Current Status of Global Ban on Cosmetic Tests on Animals

The article reviewed the cosmetic animal testing ban globally, with focusing on EU, United Kingdom, Korea, the United States, Russia, Australia, Canada and others total 15 regions and countries. The article also briefed the developments of the alternatives of animal testing in the world, and the cosmetic animal testing regulation in China as well. The article suggested China to adopt the alternatives which have been validated based on the development of technology, gradually ban animal testing for cosmetics.

Development of Alternative to Animal Testing on Cosmetics by Middle-out Strategy

The discussion on cosmetic animal testing ban started since 1990s, with the fnally implementation of full animal testing ban in both research and marketing in EU and Israel in 2013. Now it has been fully or partially banned by law in 33 countries or regions, with more and more countries lining up to do the same. Beyond animal welfare consideration, the need of mutual acceptance of data （MAD） and harmonization of global market have made non-animal testing an irresistible general trend for worldwide countries to made regulation and policy. Recently, China is in critical crossroad to shift the toxicity paradigm and explore a proper strategy to promote the development of cosmetic non-animal testing. 3R theory has been frstly introduced in Chinese legislation in 2006 that is an important step forward to seriously thinking of animal test. In the following 10 years, the alternative technology in China has been developed dramatically with the implementation of relevant legislations, holding various theoretical and hands-on training, exploration work on methods validation, adoption of internationally recognized methods, propagation of alternative standards and in-depth investigation in in vitro bioscience. The ultimate goal of alternative technology is the regulatory application, thus demands infrastructure constructing, technology capability building and national standard forming. However, concrete works should be carefully planned to facilitate the technology transformation and standardization. This paper will give a retrospective review on the progress in recent years and put forward a middle-out strategy to promote the development of cosmetics alternative in China.

Prophylactic Bactericidal Orthopedic Implants – Animal Testing Study

This paper summarizes preliminary rat studies aimed at identifying the effectiveness of using electrically stimulated silver as a bactericidal agent for indwelling residual hardware devices (RHD). A variety of bactericidal indwelling devices were designed, fabricated and surgically inserted into the medullary cavity of live rats. The rats were inoculated with Staphylococcus aureus to try and induce osteomyelitis. A total of 37 surgeries were performed by implanting the rats with both control and potentially bactericidal devices. As surgical procedures and devices were improved, it appeared that the implants produced antibiotic effects in the animals. All of the control animals and all of the animals where the device failed tested positive for Staphylococcus aureus growth. Of the rats with operational bactericidal devices (those that survived the surgery and incubation period), half tested negative for Staphylococcus aureus. The device designs are discussed in this paper along with the test procedures, operating practices and results. A statistical analysis of the results, which shows a very high confidence level in the effectiveness of electrically stimulated silver as a bactericidal agent/antibiotic, is also presented.

ChinaRegulatory Updates of Animal Testing in China and Other Courtries

YeAnimal testing for the sake of cosmetic safety has always been a very controversial topic since it’s often viewed as cruel due to its harm,or outright death,of the animals subjected to them.In the early years,animal testing was adopted to assess product safety and allergenicity during the R&D of cosmetics and daily chemical products.Since then,we have seen significant technological advancements to the extent that people argue that animal tests have become largely redundant.As a response,cruelty-free advocates have made huge headway in lobbying governments to ban animal testing.In this report,I will look at those major advancements in the global push towards a global ban on animal testing.

神经行为学实验Narrow-Alley Test及Corner Test改良:Narrow-Alley Corner Test

目的改良传统的Narrow-alley Test及Corner Test,增强实验的可操作性和结果的可靠性。方法用Narrow-alley Test、Corner Test及改良后的Narrow-alley Corner Test检测三组SD大鼠:脑出血+GCSF治疗组;脑出血+生理盐水安慰治疗组;正常对照组。结果(1)与Narrow-alley Test及Corner Test结果一致,正常大鼠在Narrow-alleyCorner Test实验装置中向左、向右"站立转身"的几率接近,而脑损伤大鼠则趋向沿损伤同侧作"站立转身"。(2)Narrow-alley Corner Test不须反复刺激大鼠,减少了人在实验现场对动物活动的影响,增强了实验的可操作性和结果的可信度。结论Narrow-alley Corner Test是一种可操作性强、结果可靠的神经行为学检测方法。

Role of the^(13)C-methacetin breath test in the assessment of acute liver injury in a rat model

AIM: To evaluate the role of the 13C-methacetin breath test(13C-MBT) in the assessment of acute liver injury in a rat model.METHODS: Acute liver injury in rats was induced by a single intraperitoneal injection of D-galactosamine(D-GalN). Forty-eight male Sprague-Dawley rats were randomly assigned to a control group(n = 8) and five model groups(each n = 8), and acute liver injury was assessed at different time points(6, 12, 24, 48 and 72 h) after D-GalN injection. The 13C-MBT, biochemical tests, 15-min retention rate of indocyanine green(ICGR15), and liver biopsy were performed and compared between the control and model groups. Correlations between parameters of the 13C-MBT(Tmax, MVmax, CUM120 and DOBmax), biochemical tests, ICGR15 and liver necrosis score were also analyzed using Spearman'scorrelation analysis.RESULTS: Tmax, MVmax, CUM120 and DOBmax, as well as most of the traditional methods, correlated with the liver necrosis score(r = 0.493, P < 0.05; r =-0.731, P < 0.01; r =-0.618, P < 0.01; r =-0.592, P < 0.01, respectively). MVmax, CUM120 and DOBmax rapidly decreased and were lower than those in the controls as early as 6 h after D-GalN injection(3.84 ± 0.84 vs 5.06 ± 0.78, P < 0.01; 3.35 ± 0.72 vs 4.21 ± 1.44, P < 0.05; 52.3 ± 20.58 vs 75.1 ± 9.57, P < 0.05, respectively) and reached the lowest point 24 h after D-GalN injection. MVmax, CUM120 and DOBmax returned to normal levels 72 h after D-GalN injection and preceded most of the traditional methods, including liver biopsy.CONCLUSION: The 13C-MBT is a sensitive tool for the timely detection of acute liver injury and early prediction of recovery in a rat model. Further clinical studies are warranted to validate its role in patients with acute liver injury.

The Effects of Task Order Administration on Test Scores from the Trail Making Test: Near-Infrared Spectroscopy Investigations

This research examines the effects of task administration on Trail Making Test performance. The TMT consists of two parts, TMT Part A and TMT Part B. Generally, it has been believed that the order the two parts are completed does not influence test results;however, there is one previous study that has suggested that the order is indeed an influential factor on test scores. To measure frontal lobe function, the present study used near-infrared spectroscopy to measure changes in oxygenated hemoglobin (oxy-Hb) in 48 young, healthy Japanese subjects as they completed Parts A and B. We subtracted the change in oxy-Hb while completing Part A from that while completing Part B (B-A Oxy-Hb) for a comparison to facilitate an investigation of how, or if, the order in which the TMT is taken influences test success. We found that when Part A was completed first, there were only small changes in the B-A oxy-Hb, but when Part B was completed first, there were larger changes. This study indicates that the order the tests are completed in may influence outcomes, thus assessments using the TMT must follow a consistent task order.

Corrigendum to“Point-of-care testing for lysine concentration in swine serum via blue-emissive carbon dots entrapped microfluidic chip”[Animal Nutrition 12(2023)236e244]

Section 2.1:Animal ethics approval number:HZAUSW-2002e0009 Change to:HZAUSW-2022e0011 Section 2.6:…200 mL solution of N-CDs(0.1 mg/mL)…Change to:…200 mL solution of N-CDs(1.5 mg/mL)…Section 3.1:…with the size ranging from 4 to 8 nm…Change to:…with the size ranging from 2 to 7 nm…

Recent advances in anxiety disorders:Focus on animal models and pathological mechanisms

Anxiety disorders have become one of the most severe psychiatric disorders,and the incidence is increasing every year.They impose an extraordinary personal and socioeconomic burden.Anxiety disorders are influenced by multiple complex and interacting genetic,psychological,social,and environmental factors,which contribute to disruption or imbalance in homeostasis and eventually cause pathologic anxiety.The selection of a suitable animal model is important for the exploration of disease etiology and pathophysiology,and the development of new drugs.Therefore,a more comprehensive understanding of the advantages and limitations of existing animal models of anxiety disorders is helpful to further study the underlying pathological mechanisms of the disease.This review summarizes animal models and the pathogenesis of anxiety disorders,and discusses the current research status to provide insights for further study of anxiety disorders.

Correlative CD4 and CD8 T-cell immunodominance in humans and mice:Implications for preclinical testing

Antigen-specific T-cell recognition is restricted by Major Histocompatibility Complex(MHC)molecules,and differences between CD4 and CD8 immunogenicity in humans and animal species used in preclinical vaccine testing are yet to be fully understood.In this study,we addressed this matter by analyzing experimentally identified epitopes based on published data curated in the Immune Epitopes DataBase(IEDB)database.We first analyzed SARS-CoV-2 spike(S)and nucleoprotein(N),which are two common targets of the immune response and well studied in both human and mouse systems.We observed a weak but statistically significant correlation between human and H-2^(b)mouse T-cell responses(CD8 S specific(r=0.206,p=1.37×10^(−13));CD4 S specific(r=0.118,p=2.63×10^(−5))and N specific(r=0.179,p=2.55×10^(−4))).Due to intrinsic differences in MHC molecules across species,we also investigated the association between the immunodominance of common Human Leukocyte Antigen(HLA)alleles for which HLA transgenic mice are available,namely,A*02:01,B*07:02,DRB1*01:01,and DRB1*04:01,and found higher significant correlations for both CD8 and CD4(maximum r=0.702,p=1.36×10^(−31)and r=0.594,p=3.04−122,respectively).Our results further indicated that some regions are commonly immunogenic between humans and mice(either H-2^(b)or HLA transgenic)but that others are human specific.Finally,we noted a significant correlation between CD8 and CD4 S-(r=0.258,p=7.33×10^(21))and N-specific(r=0.369,p=2.43×10^(14))responses,suggesting that discrete protein subregions can be simultaneously recognized by T cells.These findings were confirmed in other viral systems,providing general guidance for the use of murine models to test T-cell immunogenicity of viral antigens destined for human use.

完善实验动物废物处置质量管理体系的思考:以中国食品药品检定研究院为例

科技发展是推动人类社会前进的巨大动力,而实验动物资源是生命科学、医药等领域科技发展的条件保障。但在开展医药研发、检验检测等实验过程中,使用实验动物产生的废物也为城市管理带来了新的考验。废物的分类、回收、有效利用和生物安全危害等问题接踵而至,对法规、标准、规范等的制定提出了与时俱进的要求。质量管理体系建设是检验检测机构管理的地基和框架,具备较强的操作性和检查性,可以不断提升管理水平,加强基础管理的稳定性。随着各层级新的管理办法出台,很多单位现行的质量管理体系内关于实验动物废物管理的相关内容欠妥,存在未明确非医疗机构实验动物废物处置流程、实验动物废物分类不准确、不同分类的废物未能按照不同方式处置等问题。本文针对目前存在的问题,梳理了中国食品药品检定研究院质量管理体系需要增加或者删改的流程,并制订了现行有效的标准作业流程,在如何加强监督管理方面提出了切实可行的措施,并开创性地把6S管理内容纳入质量管理体系中。因此,针对实验动物废物的管理应从完善质量管理体系的角度出发,从源头做好废物分类和管理,有效控制生物危害,最大限度地减少环境污染,为可持续发展创造条件。

Cognitive function among military veterans with STEM occupations

Dear Editor,There is limited research on the relationship between science,technology,engineering,and mathematics(STEM)occupational history and cognitive function in later life,especially among military veterans,who may be at greater risk for later-life cognitive decline.This study examines a nationally representative sample of military veterans to address this gap in knowledge.

2013-2021年实验动物质量检测能力验证情况

目的分析我国实验动物质量检测能力现状,探讨实验动物质量检测能力验证组织实施现状,研究影响能力验证满意率的关键因素。方法通过Excel2010和Powerpoint2010软件进行实验室数量、项次、满意率以及频次的变化分析。结果2013—2021年共实施27个能力验证计划,包括22种检测能力参数,发放92种生物样本。共有70家实验室参加552个项次,整体满意率达到90.22%。结论持续参加能力验证活动可以提升实验室的检测能力。

新型鹅细小病毒徐州分离株NGPV XZ-01的分离和致病性研究

为了研究2021年6月江苏徐州某商品半番鸭养殖场所发疾病的病原及其致病性,从该养殖场发病的半番鸭群中无菌采集肝脏、脾脏、肠道等临床样品,采用PCR方法对病原进行鉴定,将所采集样本处理后接种至非免疫鸭胚中,连续多次传代后,对鸭胚组织及尿囊液进行病理学、电镜检查及动物试验。结果显示:PCR检测结果鉴定为新型鹅细小病毒阳性;鸭胚尿囊液在电镜下观察到细小病毒粒子,胚体病理切片观察显示符合细小病毒所致病变;动物试验显示,攻毒试验鸭主要表现为生长发育明显受阻,大部分试验鸭成为“僵鸭”,于20日龄后陆续出现上下喙变短、舌头外露等症状,剖检病变主要为肠内容物稀薄及泄殖腔膨大,肠道组织切片观察显示肠绒毛上皮细胞坏死、脱落及部分肠腺坏死,符合鸭短喙侏儒综合征(short beak and dwarfism syndrome,SBDS)所致雏鸭的症状与病变。结果表明:该肉鸭养殖场所发疾病为SBDS,将该场分离的病毒命名为新型鹅细小病毒徐州分离株(NGPV XZ-01株)。

建立我国自主知识产权的致癌性小鼠模型

致癌性试验是药物非临床安全性评价的重要内容之一。当前国内外普遍采用并认可基于ICH S1B指南建立的药物非临床致癌性试验替代方案。遗传修饰致癌性小鼠模型是替代方案中“卡脖子”的关键技术问题。从1997年ICH S1B指南发布至今,我国制药行业主要依赖进口获得小鼠模型,其价格高昂、进口周期长、条件严苛,且由于模型资源唯一,制药行业承受着成本高昂和供应链不稳的双重压力。本文概述了国内外致癌性试验相关指导原则,介绍了国内外主要的致癌性小鼠模型,包括Tg.rasH2、KI.C57-ras、p53^(+/-)小鼠等的构建、验证与应用历程,并展望了建立我国自主知识产权的致癌性小鼠模型以及标准化生产供应的途径。

头颈部恶性肿瘤研究模型的演化

恶性肿瘤发生发展的机制探索以及抗癌药物治疗疗效的评估均有赖于各种体内与体外研究模型的建立。近几十年间,随着生物医学技术的快速发展,恶性肿瘤的体内外研究模型也发生了巨大的变化。基因检测技术从单基因到多基因的进展促进了生物信息学飞速发展和恶性肿瘤概念的转变;体外细胞研究模型从单层的二维培养、原代培养向立体的三维构型发展,从而更好地重现肿瘤组织的细胞间交互作用与功能;体内动物研究模型由传统的致癌物诱导、细胞或组织形成移植瘤逐渐演变为基因编辑的动物模型或人源性肿瘤异种移植模型,从而可以针对性地研究相关基因在肿瘤发生发展中的作用;传统的临床研究也从简单的临床回顾性研究更多地向前瞻性研究转变,Ⅰ期/Ⅱ期/Ⅲ期临床研究,研究者发起的临床研究以及真实世界临床研究,这些研究为临床研究增添了活力。目前恶性肿瘤研究模型存在的主要不足包括模型的单一性、对肿瘤微环境的模拟不足、动物肿瘤模型与人类肿瘤差异性,以及缺乏对个性化医疗的考量。未来仍需要进一步研发和优化研究模型,并更有效地将不同模型整合起来,形成一个优化的整体实验模型系统。本文将系统回顾恶性肿瘤研究模型的演化并对相关模型进行阐述,为科研工作者进行恶性肿瘤的研究提供合理的研究模型。

Animal experiment and clinical study of effect of gamma-interferon on hepatic fibrosis

AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-gamma groups, and 10.01 +/- 3.23 in fibrotic model group. The difference was statistically significant (P【0.01). Similar results were found in DMN-induced model. Pathological fibrosis scores were 6.30 +/- 0.48, 8.10 +/- 2.72 and 8.30 +/- 2.58, in high, medium and low doses IFN-gamma groups, and 12.60 +/- 3.57 in fibrotic model group. Hydroxyl proline contents were 2.72 +/- 0.58, 3.14 +/- 0.71 and 3.62 +/- 1.02, in the three IFN-gamma groups, and 12.79 +/- 1.54 in fibrotic model group. The difference was statistically significant (P【0.01).Serum hepatic fibrosis indices decreased significantly in the 47 patients after IFN-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 192.59 +/- 89.95 vs 156.98 +/- 49.22; C-I: 156.30 +/- 44.01 vs 139.14 +/- 34.47) and the differences between the four indices were significant (P 【0.05). Thirty-three patients received two liver biopsies, one before and one after IFN-gamma treatment. In thirty of 33 patients IFN-gamma had better effects according to semi-quantitative pathological scores (8.40 +/- 5.83 vs 5.30 +/- 4.05, P【0.05). CONCLUSION: All the three doses of IFN-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.

Biocompatibility of vascular stents manufactured using metal injection molding in animal experiments

This study aimed to evaluate the feasibility and safety of a novel stent manufactured by metal injection molding(MIM)in clinical practice through animal experiments.Vessel stents were prepared using powder injection molding technology to considerably improve material utilization.The influence of MIM carbon impurity variation on the mechanical properties and corrosion resistance of 316L stainless steel was studied.In vitro cytotoxicity and animal transplantation tests were also carried out to evaluate the safety of MIM stents.The results showed that the performance of 316L stainless steel was very sensitive to the carbon content.Carbon fluctuations should be precisely controlled during MIM.All MIM stents were successfully implanted into the aortas of the dogs,and the MIM 316L stents had no significant cytotoxicity.The novel intravascular stent manufactured using MIM can maintain a stable form and structure with fast endothelialization of the luminal surface of the stent and ensure long-term patency in an animal model.The novel intravascular stent manufactured using MIM demonstrates favorable structural,physical,and chemical stability,as well as biocompatibility,offering promising application in clinical practice.

福建某三甲医院健康人群熟悉气味调查研究

目的调查福建某三甲医院健康人群熟悉气味。方法选取2022年6—8月自愿在泉州市第一医院耳鼻咽喉头颈外科门诊进行嗅觉调查的健康成年人,给予16种气味剂进行气味鉴定试验并完成《泉州市第一医院嗅觉问卷调查表》,通过统计学方法,寻找出健康人群最熟悉的8种气味。共有200名受试者被纳入调查,《泉州市第一医院嗅觉问卷调查表》由一系列多项选择问题组成,用于选择气味及气味的强度,满分为48分。结果根据测试的结果,本次研究得出:大蒜、咖啡、茉莉、薄荷、哈密瓜、香蕉、百香果、茴香和葡萄(并列第8位)是就诊泉州市第一医院耳鼻咽喉头颈外科的健康人群最熟悉的气味。该受试人群对16种气味剂型的嗅觉正常值是(34.22±5.45)分,第10百分位嗅觉正常值为41.0分。结论快速嗅觉筛查试验适合在中国其他地区推广并建立局部气味测试试验。可通过日后全国大规模的人群筛查,确定各地区的熟悉气味及嗅觉正常值,建立各地区人群的嗅觉诊断定性定量标准,将临床上嗅觉障碍的诊断客观化、标准化。