Ultrasound combined with SDF‐1α chemotactic microbubbles promotes stem cell homing in an osteoarthritis model

Osteoarthritis (OA) is a common joint disease in the middle and old age group with obvious cartilage damage, and the regeneration of cartilage is the key to alleviating or treating OA. In stem cell therapy, bone marrow stem cell (BMSC) has been confirmed to have cartilage regeneration ability. However, the role of stem cells in promoting articular cartilage regeneration is severely limited by their low homing rate. Stromal cell‐derived factor‐1α (SDF‐1α) plays a vital role in MSC migration and involves activation, mobilization, homing and retention. So, we aim to develop SDF‐1α‐loaded microbubbles MB(SDF‐1α), and to verify the migration of BMSCs with the effect of ultrasound combined with MB(SDF‐1α) in vitro and in vivo. The characteristics of microbubbles and the content of SDF‐1α were examined in vitro. To evaluate the effect of ultrasound combined with chemotactic microbubbles on stem cell migration, BMSCs were injected locally and intravenously into the knee joint of the OA model, and the markers of BMSCs in the cartilage were detected. We successfully prepared MB(SDF‐1α) through covalent bonding with impressive SDF‐1α loading efficacy loading content. In vitro study, ultrasound combined with MB(SDF‐1α) group can promote more stem cell migration with highest migrating cell counts, good cell viability and highest CXCR4 expression. In vivo experiment, more BMSCs surface markers presented in the ultrasound combined with MB(SDF‐1α) group with or without exogenous BMSCs administration. Hence, ultrasound combined with MB(SDF‐1α) could promote the homing of BMSCs to cartilage and provide a novel promising therapeutic approach for OA.     

MiR‐155 promotes interleukin‐1β‐induced chondrocyte apoptosis and catabolic activity by targeting PIK3R1‐mediated PI3K/Akt pathway

Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degradation, in which elevated chondrocyte apoptosis and catabolic activity play an important role. MicroRNA‐155 (miR‐155) has recently been shown to regulate apoptosis and catabolic activity in some pathological circumstances, yet, whether and how miR‐155 is associated with OA pathology remain unexplored. We report here that miR‐155 level is significantly up‐regulated in human OA cartilage biopsies and also in primary chondrocytes stimulated by interleukin‐1β (IL‐1β), a pivotal pro‐catabolic factor promoting cartilage degradation. Moreover, miR‐155 inhibition attenuates and its overexpression promotes IL‐1β‐induced apoptosis and catabolic activity in chondrocytes in vitro. We also demonstrate that the PIK3R1 (p85α regulatory subunit of phosphoinositide 3‐kinase (PI3K)) is a target of miR‐155 in chondrocytes, and more importantly, PIK3R1 restoration abrogates miR‐155 effects on chondrocyte apoptosis and catabolic activity. Mechanistically, PIK3R1 positively regulates the transduction of PI3K/Akt pathway, and a specific Akt inhibitor reverses miR‐155 effects on promoting chondrocyte apoptosis and catabolic activity, phenocopying the results obtained via PIK3R1 knockdown, hence establishing that miR‐155 promotes chondrocyte apoptosis and catabolic activity through targeting PIK3R1‐mediated PI3K/Akt pathway activation. Altogether, our study discovers novel roles and mechanisms of miR‐155 in regulating chondrocyte apoptosis and catabolic activity, providing an implication for therapeutically intervening cartilage degradation and OA progression.     

不同目标力线设定对开放性楔形胫骨高位截骨术治疗膝关节骨性关节炎疗效的影响

目的:探讨开放性楔形胫骨高位截骨术(OWHTO)中采用不同目标力线对单间室膝关节骨性关节炎(KOA)疗效的影响。方法:回顾性分析本院收治的2016年9月～2018年9月采用OWHTO治疗单间室KOA患者41例的临床资料,根据不同目标力线分为固定力线组和个体化力线组,固定力线组19例患者采用统一调目标力线至Fujisawa点治疗,个体化力线组22例根据术中关节软骨Outerbridge分级、个体化调定目标力线治疗,对比两组术前及术后1.5个月、3个月、6个月、12个月的疼痛视觉模拟评分(VAS)及美国特种外科医院膝关节(HSS)评分变化,并对比术前和12个月时MRI及关节镜影像。结果:术后所有患者VAS评分、HSS评分均较术前改善(P0.05),其中个体化力线组术后1.5个月、3个月时VAS评分优于固定力线组,差异有统计学意义(P0.05)。MRI及关节镜显示两组患者均有不同程度软骨再生。结论:采用OWHTO治疗单间室KOA,根据患者不同软骨磨损情况制定个体化目标力线方案有利于患者早期疼痛的改善,但其长期功能的恢复及软骨再生与固定力线方案无明显差异。     

空心钉加内侧支撑钢板与单纯空心钉治疗PauwelsⅢ型股骨颈骨折的疗效比较研究

目的:比较PauwelsⅢ型股骨颈骨折分别经单纯空心钉、空心钉加内侧支撑钢板治疗的临床疗效。方法:回顾性分析2016年3月～2019年2月期间收治的113例PauwelsⅢ型股骨颈骨折患者的临床资料,根据手术方式分为A组(n=55,单纯空心钉内固定治疗)和B组(n=58,空心钉加内侧支撑钢板治疗),比较两组患者围术期指标、髋关节功能、术后疼痛及复位质量,记录两组患者随访期间并发症发生情况。结果:B组术中出血量多于A组,手术时间长于A组(均P0.05);B组骨折愈合时间、完全负重时间短于A组(P0.05)。两组患者术后3个月、术后6个月髋关节Harrris评分呈升高趋势,视觉模拟评分量表(VAS)评分呈下降趋势(P0.05);B组术后3个月、术后6个月髋关节Harrris评分高于A组,VAS评分则低于A组(P0.05)。与术后3 d相比,A组患者术后6个月正位、侧位Garden指数降低(P0.05);B组术后6个月正位、侧位Garden指数评分高于A组(P0.05)。B组并发症发生率低于A组(P0.05)。结论:与单纯空心钉内固定治疗PauwelsⅢ型股骨颈骨折相比,空心钉加内侧支撑钢板虽然术中出血量多,手术时间略长,但其术后恢复效果更佳,且并发症发生率更低,临床应用价值较高。     

七氟烷复合麻醉对老年骨科患者术后早期认知功能的影响

摘要 目的：探讨七氟烷复合麻醉对老年骨科患者术后早期认知功能的影响。方法：选择2017年12月~2019年6月在西安医学院第二附属医院（本院）骨科诊治单侧老年全膝关节置换手术患者112例,随机数字表法分为七氟烷组与对照组,各56例。对照组给予常规静脉注射全身麻醉,在此基础上七氟烷组给予七氟烷吸入麻醉,记录与调查两组术后早期认知功能。结果：经过对比,两组手术时间、术中出血量对比差异无统计学意义(P>0.05),而七氟烷组的术后苏醒时间(7.10±0.22)min、拔管时间(8.65±0.46)min等都显著短于对照组(14.09±1.09)min、(18.76±1.44)min,两组对比有统计学意义(P<0.05)。所有患者在T1、T2、T3与T4时间点的心率和血氧饱和度均表现正常,对比均无统计学意义(P>0.05)。七氟烷组术后1 d、术后14 d的血清白介素(Interleukin,IL)-6、肿瘤坏死因子(Tumor necrosis factor,TNF)-α值显著低于对照组,对比有统计学意义(P<0.05),且两组术后14 d的血清IL-6与TNF-α值均显著低于术后1 d (P<0.05)。术后1个月七氟烷组的认知功能障碍发生率为1.8 %（1/56）,显著低于对照组的12.5 %（7/56）,两组间对比有统计学意义(x²=4.846,P=0.028)。结论：七氟烷复合麻醉在老年骨科患者中的应用能促进患者康复,安全性比较好,能抑制炎症因子的释放,从而减少术后早期认知功能障碍的发生。     

右归丸对大鼠膝骨关节炎的干预作用及其机制*

目的: 探讨右归丸对膝骨关节炎(KOA)模型鼠关节软骨组织骨诱导因子(OGN)、骨黏连蛋白(ON)和纤维蛋白原2(FBN2)的影响。方法: 将大鼠随机分为假手术组,模型组,硫酸氨基葡萄糖组(硫酸氨基葡萄糖),右归丸(高、中、低剂量)组,每组10只。采用改良Hulth法制备大鼠KOA模型,假手术组和模型组给予等体积生理盐水灌胃,右归丸高、中、低剂量组分别灌胃给予右归丸4.8,2.4,1.2 g/kg,硫酸氨基葡萄糖组灌胃给予硫酸氨基葡萄糖 0.17 g/kg,连续给药8周。干预结束24 h后取鼠膝关节软骨,采用HE染色法观察各组软骨的病理改变,并进行Mankin评分;免疫组化法检测各组关节软骨组织中OGN、ON和FBN2的表达;Western blot法检测各组关节软骨组中糖原合成酶激酶-3β(GSK-3β)的表达。结果: 与假手术组比较,模型组大鼠软骨组织Makin 评分显著升高,软骨组织FBN2蛋白表达水平上显著增加,OGN、ON和GSK-3β蛋白表达水平上的显著降低(P＜0.01);模型组关节软骨边缘严重破坏,软骨细胞排列紊乱。与模型组比较,右归丸高剂量干预组大鼠软骨组织Makin 评分和FBN2蛋白表达水平显著降低,GSK-3β蛋白表达水平上显著增加,且右归丸中、高剂量组OGN、ON蛋白表达水平均显著增加(P＜0.05或P＜0.01),软骨结构趋于正常,软骨细胞分布仅偶见不均,关节软骨表面欠光滑。结论: 右归丸能够延缓关节软骨退变,其可能机制是通过提高骨诱导因子和骨粘连蛋白的表达水平来促进关节软骨的骨化和重构。     

Effects of branched-chain amino acid supplement on knee peak torque and indicators of muscle damage following isokinetic exercise-induced delayed onset muscle soreness

[Purpose] This study aimed to investigate the effects of branched-chain amino acid (BCAA) supplement on delayed onset muscle soreness (DOMS) by analyzing the maximum muscle strength and indicators of muscle damage.[Methods] Twelve men with majors in physical education were assigned to the BCAA group and placebo group in a double-blinded design, and repeated measurements were conducted. DOMS was induced with an isokinetic exercise. Following BCAA administration, the changes in the knee extension peak torque, flexion peak torque, aspartate aminotransferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH) concentrations were analyzed. The maximum knee muscle strength was measured at the baseline (pre-D0) following BCAA administration for 5 days before exercise (-D5, -4D, -3D, -2D, -1D). In contrast, the post-treatment measurements (D3) were recorded after BCAA administration for 3 days (post-D0, D1, D2). Blood samples were obtained before (pre-D0), immediately after (post-D0), 24 h (D1), 48 h (D2), and 72 h (D3) after the exercise to analyze the indicators of muscle strength. BCAA was administered twice daily for 8 days (5 days and 3 days before inducing DOMS and during the experimental period, respectively).[Results] There was no difference in the flexion peak torque between the groups. However, the BCAA group showed a significantly higher extension peak torque at D3 (second isokinetic exercise), compared to the placebo group (p<.05). There was no difference in AST changes between the groups. Nonetheless, the CK and LDH were significantly reduced in the BCAA group, compared to the placebo group. There was no correlation between the extension peak torque and flexion peak torque. However, the CK and LDH increased proportionately in DOMS. Moreover, their concentrations significantly increased with a decreasing peak torque (p<.01).[Conclusion] An exercise-induced DOMS results in a decrease in the peak torque and a proportional increase in the CK and LDH concentrations. Moreover, the administration of BCAA inhibits the reduction of the extension peak torque and elevation of CK and LDH concentrations. Therefore, BCAA might be administered as a supplement to maintain the muscle strength and prevent muscle damage during vigorous exercises that may induce DOMS in sports settings.     

3.0 T磁共振T2×mapping成像技术定量评估膝关节骨性关节炎的临床价值及与WOMAC评分的相关性分析

摘要 目的：研究3.0 T磁共振T2×mapping成像技术定量评估膝关节骨性关节炎（OA）的临床价值及与西安大略和麦克马斯特大学骨关节炎指数（WOMAC）评分的相关性。方法：将我院于2017年4月～2019年12月期间收治的膝关节OA患者80例纳入研究。根据K-L分级标准将膝关节OA患者分成轻度组（K-L分级为Ⅰ～Ⅱ级）32例,重度组（K-L分级为Ⅲ～Ⅴ级）48例。另取同期于我院进行体检的健康者30例作为对照组。所有受试者均接受3.0 T磁共振T2×mapping扫描,比较各组膝关节不同部位软骨T2值、WOMAC评分以及血清炎症因子水平,以Pearson相关性分析膝关节OA患者膝关节不同部位软骨T2值和WOMAC评分的关系。结果：重度组膝关节不同部位软骨T2值均高于轻度组以及对照组,且轻度组膝关节不同部位软骨T2值均高于对照组（均P＜0.05）。重度组各项WOMAC评分及总分均高于轻度组以及对照组,且轻度组各项WOMAC评分及总分均高于对照组（均P＜0.05）。经Pearson相关性分析发现：膝关节OA患者膝关节不同部位软骨T2值和各项WOMAC评分及总分均呈正相关（均P＜0.05）。重度组血清白介素-1β（IL-1β）、白介素-18（IL-18）、肿瘤坏死因子α（TNF-α）均高于轻度组以及对照组,且轻度组血清IL-1β、IL-18、TNF-α均高于对照组（均P＜0.05）。结论：3.0 T磁共振T2×mapping成像技术定量评估膝关节OA的临床价值较高,且患者膝关节不同部位软骨T2值与WOMAC评分密切相关。     

不同麻醉方式对老年糖尿病患者全膝置换术后糖代谢的影响

目的:探讨不同麻醉方式对老年糖尿病患者全膝置换术(total knee arthoplasty,TKA)后糖代谢的影响。方法:2018年2月到2020年3月选择在本院进行择期TKA的老年糖尿病合并膝关节骨性关节炎患者88例,随机原则分为研究组与对照组,各44例。对照组给予常规静吸复合全身麻醉,研究组在对照组麻醉的基础上给予复合股神经阻滞,检测两组术后空腹血糖值,并记录两组膝关节功能改善情况。结果:研究组术后1 d、3 d与7 d静息状态下和活动状态下的疼痛视觉模拟评分法(Visual Analogue Scale/Score,VAS)评分都显著低于对照组(P<0.05)。研究组术后1 d、3 d与7 d的空腹血糖值都显著低于对照组(P<0.05)。研究组术后1 d、3 d与7 d的患肢膝关节活动度都显著高于对照组(P<0.05)。结论:股神经阻滞联合全麻在老年糖尿病患者TKA中的应用能缓解术后疼痛,减低术后血糖水平,并且促进提高膝关节活动度有益预后。     

The detrimental effect of iron on OA chondrocytes: Importance of pro-inflammatory cytokines induced iron influx and oxidative stress

Iron overload is common in elderly people which is implicated in the disease progression of osteoarthritis (OA), however, how iron homeostasis is regulated during the onset and progression of OA and how it contributes to the pathological transition of articular chondrocytes remain unknown. In the present study, we developed an in vitro approach to investigate the roles of iron homeostasis and iron overload mediated oxidative stress in chondrocytes under an inflammatory environment. We found that pro-inflammatory cytokines could disrupt chondrocytes iron homeostasis via upregulating iron influx transporter TfR1 and downregulating iron efflux transporter FPN, thus leading to chondrocytes iron overload. Iron overload would promote the expression of chondrocytes catabolic markers, MMP3 and MMP13 expression. In addition, we found that oxidative stress and mitochondrial dysfunction played important roles in iron overload-induced cartilage degeneration, reducing iron concentration using iron chelator or antioxidant drugs could inhibit iron overload-induced OA-related catabolic markers and mitochondrial dysfunction. Our results suggest that pro-inflammatory cytokines could disrupt chondrocytes iron homeostasis and promote iron influx, iron overload-induced oxidative stress and mitochondrial dysfunction play important roles in iron overload-induced cartilage degeneration.