Synovectomy of the rheumatoid knee using intra-articular injection of dysprosium-165-ferric hydroxide macroaggregates

One hundred and eleven patients who had seropositive rheumatoid arthritis and persistent synovitis of the knee were treated with intra-articular injection of 270 millicuries of dysprosium-165 bound to ferric hydroxide macroaggregates. A two-year follow-up was available for fifty-nine of the treated knees. Thirty-nine had a good result; nine, a fair result; and eleven, a poor result. Of the twenty-five knees that had Stage-I radiographic changes, nineteen had a good result. Of the thirty-four knees that had Stage-II radiographic changes, twenty showed a good result. Systemic spread of the radioactivity from the injected joint was minimum. The mean whole-body dose was calculated to be 0.3 rad and that to the liver twenty-four hours after injection, 3.2 rads. The results indicated that dysprosium-165-ferric hydroxide macroaggregate is an effective agent for performing radiation synovectomy, particularly in knees that have Stage-I radiographic changes. Because of the minimum rate of systemic spread of the dysprosium-165, it offers a definite advantage over agents that previously have been used.     

血管内皮生长因子165基因转染的骨髓基质细胞异位成骨的初步研究

目的：将血管内皮生长因子165（VEGF165）基因转染的大鼠骨髓基质细胞（MSCs）和β-磷酸三钙复合后,植入原大鼠肌肉中,探索转染外源基因的MSCs异位成骨能力。方法：SD大鼠12只,在全麻及无菌条件下取其左侧股骨的骨髓基质细胞,并用矿化液诱导培养。在脂质体介导下将构建成功的真核表达载体pcDNA3.1-VEGF165转染到诱导培养的MSCs,G-418筛选阳性细胞克隆,将阳性克隆细胞和未转染的MSCs共同接种于β-磷酸三钙上,体外培养7天后,植入原大鼠肌肉内。分别于4周、8周和12周处死动物,观察异位成骨情况。结果：骨髓基质细胞-β-磷酸三钙复合体植入肌肉后,材料周围血管生长较多,随着植入时间的延长,小的骨岛逐渐融合为大的骨块,并有骨髓腔样结构,表现出较好的异位成骨能力。结论：应用VEGF165基因转染MSCs作为种子细胞植入体内后,有利于发挥VEGF165的血管化作用,同时促进组织工程骨的成骨速度,将会成为组织工程骨血管化探索的方向。     

膝关节滑膜切除术与关节腔灌洗术在治疗类风湿性关节炎中的疗效分析

[目的]探讨膝关节滑膜切除术与关节腔灌洗术2种不同方法治疗类风湿性关节炎（RA）的疗效。[方法]对32例RA患者（36个膝关节）根据美国风湿病学会（ARA）进行分期，分别采用膝关节滑膜切除术与关节腔灌洗术2种不同方法进行治疗，对其中20例（22个膝关节，以Ⅰ期为主）行关节腔灌洗术配合注射透明质酸钠治疗，对12例（14个膝关节，以Ⅱ期为主）行膝关节滑膜切除术，所有患者术前、术后均给予正规抗类风湿治疗，术后随访6个月，按Lysholm标准评分，判断手术疗效。[结果]术后早期症状均改善，灌洗组优良率为86．4％；滑切组优良率为85．7％。[结论]对于早期RA患者，经系统的抗类风湿治疗后，病变局限于单侧或双侧膝关节时，行关节腔灌洗术配合注射透明质酸钠治疗，可以取得比较满意疗效，对于中期以上滑膜重度增生，关节软骨部分破坏的患者，为抢救关节功能，宜尽早施行开放滑膜切除手术。     

Transplantation of BMSCs expressing hVEGF165/hBD3 promotes wound healing in rats with combined radiation‐wound injury

The combined radiation‐wound injury is a refractory wound with decreased number or dysfunction of repairing cells and growth factors. This remains a challenge in clinical practice. The object of this study is to evaluate the therapeutic efficacy of a combination of human vascular endothelial growth factor 165 (hVEGF₁₆₅) and human beta‐defensin 3 (hBD3) in the treatment of such wounds. A plasmid‐carrying hVEGF₁₆₅ gene and hBD3 gene was used to transfect rat bone‐marrow‐derived mesenchymal stem cells (BMSCs). The supernatant from the modified BMSCs significantly promoted the proliferation and cell migration of human endothelial cells and it also inhibited the growth of bacteria and fungus, demonstrating the successful expression of the transfected genes. The hVEGF₁₆₅/hBD3‐modified BMSCs were then injected into the sites of combined radiation‐wound injury on rats. It demonstrated that wound‐healing time was shortened significantly in the treated rats. The granulation tissue formation/maturation, skin appendage regeneration and collagen deposition were also improved significantly. Strong expression of hVEGF₁₆₅ and hBD3 was detected in the wound surface at early stage of the healing. The results indicate that topical transplantation of hVEGF₁₆₅/hBD3‐modified BMSCs promoted wound healing, and this gene therapy strategy presents a promising approach in the treatment of refractory wounds such as the combined radiation‐wound injury.     

hVEGF165基因转染大鼠BMSCs的实验研究

目的构建携带hVEGF165基因的重组腺病毒载体pAdxsi-增强型绿色荧光蛋白(enhanced green fluorescent protein,EGFP)-hVEGF165,体外转染大鼠BMSCs,观察转染后hVEGF165的表达情况以及对BMSCs生长增殖的影响,为进行血管再生的基因治疗奠定实验基础。方法将hVEGF165从原始质粒切下连接到pShuttle-巨细胞病毒-EGFP重组穿梭载体,并转移至pAdxsi载体上,获得重组腺病毒载体质粒pAdxsi-EGFP-hVEGF165,进行酶切鉴定及基因测序。采用PacI限制性内切酶线性化pAdxsi-EGFP-hVEGF165,并转染人胚肾细胞HEK293,收获重组腺病毒,测定病毒滴度。贴壁法培养Wistar大鼠BMSCs,体外转染携带EGFP基因的重组腺病毒(pAdxsi-EGFP),荧光倒置相差显微镜及流式细胞术确定最佳病毒感染复数(multiplicities of infection,MOI)。依据最佳MOI转染pAdxsi-EGFP-hVEGF165至BMSCs,采用Western blot、RT-PCR及ELISA法检测转染后hVEGF165的表达;MTT法评价转染后BMSCs生长增殖情况。结果酶切鉴定及基因测序提示重组腺病毒载体质粒含有hVEGF165 cDNA;经多轮感染、扩增后,病毒滴度可达1×1010 pfu/mL。荧光倒置相差显微镜观察转染pAdxsi-EGFP后MOI为150 pfu/cell时转染效果最佳,流式细胞仪检测转染效率约88%。Western blot和RT-PCR检测示,pAdxsi-EGFP-hVEGF165转染BMSCs 48 h后在蛋白质和基因水平均可有效表达hVEGF165;ELISA检测示其含量在7 d达高峰,在20 d时仍有表达,1、3、5、7、9、11、13、15、20 d各时间点hVEGF165含量均显著高于EGFP基因转染组及未转染组(P<0.05)。MTT结果显示,各时间点转染pAdxsi-EGFP-hVEGF165的BMSCs与未转染组细胞的吸光度(A)值比较差异无统计学意义(P>0.05)。结论 BMSCs是一种较理想的基因载体细胞,成功制备的重组腺病毒载体质粒可在MOI值为150时将hVEGF165基因有效转染至BMSCs;转染后hVEGF165表达水平较高、持续时间较长,且对BMSCs的生长增殖无明显影响。     

Surgical synovectomy decreases density of sensory nerve fibers in synovial tissue of non‐inflamed controls and rheumatoid arthritis patients

Surgical synovectomy is a technique to treat synovitis and pain in patients with rheumatoid arthritis (RA) resistant to DMARDs or therapy with biologics. Indication to synovectomy is subject to tight cooperation of orthopaedic surgeons and rheumatologists. It was thought that synovectomy leads to a reduction of sensory nerve fibers, called sensory denervation. Since sensory denervation after synovectomy has never been histologically tested, we aimed to investigate sensory and sympathetic innervation in synovial tissue before and after synovectomy. Eight non‐inflamed control subjects and eight patients with RA were included in this study with a two‐stage synovectomy approach (interval 40–50 days). Nerve fibers and cells in synovial tissue were detected and counted using immunofluorescence. Density of sympathetic nerve fibers did not change after synovectomy, whereas density of sensory nerve fibers decreased in all control subjects and seven of eight patients with RA. In parallel, the density of synovial cells increased after synovectomy in all control subjects and six of eight RA patients, which is indicative of a wound healing response. In one female RA patient, density of sensory nerve fibers increased and a very marked rise of cellular density was observed, too. This indicates that probably not all patients profit from surgical synovectomy. The majority of patients (94%) demonstrated sensory denervation after surgical synovectomy accompanied by a wound healing cell response. This study can help to explain the positive effects of surgical synovectomy which usually leads to pain reduction and improved mobility. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:297–302, 2011     

下肢深静脉血栓形成165例的治疗分析

目的：观察下肢深静脉血栓形成(DVT)患者手术取栓和药物溶栓治疗的疗效。方法：对165例(175侧)下肢DVT患者进行总结。其中64例采用Fogarty导管取栓，101例采用药物溶栓治疗。结果：全组96例患者得到随访，随访率为58．2％，随访时间7--218个月，平均71个月。44例为手术取栓，52例为药物溶栓。随访发现症状完全消失取栓组占20．5％(9／44)，高于溶栓组13．5％(7／52)，溶栓组肢体发生浅静脉曲张和皮肤色素沉着占50．5％，取栓组为31．8％。结论：手术取栓可以保护部分患者下肢的主干深静脉瓣膜，可能减少下肢深静脉血栓形成后遗症。     

Synovectomy with Resection of the Distal Ulna in Rheumatoid Arthritis of the Wrist

Wrist synovectomy with resection of the distal ulna was performed in 47 cases, where rheumatoid affection in the wrist joint caused visible capsular swelling, pain and reduced range of motion. At follow-up after a mean observation time of 33 months, 31 cases had complete pain relief, eight cases had moderate pain relief. in eight cases pain during wrist motion was unchanged at follow-up and in five of these, recurrence of capsular swelling was noted. the range of motion (both supination/pronation and vola- and dorsiflection) was significantly improved, as was the subjective assessment of function. the radiographic findings showed progression in 41 cases. Deviation in the wrist was unchanged. in three cases reoperations were performed and one case had spontaneous rupture of the 4th and 5th extensor tendons 1 month postoperatively. in 15 cases dislocation of the extensor carpi ulnaris tendon in volar direction by rotational movement was noted. Stability was good in all cases and no serious postoperative complications occurred.

Wrist synovectomy with resection of the distal ulna is recommended in cases where regular medical treatment has been attempted for a minimum of 6 months without successful results.     

Synovectomy with Resection of the Distal Ulna in Rheumatoid Arthritis of the Wrist

Wrist synovectomy with resection of the distal ulna was performed in 47 cases, where rheumatoid affection in the wrist joint caused visible capsular swelling, pain and reduced range of motion. At follow-up after a mean observation time of 33 months, 31 cases had complete pain relief, eight cases had moderate pain relief. in eight cases pain during wrist motion was unchanged at follow-up and in five of these, recurrence of capsular swelling was noted. the range of motion (both supination/pronation and vola- and dorsiflection) was significantly improved, as was the subjective assessment of function. the radiographic findings showed progression in 41 cases. Deviation in the wrist was unchanged. in three cases reoperations were performed and one case had spontaneous rupture of the 4th and 5th extensor tendons 1 month postoperatively. in 15 cases dislocation of the extensor carpi ulnaris tendon in volar direction by rotational movement was noted. Stability was good in all cases and no serious postoperative complications occurred.

Wrist synovectomy with resection of the distal ulna is recommended in cases where regular medical treatment has been attempted for a minimum of 6 months without successful results.     

关节内注射复方倍他米松对兔佐剂性关节炎的效果

目的评价关节内注射复方倍他米松对兔佐剂性关节炎的效果。方法日本大耳白兔，雌雄各半，体重2～3kg，6～8月龄。采用皮内注射卵清蛋白＋非完全弗氏佐剂的方法制备佐剂性关节炎模型。佐剂性关节炎模型制备成功的48只免随机分为2组（n=24），C组双膝关节内各注射生理盐水1ml；D组注射复方倍他米松0．5mg／kg。每组各随机取6只兔，持续观察膝关节外观，分别于治疗前、治疗后2周测量髌骨上缘处双膝周径，并测定膝关节灌洗液中一氧化氮（NO）浓度，治疗后2周处死兔，打开膝关节，观察关节腔内改变，取髌上囊处滑膜，光镜下观察病理学改变。2组分别于治疗后1、2、3d各随机处死6只兔，取髌上囊滑膜，观察细胞凋亡情况。结果与c组比较，治疗后D组关节滑膜炎性反应较轻，NO浓度降低（P〈0．01）；治疗后2、3d滑膜细胞凋亡率升高（P〈0．05或0．01）。结论膝关节内注射复方倍他米松0．5mg／kg对免佐剂性关节炎有抗炎作用，可能与抑制NO的合成及促进滑膜细胞凋亡有关。     

关节镜技术在化脓性膝关节炎治疗中的应用

目的探讨应用关节镜下膝关节清理加置管持续冲洗术治疗化脓性膝关节炎的疗效。方法应用关节镜下膝关节清理加置管持续冲洗术治疗14例化脓性膝关节炎患者。结果14例均获随访,时间为12-18个月。患者均治愈,无复发。根据HSS评分标准评价膝关节功能：优11例,良2例,中1例。结论关节镜下膝关节清理加置管持续冲洗术是治疗化脓性膝关节炎的有效方法,具有损伤小,恢复快,膝关节功能恢复好的优点。     

微波辐射联合阿霉素脂质体抗兔VX2肿瘤的效果

目的 探讨应用微波辐射联合阿霉素脂质体对兔VX2肝肿瘤的治疗作用。方法将肝脏已成功接种VX2肿瘤的新西兰大白兔随机分成4组,每组8只。A组为肝动脉注入阿霉素碘化油乳剂;B组为注入阿霉素脂质体碘化油乳剂;C组微波辐射联合栓塞阿霉素碘化油乳剂;D组微波辐射联合栓塞阿霉素脂质体碘化油乳剂;4组实验动物于介入术前1d、术后14d行CT肝脏扫描,测量肿瘤大小;术前1d、术后1d、7d行肝功能检查,在微波辐射前、辐射中、辐射后30min、1h测量呼吸频率、心率和体温。术后15d处死动物,全部实验动物均取肿瘤组织及周围组织作组织病理学检查。结果术前1d各组动物肿瘤体积、肝功能无明显统计学差异。术后14d平均肿瘤体积A组为（6．02士1．21）cm^3,B组为（5．74±1．43）cm^3,C组为（3．26±0．37）cm^3,D组为（1．89±0．14）cm^3。各组肝功能检测无明显差异;微波辐射后兔的生命体征稳定,病理学检查组织坏死程度为D组最为明显（P〈0．05）。结论经动脉途径应用阿霉素脂质体联合微波辐射抗兔VX2肝肿瘤效果明显,认为微波有助于提高阿霉素脂质体的抗肿瘤效果,联合治疗安全可行。     

关节镜技术治疗血友病A膝关节滑膜炎

[目的]总结关节镜技术在血友病A膝关节滑膜炎中的应用,探讨其疗效。[方法]自2002年9月～2007年1月对25例血友病A膝关节滑膜炎患者,行关节镜下滑膜切除,围手术期内适量Ⅷ因子滴注,进行系统康复训练。采用HSS评分标准,对术前、术后结果进行综合评估。根据关节镜下软骨Outerbridge分期分组,按照Insall疗效标准,分别评估各组手术效果。[结果]23例患者得以随访,平均随访时间27个月。术前平均输血次数(23.4±4.6)次/年,术后(9.8±2.5)次/年(P<0.01)。HSS评分术前(58.6±4.7)分,术后(80.5±6.8)分(P<0.01)。OuterbridgeI期术后优良率100%(4/4),II期83.3%(10/12),Ⅳ期优良率差(0/2)。[结论]对于早中期血友病A膝关节滑膜炎,关节镜下滑膜切除是一种安全、有效的治疗方法。     

关节镜下治疗急性化脓性膝关节炎

目的探讨关节镜下病灶清除结合术后抗生素持续滴注引流对化脓性膝关节炎的治疗效果。方法对18例膝关节化脓性关节炎患者采用关节镜下病灶清除结合术后抗生素持续滴注引流治疗,患者术后积极康复训练。结果住院时间14～21 d。18例均获随访,时间2～24个月。患者均一次性治愈,无复发。关节功能根据HSS评分标准：优16例,良2例。结论关节镜下病灶清除结合术后抗生素持续滴注引流治疗化脓性膝关节炎的优点为：手术创伤小,住院时间短,关节功能恢复快,疗效肯定。     

掌指关节置换术治疗类风湿关节炎

目的 探讨应用掌指关节置换术治疗类风湿关节炎的方法和临床疗效.方法 2002年1月-2007年1月,对8例13指类风湿关节炎的患者,采用Swanson假体行掌指关节置换术.结果 术后伤口均Ⅰ期愈合,随访时间为9～24个月,平均15.8个月.掌指关节置换后按李庆泰等的疗效评定标准评价:优9指,良4指.结论 掌指关节置换术治疗类风湿关节炎疗效可靠,是一种较好的治疗方法.     

Integration of radiation and immunotherapy in breast cancer - Treatment implications

Radiation therapy (RT) has been successfully used in the treatment of breast cancer (BC) for over a century. While historically thought to be immunosuppressive, new data have shown that RT can work together with the immune system to eliminate cancer. It can cause immunogenic cell death and facilitate tumor neoantigen presentation and cross-priming of tumor-specific T-lymphocytes, turning irradiated tumor into an in-situ vaccine. Unfortunately, due to various immune escape mechanism put in place by the tumor, RT alone rarely results in a systemic response of metastatic disease sites (known as the abscopal effect). Immunotherapy, a series of agents designed to stimulate the immune system in order to generate tumor-specific immune response, is showing promise in treatment of various cancers, including BC, and can be an ideal complement to RT in stimulating a systemic immune response to reject the tumor cells. This review discusses the mechanisms in which RT can trigger an immune response for tumor rejection, and provide emerging preclinical and clinical data of combination immunoradiotherapy, and its potential in treating BC.     

应用血管内皮生长因子基因治疗股骨头缺血性坏死的实验研究

目的：通过建立犬股骨头缺血坏死模型，探讨应用脱蛋白骨复合转染血管内皮生长因子（vascular endothelial growth factor，VEGF）基因骨髓基质细胞植入治疗股骨头缺血坏死的可行性。方法：实验选取36只成年犬，随机分为3组，每组12只。A组为脱蛋白异体骨复合转染VEGF基因的自体骨髓基质细胞；B组为脱蛋白异体骨复合未转染基因的自体骨髓基质细胞；C组单纯植入脱蛋白骨材料。采用液氮冷冻法制作狗股骨头缺血坏死模型，将细胞骨材料复合物植入缺血坏死股骨头内。应用微循环灌注方法了解股骨头内的血运情况，组织形态学观察坏死股骨头的修复情况，免疫组化方法检测VEGF的表达，骨密度仪测定股骨头的骨密度。结果：A组4周后股骨头内有VEGF表达，12周后股骨头内有大量的树枝状血管生成，大量新骨形成，骨密度增高；B、C组均无VEGF基因表达，B组有部分新骨及血管生成，C组仅见少量类骨质形成，血管再生不明显。结论：利用脱蛋白骨复合转染VEGF基因的骨髓基质细胞可促进新骨形成与血管再生，有利于促进坏死骨的修复。