A Pilot First-in-Human Study of Embrace,a Polyethylene Glycol-Based Liquid Embolic Agent,in the Embolization of Malignant and Benign Hypervascular Tumors

PurposeTo investigate the safety and efficacy of an aqueous polyethylene glycol-based liquid embolic agent, Embrace Hydrogel Embolic System (HES), in the treatment of benign and malignant hypervascular tumors.Materials and MethodsA prospective, single-arm, multicenter study included 8 patients, 5 males and 3 females, with a median age of 58.5 years (30–85 years), who underwent embolization in 8 tumors between October 2019 and May 2020. Technical success was defined as successful delivery of HES to the index vessel, with disappearance of >90% of the targeted vascular enhancement or, for portal vein embolization, occlusion of the portal branches to the liver segments for future resection. The volume of HES administered, ease of use (5 point Likert scale), administration time, and adverse events (AEs) were recorded. Evaluation was performed at 7, 30, and 90 days via clinical assessment and blood testing, and follow-up imaging was performed at 30 days.ResultsEight patients were enrolled, and 10 embolizations were performed in 8 lesions. Tumors included hepatocellular carcinoma (n = 4), renal angiomyolipoma (n = 3), and intrahepatic cholangiocarcinoma (n = 1). Technical success was 100%, and the average ease of use was 3.3 ± 1.0 SD. The HES delivery time was 1–28 minutes (median, 16.5 minutes), and the HES volume injected was 0.4–4.0 mL (median, 1.3 mL). All patients reached 30-day follow-up with imaging, and 6 patients reached 90-day follow-up. There were 3 serious AEs in 2 patients that were unrelated to the embolic agent.ConclusionHES resulted in a 100% embolization technical success rate. The product ease of use was acceptable, and no target vessel recanalization was noted on follow-up imaging at 30 days.     

Survivorship Comparisons of Ultracongruent,Cruciate-Retaining and Posterior-Stabilized Tibial Inserts Using a Single Knee System Design: Results From the Australian Orthopedic Association National Joint Replacement Registry

BackgroundUltracongruent (UC) tibial inserts can increase knee replacement stability, but how survivorship compares to cruciate retaining (CR) or posterior stabilized (PS) inserts is unclear.MethodsData from a large joint registry were used to calculate the cumulative percent revision of a single popular knee design used with different inserts. There were 67,523 procedures, of which 12,434 were UC, 21,635 CR, and 33,454 PS. Revision rates and reasons for revision were analyzed.ResultsThe cumulative percent revision at 18 years was 8.3% for UC, 9.2% for CR, and 8.9% for PS. There was no difference when UC was compared to CR, but PS had a higher risk of revision. Revision reasons were similar.ConclusionCompared to the CR, an UC insert did not increase revision rates and was actually lower than a PS insert. An UC insert does not compromise long-term total knee arthroplasty survivorship in the Genesis II prosthesis.     

Matrine,oxymatrine, and compound Kushen injection from the roots of Sophora flavescens: an overview of their anticancer activities

In the present review, we updated current information on the chemistry, contents, and anticancer properties of matrine (MT), oxymatrine (OMT), and compound Kushen injection (CKI). The anticancer properties were focused on lung, breast, and liver cancer cells because they are most susceptible. Sources of information were from Google, Google Scholar, PubMed, PubMed Central, Science Direct, PubChem, J-Stage, Directory of Open Access Journals (DOAJ), and China National Knowledge Infrastructure (CNKI). Reference was also made on botanical websites, such as Flora of China and World Flora Online. MT and OMT are dominant quinolizidine alkaloids from the roots of Sophora flavescens (Kushen) of the family Fabaceae. Against lung, breast, and liver cancer cells, MT and OMT inhibit cell proliferation; induce cell cycle arrest, apoptosis, and autophagy; restrict angiogenesis; and inhibit cell metastasis, invasion, and migration. The processes involve various molecular targets and signaling pathways. CKI is a traditional Chinese medicine (TCM) composed of root extracts of S. flavescens and Smilax glabra (Baituling) of the family Smilacaceae. With MT and OMT as major components, CKI has been approved for the treatment of cancer in China more than 20 years ago. In recent years, systematic reviews and meta-analysis have been undertaken to evaluate the anticancer effects of CKI. When CKI is used alone and in combination with chemotherapy of western medicine, there is much to be learned concerning their interactions besides their individual and integrated efficacy. Some perspectives of MT, OMT, and CKI are discussed, and their suggestions for future research are provided.     

激光联合复方血栓通胶囊治疗糖尿病视网膜病变合并黄斑水肿的疗效观察

目的:分析糖尿病视网膜病变合并黄斑水肿联合采用激光与复方血栓通胶囊治疗的临床疗效。方法:选取我院2017年1月—2019年1月收治的200例糖尿病视网膜病变合并黄斑水肿患者为研究对象,随机分为两组。对照组单独行激光治疗,观察组于对照组基础上联合复方血栓通胶囊治疗,对比两组临床疗效、治疗前后IL-6(白介素-6)、VEGF(血管内皮生长因子)、NOS(血清一氧化氮合成酶)水平变化情况。结果:对照组总有效率(68.00%,68/100)较观察组总有效率(98.00%,98/100)更高(P<0.05);与对照组对比,观察组治疗后NOS水平更高,IL-6、VEGF水平更低(P<0.05)。结论:糖尿病视网膜病变合并黄斑水肿联合采用激光与复方血栓通胶囊治疗的临床疗效显著,值得推广。     

Computer-aided design of dry powder inhalers using computational fluid dynamics to assess performance

Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices. The aim of this research was to produce a new DPIs using computational fluid dynamics (CFD). The new DPIs took advantages of the Cyclohaler® and the Rotahaler®. We chose a combination of the capsule chamber of the Cyclohaler® and the mouthpiece and grid of the Rotahaler®. Computer-aided design models of the devices were created and evaluated using CFD. Prototype models were created and tested with the DPI dispersion experiments. The proposed model 3 device had a high turbulence with a good degree of deagglomeration in the CFD and the experiment data. The %fine particle fraction (FPF) was around 50% at 60?L/min. The mass median aerodynamic diameter was around 2.8–4?μm. The FPF were strongly correlated to the CFD-predicted turbulence and the mechanical impaction parameters. The drug retention in the capsule was only 5–7%. In summary, a simple modification of the Cyclohaler® and Rotahaler® could produce a better performing inhaler using the CFD-assisted design.     

Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

复方倍他米松注射液联合泛昔洛韦胶囊、普瑞巴林胶囊治疗带状疱疹的临床疗效观察

目的 对复方倍他米松注射液联合泛昔洛韦胶囊、普瑞巴林胶囊治疗带状疱疹的临床疗效进行观察并探讨。方法 选取2018 年1 月～2019 年12 月我院收治的118 例带状疱疹患者为研究对象，采用随机抽签的方式将患者分为对照组（泛昔洛韦胶囊+普瑞巴林胶囊+甲钴胺片+维生素B1 片）与观察组（联合复方倍他米松注射液），比较两组治疗总有效率、VAS 评分、QS 评分、C 反应蛋白、无新发皮疹时间、结痂时间及疼痛停止时间、随访2 个月后带状疱疹后遗神经痛发生率以及不良反应发生率。结果 观察组与对照组治疗总有效率分别为94.92%及76.27%，组间对比差异有统计学意义（P＜0.05）；治疗后，观察组VAS 评分显著低于对照组；观察组QS 评分低于对照组（P＜0.05）；治疗后，观察组C 反应蛋白显著低于对照组（P＜0.05）；观察组无新发皮疹时间、结痂时间及疼痛停止时间分别显著短于对照组（P＜0.05）；随访2 个月后，发现观察组带状疱疹后遗神经痛发生率显著低于对照组（P＜0.05）；观察组不良反应发生与对照组比较，差异无统计学意义（P＞0.05）。结论 复方倍他米松注射液联合泛昔洛韦胶囊、普瑞巴林胶囊治疗带状疱疹不仅效果好且安全性高，值得使用。     

针刺配合肠炎散保留灌肠治疗肛窦炎临床研究

目的观察肛窦炎应用针刺配合肠炎散保留灌肠治疗的效果。方法选取2017年10月-2018年10月就诊的72例肛窦炎患者,采用随机数字表法分为观察组(n=36)与对照组(n=36)。对照组给予肠炎散保留灌肠治疗,观察组为针刺配合肠炎散保留灌肠治疗,比较2组症状、疗效及安全性。结果观察组症状(放射痛、指诊症状及镜检症状)少于对照组,总有效率高于对照组,差异有统计学意义(P<0.05);2组安全性相比,差异无统计学意义(P>0.05)。结论针对肛窦炎患者,予以针刺配合肠炎散保留灌肠治疗效果确切,可减少临床症状,加快疾病转归,且治疗安全性较好。     

Revisiting the Hydrogen Storage Behavior of the Na-O-H System

Solid-state reactions between sodium hydride and sodium hydroxide are unusual among hydride-hydroxide systems since hydrogen can be stored reversibly. In order to understand the relationship between hydrogen uptake/release properties and phase/structure evolution, the dehydrogenation and hydrogenation behavior of the Na-O-H system has been investigated in detail both ex- and in-situ. Simultaneous thermogravimetric-differential thermal analysis coupled to mass spectrometry (TG-DTA-MS) experiments of NaH-NaOH composites reveal two principal features: Firstly, an H₂ desorption event occurring between 240 and 380 °C and secondly an additional endothermic process at around 170 °C with no associated weight change. In-situ high-resolution synchrotron powder X-ray diffraction showed that NaOH appears to form a solid solution with NaH yielding a new cubic complex hydride phase below 200 °C. The Na-H-OH phase persists up to the maximum temperature of the in-situ diffraction experiment shortly before dehydrogenation occurs. The present work suggests that not only is the inter-phase synergic interaction of protic hydrogen (in NaOH) and hydridic hydrogen (in NaH) important in the dehydrogenation mechanism, but that also an intra-phase H^δ+… H^δ– interaction may be a crucial step in the desorption process.