案,可为临床防治龋病提供参考。

妊娠期糖尿病患者孕6~14周血清CTRP3、FGF19及SHBG的变化及预测价值

目的探讨妊娠期糖尿病(GDM)患者孕6~14周血清补体C1q/肿瘤坏死因子相关蛋白3(CTRP3)、成纤维细胞生长因子19(FGF19)及性激素结合球蛋白(SHBG)的变化及预测价值。方法回顾性分析2019年6月至2022年10月在秦皇岛市第一医院分娩的684例单胎妊娠孕妇的临床资料。统计GDM发生率,根据是否患有GDM分为病例组(n=266)和对照组(n=418)。比较两组CTRP3、FGF19及SHBG水平,并分析其联合预测GDM的价值,采用单因素和多因素Logistic回归分析影响GDM发生的危险因素。结果684例孕妇GDM发生率为38.89%(266/684)。与对照组比较,病例组CTRP3、FGF19及SHBG水平更低(P<0.05)。受试者工作特征(ROC)曲线结果显示,CTRP3、FGF19及SHBG联合预测GDM的曲线下面积(AUC)高于单项预测(P<0.05)。两组年龄、孕前体重指数(BMI)、不良孕产史、糖尿病家族史、妊娠期高血压、月经周期紊乱、CTRP3、FGF19、SHBG比较,差异具有统计学意义(P<0.05);两组孕次、产次比较,差异无统计学意义(P>0.05)。年龄≥35岁、孕前BMI≥24 kg/m^(2)、不良孕产史、糖尿病家族史、CTRP3<417.82 ng/L、FGF19<139.23 pg/mL、SHBG<429.59 mmol/L是影响GDM发生的独立危险因素(P<0.05)。结论GDM患者孕6~14周CTRP3、FGF19及SHBG水平均会下降,通过CTRP3、FGF19及SHBG联合预测GDM具有较高的应用价值。