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关键词： 炎症性肠病   白细胞介素-1受体拮抗蛋白   孟德尔随机化分析  

摘要： 目的运用孟德尔随机化方法深入探究白细胞介素-1受体拮抗蛋白(IL-1RA)在炎症性肠病(IBD)中的作用,并着重关注中医药在IBD治疗中的研究进展,以寻求创新的治疗策略。方法筛选与IL-1RA水平密切相关的遗传变异,将阈值(P<5×10^(-8))设定为全基因组的显著水平,进行系统性的因果关系剖析。同时,广泛查阅现有文献,对中医药在IBD治疗中的研究进展予以全面梳理。结果研究表明,影响IL-1RA水平的遗传变异与IBD的发病存在显著关联,证实了IL-1RA在IBD发病机制中的关键作用。相关文献显示,在调节免疫反应方面,根据中医扶正祛邪、调和阴阳等理论,运用多种中药复方及单味中药,可以增强机体的免疫防御能力,同时抑制过度的免疫炎症反应;在减轻炎症方面,部分中药具备清热解毒、活血化瘀的功效,能够有效降低炎症因子水平;在改善IBD症状方面,中医药针对腹痛、腹泻、黏液脓血便等症状进行对症治疗,显著提升患者的生活质量。结论IL-1RA在IBD发展中的免疫调节途径极为重要,有很大可能成为治疗策略的关键靶点。此外,中医药凭借其独特的理论体系和丰富的药物资源,在IBD的治疗中展现出明显的优势和广阔的应用前景,为构建多元化、个性化的IBD治疗策略提供了有力支撑和全新方向。

关键词： 肾病   肾透析   炎症趋化因子类   比值比   淋巴细胞   中性白细胞   预后  

摘要： 【目的】探讨微炎症指标联合中性粒细胞与淋巴细胞比值(NLR)对行维持性血液透析(MHD)的终末期肾病(ESRD)患者预后的评估价值。【方法】对行MHD的76例ESRD患者,随访1年,统计患者的预后情况,并据此分为预后不良组(A组,18例)和预后良好组(B组,58例),分析影响患者预后的相关因素及微炎症指标联合NLR检测对患者预后的评估效能。【结果】76例患者,预后不良发生率为23.68%(18/76)。A组营养不良占比、感染占比、透析龄、超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)及NLR均高于B组(P<0.05),A组残肾滤过率低于B组(P<0.05)。患者预后的独立影响因素包括残肾滤过率、hs-CRP及NLR(均P<0.05)。hs-CRP、NLR单一及联合预测行MHD的ESRD患者的灵敏度分别为72.22%、83.33%、66.67%,特异度为72.41%、65.52%、98.28%,联合诊断特异度高于单一诊断(P<0.05)。【结论】hs-CRP、NLR预测行MHD的ESRD患者预后的效能较好。

关键词： 骨骼肌   急性损伤/修复   巨噬细胞   免疫代谢  

摘要： 在运动训练中,骨骼肌损伤极为常见,且大多数运动损伤为骨骼肌急性损伤。巨噬细胞是骨骼肌损伤修复进程中的关键调控者,通过改变自身活化模式参与该进程中炎症、组织新生、血管重塑、细胞外基质重建等过程。此外,巨噬细胞免疫代谢影响着骨骼肌修复进程:不同活化模式的巨噬细胞执行不同的代谢程序以支持/阻碍骨骼肌修复;另一方面,骨骼肌损伤后不同代谢微环境又会塑造巨噬细胞的不同表型与功能。本文梳理了近年来巨噬细胞免疫代谢在骨骼肌急性损伤修复中的作用研究文献,以期为运动医学领域骨骼肌急性损伤预防和治疗提供解决思路。

关键词： 胃癌   Th17细胞   IL-17   MMP2  

摘要： 目的:探讨Th17细胞、血清白细胞介素-17 (IL-17)、基质金属蛋白酶(MMP2)在评估胃癌(GC)淋巴结转移中的临床应用价值。方法:选取2023年1月~2024年10月入住于天津市武清中医院的36例胃癌患者(GC组)及38例胃良性病变患者(对照组),采用流式细胞术检测各组外周血Th17细胞水平,采用酶联免疫吸附法(ELISA)测定血清中IL-17和MMP2水平,评估这三个检测指标在GC淋巴结转移中的应用价值及三者联合检测的诊断效能。结果:与对照组对比,GC组患者外周血Th17细胞水平明显增高,血清IL-17和MMP2水平也明显较高,差异均有统计学意义(均p Objective: To explore the clinical application value of Th17 cells, serum Interleukin-17 (IL-17), and Matrix Metalloproteinases (MMP2) in assessing the lymph node metastasis of Gastric Cancer (GC). Methods: 36 GC patients (GC group) and 38 patients with benign gastric lesions (control group) admitted to Tianjin Wuqing Hospital of Traditional Chinese Medicine from January 2023 to October 2024 were selected. Flow cytometry was used to detect peripheral blood Th17 cell amount in each group, and Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure IL-17 and MMP2 levels in the serum. The application value of these three detection indicators in the lymph node metastasis of GC, as well as the diagnostic efficacy of their combined detection, were evaluated. Results: Compared with control group, patients in the GC group showed a significant increase in Th17 cell levels in peripheral blood and prominently higher serum IL-17 and MMP2 levels, with statistical significance (all p < 0.05). In the GC group, the amount of Th17 cells, serum IL-17, and MMP-2 was significantly higher in patients with lymph node metastasis compared to those without metastasis, and the differences were statistically significant (all p < 0.05). The accuracy, specificity, and sensitivity of the combined detection of Th17, IL-17, and MMP2 were 95.82%, 94.21% and 97.69%, respectively. Compared with single detection, they were significantly higher, and the differences were statistically significant (all p < 0.05). Conclusion: Th17 cells, IL-17, and MMP2 are associated with lymph node metastasis in GC, and their combined detection can help in the differential diagnosis of GC.

关键词： 微生态制剂   肝硬化   细菌性腹膜炎   肠道菌群   细胞因子  

摘要： 目的探讨微生态制剂治疗肝硬化合并细菌性腹膜炎患者的临床疗效。方法选择2019年6月至2021年6月于驻马店市中心医院就诊的肝硬化合并细菌性腹膜炎患者112例为研究对象。采用随机数字表法将患者分为对照组和观察组,每组56例。2组患者均接受保肝、抗感染及营养支持等基础治疗,观察组患者在此基础上增加微生态制剂治疗,均连续治疗3周。治疗前及治疗3周后,检测2组患者粪便中肠道菌群变化,采用酶联免疫吸附法检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1、IL-2、IL-6、IL-10等细胞因子水平,使用全自动酶标仪检测患者的血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、白蛋白(ALB)等肝功能指标水平。观察并记录2组患者腹痛、腹泻、发热改善时间,以及腹水常规、腹水培养改善时间。观察并记录2组患者肝性脑病、消化道出血、真菌感染、肝肾综合征等不良反应发生情况,并计算不良反应总发生率。结果治疗前2组患者乳杆菌属、肠球菌属、肠杆菌属、双歧杆菌属、白念珠菌属水平比较差异无统计学意义(P>0.05)。对照组患者治疗3周后白念珠菌属水平显著低于治疗前(P<0.05),乳杆菌属、肠球菌属、肠杆菌属、双歧杆菌属水平治疗前后比较差异无统计学意义(P>0.05);观察组患者治疗3周后乳杆菌属、肠球菌属、双歧杆菌属水平显著高于治疗前(P<0.05),肠杆菌属水平治疗前后比较差异无统计学意义(P>0.05)。治疗3周后,观察组患者乳杆菌属、肠球菌属、双歧杆菌属水平显著高于对照组,白念珠菌属水平显著低于对照组(P<0.05);2组患者肠杆菌属水平比较差异无统计学意义(P>0.05)。治疗前2组患者血清TNF-α、IL-1、IL-2、IL-6、IL-10水平比较差异无统计学意义(P>0.05)。对照组患者治疗3周后血清TNF-α、IL-6水平显著低于治疗前,IL-2、IL-10水平显著高于治疗前(P<0.05);IL-1水平治疗前后比较差异无统计学意义(P>0.05)。观察组患者治疗3周后TNF-α、IL-1、IL-6水平显著低于治疗前,IL-2、IL-10水平显著高于治疗前(P<0.05)。治疗3周后,观察组患者血清TNF-α、IL-1、IL-6水平显著低于对照组,IL-2、IL-10水平显著高于对照组(P<0.05)。治疗前2组患者ALT、AST、ALB水平比较差异无统计学意义(P>0.05)。2组患者治疗3周后ALT、AST水平均显著低于治疗前,ALB水平均显著高于治疗前(P<0.05)。治疗3周后,观察组患者ALT、AST水平显著低于对照组,ALB水平显著高于对照组(P<0.05)。观察组患者腹痛、腹泻、发热症状缓解时间及腹水常规、腹水培养改善时间均短于对照组(P<0.05)。对照组和观察组患者并发症总发生率分别为8.93%(5/56)、10.71%(6/56),2组患者并发症总发生率比较差异无统计学意义(χ^(2)=0.101,P>0.05)。结论微生态制剂可改善肝硬化合并细菌性腹膜炎患者肠道菌群和细胞因子水平,改善肝功能,加快症状缓解,且安全性较高。

关键词： 有机微量元素   无机微量元素   生物利用度   免疫应答反应   饲料转化率   抗营养因子   体液免疫   肉种鸡  

摘要： 有机微量元素指在动物体内含量不超过0.01%的元素,主要包括锌、锰、铜、铁、碘、硒等,各元素虽然含量极低,但在动物机体代谢过程中,发挥着极其重要的作用。目前饲料中添加的微量元素多为无机形式,但在消化过程中易分解,容易与肠道中植酸、单宁等抗营养因子结合形成不溶性化合物,导致生物利用度低,同时过量添加还会导致机体氧化损伤。相比无机微量元素,有机微量元素具有更高的生物利用度,可提高机体细胞免疫和体液免疫的免疫应答反应,增强肝脏和脾脏组织抗氧化能力,促进机体酶的活性,提高饲料转化率,从而对动物生长、采食等均有明显促进作用。为验证有机微量元素在父母代肉种鸡上的应用效果,本试验以AA+父母代白羽肉种鸡为研究对象,研究有机微量元素对肉种鸡生产性能的影响。

关键词： Non-Radiographic Axial Spondyloarthritis   nr-ax SPA   JAKi   Interleukin 17 Inhibitors   IL-17i   Janus Kinase Inhibitors  

摘要： Background: Non-radiographic axial spondyloarthritis is a progressive and disabling inflammatory disease affecting young adults, with limited treatment options. TNFi are more efficacious than JAKi and IL1-7i in nr-ax SPA and it has a well-known safety profile over a longer duration. Recently, many IL-17i and JAKi were approved for the treatment of nr-ax SPA;however, data comparing IL1-7i and JAKi in terms of efficacy and safety is lacking. This systematized review aimed to compare the existing efficacy and safety data of JAKi vs IL-17i in the treatment of patients with nr-ax SPA. Methods: A systematic literature search was performed using relevant keywords in many databases. According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA, 2020), relevant articles were included and evaluated in this review. Efficacy and safety data were collected, analyzed and compared through week 52. The first check was done by the end of week 14 and week 16 for upadacitinib and IL-17i respectively. Results: Data from four RCTs evaluating upadacitinib, secukinumab, ixekizumab, and bimekizumab comprising 1425 patients were analyzed. Overall, a comparable efficacy and safety profile were observed across different treatment arms through week 52;however, non-significant variations were encountered in some outcome measures. The primary endpoint among these RCTs (ASAS40 response rate) was met and it was higher in patients treated with bimekizumab 160 mg sc Q 4 weeks in TNFi non responders (48%) and lowest in ixekizumab 80 mg sc Q 4 weeks treated patients, (35%) (p Conclusion: The above-mentioned three IL-17i and the only one JAKi demonstrated comparable safety and efficacy profiles with some minor variations. A head-to-head trial comparing the effectiveness and safety characteristics of JAKi vs IL-17i may be needed in patients with active nr-ax SpA.

关键词： 带状疱疹后神经痛   火针   镇痛   IL-10   β-内啡肽   炎症  

摘要： 目的:探讨火针对带状疱疹后神经痛(PHN)大鼠的镇痛作用及其对IL-10/β-内啡肽(β-EP)信号通路的影响。方法:40只大鼠随机分为4组:对照组、模型组、火针组与药物组,每组10只。树脂毒素腹腔注射构建PHN模型,造模成功后,火针组予以L4~6夹脊穴火针干预,药物组腹腔注射加巴喷丁。Von Frey电子测痛仪测定各组大鼠缩爪机械阈值(PWMT),热辐射刺激器测定大鼠缩爪热潜伏期(PWTL),ELISA检测背根神经节组织前列腺素E2(PGE2)、P物质(SP)、血清IL-6、TNF-α、IL-1β水平,Western blot检测大鼠脊髓IL-10、β-EP蛋白表达。结果:与对照组相比,模型组PWMT显著下降(P<0.05),PWTL、脊髓组织PGE2、SP水平和血清IL-6、TNF-α和IL-1β水平显著上升(P<0.05),脊髓背角IL-10、β-EP蛋白表达显著下降(P<0.05);相比模型组,火针组、药物组PWMT显著升高(P<0.05),PWTL、脊髓组织PGE2、SP水平和血清IL-6、TNF-α和IL-1β水平显著下降(P<0.05),IL-10、β-EP蛋白表达显著升高(P<0.05)。结论:火针能够改善PHN大鼠疼痛反应,降低外周血炎症水平,其作用可能与激活IL-10/β-EP信号通路有关。

关键词： anti-inflammation   interleukin-37   MERS-CoV   pneumonia  

摘要： Background:The aim was to elucidate the function of IL-37 in middle east respiratory syndrome coronavirus(MERS-CoV)infection,thereby providing a novel therapeutic strategy for managing the clinical treatment of inflammatory response caused by respiratory virus ***:We investigated the development of MERS by infecting hDPP4 mice with hCoV-EMC(107 TCID50[50%tissue culture infectious dose])*** infected A549 cells with MERS-CoV,which concurrently interfered with IL-37,detecting the viral titer,viral load,and cytokine expression at certain points ***,we administered IL-37(12.5μg/kg)intravenously to hDPP4 mice 2 h after MERS-CoV-2 infection and collected the serum and lungs 5 days after infection to investigate the efficacy of IL-37 in MERS-CoV ***:The viral titer of MERS-CoV-infected A549 cells interfering with IL-37 was significantly reduced by 4.7-fold,and the viral load of MERS-CoV-infected hDPP4 mice was decreased by 59-fold in lung ***,the administration of IL-37 suppressed inflammatory cytokine and chemokine(monocyte chemoattractant protein 1,interferon-γ,and IL-17A)expression and ameliorated the infiltration of inflammatory cells in hDPP4 ***:IL-37 exhibits protective properties in severe pneumonia induced by MERS-CoV *** effect is achieved through attenuation of lung viral load,suppression of inflammatory cytokine secretion,reduction in inflammatory cell infiltration,and mitigation of pulmonary injury.

关键词： 牛膝多糖   髓核细胞   沉默信息调节因子3   帕金森蛋白   线粒体自噬  

摘要： 目的探究牛膝多糖(Achyranthis Bidentatae Radix polysaccharides,ABPS)对髓核细胞退变的保护作用及其机制。方法分离大鼠椎间盘髓核细胞,采用白细胞介素-1β(interlenkin1β,1L-1β)处理构建髓核细胞退变模型,将细胞分为对照组、IL-1β组、ABPS(100 mg/L)+IL-1β组、ABPS(200 mg/L)+IL-1β组,研究ABPS对1L-1β处理大鼠髓核细胞增殖、氧化应激、NOD样受体蛋白3(NOD-Like Receptor Protein 3,NLRP3)和线粒体自噬的影响。采用慢病毒技术转染帕金森疾病蛋白2(Parkinson disease protein 2,Parkin)shRNA,随后采用IL-1β和ABPS处理,研究线粒体自噬在ABPS抑制1L-1β处理髓核细胞氧化应激和NLRP3炎性小体活化中的作用。将细胞分为对照组、IL-1β组、ABPS+IL-1β组、ABPS+IL-1β+沉默信息调节因子3(silent information regulators 3,SIRT3)抑制剂(3-TYP)组,研究SIRT3在ABPS调控细胞线粒体自噬中的作用。免疫荧光法检测细胞增殖核抗原(proliferation related Ki 67 antigen,Ki67)和半胱氨酸天冬氨酸蛋白酶-3(cystein-asparate protease-3,Caspase-3)以及微管相关蛋白1轻链3(microtubule-associated protein 1 light 3,LC3)与线粒体的共定位情况;流式细胞术检测细胞周期分布;Western blotting检测Ⅱ型胶原(typeⅡCollagen)、蛋白聚糖(aggrecan)、活化型Caspase-3(cleaved Casase-3)、NLRP3、Caspase-1、Parkin、LC3、选择性自噬接头蛋白-1(sequestosome-1,SQSTM1/p62)、研究SIRT3、B细胞淋巴瘤-2(B-cell lymphoma-2,Bcl-2)以及Bcl-2关联X蛋白(Bcl-2 associated X protein,Bax)蛋白表达;原位末端标记法(Td T-mediated dUTP nick end labeling,TUNEL)检测细胞凋亡;荧光探针检测活性氧(reactive oxygen species,ROS)、线粒体膜电位(mitochondrial membrane potential,MMP)和线粒体活性氧(mitochondrial ROS,mt ROS);比色法检测超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽(glutathione,GSH)和丙二醛(malondialdehyde,MDA)水平。结果与对照组比较,IL-1β组髓核细胞存活率、typeⅡCollagen和aggrecan水平以及Ki67荧光强度均显著降低(P<0.05),而G0/G1期细胞分布比例则明显升高(P<0.05)。与IL-1β组比较,ABPS处理组细胞存活率、typeⅡcollagen和aggrecan蛋白水平以及Ki67荧光强度升高(P<0.05),G0/G1期细胞分布比例明显降低(P<0.05)。此外,与对照组比较,IL-1β组髓核细胞中SOD和GSH水平降低(P<0.05),MDA、ROS、TUNEL阳性细胞、NLRP3、Caspase-3、cleaved Caspase-3和Caspase-1蛋白水平明显升高(P<0.05)。ABPS处理逆转了IL-1β处理对髓核细胞氧化应激、凋亡和NLRP3炎性小体活化的影响。此外,ABPS处理减弱了IL-1β处理诱导的髓核细胞MMP降低和mtROS升高(P<0.05)。ABPS增强了IL-1β处理髓核细胞中Parkin和LC3的表达(P<0.05),SQSTM1/p62蛋白表达进一步降低(P<0.05)。Parkin shRNA阻断了ABPS对IL-1β处理髓核细胞线粒体自噬、氧化应激、凋亡和NLRP3炎性小体的影响(P<0.05)。此外,IL-1β处理组髓核细胞中的SIRT3蛋白水平降低(P<0.05),ABPS处理后细胞中的SIRT3蛋白水平升高(P<0.05)。3-TYP阻断了ABPS对IL-1β处理髓核细胞中Parkin介导线粒体自噬的调节作用(P<0.05)。结论ABPS可通过调控SIRT3/Parkin信号通路介导的线粒体自噬,减轻IL-1β诱导的髓核细胞氧化应激和NLRP3炎性小体活化。