携载rhBMP-2微球的新型复合人工骨的释药及成骨活性研究

目的 制备一种具有良好降解性和成骨活性，可注射的自凝固新型骨修复材料。方法制备携载rhBMP-2的聚乳酸与聚乙醇酸共聚物（PLGA）微球，并将其与rhBMP-2／磷酸钙骨水泥（CPC）复合。制备出rhBMP-2／PLGA微球／CPC复合人工骨。测定了复合材料释药速度，将复合材料及rhBMP-2-CPC分别植入兔双侧股骨髁骨缺损区域，通过X线、组织学观察比较不同时期材料的降解及成骨情况。结果 复合材料各时间点的体外释药量均大于单纯rhBMP-2／CPC组．与单纯rhBMP-2／CPC材料相比较，复合材料植入体内后不同时间点材料的降解和新骨生成均高于单纯rhBMP-2／CPC植入组。结论 rhBMP-2／PLGA微球的掺入可明显加快rhBMP-2的释放。提高材料的降解速度和成骨活性。     

多孔载因子CPC促进骨缺损愈合的实验研究

[目的]探讨磷酸钙骨水泥复合rhBMP-2/明胶微球复合材料在治疗骨缺损时的降解、成骨性能。[方法]制备携载rhBMP-2的明胶微球(GMs),与磷酸钙骨水泥(CPC)复合,制备出rhBMP-2/GMs/CPC复合人工骨。取30只新西兰大白兔,在前臂桡骨中段制造人工骨缺损,随机分成3组,分别植入rhBMP-2/GMs/CPC/复合物(A组)、GMs/CPC(B组)、rhBMP-2/CPC(C组),术后6、12周分别进行X线检测、骨密度测定,术后12周处死动物,分别行生物力学测定,脱钙切片、HE染色,不脱钙切片进行荧光显微镜下观察双标间距,计算平均矿化率。[结果]与GMs/CPC、rhBMP-2/CPC组比较,复合材料植入后不同时间点的材料降解及成骨均高于对照组。12周A组标本生物力学实验测定结果表明指标接近正常,与B、C组比较有统计学差异。骨密度12周、新骨矿化率提示有统计学差异。[结论]rhBMP-2/GMs/CPC微球系统复合材料在体内易降解,具有良好成骨活性,是良好的骨修复材料。     

复合rhBMP-2壳聚糖微球可注射磷酸钙骨水泥制备及成骨性能研究

[目的]研究复合重组人骨形态发生蛋白-2(rhBMP-2)壳聚糖微球的可注射磷酸钙骨水泥的成骨性能,从而构建一种具有骨传导和骨诱导性的新型可注射性植骨材料.[方法]制备负载rhBMP-2壳聚糖微球磷酸钙骨水泥材料,并将单纯磷酸钙骨水泥和单纯壳聚糖微球磷酸钙骨水泥材料作为对照.检测负载rhBMP-2壳聚糖微球骨水泥的rhBMP-2体外释药.在体外将青山羊骨髓干细胞(MSCs)与3种材料浸提液共同培养,通过检测碱性磷酸酶活性和骨钙素含量评价MSCs成骨分化.在体内,将3种材料植入青山羊骨缺损模型,通过组织学检测研究复合材料成骨能力.[结果]rhBMP-2在1 d时的释放量为12.6%,随后呈持续缓慢释放.在培养7、14 d,负载rhBMP-2壳聚糖微球磷酸钙骨水泥复合材料浸提液可显著提高MSCs的ALP活性和骨钙素含量,差异有统计学意义(P<0.05).组织学显示负载rhBMP-2壳聚糖微球磷酸钙骨水泥复合材料的新骨形成均优于其他组.[结论]复合rhBMP-2壳聚糖微球的可注射磷酸钙骨水泥复合材料是一种有应用前景的新型可注射骨移植材料.     

明胶微球/rhBMP-2/CPC的制备及其异位成骨效应研究

目的：制备多孔复合材料明胶微球／rhBMp-2／CPC并研究其异位成骨效应。方法：双相乳化冷凝聚合法制备明胶微球,京尼平进行交联,喷金后电镜观察。交联微球携载rhBMP-2,以2．5％的比例掺入磷酸钙骨水泥（calcium phosphate cements,CPC）固化,制成实验用多孔明胶微球／rhBMP-2／CPC,rhBMP-2／CPC作为对照组．两组材料固化后分别浸入生理盐水,1、3周后进行生物力学压缩实验,扫描电镜观察材料断面：ELISA法测定不同时间点生理盐水中rhBMP-2浓度,计算rhBMP-2的累积释放量。材料植入小鼠大腿肌袋,术后3周处死小鼠,切取材料及周围组织,HE染色后进行组织学观察,同时测定材料周围组织中碱性磷酸酶及钙含量。结果：交联的明胶微球呈规则圆形,粒径（62±18）um,分散性好。1、3周后实验组材料断面可见大量大孔形成,对照组未见明显大孔,实验组的总孔径率、大孔率及rhBMP-2的累积释放量均高于对照组：3周后实验组最大压缩强度（7．8±1．2）MPa,较对照组（11.2±1．6）MPa稍低。HE染色两组均可见软骨形成,但实验组更多,碱性磷酸酶及钙含量测定实验组分别为（4.33±0．52）IU／g和（6．12±1.22）ug／mg,高于对照组的（2．67±0．23）IU／g和（3．12±0．41）ug／mg。结论：明胶微球／rhBMp-2／CPC在微球降解后形成多孔磷酸钙复合材料,使rhBMp2的释放量增加,具有强大的异位成骨性能,是一种优秀的骨组织工程材料。     

多孔明胶微球/磷酸钙骨水泥的制备及其性能研究

[目的]制备多孔明胶微球/磷酸钙骨水泥,并于体内体外研究其各种性能.[方法]双相乳化冷凝聚合法制备明胶微球,以不同比例与磷酸钙骨水泥复合(0%,2.5%,5%),制备多孔磷酸钙骨水泥,测定材料孔径率及抗压强度,筛选出最佳比例.消化法培养成骨细胞接种于常规及多孔磷酸钙骨水泥支架上,扫描电镜观察细胞形态;不同材料浸提液(0%,2.5%明胶微球/磷酸钙骨水泥及聚苯乙烯)分别与成骨细胞共培养,以MTT法测定细胞增殖率,试剂盒检测碱性磷酸酶水平.将磷酸钙骨水泥及2.5%明胶微球/磷酸钙骨水泥分别植入山羊椎体内,6个月后收集标本,分别进行X线影像学及组织学观察,评估其降解情况.[结果]不同比例明胶微球/磷酸钙骨水泥的总孔径率、大孔率及抗压强度分别为:38.7%、0%、12.1 MPa(0%);67.5%、40.6%、8.0 MPa(2.5%);72.2%、45.6%、5.0 MPa(5%).成骨细胞在明胶微球/磷酸钙骨水泥上生长良好,细胞增殖及碱性磷酸酶水平均明显高于单纯磷酸钙骨水泥组,与聚苯乙烯组未见明显差异.多孔明胶微球/磷酸钙骨水泥6个月后在体内大部分已降解,而磷酸钙骨水泥未见明显降解.[结论]复合明胶微球可显著提高磷酸钙骨水泥的孔径率促进其降解,增加其生物活性,这种多孔磷酸钙骨水泥可作为非负重部位的骨替代物.     

颗粒骨的制备及修复骨缺损的研究

目的 观察聚磷酸钙纤维(CPPF)磷酸钙骨水泥(CPC)、微小颗粒骨复合物体外降解特性及体内修复骨缺损的能力.方法 将CPPF、CPC、微小颗粒骨按质量比1∶4∶4制成复合人工骨,通过PH值、重量、抗压强度的变化,观察人工骨在pH7.4的37℃磷酸盐缓冲液(PBS)中的降解性能.通过大体、X光片、组织学观察及力学测试来检测复合人工骨的体内修复骨缺损的能力.结果 体外实验证实:CPPF/CPC/颗粒骨复合材料孔隙率为72.1%,CPC/颗粒骨孔隙率为58.2%;扫描电镜显示CPPF/CPC/颗粒骨复合材料的孔径为100～400 μm,CPC/颗粒骨为50～300 μm;两组样品溶液pH值在12周内基本维持恒定;CPPF/CPC/颗粒骨复合材料0～4周重量变化较小,4～8周下降较快,12周为初始重量50%,CPC/颗粒骨复合材料在0～6周变化较小,6周后重量下降较快,12周时为初始重量70%;CPPF/CPC/颗粒骨复合材料初始抗压强度9.28 MPa,CPC/颗粒骨复合材料初始抗压强度6.21 Mpa,两者有统计学意义.CPPF/CPC/颗粒骨强度在0～4周下降较慢,4周后下降较快,12周时为0.1,8 MPa,CPC/颗粒骨强度均匀下降,12周时为0.24 MPa.体内实验:CPPF/CPC/颗粒骨复合材料修复骨缺损效果优于其他各组,且差异有统计学意义(P＜0.05).结论 复合材料以其优良的生物学性能有望成为理想的骨替代材料.     

胶原支架增强自固化磷酸钙骨水泥的力学及成骨性能研究

[目的]研究胶原支架（CS）对磷酸钙骨水泥（CPC）的力学及其在体内成骨的影响。[方法]试验分CPC／CS及CPC两组，三点弯曲试验测试材料的强度和弹性模量；组织学观察材料植入兔股骨22及54周的成骨状况。[结果]CPC／CS比CPC的弯曲强度、韧性强度分别提高了64．2％、3933．3％，弹性模量降低了45．7％；组织学显示22周CPC／CS内的胶原支架已完全被新骨替代，CPC只在边缘有少量成骨及材料降解而内部无成骨；54周CPC／CS已大部分降解孔化，孔内充满大量新骨及髓样组织，而CPC边缘区的成骨及材料降解虽比22周时明显，但其内部仍未见成骨。[结论]胶原支架既可改善CPC的力学性能，又能促进新骨长入CPC／CS复合材料内部，因此，CPC／胶原支架是较好的骨缺损修复材料。     

三种充填材料应用于山羊经皮椎体成形术的组织学评价

经皮椎体成形术（PVP）充填材料性能的优劣直接关系到PVP的成败，我们在山羊骨质疏松症（OP）模型上行PVP．充填聚甲基丙烯酸甲酯（PMMA）、可注射型的自固化磷酸钙人工骨（CPC）和复合重组人类骨形态发生蛋白-2（rhBMP-2）的CPC（rhBMP-2／CPC）三种材料。并行光镜观察，为寻找理想的PVP充填材料提供组织学依据。     

磷酸钙骨水泥的临床应用进展

1985年，Brown和Chow首次以磷酸四钙和磷酸氢钙为原料研制出了磷酸钙生物活性骨水泥，从此拉开了磷酸钙骨水泥（calcium phosphate cement，CPC）研究的序幕。CPC又称羟基磷灰石骨水泥（hydroxyapatite cement，HAC），是一类以磷酸钙盐为主要成分，在生理条件下具有自固化能力、降解活性及成骨活性的无机材料，是一种良好的骨折内固定和骨填充修复材料，其固化时间为15～30min。[第一段]     

可注射磷酸钙骨水泥临床应用新进展

磷酸钙骨水泥(calcium phosphate cement,CPC)又称自固化磷酸钙,它是上世纪80年代中期由Brown等研制出的自固化型(self-setting)、非陶瓷型羟基磷灰石类人工骨材料。与羟基磷灰石陶瓷相比,它除具有引导成骨和骨性结合的特点外,更具有制备简便、塑型容易和缓慢降解的优点。 可注射CPC固化过程中产热极少,抗压强度高,可     

缓激肽B2受体基因多态性对膝关节骨关节炎易感性的影响

目的明确BDKRB2基因多态性与OA易感性的相关性,并检测OA患者基因多态性对滑膜组织中BDKRB2表达的影响。方法共有278名膝关节骨关节炎患者和291名健康志愿者参与实验。测定实验对象的BDKRB2基因多态性,在OA患者滑膜组织中通过RT-PCR和Western Blot检测BDKRB2的m RNA和蛋白水平。结果 OA组和对照组中+9/-9 bp多态性的基因型分布和等位基因频率差异明显。-9/-9 bp多态性和+9/+9 bp相比,与OA的罹患风险和严重程度存在明显相关性(OR=2.35,95%CI:1.409~3.937,P0.001)。-9 bp等位基因的表达,与OA的Kellgren-Lawrence分型相关(OR=1.545,,P=0.011)。另外,+9/-9 bp多态性显著影响OA患者滑膜组织中BDKRB2的m RNA和蛋白表达。+9/-9和-9/-9基因型在滑膜组织中BDKRB2的表达水平显著升高,同时KL4型OA患者平均BDKRB2 m RNA和蛋白水平明显高于其他对象(2.502±1.319 vs.1.471±1.002和1.895±1.174,P0.001)。结论本研究提示BDKRB2基因+9/-9bp多态性可能成为OA易感性和严重性筛查的分子标记。     

大承气汤对肠源性内毒素血症大鼠组织PLA_2、SOD活性变化的影响

采用静注５－ＨＴ、Ｐｂ－Ａｃｅｔ同时口灌ＬＰＳ对大鼠进行肠源性内毒素血症造模。造模后三小时，测血、组织ＰＬＡ２和ＳＯＤ活性。结果表明，模型组大鼠血清、肺、肝、肾组织匀浆的ＦＬＡ２活性明显高于正常组，而大承气汤治疗组则与正常组无异；相反模型组肺、肝、肾组织匀浆ＳＵＤ活性，则较正常组明显下降，而大承气汤治疗组则与正常组无异，说明大承气汤在肠源性内毒素血症病理形成过程中能明显抑制ＰＬＡ２活性的升高，有益于减轻组织的损害；此外，又可阻止ＳＯＤ活力的下降，从而增强对过量产生的Ｏ２的消除能力。     

IL-2 perfusion to the liver augments the hepatic extraction rate of accompanying anticancer drugs

A pilot study we conducted on hepatic infusion chemotherapy combined with interleukin-2 (IL-2) for metastatic liver malignancies revealed very encouraging results indicating that this treatment modality is more effective than either of the anticancer drugs used alone. To clarify the mechanisms underlying the synergism of these modalities, the pharmacokinetics of anticancer drugs were examined in a rat model. Adult rats were given 5-fluorouracil (5-FU) or mitomycin C (MMC) combined with various doses of IL-2 up to 7500 JRU/kg per minute for the measurement of hepatic extraction rates (HER). The HER of 5-FU was significantly increased (P<0.01) in combination with IL-2 in a dose-dependent fashion while that of MMC also showed a tendency to increase. Thus, it is conceivable that the increase of vascular permeability caused by IL-2 results in augmentation of the HER of associated anticancer drugs. This effect may improve the delivery of anticancer drugs to the liver and alleviate general toxicity by reducing the amount of circulating anticancer agents.     

PR-AⅡ、PGI_2-TXA_2在ESWL后高血压中的作用

通过对60例患者血液标本的检测,发现体外震波碎石术(ESWL)后出现高血压的患者其血浆肾素(PR)—血管肾张素Ⅱ(AⅡ)系统活性及血栓素A_2(TXA_2)浓度明显高于ESWL后血压正常者,而血浆前列腺素(PGI_2)浓度则正好相反。认为PGI_2合成减少和TXA_2合成相对增多,PGI_2/TXA_2比率下降,导致PR—AⅡ系统活性升高,血管壁对PR—AⅡ系统的敏感性增加,是ESWL后患者出现高血压的主要原因。     

Effects of interleukin-2 on hypothalamic and plasma luteinizing hormone-releasing hormone levels in rats

To investigate the effects of interleukin-2 (IL-2) on the hy-pothalamic and plasma luteinizing hormone-releasing hormone(LHRH) levels and serum testosterone (T) level in rats. The hor-mones were measured by radioimmunoassay. Two different dosesof IL-2 (1000 U and 2000 U) were injected. The results showedthat IL-2 slightly decreased the hypothalamic and plasma LHRHlevels, but the differences with the controls were not significant.The administration of 2000 U IL-2 significantly decreased the serumT level. Results suggest that IL-2 may play an inhibitory role onhypothalamic LHRH secretion and decrease serum T level in Rats.(Chin J Androl 2001; 2: 85-6, 91)     

急性胰腺炎合并肝损伤时IL-6、氧自由基变化及IL-2、川芎嗪干预的实验研究

目的：探讨IL－6、氧自由基在急性胰腺炎（acute pancreatitis，AP）合并肝损伤中的作用，及重组人白介素－2（IL－2）、川芎嗪的治疗价值。方法：SD大鼠112只，随机分为14只，每组8只，5％牛磺胆酸钠逆行胰胆管内注射诱发大鼠AP动物模型，检测血浆IL－6、SOD、MDA、ALT、AST、LDH、LIP、AMY，并观察肝、胰病理变化。结果；①AP组血浆AMY、LIP、ALT、AST、LDH明显升高（P＜0．05或0．01），镜下可见胰腺水肿、炎细胞浸润、坏死1肝脏肝窦充血、细胞浊肝及坏死，且损伤程度随时限延长而加重；②AP各组血浆IL－6明显升同（P＜0．01）；③AP各组MDA明显高（P＜0．01）、SOD明显降低（P＜0．01）。④IL－2治疗组、川芎嗪治疗组有IL－2、川芎嗪联合且与NS组比较血浆IL－6、MDA水平明显下降（P＜0．05），SOD明显升高（P＜0．05），胰、肝病理损害程度减轻，并且AMY、LIP、ALT、AST、LDH均明显降低（P＜0．05），平均存活时间明显延长（P＜0．05）；联合应用组降低IL－6、MDSA水平和减轻胰腺坏死优于单药组。结论：①IL－6、氧自由基在急性胰腺炎合并肝损伤程度和明显升同，起损伤作用，而SOD明显降低，其保护作用减弱。检测血浆IL－6、MDA、SOD可作为判断AP合并肝脏损伤程度和预后的指标；②大鼠急性胰腺合并肝损伤过程中应用IL－2、川芎嗪显示出良好的效果，联合应用于亿于这两药的单独应用。     

SGLT2抑制剂对2型糖尿病患者骨骼的影响

钠葡萄糖共转运体2(sodium-glucose cotransporter 2,SGLT2)抑制剂是一种新型降糖药物,其作用机理是通过抑制肾小管对尿糖的重吸收,以增加尿糖排泄降低血糖。近期来自国外的多个临床药物试验发现SGLT2抑制剂可能对2型糖尿病患者的骨代谢、骨密度以及骨折率产生影响。本文将通过复习国内外相关研究,尝试综述SGLT2抑制剂对2型糖尿病患者骨骼的影响。     

Retrosigmoid Craniotomy for Auditory Brainstem Implantation in Adult Patients with Neurofibromatosis Type 2

Objective To report our technique and experience using a retrosigmoid craniotomy approach for auditory brainstem implantation (ABI) placement in adult neurofibromatosis type 2 (NF2) patients. Design Retrospective case series. Setting Single-center study, Boston, Massachusetts, United States. Participants All NF2 patients who underwent evaluation at Massachusetts Eye and Ear Infirmary and surgery at Massachusetts General Hospital from 2009 to 2013 were reviewed. Six cases of retrosigmoid craniotomy for ABI surgery in five adult NF2 patients were identified. The clinical history, operative course, and outcomes in these patients were reviewed. Main Outcome Measures Postoperative complications and audiological outcomes. Results Indications for ABI surgery were profound hearing loss associated with growth or treatment of bilateral vestibular schwannomas. In all cases, a retrosigmoid craniotomy was performed for tumor resection and ABI placement without complication. Electrode placement was confirmed intraoperatively using electrical-evoked auditory brainstem responses. The ABI was activated in the awake patient 4 to 6 weeks postoperatively. Audiological testing was used to evaluate sound detection and speech perception with the ABI. There were no cases of cerebrospinal fluid leak. Conclusion Retrosigmoid craniotomy is a safe and effective means to provide access to the cochlear nucleus for ABI placement following tumor resection in the adult NF2 patient. Preliminary data indicate that this approach has few complications while offering benefits for hearing. The retrosigmoid craniotomy should be considered a reasonable alternative to the traditional translabyrinthine approach for placement of the ABI in deaf patients who are not candidates for the cochlear implant.     

Changes of serum advanced glycation end products (AGEs), matrix metalloprotein-2 (MMP-2), and urinary microalbuminuria (mALB) in diabetic nephropathy and their predictive value for heart failure

BackgroundDiabetic nephropathy is a common complication in diabetic patients, with a high rate of disability and mortality. This study aims to explore the changes in serum advanced glycation end products (AGEs), matrix metalloprotein-2 (MMP-2), and urinary microalbuminuria (mALB) in diabetic nephropathy and their predictive value for heart failure.MethodsThe 134 patients with diabetic nephropathy treated in our hospital from January 2014 to December 2017 were enrolled and divided into two groups resulting in 64 cases in an observation group with heart failure, and 70 cases without heart failure in a control group. In addition, 80 patients with simple diabetes who were treated during the same period were selected as the simple diabetes group. Levels of AGEs, MMP-2, and mALB between the groups were compared, risk factors affecting diabetic nephropathy patients with heart failure were analyzed, and an ROC curve was drawn to evaluate the predictive value of AGEs, MMP-2, and mALB for heart failureResultsThe levels of AGEs and mALB in the diabetic nephropathy group were significantly higher than those in the simple diabetes group, and the levels of MMP-2 were significantly lower than those in the simple diabetes group (P<0.05). The levels of AGEs and mALB in the observation group were significantly higher than those in the control group, and the levels of MMP-2 were significantly lower than that in the control group (P<0.05). Smoking history hypertension history, blood creatinine (abnormal increase), blood uric acid (abnormal increase), AGEs (abnormal increase), MMP-2 (abnormal decrease), and mALB (abnormal increase) were independent risk factors affecting diabetic nephropathy patients with heart failure. The area under the ROC curve of AGEs, MMP-2, mALB, and their combined detection were: 0.821, 0.909, 0.897, and 0.991, respectively, showing the area under the curve of combined detection to be the largest.ConclusionsAGEs, MMP-2, and mALB have high predictive value for heart failure in patients with diabetic nephropathy. Their sensitivity and specificity are high, indicating they may hold considerable clinical value.     

The Role of Oxidative Stress in Aseptic Loosening of Total Hip Arthroplasties

This study investigated the hypothesis that wear particle-induced oxidative stress initiates osteolysis after total hip arthroplasty (THA). Patient radiographs were scored for osteolysis and periprosthetic tissues were immunostained and imaged to quantify polyethylene wear, inflammation, and five osteoinflammatory and oxidative stress-responsive factors. These included high mobility group protein-B1 (HMGB1), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), 4-hydroxynonenal (4-HNE), and nitrotyrosine (NT). The results show wear debris correlated with inflammation, 4-HNE, NT and HMGB1, whereas inflammation only correlated with NT and HMGB1. Similar to wear debris and inflammation, osteolysis correlated with HMGB1. Additionally, osteolysis correlated with COX2 and 4-HNE, but not iNOS or NT. Understanding the involvement of oxidative stress in wear-induced osteolysis will help identify diagnostic biomarkers and therapeutic targets to prevent osteolysis after THA.