In vivo epigenetic effects induced by engineered nanomaterials: A case study of copper oxide and laser printer-emitted engineered nanoparticles

Evidence continues to grow on potential environmental health hazards associated with engineered nanomaterials (ENMs). While the geno- and cytotoxic effects of ENMs have been investigated, their potential to target the epigenome remains largely unknown. The aim of this study is two-fold: 1) determining whether or not industry relevant ENMs can affect the epigenome in vivo and 2) validating a recently developed in vitro epigenetic screening platform for inhaled ENMs. Laser printer-emitted engineered nanoparticles (PEPs) released from nano-enabled toners during consumer use and copper oxide (CuO) were chosen since these particles induced significant epigenetic changes in a recent in vitro companion study. In this study, the epigenetic alterations in lung tissue, alveolar macrophages and peripheral blood from intratracheally instilled mice were evaluated. The methylation of global DNA and transposable elements (TEs), the expression of the DNA methylation machinery and TEs, in addition to general toxicological effects in the lung were assessed. CuO exhibited higher cell-damaging potential to the lung, while PEPs showed a greater ability to target the epigenome. Alterations in the methylation status of global DNA and TEs, and expression of TEs and DNA machinery in mouse lung were observed after exposure to CuO and PEPs. Additionally, epigenetic changes were detected in the peripheral blood after PEPs exposure. Altogether, CuO and PEPs can induce epigenetic alterations in a mouse experimental model, which in turn confirms that the recently developed in vitro epigenetic platform using macrophage and epithelial cell lines can be successfully utilized in the epigenetic screening of ENMs.     

Gender differences in pharmacokinetics and tissue distribution of 3 perfluoroalkyl and polyfluoroalkyl substances in rats

The aim of this study was to confirm and investigate the gender differences in pharmacokinetic (PK) characteristics and tissue distribution of 3 perfluoroalkyl and polyfluoroalkyl substances (PFASs) consisted of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) in both male and female rats. For this study, a simultaneous determination method of the 3 PFASs in rat plasma and tissues was developed and validated using a UPLC-MS/MS system. The PK parameters after a single oral or intravenous administration of the 3 PFASs in both rats were calculated using WinNonlin^® software. The mean half-life of the 3 PFASs in female and male rats was in the range of 0.15–0.19 and 1.6–1.8 days for PFOA, 23.5–24.8 and 26.4–28.7 days for PFOS, and 0.9–1.7 and 20.7–26.9 days for PFHxS, respectively. The 3 PFASs were highly distributed in the liver and kidney. These results suggest that there are gender differences in the PKs for PFOA and PFHxS in rats, whereas the PFOS represented no significant gender differences except the Kp value of liver. The validated simultaneous determination method of the 3 PFASs was also within the accepted criteria of the international guidance.     

Restoration of functional network state towards more physiological condition as the correlate of clinical effects of pallidal deep brain stimulation in dystonia

BackgroundDeep brain stimulation of the internal globus pallidus (GPi DBS) is an invasive therapeutic modality intended to retune abnormal central nervous system patterns and relieve the patient of dystonic or other motor symptoms.ObjectivesThe aim of the presented research was to determine the neuroanatomical signature of GPi DBS modulation and its association with the clinical outcome.MethodsThis open-label fixed-order study with cross-sectional validation against healthy controls analysed the resting-state functional MRI activity changes induced by GPi DBS in 18 dystonia patients of heterogeneous aetiology, focusing on both global (full brain) and local connectivity (local signal homogeneity).ResultsCompared to the switched-off state, the activation of GPi DBS led to the restoration of global subcortical connectivity patterns (in both putamina, diencephalon and brainstem) towards those of healthy controls, with positive direct correlation over large-scale cortico-basal ganglia-thalamo-cortical and cerebellar networks with the clinical improvement. Nonetheless, on average, GPi DBS also seemed to bring local connectivity both in the cortical and subcortical regions farther away from the state detected in healthy controls. Interestingly, its correlation with clinical outcome showed that in better DBS responders, local connectivity defied this effect and approached healthy controls.ConclusionsAll in all, the extent of restoration of both these main metrics of interest towards the levels found in healthy controls clearly correlated with the clinical improvement, indicating that the restoration of network state towards more physiological condition may be a precondition for successful GPi DBS outcome in dystonia.     

Use of Autologous Costal Cartilage Combined with Expanded Polytetrafluoroethylene in Asian Rhinoplasty

BackgroundThe corresponding author's experience and recent methods employed in autologous costal cartilage grafts combined with expanded polytetrafluoroethylene (ePTFE) in Asian rhinoplasty were presented in this study.ObjectivesThe purpose of this study was to assess the outcomes of rhinoplasty performed on patients using autogenous costal cartilage grafts combined with an ePTFE implant.MethodsSeventy-five rhinoplasty cases with autologous costal cartilage grafts and an ePTFE implant were retrospectively reviewed. Graft types, complications associated with the graft itself or graft harvesting, surgical outcomes, and patient satisfaction were assessed.ResultsThe mean follow-up time post-operation was 13.5 months. A total of 42/75 patients underwent revision surgeries. Graft-related complications were found in 8% of cases, including two warped graft and four infection cases. Three individuals with infections had mild graft resorption. One patient with an infection removed the implant. Graft exposure, mobility, and substantial resorption were not recorded. A total of two cases underwent revision procedures for infection and perforation, respectively. Chest incision lengths for graft harvesting averaged 2.1 cm. No pneumothorax or significant donor-site pain was found. Donor-site scars were negligible, although two cases had hypertrophic chest scars. In general, functional and esthetic outcomes were mostly satisfactory among the assessed patients.ConclusionsRhinoplasty using autologous rib cartilage provides adequate support and sufficient cartilage amounts for correcting nasal contouring. Meanwhile, ePTFE alone for nasal dorsum augmentation safely achieves satisfactory outcomes. Rib cartilage rhinoplasty performed by an experienced surgeon yields excellent, long-lasting results with minimal risk; however, the potential for infection should be considered following revision surgery.     

Optimization of immunohistochemical detection of collagen type II in osteochondral sections by comparing decalcification and antigen retrieval agent combinations

Bone containing tissues such as osteochondral joint are resistant to routine tissue processing, therefore require decalcification. This technique causes removal of mineral salts, but in the process may macerate the organic tissue, hence the need for tissue fixation. Such severe processing demands careful antigen retrieval to necessitate optimal staining. The aim of our study was to compare five different antigen retrieval protocols (heat retrieval and protein digestion) following decalcification of rabbit knee joints using two different techniques (20% formic acid and 10% ethylenediamine-tetra acetic acid: EDTA). Osteochondral sections were compared based on time required for decalcification, ease of sectioning, morphological integrity using HE staining and antigen preservation (Collagen type II) using immunohistochemistry. The two decalcification solutions did not impair the tissue morphology and ease of sectioning. Joints processed with formic acid decalcified four times faster than EDTA. Among the five antigen retrieval approaches, maximal collagen II uptake with minimal nonspecific staining was found with protein digestion (pronase and hyaluronidase) in both formic acid and EDTA sections. For osteo-chondral sections, we recommend using 10% EDTA for decalcification and pronase plus hyaluronidase for antigen retrieval if maintaining tissue morphology is crucial, whereas if time is of the essence, 20% FA with pronase plus hyaluronidase is the faster option while still preserving structural integrity. Clin. Anat. 33:343–349, 2020. © 2019 Wiley Periodicals, Inc.     

Serum matrix metallopeptidase-9 and tissue inhibitor of metalloproteinase-1 levels in autoimmune encephalitis

ObjectiveSome pediatric patients with autoimmune encephalitis (AE) experience sequelae in spite of immunotherapy. In this study, we aimed to evaluate the association of serum matrix metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels with the neurological prognosis of AE.MethodsWe retrospectively included 13 patients with AE who had been referred to Saitama Children’s Medical Center from February 2011 to May 2019. We compared serum MMP-9 levels, TIMP-1 levels, and MMP-9/TIMP-1 ratio in the acute period (within 30 days from the onset of AE) and subacute period (30-day period following the acute period). We also compared these biomarker levels between patients with (group A) and without sequelae (group B). Sequelae were evaluated at discharge or the last visit.ResultsGroup A (median age, 7.8 years; range, 5.3–10.7 years) and group B (median age, 13.3 years; range, 11.1–15.4 years) had 6 patients each; 1 patient was excluded because the time of AE onset was unknown. In the acute period, there were no significant differences in MMP-9 levels, TIMP-1 levels, and MMP-9/TIMP-1 ratio between groups A and B. In the subacute period, serum MMP-9/TIMP-1 ratio was higher in group A than in group B (p < 0.01). There were no significant differences in MMP-9 and TIMP-1 levels between groups A and B.ConclusionsPatients with sequelae of AE showed a high MMP-9/TIMP-1 ratio in the subacute period. Our study demonstrates that elevation of serum MMP-9/TIMP-1 ratio in the subacute period may be a predictive factor of sequelae of AE.     

髌股关节骨性关节炎严重程度不影响保留髌骨全膝关节置换患者的预后

文题释义： 髌骨适合角：自股骨内外髁最高点分别向股骨髁间沟的最低点画2条直线，这2条线的夹角即为沟角，其角平分线和其顶点与髌骨下级之间的连线形成的夹角为适合角。 髌韧带比值：屈膝30°侧位像上使用Insall-Salvati指数评价髌骨的高度，测量髌腱长度即自髌骨下级至胫骨结节定点上缘，再测量髌骨最长对角线的长度，两者之间比为髌韧带比值。 背景：目前关于全膝关节置换过程中髌骨是否置换尚没有统一标准，对于髌骨置换和不置换的对照研究很多，但是在全膝关节置换不置换髌骨的研究中根据髌股关节炎严重程度分级来比较预后的研究很少。 目的：根据髌股关节炎的严重程度进行分级，比较髌股关节炎的轻重对保留髌骨的全膝关节置换疗效的影响。 方法：回顾性分析2016年1月至2017年1月郑州大学第一附属医院使用强生假体行髌骨保留的全膝关节置换患者192例的临床资料，随访时间大于2年。根据髌股关节炎影像学严重程度Lwano分类系统将患者分为2组，轻度组(0-Ⅰ期)83例，重度组(Ⅱ-Ⅳ期)109例。所有患者对治疗及试验方案均知情同意，且得到医院伦理委员会批准。使用美国膝关节协会评分、功能评分、Feller评分、膝前疼痛评分评估临床预后，使用髌骨倾斜角、适合角、髌骨外移距离、髌韧带比值评估影像学预后。运用t检验，分析患者术前、术后的临床和影像学结果。 结果与结论：①术后1例患者出现持续性膝前疼痛，1例患者伤口渗液，清创后二期愈合，其余均一期愈合；②术前轻度组和重度组患者的功能评分和美国膝关节协会评分差异有显著性意义(P < 0.05)，但术后2组功能评分和美国膝关节协会评分差异均无显著性意义(P > 0.05)；③影像学上，2组术前髌骨倾斜角、适合角、髌骨外移距离差异有显著性意义(P < 0.05)，但术后2组髌骨倾斜角、适合角、髌骨外移距离差异均无显著性意义(P > 0.05)；④提示在对保留髌骨的全膝关节置换患者进行至少2年的随访后发现，髌股关节炎的严重程度对患者的临床和影像学预后没有影响；即使在重度髌股关节炎患者中，保留髌骨的全膝关节置换后也能获得良好的预后。 ORCID: 0000-0002-2784-1542(徐长波) 中国组织工程研究杂志出版内容重点：人工关节；骨植入物；脊柱；骨折；内固定；数字化骨科；组织工程     

白癜风的移植治疗进展

白癜风(vitiligo)是一种常见的色素脱失性皮肤病,其发病可能与遗传、免疫、氧化应激等因素有关。当前白癜风的治疗主要有物理、药物及外科移植治疗等。其中,外科移植治疗适用于其他治疗方法无效的稳定期白癜风患者,其具有复色时间短、疗效肯定等优点。白癜风的外科移植治疗包括两大类:组织移植和细胞移植。组织移植一般适用于较小面积以及特殊部位的皮损,而细胞移植适用于大面积部位的皮损,优势明显。本文针对当前白癜风的移植治疗方面取得的新进展进行综述。