Assessing the Effects of Geniculate Artery Embolization in a Nonsurgical Animal Model of Osteoarthritis

PurposeTo create a nonsurgical animal model of osteoarthritis (OA) to evaluate the effects of embolotherapy during geniculate artery embolization (GAE).Materials and MethodsFluoroscopy-guided injections of 700 mg of sodium monoiodoacetate were performed into the left stifle in 6 rams. Kinematic data were collected before and after induction. At 10 weeks after induction, Subjects 1 and 4–6 underwent magnetic resonance (MR) imaging with dynamic contrast enhancement (DCE) and Subjects 1, 3, and 4–6 underwent angiography with angiographic scoring to identify regions with greatest disease severity for superselective embolization (75–250-μm microspheres). Target vessel size was measured. At 24 weeks after angiography, DCE-MR imaging, angiography, and euthanasia were performed, and bilateral stifles were harvested. Medial/lateral tibial and femoral condylar, patellar, and synovial samples were cut, preserved, decalcified, and scored using the Osteoarthritis Research Society International criteria. The stifle and synovium Whole-Organ Magnetic Resonance Imaging Score and Multicenter Osteoarthritis Study score were determined. The volume transfer constant (K_trans) and extracellular volume fraction (v_e) were calculated from DCE-MR imaging along the lateral synovial regions of interest.ResultsThe mean gross and microscopic pathological scores were elevated at 38 and 61, respectively. Mean synovitis score was elevated at 9.2. Mean pre-embolization and postembolization angiographic scores were 5 and 3.8, respectively. Mean superior, transverse, and inferior geniculate artery diameters were 3.1 mm ± 1.21, 2.0 mm ± 0.50, and 1.6 mm ± 0.41 mm, respectively. Mean pre-embolization and postembolization cartilage and synovitis scores were elevated at 35.13 and 73.3 and 5.5 and 9.2, respectively. The K_trans/v_e values of Subjects 4, 5, and 6 were elevated at 0.049/0.38, 0.074/0.53, and 0.065/0.51, respectively. Altered gait of the hind limb was observed in all subjects after induction, with reduced joint mobility. No skin necrosis or osteonecrosis was observed.ConclusionsA nonsurgical ovine animal knee OA model was created, which allowed the collection of angiographic, histopathological, MR imaging, and kinematic data to study the effects of GAE.     

Comparison of Foaming Properties Between the Shirasu Porous Glass Membrane Device and Tessari’s Three-way Stopcock Technique for Polidocanol and Ethanolamine Oleate Foam Production: A Benchtop Study

PurposeTo compare the characteristics of polidocanol (POL) and ethanolamine oleate (EO) sclerosing foams produced by a Shirasu porous glass membrane (SPGM) device with those made using a 3-way stopcock (3WSC).Materials and MethodsFoam half-life times were measured in an ex-vivo benchtop study. Computed tomography (CT) images of each foam were obtained over the time course, and a CT texture analysis was conducted. The bubble size in each foam was measured by an optical microscope.ResultsMedian foam half-life times were longer in the SPGM group than in the 3WSC group (POL: 198 vs 166 s, P = .02; EO: 640 vs 391 s, P < .01). In the CT texture analysis, median standard deviation (SD) and entropy (randomness) were lower, and median energy (uniformity) and gray-level cooccurrence matrix (GLCM) homogeneity were higher in the SPGM group than in the 3WSC group (POL SD: at 30 s and 50–300 s; POL entropy: at 0–60 s; EO SD: at 0–600 s; EO entropy: at 0–460 s; POL energy: at 0–40 s; POL GLCM homogeneity: at 0–250 s; EO energy: at 0–360 s; EO GLCM homogeneity: at 0–480 s; all P < .05). Median bubble diameters in the SPGM group and in the 3WSC group were 69 and 83 μm (P < .01), respectively, in the POL foam; and 36 and 36 μm (P = .45), respectively, in the EO foam.ConclusionsPOL and EO foams had greater uniformity and longer foam half-life time when prepared with an SPGM device than with a 3WSC.     

孟鲁司特治疗呼吸道合胞病毒毛细支气管炎症状及反复喘息疗效研究

背景　呼吸道合胞病毒（RSV）毛细支气管炎易出现反复喘息，且下呼吸道分泌物中半胱氨酸白三烯（CysLTs）水平升高。而孟鲁司特是一种白三烯受体拮抗剂，关于其治疗RSV毛细支气管炎症状的研究相对较少。目的　探讨孟鲁司特改善婴幼儿RSV毛细支气管炎后症状及减轻反复喘息发作的有效性和安全性。方法　2015年6月-2017年6月连续纳入在潍坊市妇幼保健院出院的RSV毛细支气管炎患儿，随机分为治疗组、对照组。Ⅰ期，治疗组：口服孟鲁司特颗粒（4 mg）12周，1次/d；对照组：口服安慰剂12周，1次/d。对两组无症状天数、个人日记评分进行评估。随访9个月（Ⅱ期），观察Ⅰ+Ⅱ期反复喘息人数和医疗资源应用情况等。依据意向性分析（ITT）原则，应用全分析集（FAS）分析数据。结果　共纳入研究对象186例，治疗组92例，对照组94例。治疗组完成Ⅰ期研究的患儿为89例，对照组为90例；治疗组完成Ⅰ+Ⅱ期的患儿为84例，对照组为86例。治疗组平均依从性为97.8%（7 560/7 728），对照组平均依从性为97.4%（7 690/7 896），两组患儿平均依从性比较，差异无统计学意义（χ2=3.16，P=0.07）。在Ⅰ期研究期间，两组无症状天数、日间无症状天数、夜间无症状天数、个人日记评分比较，差异均无统计学意义（P>0.05）。在整个研究过程中（Ⅰ+Ⅱ期），治疗组RSV毛细支气管炎喘息复发人数少于对照组（P<0.05），治疗组喘息患儿出现2次及以上喘息比例低于对照组（χ2=5.14，P=0.02）。Ⅰ+Ⅱ期研究期间治疗组医疗资源应用人数、β-受体激动剂应用人数、糖皮质激素应用人数、住院人数低于对照组（P<0.05）。在事后亚组分析中，治疗组有湿疹史与父母哮喘史的患儿中无症状天数〔（49.7±20.2）、（51.3±20.9）d〕多于对照组〔（36.3±20.4）、（37.8±19.3）d〕（t=2.19，P=0.03；t=2.24，P=0.03）。整个研究过程中没有患儿因不良反应退出研究，两组间胃肠道紊乱、皮疹、转氨酶升高发生率比较，差异均无统计学意义（χ2=0.23，P=0.63；χ2=0.03，P=0.86；χ2=0.15，P=0.69）。结论　口服孟鲁司特（4 mg）12周不能改善RSV毛细支气管炎患儿呼吸道症状，但能降低患儿反复喘息发作次数。口服孟鲁司特（4 mg）有一定效果且安全。     

胃肠安丸对葡聚糖硫酸钠诱导溃疡性结肠炎小鼠的治疗作用及机制

目的探讨胃肠安丸对葡聚糖硫酸钠(DSS)诱导溃疡性结肠炎小鼠的治疗作用及机制。方法SPF级C57BL/6小鼠60只,除正常对照组小鼠外,其余小鼠均给予2.5%DSS水溶液,自由饮用7 d制备溃疡性结肠炎模型,模型评价后再随机分为模型组、美沙拉嗪组及胃肠安丸高剂量组、中剂量组、低剂量组。胃肠安丸低、中、高剂量组分别给予0.015、0.03、0.06 g/(kg·d)胃肠安丸混悬液0.5 mL灌胃,1次/d;美沙拉嗪组给予0.52 g/(kg·d)美沙拉嗪混悬液0.5 mL灌胃,1次/d;正常对照组和模型组给予等体积纯水灌胃,均连续干预10 d。对比各组小鼠疾病活动指数(DAI)评分、结肠长度,用HE染色观察小鼠结肠组织病理形态学变化,用流式细胞术检测脾组织中Treg、Th17、CD4^+、CD8^+细胞百分比,ELISA法检测血清细胞因子TNF-α、IL-6、IL-8、IL-10、CRP水平。结果药物干预过程中,各组小鼠体质量均逐日增加,腹泻、便血、体质量下降等症状逐日缓解,与模型组相比,美沙拉嗪组和胃肠安丸高剂量组能更快地缓解上述症状,2组DAI评分逐日下降(P<0.05)。药物干预结束后,与模型组比较,胃肠安丸高剂量组和美沙拉嗪组小鼠结肠较长(P<0.05),结肠组织充血、间质水肿及炎性细胞浸润较轻,CD4^+、CD8^+、Treg细胞百分比及血清IL-10水平较高(P<0.05),Th17细胞百分比及血清TNF-α、IL-6、IL-8、CRP水平较低(P<0.05)。结论胃肠安丸对DSS诱导的小鼠肠道黏膜损伤有一定的修复作用,其作用机制可能与恢复Treg/Th17免疫平衡以及调节相关细胞因子水平有关。     

Targeted drug delivery of Methotrexate in situ gels for the treatment of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is considered a debilitating disease that increases the risk of significant morbidity and premature mortality. To circumvent drug-related toxicity and ineffectiveness of anti-inflammatory drugs, there is a significant need for an advanced delivery system that increases bioavailability. The feasibility of in situ gel of methotrexate sodium (MTS) as an effective management for Rheumatoid arthritis was investigated. It was formulated with pluronic F-127 (PLF-127) as primary polymer, hydroxypropyl methylcellulose K4M (HK4M), and polycarbophil (PCL) as a copolymer and characterized by various parameters. The efficacy evaluation by Freund's complete adjuvant (FCA) model, biocompatibility assessment by histopathological studies conducted. The optimized in situ gel (M4) was thermoresponsive, released 93.26 ± 2.39% MTS at 96 hours. In addition, distribution of MTS was even in the optimized sterile and syringeable in situ gel. In vivo studies on wistar rats demonstrated a substantial reduction in paw oedema during the 28-day study period and were biocompatible with the tissues at the injection site. The study was successful in formulating, optimizing MTS in situ gel for effective management of RA.     

血抗栓汤内服联合西医治疗急性脑梗死疗效分析

目的观察活血抗栓汤联合奥扎格雷钠治疗急性脑梗死疗效。方法将80患者按抽签法分为观察组和对照组各40例。对照组奥扎格雷钠氯化钠注射液,500 mL/次,2次/d,静滴,治疗2周。治疗组在对照组基础上加用活血抗栓汤,水煎200 mL,1剂/d,2次/d,治疗2周。观测临床症状、神经功能、日常生活能力、凝血功能。结果治疗后,观察组红细胞聚集指数、血细胞容积、纤维蛋白原、全血高切黏度、血浆比黏度改善程度高于对照组(P<0.05)。治疗前,两组ADL评分、NIHSS评分比较,无显著差异(P>0.05),治疗后,观察组NIHSS评分低于对照组,ADL评分高于对照组(P<0.05)。结论血抗栓汤内服联合西医治疗急性脑梗死,可改善凝血功,值得推广。     

补肾壮骨汤联合针灸及阿仑膦酸钠治疗骨质疏松症的临床效果评估

目的:探讨补肾壮骨汤联合针灸及阿仑膦酸钠治疗骨质疏松症的临床效果。方法:将2018年5月-2019年5月本院接收的骨质疏松症患者94例作为本次研究中的主要观察对象。通过电脑随机法,予以分组探讨,包括常规组(予以阿仑膦酸钠治疗)、研究组(阿仑膦酸钠,补肾壮骨汤联合针灸),各47例。结果:研究组临床疗效高于常规组(P<0.05);研究组治疗后中医证候积分、疼痛视觉模拟评分量表(Visual Analogue Scale,VAS)评分均低于常规组(P<0.05);研究组全髋以及腰椎L1-4骨密度高于常规组(P<0.05);研究组血清骨钙素(Bone Gla Protein,BGP)以及血清钙(Calcium,Ca)骨代谢指标高于常规组,碱性磷酸酶(Alkaline Phosphatase,ALP)低于常规组(P<0.05),两组血清磷(Phosphorus,P)水平无显著差异(P>0.05)。结论:应用阿仑膦酸钠治疗的同时,予以针灸联合补肾壮骨汤口服治疗,能够显著减轻患者症状,增加骨密度,优化骨代谢,效果确切,值得临床大力推荐。