预制血管化骨瓣修复大面积骨缺损的研究进展

创伤、炎症、肿瘤、先天性畸形所引起的骨缺损修复一直是医学难题,而骨组织工程在骨缺损修复的研究中日益增多,预制骨瓣具有创伤小、血运好、抗感染能力强、可以带软组织、按照支架形状进行预制等优点,成为骨组织修复工程的研究热点.本文就预制血管化骨瓣修复大面积骨缺损的基础和临床研究做一综述.     

Bone morphogenetic protein-7 accelerates fracture healing in osteoporotic rats

Background:

Osteoporosis is characterized by low bone mass, bone fragility and increased susceptibility to fracture. Fracture healing in osteoporosis is delayed and rates of implant failure are high with few biological treatment options available. This study aimed to determine whether a single dose of bone morphogenetic protein-7 (BMP-7) in a collagen/carboxy-methyl cellulose (CMC) composite enhanced fracture healing in an osteoporotic rat model.

Materials and Methods:

An open femoral midshaft osteotomy was performed in female rats 3 months post-ovarectomy. Rats were randomized to receive either BMP-7 composite (n = 30) or composite alone (n = 30) at the fracture site during surgery. Thereafter calluses were collected on days 12, 20 and 31. Callus cross-sectional area, bone mineral density, biomechanical stiffness and maximum torque, radiographic bony union and histological callus maturity were evaluated at each time point.

Results:

There were statistically significant increases in bone mineral density and callus cross-section area at all time points in the BMP-7 group as compared to controls and biomechanical readings showed stronger bones at day 31 in the BMP-7 group. Histological and radiographic evaluation indicated significant acceleration of bony union in the BMP-7 group as compared to controls.

Conclusion:

This study demonstrated that BMP-7 accelerates fracture healing in an oestrogen-deficient environment in a rat femoral fracture healing model to scientific relevance level I. The use of BMP-7 composite could offer orthopedic surgeons an advantage over oestrogen therapy, enhancing osteoporotic fracture healing with a single, locally applied dose at the time of surgery, potentially overcoming delays in healing caused by the osteoporotic state.     

A multicentre,prospective, randomised comparison of the sliding hip screw with the Medoff sliding screw and side plate for unstable intertrochanteric hip fractures

Objective

This study aimed to compare the dynamic hip screw (DHS) and Medoff sliding plate (MSP) for unstable intertrochanteric hip fractures.

Design

A randomised, prospective trial design was used.

Setting

The study was undertaken in two level-1 trauma centres and one community hospital.

Patients/participants

A total of 163 patients with unstable intertrochanteric hip fractures (Orthopaedic Trauma Association (OTA) 31-A2) were randomised to DHS or MSP. Inclusion and exclusion criteria were designed to focus on isolated unstable intertrochanteric hip fractures in ambulatory patients.

Intervention

Randomisation was performed intra-operatively, after placement of a 135° guide wire. Follow-up assessments were performed at regular intervals for a minimum of 6 months.

Main outcome measurements

The primary outcome measure was re-operation rate. The secondary outcome was patient function, evaluated using a validated outcome measure, the Hip Fracture Functional Recovery Score. Tertiary outcomes included: mortality, hospital stay, quality of reduction and malunion rate.

Results

A total of 86 patients were randomised to DHS and 77 to MSP. The groups had similar patient demographics, pre-fracture status and in-hospital course. The quality of reduction was the same for each group, but the operative time was longer in the MSP group (61.6 vs. 50.1 min, P = 0.01). The rate of re-operation was low (3/86 in DHS and 2/77 in MSP) with no statistically significant difference. The functional outcomes were the same for both groups, with functional recovery scores at 6 months of 51.0% in the DHS arm and 49.7% in the MSP arm.

Conclusions

The two techniques produced similar results for the clinically important outcomes of the need for further surgery and functional status of the patients at 6 months’ follow-up.     

骨髓间充质干细胞移植对大鼠暴发性肝功能衰竭治疗作用的初步观察

目的 探讨骨髓间充质干细胞(MSC)移植对大鼠暴发性肝功能衰竭(FHF)的治疗作用.方法 全骨髓细胞贴壁培养筛选法分离纯化大鼠MSC;四氯化碳灌胃制作大鼠FHF模型,分为实验组和模型对照组,各20只,8只灌服等剂量0.9％氯化钠溶液作为空白对照组.将4 ’,6-二脒基-2-苯基吲哚(DAPI)标记的大鼠MSC 1.0×106从尾静脉移植入实验组和空白对照组,等剂量0.9％氯化钠溶液尾静脉注入模型对照组;分别于术后7、14 d处死各组部分大鼠,评价实验组与模型对照组大鼠一般状况、生存率、肝功能、TNF-α水平、肝脏病理、MSC归巢至肝脏的情况.正态分布资料采用两个独立样本t检验,非正态分布资料采用非参数检验.结果 术后3d开始,实验组存活大鼠一般情况比模型对照组好转更加明显;术后7d,实验组与模型对照组各有15只和8只大鼠存活,差异有统计学意义(x2 =4.122,P＜0.05);术后7d以及14 d,实验组与模型对照组相比,肝功能指标、TNF-α水平均差异均有统计学意义(均P＜0.05),病理学检查肝组织炎性反应改善情况实验组均更为明显;术后实验组MSC归巢细胞逐渐增多,空白对照组只观察到很少量归巢细胞.结论 MSC经尾静脉同种异体移植,可以归巢到肝功能衰竭大鼠肝脏,改善大鼠免疫和肝脏组织炎性反应坏死状态,促进FHF大鼠肝功能的恢复,对FHF具有明显的治疗作用.     

PPARγ2内源性配体对成骨细胞骨代谢相关基因表达的影响

目的 探讨PPARγ2内源性配体氧化低密度脂蛋白(Ox-LDL)、15脱氧-前列腺素J2( 15d-PGJ2)、白三烯B4(LTB4)在骨代谢中的作用.方法 体外培养大鼠成骨细胞,分别加入不同浓度Ox-LDL、15d-PGJ2、LTB4干预24 h,RT-PCR检测成骨细胞PPARγ2、NF-κB活化受体配体(RANKL)、碱性磷酸酶(ALP)、护骨素mRNA表达水平,分别比较上述3种PPAR-γ2内源性配体对骨代谢相关基因表达的影响.结果 不同浓度Ox-LDL、15d-PGJ2、LTB4均呈剂量依赖性下调成骨细胞RANKL、ALP、护骨素mRNA的表达水平,同时呈剂量依赖性上调PPARγ2 mRNA的表达水平,组间比较差异有统计学意义(P＜0.05或P＜0.01).结论 PPARγ2内源性活化配体Ox-LDL、15d-PGJ2、LTB4可能通过激活PPARγ2转录活性抑制成骨细胞成骨标记物基因的表达,从而参与增龄相关的骨质疏松的发病过程.     

三氧化二砷联合化疗治疗急性早幼粒细胞白血病的疗效观察

目的:观察三氧化二砷(As2O3)联合化疗治疗急性早幼粒细胞白血病(APL)的疗效.方法:46例初治APL患者均采用As2O3诱导治疗,完全缓解(CR)后用DA或MA方案巩固1个疗程,以后As2O3与化疗交替治疗,每3月1次,连续治疗3年.再继以甲氧蝶呤片与巯嘌呤片维持治疗1年.结果:46例患者有38例(82.6％)达到CR,34例坚持治疗者持续缓解,缓解时间17～119个月,中位缓解时间67个月;4例CR2患者缓解时间43～ 71个月,中位缓解时间54个月.38例患者仍处于CR,生存时间131～ 18个月,中位生存时间65个月.结论:APL患者CR后,采取每年4个周期的巩固和维持方案序贯治疗,减少了化疗及As2O3的疗程,避免了长期连续用药所致的耐药,减少了药物的副作用,复发率很低.     

骨髓间质干细胞对炎症性肠病肠上皮重建的作用机制

骨髓间质干细胞（MSCs）移植是治疗炎症性肠病（IBD）的一种新方法,其可通过促进肠上皮重建修复受损组织,但其作用机制仍未完全明确。相关机制的研究主要集中在MSCs的多向分化、分泌细胞因子、调节肠道干细胞微环境三个方面。本文就相关研究进展作一综述。     

结肠炎大鼠炎症黏膜提取液对骨髓间质干细胞增殖和表面分化抗原的影响

背景:动物实验和临床试验均表明间质干细胞(MSCs)对受损肠道组织有一定修复作用,然而目前尚不清楚肠道炎症微环境对MSCs移植治疗炎症性肠病(IBD)有何影响。目的:通过体外实验观察结肠炎大鼠模型肠道炎症黏膜提取液对骨髓MSCs增殖和表面分化抗原的影响。方法:以全骨髓贴壁法分离和原代培养大鼠MSCs并行传代扩增。取三硝基苯磺酸(TNBS)结肠炎大鼠模型肠道炎症黏膜提取液(0、1、2、3 ml)与MSCs共培养,倒置相差显微镜观察各组细胞贴壁和生长情况,绝对计数法绘制细胞生长曲线,流式细胞术检测细胞表面分化抗原表达。结果:全骨髓贴壁法可成功分离MSCs,所获细胞CD29、CD44表达阳性,CD105表达低度阳性,CD34、CD45表达阴性。3 ml炎症黏膜提取液处理组MSCs接种6 h后见细胞贴壁,36 h开始克隆性增生,此后细胞增殖速度较空白对照组明显加快,第6 d即达100%融合,但表面分化抗原表达与空白对照组相比无明显变化。结论:结肠炎大鼠炎症黏膜提取液可促进骨髓MSCs增殖,但对细胞表面分化抗原无明显影响。     

类风湿关节炎合并间质性肺病患者血清中转化生长因子-β1骨形成蛋白-4检测及其意义

目的 探讨类风湿关节炎(RA)合并间质性肺病( ILD)患者的临床特点和转化生长因子(TGF)-β1、骨形成蛋白(BMP)-4在血清中的水平.方法 人选28例RA-ILD患者、32例单纯RA患者和20名健康对照,RA-ILD组进一步分为早期组(16例)和中晚期组(12例),酶联免疫吸附试验(ELISA)法测定血清中TGF-β1、BMP-4水平,并分析血清TGF-β1、BMP-4水平与实验室指标的相关性.采用t检验、单因素方差分析及Spearman相关分析法进行数据分析.结果 与单纯RA患者相比,RA-ILD组患者初次发生关节炎时年龄较大,关节功能优于单纯RA组患者,血清类风湿因子(RF)滴度高(P＜0.05,P＜0.05,P＜0.01),出现肺间质病变时间为2～6年,平均(3.0±1.2)年.TGF-β1水平在RA-ILD组稍增高,但3组相比差异无统计学意义(P＞0.05).早期RA-ILD组患者TGF-β1血清水平明显增高,与中晚期RA-ILD组及单纯RA组、健康对照组相比较差异均有统计学意义(P＜0.01).RA-ILD组患者BMP-4水平低于单纯RA组及健康对照组,差异有统计学意义(P＜0.05),且早期RA-ILD组患者BMP-4水平显著下降,与中晚期RA-ILD组及单纯RA组、健康对照组相比较差异均有统计学意义(P＜0.05).血清BMP-4水平与TGF-β1水平之间无相关性(P＞0.05),血清TGF-β1、BMP-4水平与实验室指标红细胞沉降率、C反应蛋白、RF、抗环瓜氨酸肽(CCP)抗体等均无明显相关性(P均＞0.05).结论 在早期RA-ILD患者中血清TGF-β1水平增高,BMP-4水平减低,二者可能参与了RA患者ILD的发生.     

骨保护素和RANKL基因单核苷酸多态性对类风湿关节炎易感性及其骨密度和疾病活动性的影响

目的 探讨骨保护素基因(TNFRSF11B) 1181G＞C(rs2073618)、163A＞G(rs3102735)位点和核因子κB活化因子受体配体(RANKL)基因(TNFRSF 11)401A＞G (rs2277438)位点单核苷酸多态性(SNP)对类风湿关节炎(RA)疾病易感性及其骨密度和疾病活动性的影响.方法 采用连接酶检测反应(LDR)聚合酶链反应(PCR)方法检测200例RA患者和201名健康对照组骨保护素基因rs2073618、rs3102735位点和RANKL基因rs2277438位点SNP;采用双能X线骨密度仪(DEXA)法测定其股骨和腰椎部位骨密度.比较其等位基因分布频率、基因型频率及单倍体型在2组中的分布,并比较不同基因型RA患者骨密度及疾病活动性的差别.统计学方法采用方差分析,t检验和x2检验.结果 ①骨保护素基因rs2073618位点、rs3102735位点和RANKL基因rs2277438位点各等位基因及基因型分布频率在RA组与对照组中差异均无统计学意义(P＞0.05).3个位点单倍体型研究表明:骨保护素和RANKL基因单倍体型(rs2073618G-rs2277438G-rs3102735G)携带者RA疾病易感性明显降低(1.5％与6.0％,OR:0.216,95％CI:0.081～0.575,P=0.0008),骨保护素和RANKL基因单倍体型(rs2073618G-rs2277438A-rs31 02735G)携带者RA易感性明显增加(14.5％与8.4％,OR:1.862,95％CI:1.179～2.943,P=0.007).②RANKL基因rs2277438位点表达为纯合型(AA和GG型)的RA患者(62例)腰椎3(1.05±0.22与0.93±0.26,t=2.314,P=0.023)、腰椎4(1.06±0.24与0.94±0.28,t=2.207,P=0.030)、腰椎2～4(1.04±0.21与0.89±0.28,t=2.788,P=0.007)部位骨密度均明显高于杂合型(AG型)RA患者(39例);骨保护素基因rs2073618和rs3102735位点不同基因型RA患者间骨密度差异无统计学意义(P＞0.05).③骨保护素基因rs2073618位点表达为纯合型(CC、GG型)的RA患者(60例)在以下疾病活动性指标上明显高于表达为杂合型(CG型)的RA患者(40例):压痛关节数(13±7与10±6,t=2.154,P=0.034)、压痛关节指数(19±11与13±9,t=2.318,P=0.023)、疼痛视觉模拟(VAS)评分(5.7±1.9与4.8±1.8,t=2.481,P=0.015).RANKL基因rs2277438位点、骨保护素基因rs3102735位点不同基因型RA患者间各疾病活动性指标差异无统计学意义(P＞0.05).结论 骨保护素基因rs2073618、rs3102735位点和RANKL基因rs2277438位点SNP与中国籍汉族RA患者易感性无关,但骨保护素和RANKL基因单倍体型(rs2073618G-rs2277438G-rs3102735G)为RA的保护性因素,而单倍体型(rs 2073618G-rs2277438A-rs31 02735G)是危险因素.RANKL基因rs2277438位点SNP与RA骨代谢相关;骨保护素基因rs2073618位点SNP与RA患者疾病活动性相关.