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     

Quinaldic acid in synovial fluid of patients with rheumatoid arthritis and osteoarthritis and its effect on synoviocytes in vitro

Background

Previously, we have demonstrated that kynurenic acid (KYNA), an endogenous metabolite of tryptophan formed along kynurenine pathway, is present in synovial fluid of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. In this study, the goal was to investigate the presence of quinaldic acid (QUDA), a putative metabolite of KYNA, in synovial fluid of RA and OA patients.

地佐辛超前镇痛对腹腔镜手术患者血清白细胞介素-6和P物质的影响

目的 探讨地佐辛超前镇痛对腹腔镜手术患者血清IL-6和P物质的影响.方法 82例行腹腔镜手术的患者按数字表法随机分为两组,观察组41例,对照组41例.观察组采用常规麻醉加用地佐辛超前镇痛,对照组采用常规麻醉.采用视觉模拟评分（VAS）进行镇痛评分,测定两组血清IL-6和P物质.结果 观察组术后2h、12 h、24h的VAS评分分别为（1.02±0.42）分、（2.19±0.87）分、（1.69 ＆#177;0.96）分,均小于对照组的（1.39±0.77）分、（3.08±1.15）分、（2.27±1.21）分（t=5.536 2、2.0644、3.756 4,均P＜0.05）.观察组手术前、后血清IL-6、P物质分别为（117.4±17.2） mg/L、（204.4±23.6） mg/L、（4.21±0.96）mg/L、（4.33±1.03） mg/L,对照组分别为（115.3±14.7） mg/L、（276.5±29.1） mg/L、（4.19±0.94） mg/L、（6.92±1.37） mg/L,两组术后血清IL-6、P物质均明显升高,与对照组比较,观察组术后升高程度小（t=3.7544、7.643 0,均P＜0.05）.结论 地佐辛超前镇痛可明显减少腹腔镜手术患者血清IL-6和P物质的表达.     

Pain relief and pain-related sleep disturbance with extended-release tramadol in patients with osteoarthritis

ABSTRACT

Objective: This analysis evaluated changes in pain and pain-related sleep disturbance with extended-release tramadol (tramadol ER) in patients with moderate, chronic osteoarthritis pain, and the influence of pain reduction on pain-related sleep disturbance.

Methods: Data were obtained from a 12?week, randomized, double-blind, placebo-controlled, fixed-dose study of tramadol ER 100?mg, 200?mg, 300?mg, or 400?mg once daily. Subjects reported osteoarthritis pain intensity with a 100?mm visual analog scale (VAS; 0 = no pain, 100 = extreme pain). A Sleep Problems Index score from 0 to 100?mm (0 = never, 100 = always) was determined from the mean of three subject-reported scores of pain-related sleep disturbance.

Results: A total of 815 subjects received tramadol ER (all doses combined) and 205 received placebo. Mean pain reduction at 12 weeks was –30.4?mm and –21.5?mm for tramadol ER and placebo, respectively (?p < 0.001). Tramadol ER-treated subjects were nearly twice as likely as placebo subjects to have clinically meaningful pain reduction at 12 weeks, defined as 30?mm or greater reduction (odds ratio [OR] = 1.84, p < 0.001) or 30% or greater reduction (OR = 1.95, p < 0.001) in pain. Clinically meaningful reduction of pain-related sleep disturbance at 12 weeks, defined as 16?mm or greater improvement on the Sleep Problems Index, was more common for tramadol ER than placebo (51% vs. 42%, respectively, p = 0.022). Pain reduction was associated with reduced pain-related sleep disturbance (R = 0.51). Study treatment was generally well tolerated. Possible limitations included homogeneity of pain scores at baseline and the effect of adverse events on sleep analyses.

Conclusions: In patients with chronic osteoarthritis pain, pain reduction is associated with decreased pain-related sleep disturbance.     

曲马多和吗啡预先给药对小儿静脉血T淋巴细胞增殖及IL-2水平的影响

目的 观察曲马多和吗啡预先给药对小儿静脉血T淋巴细胞增殖及IL-2水平的影响。方法 采集无免疫性疾病的60例门诊小手术患儿外周静脉血5mL,进行全血和外周血单个核细胞（PBMCs）培养。随机分为空白对照组（C组）、吗啡（100ng·mL^-1）组（M组）及曲马多（500ng．mL^-1）组（T组）,每组20例。培养的PBMCs和全血在体外均用相应药物预先作用48h,用刺激剂刺激后测定T淋巴细胞增殖状态及血清白细胞介素2（IL-2）分泌水平。结果 与C组比较,M组cpm值明显降低（P〈0．01）;T组cpm值增高（P〈0．05）。与C组比较,M组IL-2水平明显降低（P〈0．01）;T组IL-2水平增高（P〈0．0S）。结论 吗啡和曲马多对小儿免疫功能有不同的影响。选择曲马多作为小儿术后镇痛的药物更为合适,可以减少对免疫功能的抑制。     

Extended-release tramadol/paracetamol in moderate-to-severe pain: a randomized,placebo-controlled study in patients with acute low back pain

Abstract

Objective:

Combinations of oral analgesics may offer several potential benefits compared with an individual agent. The objective of this study was to investigate the efficacy and safety of an extended-release, twice-daily fixed combination of 75?mg tramadol/650?mg paracetamol (DDS-06C) in the treatment of moderate-to-severe pain, using acute low back pain as a model.     

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.     

膝关节液透明质酸含量与滑膜炎程度的关系

目的探讨膝关节液透明质酸含量与滑膜炎程度之间的关系。方法酶联免疫吸附试验(ELISA)检测膝关节疾病(OA)患者102例共104膝的关节液透明质酸含量,并在关节镜下应用Ayral滑膜炎评分法和Outerbridge关节软骨损伤评分法评价膝滑膜炎和关节软骨损伤程度。采用t'检验、Spearman相关分析和多元线性回归分析进行统计分析。结果Ayral滑膜炎评分≥60分组的关节液透明质酸含量比Ayral滑膜炎评分<60分组高(P<0.001)。104膝关节液透明质酸含量与Ayral滑膜炎评分呈正相关(茁'A=0.497,P<0.001),与Outerbridge软骨损伤累计评分呈负相关(茁'o=-0.364,P<0.001),且Ayral滑膜炎评分的影响较大。关节液透明质酸含量与Ayral滑膜炎评分在Ayral滑膜炎评分≥60分组呈正相关(r=0.306,P<0.05),在Ayral滑膜炎评分<60分组无相关性(r=-0.144,P>0.05)。与非OA组相比,OA组的关节液透明质酸含量较低(P<0.05),而Ayral滑膜炎评分较高(P<0.01)。结论膝关节液透明质酸可作为生物标记物反映滑膜炎的程度,关节液透明质酸含量的增高提示滑膜炎较重。     

关节腔内注射舒血宁治疗骨性关节炎的疗效及对关节液细胞因子的影响分析

目的：探讨关节腔内注射舒血宁治疗骨性关节炎的疗效及对关节液中细胞因子的影响。方法将120例骨关节炎患者按照数字表法分为两组,每组60例。观察组给予舒血宁关节腔内注射治疗,对照组予以透明质酸钠,比较两组疗效及关节液中白细胞介素1β（ IL-1β）和肿瘤坏死因子α（ TNF-α）的水平。结果治疗后,观察组评分明显低于对照组（t＝16．282,P＜0．05）。观察组总有效率为95．0％,明显高于对照组的81．7％（χ2＝5．175,P＜0．05）。治疗后IL-1β和TNF-α水平均明显低于对照组（t＝4．95、6．656,均P＜0．05）。结论舒血宁注射液不仅能缓解症状,提高疗效,还能降低关节液中IL-1β和TNF-α的水平。     

曲马朵对肺叶切除术患者围手术期胰岛素抵抗的影响

探讨静脉注射曲马朵对肺叶切除术患者围术期胰岛素抵抗的影响。方法30例择期全麻下行肺叶切除手术的患者,随机分为曲马朵组（T组）和对照组（C组）。T组切皮之前5min,给予患者曲马朵1．5mg／kg,术中持续0．5mg·kg^-1·h^-1“泵人曲马朵。C组给予等量0．9％氯化钠注射液。分别检测麻醉诱导前即刻（T0）、手术结束时（T1）、手术结束后4h（T2）、术后第2天早晨7：00（L3）患者血糖、胰岛素、白介素45（IL-6）和肿瘤坏死因子（TNF-α）的水平,并计算胰岛素敏感性。结果与T0比较,TI、T2和L3时血糖、胰岛素、IL-6、TNF-α浓度均升高（均P〈0．05）,胰岛素敏感性均降低（P〈0．05）。与C组比较,Tl、T2、T2时T组血浆血糖、胰岛素、IL-6、TNF-α仪浓度均较低（均P〈0．05）,胰岛素敏感性均较高（均P〈0．05）。结论曲马朵可通过降低血浆TNF-α、IL-6的水平从而减轻手术创伤引起的围术期胰岛素抵抗。     

Capsaicin in adult frogs: Effects on nociceptive responses to cutaneous stimuli and on nervous tissue concentrations of immunoreactive substance P,somatostatin and cholecystokinin

Summary Adult frogs (Rana esculenta) were given subcutaneous injections of 10, 20, 30, 50 and 100 mg/kg capsaicin in sequential order over 5 days, or the vehicle only. The nociceptive thresholds to electrical, thermal and chemical stimuli were measured before, and 1, 5 and 24 h after each injection. Capsaicin was followed by a dose-related reduction of nociceptive responses to all stimuli, but these effects lasted for only 1–5 h after the given injection. Water/acetic extracts of undivided brains and spinal cords were prepared at the corresponding time periods for the radioimmunoassay of peptides. Spinal cord concentrations of immunoreactive substance P were essentially unaffected by capsaicin, while those of immunoreactive somatostatin were significantly increased after the second for fourth injections (20, 30 and 50 mg/kg) of capsaicin. Brain extracts showed an increase of somatostatin and substance P concentrations after the dose of 50 mg/kg. In an additional experiment, immunoreactive substance P, somatostatin and cholecystokinin were measured in tissue samples taken at 2 and 10 min, and 1, 5 and 24 h after a single dose of either 50 mg/kg capsaicin or the vehicle. The only signficant effect of capsaicin was an increase of immunoreactive somatostatin concentration in brain homogenates at 5 h, while the vehicle in itself elicited major variations of all three peptides in spinal cord and/or brain. These results indicate that capsaicin reduces the nociceptive responses to cutaneous stimuli in adult frogs. This effect is transient, and bears no clear relationship to the variations of spinal cord nor of brain concentrations of immunoreactive substance P, somatostatin and cholecystokinin. In the present experimental conditions, the effects of the vehicle injection to neuropeptides far exceeded those of capsaicin itself.     

单侧重症肺炎感染侧和非感染侧肺泡灌洗液中IL-6和IL-10水平的比较

目的 探讨局部促炎因子白细胞介素6(IL-6)和抑炎因子白细胞介素10(IL-10)与肺炎的关系.方法 选择单侧重症肺炎患者25例,在明确诊断后24 h内行双侧肺泡灌洗,收集感染侧和非感染侧的肺泡灌洗液,放射免疫法测定其中细胞因子IL-6、IL-10的浓度.对照组非肺炎患者10例,相同方法测定肺泡灌洗液中IL-6、IL-10的浓度.结果 单侧重症肺炎患者感染侧BALF中IL-6、IL-10的浓度比非感染侧增高,两者有显著性差异(P＜0.01);肺炎组两侧BALF中IL-6、IL-10的浓度均比对照组显著增高(P＜0.01).结论 单侧重症肺炎患者感染侧局部的炎症反应程度比非感染侧强烈,BALF中IL-6和IL-10的浓度能反映局部炎症的严重程度.     

氨酚曲马多联合普瑞巴林治疗癌性神经病理性疼痛的疗效观察

目的探究氨酚曲马多片联合普瑞巴林胶囊治疗癌性神经病理性疼痛的临床疗效。方法选取2015年4月—2017年4月郑州大学附属郑州中心医院收治的癌性神经病理性疼痛患者150例为研究对象,所有患者随机分为普瑞巴林组、氨酚曲马多组和联合治疗组,每组各50例。普瑞巴林组口服普瑞巴林胶囊,75 mg/次,2次/d;氨酚曲马多组口服氨酚曲马多片,100 mg/次,1次/d;联合治疗组口服普瑞巴林胶囊和氨酚曲马多片,用法同上。所有患者均连续治疗4周。观察两组的临床疗效,比较两组的疼痛数字(NRS)评分、生活质量(QOL)评分和睡眠质量(MOS)评分。结果治疗后,普瑞巴林组、氨酚曲马多组、联合治疗组疼痛总缓解率分别为62.00%、64.00%、82.00%,联合治疗组与普瑞巴林组、氨酚曲马多组比较差异具有统计学意义(P0.05)。治疗后,3组NRS评分均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且联合治疗组NRS评分明显低于普瑞巴林组、氨酚曲马多组,两组比较差异具有统计学意义(P0.05)。治疗后,3组QOL评分均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且联合治疗组QOL评分明显低于普瑞巴林组、氨酚曲马多组,两组比较差异具有统计学意义(P0.05)。治疗后,普瑞巴林组、联合治疗组睡眠干扰(SLPD)、睡眠量(SLPQ)评分显著降低,睡眠充足度(SLPA)评分显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且联合治疗组这些观察指标的改善程度明显优于普瑞巴林组、氨酚曲马多组,3组比较差异具有统计学意义(P0.05)。结论氨酚曲马多片联合普瑞巴林胶囊治疗癌性神经病理性疼痛具有较好的临床疗效,可缓解患者癌性疼痛,改善患者生活质量和睡眠质量,安全性较好,具有一定的临床推广应用价值。     

脑梗死患者治疗前后血浆生长抑素和P物质含量的变化及临床意义

目的：探讨脑梗死患治疗前后血浆生长抑素（SS）和P物质（SP）含量的变化。方法：应用放射免疫分析法对33例脑梗死患进行了治疗前后血浆SS、SP含量测定，并以35名正常健康人作对照。结果：脑梗死患在治疗前血浆SS水平高于正常人组（P＜0．01），治疗后2周则与正常人组差异无显性（P＞0．05），SP在治疗前则显地低于正常人组（P＜0．01），治疗后2周SP水平有所升高，但与正常人比较差异有显性（P＜0．05）。结论：血浆SS、SP水平与脑梗死有关，可能参与脑梗死的发生与发展过程。     

Analgesic activity of substance P in rats: tolerance and cross-tolerance with enkephalin

In rats, tolerance to the analgesic effect of intraventricular substance P (SP) develops quickly. In rats made tolerant to [D-Ala2, D-Leu5]enkephalin the analgesic efficacy of SP is reduced significantly. The latter result suggests some overlap in the sites of action of SP and [D-Ala2,D-Leu5] enkephalin. Since SP seems to lack any direct effect on opiate receptors of the brain, the present data suggest that the analgesic effect of SP is mediated by enkephalin release at supraspinal levels which are related to pain control.     

不孕症病人血清白细胞介素-6和甲状腺功能的相关性研究

目的 了解不孕症病人血清白细胞介素-6(IL-6)的水平及其与甲状腺功能的相关性.方法 选取66例不孕症女性为不孕组,根据其血清甲状腺激素水平将其分为不孕合并甲状腺功能减退组(32例)和不孕未合并甲状腺功能减退组(34例),另外选取健康孕龄期妇女29例为对照组,分别测定三组血清中IL-6、甲状腺激素及甲状腺自身抗体的水平.结果 (1)与对照组相比,不孕组病人血清IL-6水平升高(P<0.01);(2)在不孕症病人中,不孕合并甲减病人较不孕未合并甲减病人血清IL-6水平升高(P<0.01);(3)不孕症女性中,血清抗甲状腺球蛋白抗体(ATG)、抗甲状腺过氧化物酶抗体(TPO-Ab)阳性病人较阴性病人血清IL-6水平升高(P<0.01);(4)不孕症病人血清IL-6水平与游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)、ATG、TPO-Ab均呈线性相关(P<0.01).多元线性回归分析调整混杂因素后,IL-6与FT3、FT4的相关性更为显著(P<0.05).结论 不孕症病人血清IL-6水平升高,尤其在合并甲减时更为明显,提示IL-6与甲状腺激素水平有一定的相关性.同时,甲状腺自身抗体阳性的不孕症病人也可通过影响IL-6的水平参与不孕症的发生发展.     

膝骨性关节炎患者膝关节疼痛指数与足底压力变化的相关性研究

目的 探讨膝骨性关节炎患者足底压力改变及疼痛对足底压力的影响。方法 运用足底压力测试系统对28例单侧膝骨性关节炎疼痛患者自然行走时的步态进行测试,观察受试者单足支撑分期时段参数、足角及膝关节疼痛指数,对健、患侧足底压力各指标进行统计学分析并分析膝关节疼痛指数与各指标相关性。结果 膝骨性关节炎患者患侧前足着地阶段时间百分比为(57.90±32.93)、全足支撑阶段时间百分比为(57.93±2.93)低于健侧对应百分比(60.26±2.66,P=0.007; 51.53±3.84, P < 0.001);患侧足角(16.24±4.50)明显高于健侧足角(14.67±4.09),差异有统计学意义(P=0.014);膝关节疼痛指数与患侧前足着地阶段时间百分比(r=-0.53,P=0.004)、全足支撑阶段时间百分比(r=-0.56,P=0.002)呈负相关;与患侧足角无明显相关性(r=0.245,P=0.193)。结论 膝骨性关节炎患者足底压力具有特征性,前足着地时段、全足支撑时段明显缩短、足角变大,疼痛严重影响膝骨性关节炎患者步态。     

多发伤患者血清IL-6的变化(附42例分析)

目的研究多发伤后血清白细胞介素6(IL-6)的变化及其与创伤评分的关系,探讨其临床意义。方法选择多发性创伤患者42例,采用ELISA法测定血清IL-6含量。结果血清IL-6值于创伤后24 h内明显高于正常对照组(P<0.05),动态观察一周,创伤患者呈持续性上升变化,轻度患者血清IL-6含量低于重度、极重度患者,血清IL-6的含量随创伤严重程度增加(P<0.05)。结论IL-6可作为判别创伤严重程度的灵敏指标之一,可能参与了多发性创伤病理生理过程。     

骨关节炎患者血浆IL-18、IL-21的水平变化及其意义探讨

目的 探讨骨关节炎患者血浆中IL-18、IL-21的水平变化及其与疾病的关系.方法 通过检测26例骨关节炎患者与27例健康成人血浆中IL-18、IL-21水平的差异,探讨其与骨关节炎的关系.结果 26例骨关节炎患者血浆中IL-18和IL-21水平均高于27例健康成人,差异均有统计学意义（P＜0.05）.结论 IL-18、IL-21水平在骨关节炎患者中明显增高,可能与疾病的发生有一定联系.     

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.