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.     

基于网络药理学和实验验证研究柴胡疏肝散治疗慢性萎缩性胃炎的作用机制＊

目的 通过网络药理学的方法进行预测，再深一步进行动物实验验证来研究柴胡疏肝散治疗CAG的作用机制。方法 首先在TCMSP数据库中检索柴胡疏肝散的所有活性成分与药物靶点；通过收集PharmGkb、OMIM、GeneCards和DrugBank数据库中收录的慢性萎缩性胃炎的相关靶点。将药物靶点与疾病靶点进行映射筛选出交集靶点，将得到的交集靶点构建PPI网络与活性成分-共同靶点网络，并对其进行GO和KEGG富集分析。最后利用Vina软件进行分子对接实验验证，并通过免疫印迹法验证柴胡疏肝散对两种受体蛋白EGFR和STAT1的影响。结果 最终筛选得到柴胡疏肝散活性成分104个，潜在靶点238个，与慢性萎缩性胃炎的交集靶点52个；GO与KEGG富集分析分别得到2166条目和148条目，主要涉及到JAK-STAT信号通路、TNF信号通路、HIF-1信号通路等；分子对接结果显示EGFR、STAT1两个靶点能够与核心活性成分能够自发结合成较为稳定的构像；免疫印迹法实验证明柴胡疏肝散能够降低大鼠胃黏膜组织EGFR和STAT1蛋白表达。结论 通过网络药理学和实验验证，发现柴胡疏肝散可能通过调节EGFR和STAT1蛋白表达来共同调控胃黏膜细胞增殖与凋亡，进而发挥着治疗慢性萎缩性胃炎的效果，为深入进行柴胡疏肝散治疗慢性萎缩性胃炎的作用机制研究提供新思路和新方法。     

Selective Laser Melting of Al-Based Matrix Composites with Al2O3 Reinforcement: Features and Advantages

Aluminum matrix composites (AMC) are of great interest and importance as high-performance materials with enhanced mechanical properties. Al₂O₃ is a commonly used reinforcement in AMCs fabricated by means of various technological methods, including casting and sintering. Selective laser melting (SLM) is a suitable modern method of the fabrication of net-shape fully dense parts from AMC with alumina. The main results, achievements, and difficulties of SLM applied to AMCs with alumina are discussed in this review and compared with conventional methods. It was shown that the initial powder preparation, namely the particle size distribution, sphericity, and thorough mixing, affected the final microstructure and properties of SLMed materials drastically. The distribution of reinforcing particles tends to consolidate the near-melting pool-edges process because of pushing by the liquid–solid interface during the solidification process that is a common problem of various fabrication methods. The achievement of an homogeneous distribution was shown to be possible through both the thorough mixing of the initial powders and the precise optimization of SLM parameters. The strength of the AMCs fabricated by the SLM method was relatively low compared with materials produced by conventional methods, while for superior relative densities of more than 99%, hardness and tribological properties were obtained, making SLM a promising method for the Al-based matrix composites with Al₂O₃.     

Disengagement of tibial insert locking pin in total knee arthroplasty - A rare failure case report

Total Knee Arthroplasty (TKA) has seen many advancements over the years. One such advancement is development of locking mechanism for polyethylene insert in modular implants. It aims to reduce micro motion and wear problems. Disengagement of locking pin from insert after primary TKA without trauma is rare complication. The author describes a rare case of disengagement of the polyethylene insert locking pin in primary total knee arthroplasty. Disengagement of the locking clip was observed 8 months after index operation without any trauma.     

基于《金匮要略》头风摩散结合摩法治疗偏头痛思路探究

偏头痛是临床常见头面部疾病,现在医学多采用特异性治疗药物跟非特异性止痛药物治疗。长期服药造成一定的并发症及不良反应,中西医结合治疗偏头痛是临床研究的重点。张仲景《金匮要略.中风历节病脉证并治》篇中初次记录头风摩散,该外治方的主要功效是用来治疗头风病,同时开创了摩顶膏法的先河。 摩法是最古老、最常用的手法之一。记载摩法的古代文献颇多,可追溯至《素问.病能》曰；“摩之切之。” 《素问.至真要大论》曰：“摩之、浴之。”并由此演绎出一系列实用手法。本文旨在探究摩法结合头风摩散治疗偏头痛的操作应用及其原理,进一步考究摩法与头风摩散结合治疗偏头痛的协同作用,以期对临床有一定指导意义。     

《邵氏医案》从血辨治痛经浅析

[目的]分析总结浙江近代著名临床医家邵兰荪治疗痛经的经验,以期为临床治疗提供借鉴。[方法]通过研读裘吉生编《邵氏医案》,筛选出其中治疗痛经的医案十余则,并结合邵氏在妇科方面的学术思想,进一步分析其辨证立法遣方特色,从而总结邵氏治疗痛经的临证经验。[结果]邵氏治疗痛经多从血辨治,且分虚实两端,其中属虚者血虚内热用益母胜金丹养血清热、活血止痛,血虚肝风治以养血柔肝、息风止痛;属实者水结血瘀用五苓散利水散瘀、行气止痛,气阻血滞治从行气活血、调经止痛。[结论]在治疗妇人痛经方面,邵氏辨治遣方确有独特经验,这些经验可为中医药治疗此类疾病拓宽诊治思路,有助于提高临床疗效。     

Establishment of an Evaluation Method for Gene Silencing by Serial Pulmonary Administration of siRNA and pDNA Powders: Naked siRNA Inhalation Powder Suppresses Luciferase Gene Expression in the Lung

In order to evaluate the in vivo effect of inhaled formulations, it is a gold standard to create a lung metastasis model by intravenously injecting cancer cells into an animal. Because the cancer grows from the blood vessel side, there is a possibility of underestimating the effect of an inhaled formulation administered to the lung epithelium side. In addition, the metastasis model has disadvantages in terms of preparation time and expense. The present study aimed to establish a new method to evaluate the effect of an inhaled small interfering RNA (siRNA) formulation that is more correct, more rapid, and less expensive. We investigated whether siRNA can suppress gene expression of plasmid DNA (pDNA) by serial pulmonary administration of siRNA and pDNA powders prepared by spray-freeze-drying. We revealed that formulations of dry siRNA powder significantly suppressed gene expression of pDNA powder compared with a control group with no siRNA. Naked siRNA inhalation powder with no vector showed the suppression of gene expression equivalent to that of an siRNA-polyethyleneimine complex without damaging tissues. These results show that the present method is suitable for evaluating the gene-silencing effect of inhaled siRNA powders.     

Polyethylene glycol 35 ameliorates pancreatic inflammatory response in cerulein-induced acute pancreatitis in rats

BACKGROUND Acute pancreatitis(AP) is a sudden inflammatory process of the pancreas that may also involve surrounding tissues and/or remote organs. Inflammation and parenchymal cell death are common pathological features of this condition and determinants of disease severity. Polyethylene glycols(PEGs) are nonimmunogenic, non-toxic water-soluble polymers widely used in biological, chemical, clinical and pharmaceutical settings.AIM To evaluate the protective effect of a 35-k Da molecular weight PEG(PEG35) on the pancreatic damage associated to cerulein-induced acute pancreatitis in vivo and in vitro.METHODS Wistar rats were assigned at random to a control group, a cerulein–induced AP group and a PEG35 treatment group. AP was induced by five hourly intraperitoneal injections of cerulein(50 μg/kg/bw), while the control animals received saline solution. PEG35 was administered intraperitoneally 10 minutes before each cerulein injection in a dose of 10 mg/kg. After AP induction, samples of pancreatic tissue and blood were collected for analysis. AR42 J pancreatic acinar cells were treated with increasing concentrations of PEG35 prior to exposure with tumor necrosis factor α(TNFα), staurosporine or cerulein. The severity of AP wasdetermined on the basis of plasma levels of lipase, lactate dehydrogenase activity, pancreatic edema and histological changes. To evaluate the extent of the inflammatory response, the gene expression of inflammation-associated markers was determined in the pancreas and in AR42 J-treated cells. Inflammation-induced cell death was also measured in models of in vivo and in vitro pancreatic damage.RESULTS Administration of PEG35 significantly improved pancreatic damage through reduction on lipase levels and tissue edema in cerulein-induced AP rats. The increased associated inflammatory response caused by cerulein administration was attenuated by a decrease in the gene expression of inflammation-related cytokines and inducible nitric oxide synthase enzyme in the pancreas. In contrast, pancreatic tissue m RNA expression of interleukin 10 was markedly increased. PEG35 treatment also protected against inflammation-induced cell death by attenuating lactate dehydrogenase activity and modulating the pancreatic levels of apoptosis regulator protein BCL-2 in cerulein hyperstimulated rats. Furthermore, the activation of pro-inflammatory markers and inflammationinduced cell death in pancreatic acinar cells treated with TNFα, cerulein or staurosporine was significantly reduced by PEG35 treatment, in a dose-dependent manner.CONCLUSION PEG35 ameliorates pancreatic damage in cerulein-induced AP and AR42 J-treated cells through the attenuation of the inflammatory response and associated cell death. PEG35 may be a valuable option in the management of AP.