温针灸联合塞来昔布对膝骨关节炎患者血清炎症因子及关节功能的影响

目的 探讨温针灸联合塞来昔布对膝骨关节炎患者血清炎症因子及关节功能的影响。方法 80例膝骨关节炎患者,按随机数字表法分为对照组和观察组,每组40例。对照组患者单纯口服塞来昔布治疗,观察组患者给予温针灸联合塞来昔布治疗。比较两组患者临床治疗效果、不良反应发生情况及治疗前后视觉模拟评分法(VAS)评分、美国膝关节协会(AKS)评分、膝关节活动度、血清炎症因子(白细胞介素-6、肿瘤坏死因子-α、超敏C反应蛋白)。结果 治疗3周后,两组VAS评分低于本组治疗前, AKS膝评分、功能评分高于本组治疗前,且观察组VAS评分(2.02±0.70)分明显低于对照组的(3.66±0.84)分, AKS膝评分、功能评分分别为(90.65±4.26)、(88.14±5.63)分,明显高于对照组的(76.36±4.12)、(77.55±5.02)分,差异有统计学意义(P<0.05)。治疗3周后,观察组膝关节伸直度、屈曲度分别为(-3.12±0.30)、(127.18±19.65)°,明显高于对照组的(-4.76±0.38)、(106.40±18.76)°,差异有统计学意义(P<0.05)。治疗3周...     

膝骨关节炎关节液和滑膜中微小 RNA-140-5p的表达及临床意义

目的研究膝骨关节炎(KOA)病人关节液和滑膜中微小 RNA(miR)-140-5p的表达及临床意义。方法选取 2018年 5月至 2019年 5月于北京中医药大学东方医院就诊的 51例 KOA病人为观察组,依据凯尔格伦 -劳伦斯( K-L)分级标准将观察组分为 3个亚组: KOA Ⅱ组( 12例)、 KOA Ⅲ组( 24例)、 KOA Ⅳ组( 15例)另外选取 55例同期该院因骨折、截肢等手术治疗的无骨关节炎病人为对照组。采用实时荧光定量逆转录聚合酶链反应( qRT-,PCR)检测并比较各组关节液和滑膜中 miR-140-5p的表达,分析 miR-140-5p与 KOA病情进展的关系;采用受试者工作曲线( ROC)分析 miR-140-5p对 KOA的诊断价值。结果观察组关节液( 0.51±0.16)、滑膜( 0.67±0.21)中 miR-140-5p均比对照组［( 1.08±0.38)、(1.54±0.35)］低( P<0.05); KOA Ⅱ组、 KOA Ⅲ组、 KOA Ⅳ组相比,关节液［( 0.65±0.17)、(0.51±0.14)、(0.42±0.12)］、滑膜［( 0.86±0.22)、(0.69±0.15)、(0.49±0.13)］中 miR140-5p均呈依次降低趋势,两两相比差异有统计学意义( P<0.05); Spearman相关性分析结果显示, KOA病人关节液、滑膜中 miR-140-5p与 K-L分级均呈负相关( P<0.05); ROC结果显示,关节液、滑膜 miR-140-5p诊断 KOA的曲线下面积( AUC)分别为     

体外冲击波对膝骨关节炎患者血清及关节液中Chemerin含量的影响

目的：探讨体外冲击波（ extracorporeal shock wave,ESW）对膝骨关节炎（ knee osteoarthritis,KOA）的疗效及对患者血清及关节液趋化素（ Chemerin）的影响。方法60例KOA患者随机分为ESW组（ n＝30）和对照组（ n＝30）,ESW组以体外冲击波治疗,对照组以常规治疗。在干预前和8周后,采用活动时疼痛视觉模拟评分（ VAS）、膝关节炎病人疼痛指数（ Le?quesne index）评分和美国西部 Ontario 与 McMaster 大学骨关节炎指数（ western Ontario and McMaster osteoarthritis index, WOMAC）评分进行评定,以及血清及关节液中 Chemerin 水平的变化。结果治疗后, ESW 组 VAS、Lequesne 指数评分和WOMAC骨关节炎指数评分均明显好于对照组（ P＜0．05）。治疗后患者血清和关节液中Chemerin含量均比治疗前显著下降（P＜0．05或0．01）;治疗后ESW组血清和关节液中Chemerin含量显著低于对照组（均P＜0．05）。结论膝关节液和血清中Chemerin含量反映了关节炎症的严重程度,ESW治疗有效的降低了血清和关节液中Chemerin含量,ESW对KOA患者治疗有效,Chemerin可作为OA早期诊断及判断严重程度的参考指标。     

膝骨关节炎患者关节液中IL-18、MMP-3表达水平及二者相关性研究

骨性关节炎(Osteoarthritis OA)目前己成为最常见的关节疾病之一,其中以膝关节骨性关节炎(knee osteoarthritis,KOA)发病最高。由于人群预期寿命的延长和生活质量的提高,在本世纪内膝骨关节炎的发病率明显增高,尤其是在肥胖的老年人群。但KOA的病因至今尚未研究明确。研究表明,多种细胞因子和生长因子都参与KOA的致病过程,其发     

骨关节炎患者关节液中亚硫酸盐及P物质含量变化

目的 探讨亚硫酸盐和P物质在膝骨关节炎患者膝关节液中的含量变化及其临床意义.方法 选择2008年8月至2010年8月骨科住院患者36例,均为初诊患者.根据骨关节炎诊断标准确诊为膝骨关节炎,留取治疗前常规关节腔减压治疗时抽吸的关节液,以及治疗后复查时留取的关节液.测定关节液中的亚硫酸盐及P物质的含量变化.结果 在中重度膝骨关节炎患者的关节液中,亚硫酸盐含量在恢复期较急性期显著降低,差异有统计学意义(t=12.975,P＜0.01);而随访期关节液中亚硫酸盐含量较恢复期虽然有所降低,但差异无统计学意义(P＞0.05).膝关节液中P物质、白介素-1(IL-1)、白介素-6(IL-6)和白介素-8(IL-8)在膝关节液中的含量变化与亚硫酸盐基本一致,恢复期较急性期显著降低(P＜0.01);但随访期P物质和IL-1较恢复期进一步降低,差异有统计学意义(P＜0.01);而IL-6和IL-8虽然也有降低,但差异无统计学意义(P＞0.05).亚硫酸盐和P物质有相关性0.804(P＜0.05).结论 亚硫酸盐与P物质共同参与了膝骨关节炎局部的炎性反应.     

关节液和血清中瘦素含量与膝关节滑膜炎之间的关系

目的探讨膝关节液和血清中瘦素含量与膝关节滑膜炎之间的关系。方法收集行膝关节镜手术患者血清和关节液95例,采用酶联免疫吸附试验(ELISA)法对其血清和关节液中的瘦素浓度进行检测。在关节镜下,对膝关节滑膜炎的炎症程度采用Ayral评分方法进行评测。结果骨关节炎患者关节液和血清中瘦素浓度[(39±9)ng/ml;(26±8)ng/ml]较非骨关节炎患者中的浓度[(17±6)ng/ml;(19±8)ng/ml]明显增高(P<0.05)。所有患者关节液中瘦素浓度与Ayral评分呈正相关(r=0.678,P=0.000);所有患者血清中瘦素浓度与Ayral评分呈正相关(r=0.517,P=0.000);OA患者关节液中瘦素浓度与Ayral评分呈正相关(r=0.327,P=0.035);骨关节炎患者血清中瘦素浓度与Ayral评分呈正相关(r=0.333,P=0.031);非骨关节炎患者关节液中瘦素浓度与Ayral评分呈正相关(r=0.311,P=0.023);非OA患者血清中瘦素浓度与Ayral评分呈正相关(r=0.397,P=0.003)。结论膝关节液及血清中瘦素含量可以反映关节滑膜的炎症程度,并且关节液比血清能更好地反映这种变化。     

炎性因子及信号通路在膝骨关节炎中的研究进展

膝骨关节炎(knee osteoarthritis, KOA)是骨伤科的常见病、多发病,已成为医学界的热点和难点。随着KOA研究的不断深入,炎性因子及相关信号通路在KOA发病机制中的作用逐渐被认识,已成为探索KOA发病机制的突破口。本文从炎症及相关信号通路的角度对KOA病理机制进行综述,发现与KOA相关的致炎因子主要有白介素-1β(interleukin-1β,IL-1β)、白介素-6(interleukin-6,IL-6)、白介素-17(interleukin-17,IL-17)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α);抗炎因子主要为转化生长因子-β(transforming growth factor-β,TGF-β)和白介素-10(interleukin-10,IL-10)。与炎性反应关系密切并和KOA病理过程相关的信号通路,主要有NF-κB信号通路、JAK/STAT信号通路及Wnt信号通路。这些致炎因子通过激活相关信号通路,促进炎性反应的发生,炎性反应又加重骨及软骨的退变,最终导致KOA的发生并进一步加重。而抗炎因子通过拮抗致炎因子,降低...     

支原体肺炎合并心肌炎患儿促炎与抑炎因子表达的变化观察

目的观察支原体肺炎合并心肌炎患儿促炎与抑炎因子表达的变化情况。方法选取2016年2月至2017年8月期间的35例支原体肺炎患儿为A组,同期的35例心肌炎患儿为B组,35例支原体肺炎合并心肌炎患儿为C组,检测与比较三组患儿的血清促炎因子(TNF-α、IL-1β及IL-6)及抑炎因子(IL-10及IL-13)水平。结果 C组的血清促炎与抑炎因子表达均高于A组及B组,而B组则高于A组,差异有统计学意义(P <0.05)。结论支原体肺炎合并心肌炎患儿促炎与抑炎因子均呈现显著升高的状态,应重视对此类患儿进行炎性反应的监控与调节。     

骨关节炎患者单侧膝关节置换对非术侧膝功能变化的影响分析

目的 探索双膝骨关节炎患者的一侧膝关节置换手术对另一侧膝病情变化的影响.方法 对比单侧膝关节置换术患者的非术侧膝关节和保守治疗的膝关节的临床和放射学结果.按纳入和排除标准手术组共103例(男28例、女75例),保守组108例(男31例、女77例),随访至少1年.结果 手术组与保守组在研究侧膝关节的临床评分方面无显著差异,膝关节日常活动状况量表和简明生活质量评价量表评分上2组差异有统计学意义(P<0.05).按照膝关节骨关节炎的放射学分级,手术组研究侧膝关节Ⅱ级进展为Ⅲ级的明显少于保守组(P<0.05);而2组在Ⅲ级进展为Ⅳ级方面差异无统计学意义(P>0.05).结论 对于双膝骨关节炎的患者,一侧的关节置换手术能延缓对侧病情的进展,尤其对于初始病情较轻的患者效果显著.     

Naproxen kinetics in synovial fluid of patients with osteoarthritis.

1. The kinetics of naproxen in synovial fluid were studied in 407 osteoarthritic outpatients with knee effusion requiring aspiration, following a single 1100 mg oral dose of naproxen sodium. 2. The drug concentration-time profiles were described by a biexponential function. Naproxen entered synovial fluid rapidly, reaching a maximum concentration of 36 mg l-1 (Cmax) at 7.5 h. The first order input rate constant (kOs) was 0.41 +/- 0.15 h-1 with a lag time (tlag) of 0.24 +/- 0.36 h. 3. Elimination from the fluid was slow (t1/2 = 31 +/- 12 h) and appreciable drug concentrations were still measurable (27 mg l-1) after 24 h. 4. During once daily dosing of naproxen sodium, naproxen should accumulate in synovial fluid, a steady-state being achieved within a week of treatment. The predicted accumulation ratio based on trough concentration was 2.4.     

Integrated plasma and synovial fluid pharmacokinetics of tenoxicam in patients with rheumatoid arthritis and osteoarthritis: factors determining the synovial fluid/plasma distribution ratio

Single oral doses of 40 mg of the nonsteroidal antiinflammatory drug, tenoxicam, were given to four patients (three with rheumatoid arthritis, one with osteoarthritis). The concentrations of the drug in synovial fluid and plasma were measured by a specific high-performance liquid chromatography method. The unbound fractions of the drug in both fluids were determined at pH 7.4 and 37 degrees C by equilibrium dialysis. The possible influence of the pH on the protein binding was also assessed. The total concentration time curves in plasma and synovial fluid were fitted to linear oral 1 and 2 compartment body models with an additional synovial fluid compartment connected to the central compartment. The unbound fractions of drug in synovial fluid and plasma were on average 0.015 and 0.011, respectively: not significantly different from each other. The protein binding of tenoxicam was pH dependent with increased free fractions at pH values less than 7.4. The average peak concentrations of tenoxicam in plasma and synovial fluid were 4.3 and 1.4 micrograms/ml, respectively. The mean ratio of the areas under the total concentration time curves in synovial fluid and plasma was 0.42, which corresponded to the steady state of equilibrium ratio of the total drug concentrations in the two body fluids. Two hypotheses were tested: hypothesis I assuming that equilibration across the synovial tissue takes place between the unbound, unionized tenoxicam molecules; hypothesis II assuming that equilibration across the synovial tissue is established between the unbound (unionized + ionized) tenoxicam molecules. Based on the available evidence hypothesis II was rejected.     

膝骨性关节炎患者血清和关节液FGF-21与IL-1及TNF-a水平的变化及意义

目的 探讨膝骨关节炎(Knee osteoarthritis,KOA)患者血清、关节液中成纤维细胞生长因子-21(Fibroblast growth factor 21,FGF-21)、白介素-1(interleukin-1,IL-1)、肿瘤坏死因子-a(tumor necrosis factor-a,TNF-a)的水平变化情况,阐述其在膝骨关节炎发病过程中的作用.方法 采用酶联免疫吸附测定法(Enzyme-linked immunosorbent assay,ELISA)检测2013年3月至2015年12月本院门诊及住院部诊治的97例膝骨关节炎患者血清、关节液中FGF-21、IL-1、TNF-a的含量.其中,97例KOA患者依据膝关节X线的Kellgren& Lawrence(K-L)分级,分为对照组(KOA 0级,n=18)和实验组(KOA 1,n=20;KOA 2,n=20;KOA 3,n=19;KOA 4,n=20).结果 与对照组血清FGF-21水平[(323.15±97.63)pg/ml]相比较,实验组各组血清FGF-21水平变化不大,差异无统计学意义(均P＞0.05).实验组各组间血清IL-1、TNF-a水平随着膝骨关节炎疾病进程,浓度逐渐增大,差异有统计学意义(均P＜0.05).与对照组关节液FGF-21水平[(198.23±65.41) pg/ml]、IL-1水平[(36.17±6.89) pg/ml]、TNF-a水平[(18.94±5.81) pg/ml]相比较,实验组各组关节液FGF-21、IL-1、TNF-a水平随着膝骨关节炎疾病进程,浓度逐渐增大,差异有统计学意义(均P＜ 0.05).相关性分析结果表明,血清IL-1、TNF-a水平与K-L分级呈现正相关(相关系数r=0.899、0.942,P＜0.05),而血清FGF-21与K-L分级呈现负相关(相关系数r=-0.121,P＞ 0.05).关节液FGF-21、IL-1、TNF-a水平与K-L分级均呈现正相关(相关系数r=0.876、0.941、0.916,P＜ 0.05).结论 膝骨关节炎血清及关节液FGF-21、IL-1与TNF-a因子参与膝骨关节炎疾病进程,有一定的参考意义.     

亚硫酸盐和雌激素及炎症因子在老年女性膝骨关节炎血清与关节液中的水平及意义

目的探讨亚硫酸盐和雌激素及炎症因子在老年女性骨关节炎患者血清及关节液中的含量变化及其抗炎效应。方法选择住院老年女性患者26例,年龄55～75岁,中位年龄67岁;病史1.8～25.6年,平均10年。均为我科初诊患者,根据骨性关节炎诊断标准确诊为膝骨关节炎,留取治疗前常规关节腔减压治疗时抽吸的关节液,及治疗后复查时的关节液。测定血清雌二醇水平、血清及关节液中的亚硫酸盐及白介素(IL-1、IL-6、IL-8)的含量变化。结果老年女性膝骨关节炎患者的血清雌激素(雌二醇)水平显著低于对照组(P<0.01);急性期血清关节液中亚硫酸盐和炎性因子(IL-1、IL-6和IL-8)均较高,经治疗后恢复期时各值均显著下降(P<0.01)。再根据不同年龄段分组,测定不同年龄段的膝骨关节炎患者急性期血清及关节液中亚硫酸盐和炎症因子(IL-1、IL-6和IL-8)的变化,各炎症因子变化差异无统计学意义(P>0.05);而血清雌二醇水平随年龄增加而减低,差异有统计学意义(P<0.01);急性期骨关节液中亚硫酸盐水平随年龄增加而减低,差异有统计学意义(P<0.01)。随着年龄的增长,骨关节炎患者血清雌二醇水平与关节液中亚硫酸盐含量之间有相关性(R2=-0.991,P<0.05)。结论亚硫酸盐和雌激素及炎症因子共同参与老年女性骨关节炎的发病过程,可能是一种生物活性分子在炎症局部发挥一定的病理生理学作用。     

Changes of the levels of sulfite,estrogen and inflammatory factors in serum and synovial fluids in elderly women with knee osteoarthritis

目的 探讨亚硫酸盐和雌激素及炎症因子在老年女性骨关节炎患者血清及关节液中的含量变化及其抗炎效应.方法 选择住院老年女性患者26例,年龄55 ～ 75岁,中位年龄67岁;病史1.8 ～25.6年,平均10年.均为我科初诊患者,根据骨性关节炎诊断标准确诊为膝骨关节炎,留取治疗前常规关节腔减压治疗时抽吸的关节液,及治疗后复查时的关节液.测定血清雌二醇水平、血清及关节液中的亚硫酸盐及白介素(IL-1、IL-6、IL-8)的含量变化.结果 老年女性膝骨关节炎患者的血清雌激素(雌二醇)水平显著低于对照组(P＜0.01);急性期血清关节液中亚硫酸盐和炎性因子(IL-1、IL-6和IL-8)均较高,经治疗后恢复期时各值均显著下降(P＜0.01).再根据不同年龄段分组,测定不同年龄段的膝骨关节炎患者急性期血清及关节液中亚硫酸盐和炎症因子(IL-1、IL-6和IL-8)的变化,各炎症因子变化差异无统计学意义(P＞0.05);而血清雌二醇水平随年龄增加而减低,差异有统计学意义(P＜0.01);急性期骨关节液中亚硫酸盐水平随年龄增加而减低,差异有统计学意义(P＜0.01).随着年龄的增长,骨关节炎患者血清雌二醇水平与关节液中亚硫酸盐含量之间有相关性(R2=-0.991,P＜0.05).结论 亚硫酸盐和雌激素及炎症因子共同参与老年女性骨关节炎的发病过程,可能是一种生物活性分子在炎症局部发挥一定的病理生理学作用.     

Effects of tramadol on synovial fluid concentrations of substance P and interleukin-6 in patients with knee osteoarthritis: comparison with paracetamol

Both the analgesic drugs tramadol and paracetamol are widely used for the symptomatic therapy of osteoarthritis (OA). The aim of this double-blind, randomised study in patients with knee OA was to compare their effects on synovial fluid concentrations of interleukin (IL)-6 and substance P (SP). Moreover, we evaluated plasma and synovial fluid concentrations of tramadol and its active metabolite (O-desmethyl-tramadol, M1) after oral treatment with this drug. Twenty patients were enrolled. A group of 10 patients received tramadol (50 mg three times a day), and another group of 10 patients were treated with paracetamol (500 mg three times a day) for 7 days. Both drugs significantly reduced the intensity of joint pain. The synovial fluid concentrations of SP were significantly reduced only by the treatment with tramadol. In this group of patients, IL-6 synovial fluid concentrations were slightly, but not significantly, decreased. Paracetamol did not significantly change the synovial fluid concentrations of SP and IL-6. After oral administration, a considerable amount of tramadol was measurable in synovial fluid. Both in plasma and synovial fluid the concentrations of M1 were markedly lower than those of tramadol, with a T/M1 ratio of 14.7+/-4.6 and 9.3+/-3.9, respectively. These data demonstrate that the activity of tramadol may involve the modulation of inflammatory mediators. Moreover, they indicate that after oral treatment with tramadol, both the parent drug and its active metabolite can penetrate into synovial fluid.     

奇正消痛贴膏对早中期膝骨性关节炎关节液NO和MMP-13的影响研究

目的：观察奇正消痛贴膏对早中期膝关节骨性关节炎关节液中一氧化氮（NO）和基质金属蛋白酶-13（MMP-13）含量的影响及临床疗效,并与扶他林乳胶剂组做对照。方法：将60例患者分成治疗组和对照组,奇正消痛贴膏为治疗组,扶他林乳胶剂作对照组,治疗1周及2周后,分别观察患者的美国特种外科医院膝关节评分（HSS）总分、疼痛积分,并进行计分对比分析,同时测定治疗组治疗前后关节液中NO和MMP-13含量,评价其临床疗效,进行疗效观察。结果：通过统计学分析,治疗组治疗1周及治疗2周后与治疗前进行HSS量表中HSS总分、疼痛积分比较,P〈0.05;治疗组按疗程治疗前后关节液中NO含量经配对t检验,P〈0.05。结论：奇正消痛贴膏对早中期膝关节骨性关节炎有较好的治疗作用。     

Plasma and synovial fluid meclofenamic acid concentrations in patients with rheumatoid arthritis of the knee

Summary We have measured plasma and synovial fluid concentrations of meclofenamic acid at 2, 4, 8, and 12 h during steady-state administration (100 mg three times daily for 4–7 days). Paired plasma and synovial samples were obtained pre-treatment and at one of the above times in twelve patients with a diagnosis of rheumatoid arthritis. In addition, the extent of protein binding of meclofenamic acid was assessed in vitro in the pre-treatment plasma and synovial fluid specimens.Peak total concentrations of 1.73 and 0.86 µg·ml^–1 were observed in plasma (at 2 h) and synovial fluid (at 4 h) respectively. The extent of protein binding was 99.7 and 99.6% (not significantly different) in plasma and synovial fluid respectively.The results of this study are compared to those from similar reported studies of other nonsteroidal anti-inflamatory compounds.     

Pharmacokinetics of nonsteroidal anti-inflammatory drugs in synovial fluid

The major site of action for nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatic diseases is probably within the synovial compartment. There has been little work on the disposition of NSAIDs in the synovium and most studies have involved the measurement of their concentrations in synovial fluid. The concentrations of NSAIDs are more sustained in synovial fluid than in plasma, the difference being particularly noted with NSAIDs with short elimination half-lives. The more sustained concentrations may contribute to the prolonged effect of the short half-life NSAIDs, which are usually administered at intervals longer than their half-lives in plasma. The most widely used method of kinetic analysis of NSAIDs in synovial fluid is a compartmental model in which synovial fluid is a peripheral compartment of distribution of the drug. Repeated samples of synovial fluid from individual patients are difficult to collect, but even 1 sample of synovial fluid and plasma from each patient can provide useful data when analysed using the population approach to pharmacokinetic analysis. According to the compartmental model, the mean half-lives of efflux of the NSAIDs from synovial fluid range from 1.5 to 7 hours. The mean partition coefficient of most NSAIDs between synovial fluid and plasma is approximately 0.6. The NSAIDs are highly protein-bound, and the lower mean concentrations in synovial fluid are largely because of the lower concentrations of the binding protein, albumin. The NSAIDs diffuse into and out of synovial fluid in their unbound forms, but there is some diffusion in the protein-bound forms, particularly out of synovial fluid. The mean rates of diffusion of NSAIDs into and out of skin blisters in humans are similar to the rates of influx and efflux in the synovial fluid of the knee, but there is considerable variation between the pharmacokinetics of transfer at the 2 sites in individual patients. NSAIDs decrease the synthesis of prostaglandins in synovial fluid, but there are few data on the relationship between the kinetics of NSAIDs in synovial fluid and the effects on prostaglandin synthesis.