基于可行方向法的脂肪组织本构模型参数反求优化

目的研究脂肪组织在中等应变率下本构模型及其参数反求。方法基于脂肪组织力学性能实验,通过有限元方法重构脂肪组织压缩实验,并对常见表征脂肪组织的本构模型进行参数筛选。结合最优化方法中的可行方向法(method of feasible direction,MFD),进行中应变率下脂肪组织本构模型相关参数的反求。结果中应变率(260 s~(-1))下黏弹性本构模型相比Ogden本构模型更适合表征脂肪组织的力学响应,并反求得到适用于仿真的本构模型参数。结论中等应变率下黏弹性本构模型更适合表征脂肪组织力学响应。研究结果为汽车碰撞有限元仿真中探究人体脂肪组织对人体损伤的影响提供参考。     

Human facial dysostoses

The human facial dysostoses can be subdivided into mandibulofacial dysostoses (MFDs) and acrofacial dysostoses (AFDs). The craniofacial phenotypes of the two groups of patients are similar. Both types are thought to be related to abnormal migration of neural crest cells to the pharyngeal arches and the face. The craniofacial anomalies shared by the two groups consist of downslanting palpebral fissures, coloboma of the lower eyelid, from which the eyelashes medial to the defect may be absent, hypoplasia of the zygomatic complex, micrognathia, and microtia, which is often associated with hearing loss. These facial deformities are associated with limb anomalies in the AFDs. All MFDs present with the typical craniofacial phenotype, but some have additional features that help to distinguish them clinically: intellectual disability, microcephaly, chest deformity, ptosis, cleft lip/palate, macroblepharon, or blepharophimosis. The limb anomalies in the AFDs can be classified into pre‐axial, post‐axial, and others not fitting into the first two AFD types. Of the pre‐axial types, Nager syndrome and of the post‐axial types, Miller syndrome are the best‐known disorders of their AFD subgroups. Several other AFDs with unknown molecular genetic bases, including lethal ones, have been described. This article reviews the MFDs and AFDs published to date.     

Outcomes of Patients with Hepatocellular Carcinoma Treated with Conventional Transarterial Chemoembolization Using Guidance Software

Purpose

To evaluate the outcomes of conventional transarterial chemoembolization using guidance software for hepatocellular carcinoma (HCC) patients.

Nrf2/ARE is the potential pathway to protect Sprague–Dawley rats against oxidative stress induced by quinocetone

3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide (Quinocetone, QCT) is a newly used veterinary drug which has been proven to promote feed efficiency and growth of animals; however, its potential toxicity can’t be ignored. Therefore, the present study was aimed to investigate the nephrotoxicity of QCT and the oxidative stress induced by it. Sprague–Dawley rats (SD rats) were randomly divided into four groups with doses of 2400, 800, 50 and 0 mg/kg/day with administration of QCT for 4 weeks. Results proved that QCT could induce nephrotoxicity and this phenomenon had dose dependent manner. Simultaneously, this phenomenon was accompanied by intracellular reactive oxygen species (ROS) accumulation, enhanced lipid peroxidation and inhibited antioxidant system, i.e. glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GSH). Additionally, the higher expression of Nrf2 in QCT treated groups illustrated that QCT-induced oxidative stress would be partly mitigated by the induction of phase II detoxifying enzymes via increasing Nrf2 expression.     

Indole-3-carbinol (I3C) exhibits inhibitory and preventive effects on prostate tumors in mice.

Prostate cancer (PC) is the most commonly diagnosed malignancy for men in Western countries. Research showed that cruciferous vegetables containing indole derivatives were involved in cancer prevention. This study was designed to investigate the effect of indole-3-carbinol (I3C) in cell lines and on PC tumor growth in mice when given as a therapeutic and as a preventive treatment. The effect in vitro of 13C on the viability, proliferation and apoptosis of mouse PC cell line TRAMP-C2 and on bovine capillary endothelial (BCE) cells was examined using MTT, BrdU and FACS analyses. The effect of I3C (20 mg/kg body weight) as both a therapeutic and a preventive treatment on the growth of PC cells, inoculated subcutaneously in C57BL/6 mice, was evaluated using tumor volume measurements and immunohistochemistry. I3C decreased the proliferation rate in 3-folds (staining to Ki-67), and promoted apoptosis (staining with caspase 3). I3C, injected intraperitonially (I.P.), significantly inhibited the tumor growth (a 78% decrease in tumor volume) and affected the angiogenesis process by decreasing the microvessel density (CD31 endothelial marker) and complexity. I3C has a significant inhibitory effect on PC cells in vitro and in vivo, and offers a potential usage as both preventive and therapeutic agent for humans.     

Under the mask of Kabuki syndrome: Elucidation of genetic-and phenotypic heterogeneity in patients with Kabuki-like phenotype

Kabuki syndrome is mainly caused by dominant de-novo pathogenic variants in the KMT2D and KDM6A genes. The clinical features of this syndrome are highly variable, making the diagnosis of Kabuki-like phenotypes difficult, even for experienced clinical geneticists. Herein we present molecular genetic findings of causal genetic variation using array comparative genome hybridization and a Mendeliome analysis, utilizing targeted exome analysis focusing on regions harboring rare disease-causing variants in Kabuki-like patients which remained KMT2D/KDM6A-negative. The aCGH analysis revealed a pathogenic CNV in the 14q11.2 region, while targeted exome sequencing revealed pathogenic variants in genes associated with intellectual disability (HUWE1, GRIN1), including a gene coding for mandibulofacial dysostosis with microcephaly (EFTUD2). Lower values of the MLL2-Kabuki phenotypic score are indicative of Kabuki-like phenotype (rather than true Kabuki syndrome), where aCGH and Mendeliome analyses have high diagnostic yield. Based on our findings we conclude that for new patients with Kabuki-like phenotypes it is possible to choose a specific molecular testing approach that has the highest detection rate for a given MLL2-Kabuki score, thus fostering more precise patient diagnosis and improved management in these genetically- and phenotypically heterogeneous clinical entities.     

Significant Drying Time Reduction Using Microwave-Assisted Freeze-Drying for a Monoclonal Antibody

Microwave-assisted freeze-drying (MFD) is a rapid drying process well known in food technology. However, little is known about its application to biologicals. In this study, we investigated the applicability and feasibility of this technology to different monoclonal antibody formulations and the influence on the resulting product properties. Moreover, one of our main objectives was to study if significant reductions in drying times could be achieved. In addition, the effect of the drying process on the accelerated stability of a sucrose-based antibody formulation at 40°C and 25°C over 12 weeks was investigated. MFD resulted in drying time reduction >75%. For all model formulations, cake appearance and solid state properties were found to be comparable to standard lyophilized products. These formulations covered a wider range of lyophilization excipients comprising sucrose and trehalose, semi-crystalline forming solids like mannitol:sucrose mixtures and others like arginine phosphate and a mixture of 2-hydroxypropyl-β-cyclodextrin with sucrose. Moreover, comparable low changes in relative monomer content, the relative amount of soluble aggregates and cumulative particles ≥1 μm per mL were observed over 12 weeks of storage, regardless of the drying technology. This makes MFD a promising innovative alternative for the rapid production of freeze-dried biologicals while maintaining product quality.     

Nanosecond pulsed electric field (nsPEF) treatment for hepatocellular carcinoma: A novel locoregional ablation decreasing lung metastasis

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy. Nanosecond pulsed electric field (nsPEF) is a new technology destroying tumor cells with a non-thermal high voltage electric field using ultra-short pulses. The study’s aim was to evaluate the ablation efficacy of nsPEFs with human HCC cell lines and a highly metastatic potential HCC xenograft model on BALB/c nude mice. The in vivo study showed nsPEFs induced HCC cell death in a dose dependent manner. On the high metastatic hepatocellular carcinoma cell line (HCCLM3) xenograft mice model, tumor growth was inhibited significantly in nsPEF-treated- groups (single dose and multi-fractionated dose). Besides a local effect, the nsPEF treatment reduced pulmonary metastases. The nsPEFs also enhanced HCC cell phagocytosis by human macrophage cell (THP1) in vitro. The nsPEF is efficient in controlling HCC progression and reducing its metastasis. NsPEF treatment may elicit a host immune response against tumor cells. This study suggests nsPEF therapy could be used as a potential locoregional therapy for hepatocellular carcinoma.