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    General Anesthetics Commonly Used for Laboratory Animals
    Xiao LU, Lingzhi YU, Sonja Tsung-Ying CHOU, Ruying LI, Wenjun CHEN, Shanxiang JIANG
    Laboratory Animal and Comparative Medicine    2022, 42 (1): 18-26.   DOI: 10.12300/j.issn.1674-5817.2022.011
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    General anesthetics used for laboratory animals are mostly controlled drugs, and are subject to strict supervision by the competent government agency in China. Many general anesthetics recommended in the literature are either unavailable or difficult to procure/access in the market, resulting in limited options for clinical use. Furthermore, not all laboratory veterinarians have practical experience in species-specific anesthetic selection and use. Owing to these factors, general anesthesia presents a common institutional challenge in animal surgical programs and serves as a bottleneck that restricts the sustainable development of biomedical industries working with laboratory animal species. This article summarizes the pharmacological properties of common general anesthetics and provides suggestions for general anesthesia in different laboratory animal species.

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    Progress in Pathogenesis and Immune Response of Enterovirus 71#br#
    SHI Meiyan, LU Caixia, DAI Jiejie
    Laboratory Animal and Comparative Medicine    2020, 40 (5): 449-.   DOI: 10.3969/j.issn.1674-5817.2020.05.015
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    Enterovirus 71 (EV71) mainly infects humans through the gastrointestinal or respiratory tracts, which is one of the main pathogens of hand, foot and mouth disease. It can also cause neurological diseases such as neurogenic pulmonary edema and even death, threatening the safety of infants and young children. Although the whole-virus inactivated vaccine of EV71 has been marketed, the pathogenesis and immune response of complications caused by its infection have not been fully clarified. This article reviews the pathogenesis, immune response and immunogenicity response of EV71, which will pave the way for further research on EV71. 

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    A Simple gRNA in vitro Screening Method
    CHENG Da-xin, XU Li-ran, YU Qing-qing, GAO Shou-cui, WANG Xiao-jing, LIU Yi, LIU En-qi, ZHAO Si-hai
    Laboratory Animal and Comparative Medicine    2018, 38 (2): 126-129.   DOI: 10.3969/j.issn.1674-5817.2018.02.009
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    Objective To explore a simple guide ribonucleic acid (gRNA) in vitro screening method. Methods gRNAs target rabbits torsin family 2 member A (TOR2A) gene were used as an example and screened out two efficiency gRNAs.First,design the gRNAs by online software.Three or more gRNA sequences were choose and inserted behind T7 promoter.After in vitro transcription,gRNAs were purified and then quantified by NanoDrop.Secondly,a pair of primers were designed to amplify about 300~1000 bp genomic sequence which included the gRNAs target sequences.The last step,PCR products,gRNA candidate and Cas9 nuclease were incubated together and then were checked by agarose gel electrophoresis. Results In this study,three gRNAs that target rabbits TOR2A gene were screened.The gRNA1 was failed to guide Cas9 to cleave the PCR products that contain the target sequences,while gRNA2 and gRNA3 were identified to successfully guide the Cas9 cleavage. Conclusion The gRNA in vitro screening method that used in this experiment was simple and efficient.
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    Progress in Animal Models of Ischemic Stroke
    Bo DONG, Jiaxin LIU, Wei XIONG, Songqi TANG, Wei HUANG
    Laboratory Animal and Comparative Medicine    2022, 42 (1): 54-61.   DOI: 10.12300/j.issn.1674-5817.2021.049
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    Ischemic stroke refers to the ischemic necrosis or softening of limited brain tissue caused by cerebral blood circulation disorder, ischemia and hypoxia, resulting in corresponding neurological functional defects. Ischemic stroke is one of the primary causes of human disability, seriously threatens human health, and there is still no effective treatment by now. In order to study the pathogenesis of ischemic stroke and prevent and treat it better, it is very important to establish appropriate animal models.This paper aims to summarize the animal models of ischemic stroke and its advantages and disadvantages.

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    A Comparative Analysis of CNAS Laboratory Animal Institutions Accreditation and AAALAC Certification
    Xiaohuai WU, Qiaozhe XIAO, Wanyong PANG, Yu BAI, Yao LI, Xuancheng LU, Tao FENG
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 237-243.   DOI: 10.12300/j.issn.1674-5817.2022.033
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    China National Accreditation Service for Conformity Assessment (CNAS) laboratory animal institutions accreditation is an important system for the management of laboratory animals in China. It is a third-party evaluation on Chinese characteristics dedicated to ensuring the quality and welfare of laboratory animals in China. The American Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) certification provides global services about animal welfare evaluation and ethical certification, which are important for management and use of laboratory animals. This study compared and analyzed the nature of CNAS and AAALAC, the nature of CNAS accreditation and AAALAC certification, the evaluation principles, required documents, the evaluation process, the management of reviewers, and the acceptance of results, and discussed the differences and characteristics of the two evaluation systems for laboratory animal institutions.

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    Research Progress in Animal Models of Ulcerative Colitis
    Yu HU, Yunxi LAN, Xiaoxiao CHEN, Wei XIONG, Songqi TANG, Bo JIA, Wei HUANG
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 220-228.   DOI: 10.12300/j.issn.1674-5817.2021.155
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    Ulcerative colitis (UC) is a chronic, idiopathic inflammatory bowel disease. Its pathogenesis has not been fully revealed. Moreover, the lack of effective and safe treatment strategies is an obstacle for UC treatment currently. Animal models are essential tools in disease research. Therefore, the establishment of animal models with pathological manifestations similar to human UC is conducive to the full study of this disease. In this review, we reviewed the research progress of animal models of UC, and found that chemical induction is the most commonly used method for modeling UC. Based on the development of genomics technology, gene editing or knockout-induced spontaneous colitis is a vital direction for animal models research in the future. In addition, the indexes for evaluating the modeling results of UC animal models need to be further explored.

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    A Comparative Study of Chronic Obstructive Pulmonary Disease Rat Models Established by Different Methods
    Xinpeng LU, Rong LIU, Wenbo Huang, Jin ZHAO, Hongtao LI
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 201-206.   DOI: 10.12300/j.issn.1674-5817.2021.118
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    Objective To compare the effects and characteristics of cigarette smoke exposure (CSE) alone and CSE combined with airway instillation of bacterial lipopolysaccharide (LPS) in chronic obstructive pulmonary disease (COPD).Methods Male SD rats were randomly divided into control, CSE, and CSE+LPS groups, with 10 rats in each group. After 24 weeks, the models were established and the lung function of the rats was measured. Hematoxylin-eosin (HE) staining was performed to observe the pathological changes in the airway and lung tissue. The ELISA method was used to detect the level of serum interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) in peripheral blood.Results Airway resistance (RI), functional residual capacity (FRC), and chord compliance (Cchord) of the CSE and LPS+CSE groups were higher than those of the control group (all P < 0.05), while the tidal volume (TV), minute volume (MV), and forced expiratory volume in 50 ms (FEV50) / forced vital capacity (FVC) of the CSE and LPS+CSE groups were lower than those of the control group (all P < 0.05). HE staining of lung tissue showed that the average alveolar intercept and thickness of the small airway walls were higher in the CSE and LPS+CSE groups than those in the control group. Compensatory enlargement was evident in the alveolar cavity of the CSE and CSE+LPS groups, and the alveolar septum widened, with a fusion of pulmonary alveoli in the CSE+LPS group. The levels of IL-8 and TNF-α in serum of the CSE and CSE+LPS groups were higher than those of the control group (all P < 0.05). The level of TNF-α in serum of the CSE+LPS group was higher than that of the CSE group (P < 0.05).Conclusion The CSE combined with LPS method is superior to CSE alone for establishing the COPD rat model, and the combined model is closer to clinical manifestations.

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    Biosafety Problems and Countermeasures in the Management of Barrier Facilities for Laboratory Animals
    Yuqin YANG
    Laboratory Animal and Comparative Medicine    2022, 42 (2): 95-101.   DOI: 10.12300/j.issn.1674-5817.2021.164
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    Biosafety is an important part of national security, and effective control of biological hazards of laboratory animals is the basis of using laboratory animals. Based on the experience of biosafety management in the Laboratory Animal Center of Shanghai General Hospital, this paper analyzed the potential biosafety threats faced by laboratory animal barrier facilities in the process of ensuring the smooth conducting of animal experiments from the perspective of a laboratory animal facility manager, and discussed the relevant countermeasures to reduce such risks, in order to provide a reference for the proper control of biosafety problems in animal experiments.

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    Comparative Study on the Presentation Effect of Photochemical Method and Wire Embolization Method for Making Focal Cerebral Infarction Model
    Huijuan LOU, Hongshi ZHANG, Yufeng WANG, Meng JIA, Deyu CONG
    Laboratory Animal and Comparative Medicine    2022, 42 (1): 48-53.   DOI: 10.12300/j.issn.1674-5817.2021.095
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    Objective To investigate the two different methods of making animal models of focal cerebral infarction by photochemical method and wire embolization method, and to analyze the correlation between infarct volume and behavior of experimental animals due to different modeling methods. Methods Totally sixty-four male Sprague-Dawley rats of 300-330 g were randomly divided into three groups: normal group, photochemical group and middle cerebral artery occlusion (MCAO) group. The neurological function scores and behavioral tests on the rats were performed 24 hours after surgery. Then brain tissues were removed by anesthesia and execution, and 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to assess the brain infarct volume in rats. Results There were different volume infarct foci in the brain of SD rats in photochemical group and MCAO group. In MCAO model, most of the hemispheric cortex, striatum, thalamus, hippocampus and subventricular zone were involved in ischemia, and there were good correlations of neurological function scores and balance beam test scores with infarct volumes. In the photochemical model, the infarct foci were in cerebral cortex, and the neurobehavioral abnormalities were well correlated with the cortical infarct location, but the correlation with the infarct volume was relatively poor. Conclusion In MCAO modeling experiment, the behavioral outcomes closely correlated with infarct volume size, while the photochemical model can produce site-specific lesions and site-specific behavioral changed, and the behavioral outcomes have poor correlation with infarct volume.

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    A Preliminary Method for Continuous Drainage of Mesenteric Lymph Fluid in Rats
    Xiaorui ZHANG, Jing CAO, Qianqian WU, Kang KANG, Guoyuan CHEN, Baojin WU
    Laboratory Animal and Comparative Medicine    2022, 42 (4): 267-274.   DOI: 10.12300/j.issn.1674-5817.2022.024
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    Objective To establish a novel sustained collection method for mesenteric lymph fluid by means of assisted reflux from the mesenteric-jugular lymphatic duct in rats. Methods Sixteen male Sprague-Dawley (SD) rats were randomly divided into two groups. The control group underwent duodenal and intestinal lymphatic duct cannulation, after which intestinal lymph fluid was collected. The experimental group underwent jugular vein and intestinal lymphatic duct cannulation to establish intestinal-jugular lymphatic duct assisted reflux. The intestinal lymph fluid was collected on the 7th day after the operation using an awake mobility device. The flow rate of intestinal lymph fluid was recorded, and its cellular components and some biochemical indicators were detected. Results Mesenteric-jugular lymphatic duct vein cannulation assisted reflux was successfully established in rats, and the rat models could be maintained for more than seven days. The intestinal lymph flow rate was (2.01±0.12) mL/h in the experimental group, which was higher than that of the control group [(0.92±0.09) mL/h, P<0.01]. The number of lymphocytes (LYM#) and percentage of lymphocytes (LYM/%) in the experimental group were higher than those in the control group (P<0.01). The percentage of neutrophils (NEUT/%) and percentage of monocytes (MONO/%) were lower than those in the control group (P<0.01, P<0.05, respectively). The concentrations of K+, Na+, CO2, and urea in the lymph fluid of the experimental group were higher than those of the control group (P<0.01). However, the concentrations of triacylglycerol (TG) and P3+ were lower than those of the control group (P<0.01). Conclusion This novel method can achieve real-time and long-term collection of mesenteric lymph fluid in rats under the condition of being awake, unrestricted in diet and in normal state, avoiding the influence of surgical stress, general anesthesia or animal restraint on the experimental results.

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    Observation on Oxidative Stress in Chronic Myocardial Ischemia in Mini-pig
    XU Xiao-ping, PAN Yong-ming, CHEN Liang, XU Jian-qin, WANG De-jun, ZHU Ke-yan, YANG Yu-wei, CHEN Min-li
    Laboratory Animal and Comparative Medicine    2012, 32 (5): 401-406.   DOI: 10.3969/j.issn.1674-5817.2012.05.006
    Abstract276)      PDF (1584KB)(685)       Save
    Objective To observe the effects of oxidative stress on chronic myocardial ischemia in mini-pigs. Methods Fifty-five Bama mini-pigs were randomly divided into three groups: normal control (Ctr) group, high-fat (HF) group and chronic myocardial ischemia (CMI) group, five animals in each group. The chronic myocardial ischemia model was made induced by vitamin D 3, isoproterenol and high-fat diet for 24 weeks. The changes of phosphokinase isoenzyme (CK-MB), platelet aggregation rate (PAR) and the SOD, MDA, GSH-Px, NO, LD, ATPase in myocardial tissues were detected. Results Compared with normal control group, the serum CK-MB activity, PAR, the myocardial tissues of MDA and LD contents in CMI group were significant increased ( P<0.05, P<0.01), the myocardial tissues of SOD, SOD/MDA ratio, GSH-Px, NO, Na +-K +-ATPase, Ca ++-ATPase and Mg ++-ATPase in CMI group were lowered ( P<0.05, P<0.01). PAR and the myocardial tissues of SOD/MDA ratio and MDA content in HF group were significant increased ( P<0.05, P<0.01), while the myocardial tissues of SOD, GSH-Px, Na +-K +-ATPase and Mg ++-ATPase were significant decreased ( P<0.05). Compared with HF group, the serum CK-MB activity in CMI group was significant higher than that of HF group ( P<0.01) and the myocardial tissues of Na +-K +-ATPase and Ca ++-ATPase were significant lower than those of HF group ( P<0.05, P<0.01). Correlation analysis showed that there was a positive correlation between CK-MB and PAR, MDA in CMI group ( P<0.05, P<0.01), and a significant negative correlation between CK-MB and SOD, SOD/MDA, GSH-Px, NO respectively( P<0.05, P<0.01). The platelet aggregation rate was positively correlated with CK-MB and MDA ( P<0.05), and was negative relation with SOD, SOD/MDA and Na +-K +-ATPase ( P<0.05, P<0.01). There was a significant positively correlation between LD and MDA in myocardial tissues ( P<0.05), and LD was negatively correlated with SOD/MDA, Na +-K +-ATPase, Ca ++-ATPase and Mg ++-ATPase (P<0.05). NO level was positively correlated with SOD, SOD/MDA, GSH-Px in myocardial tissues( P<0.05, P<0.01), and was negatively related with CK-MB and MDA ( P<0.05). Conclusion Oxidative stress injury was participated in the formation of chronic myocardial ischemia.
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    Advances in the Application of Mouse Models to Study Digestive Mucosal Immunity and Infectious Diseases
    Shiyan YU
    Laboratory Animal and Comparative Medicine    2022, 42 (1): 3-10.   DOI: 10.12300/j.issn.1674-5817.2021.170
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    The host digestive tract comprises trillions of commensal microbes, collectively called microbiota. These microbes interact with a various host cell types and have a significant impact on health and disease. High-throughput sequencing technologies have accelerated the identification of numerous poorly studied microbes associated with health and disease. Genetic and humanized mouse models with and without environmental exposure were established to study the roles of these microbes in human physiologies and pathologies. Important findings related to the microbiota, mucosal immunity, and infectious diseases in mouse models are summarized. Furthermore, challenges and opportunities in leveraging genetic approaches and environmental exposure to optimize mouse models are discussed.

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    Analysis on the Development Status of Laboratory Animals in Japan
    Huan GOU, Xinying AN, Yujia TONG, Yan WANG, Shuang YANG
    Laboratory Animal and Comparative Medicine    2023, 43 (2): 194-204.   DOI: 10.12300/j.issn.1674-5817.2022.141
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    Experimental animals have made important contributions to human medical research and life and health. It is known that the development of laboratory animal science in Japan has been relatively rapid in the past few decades, providing important support for the development of the world's experimental animal field. Therefore, it is of great significance to understand the management mode and resource storage situation of Japanese experimental animals, analyze the advantages of Japanese experimental animal development, and propose suggestions to strengthen the high-quality development of experimental animals in China. Through literature research, the authors first analyzed the management system of experimental animals in Japan, including regulations and policies, research funding management, experimental animal management, talent cultivation, and standard and normative systems. Then, the current status of experimental animal research in Japan was summarized, including experimental animal resources, major research institutions, and production enterprises. On this basis, it was found that the field of experimental animal research in Japan currently exhibits characteristics such as a complete policy system, flexible management methods, rich resource reserves, and large-scale industrial development. Finally, by comparing the existing problems in China, suggestions for the development of experimental animal technology in China are proposed: (1) drawing on the legal management method of experimental animals in Japan, strengthening and improving the legislation and management model of experimental animals in China; (2) increaseing investment in scientific research funds, playing the role of research institutions, societies and industries, and promoting the incremental construction and industrial development of experimental animal resources.

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    Model of Diffuse Cerebral Thrombosis Induced by Arachidonic Acid in Rats
    Long NING, Hang SUN, Jin FENG, Qingting MENG, Qian YANG, Fangyan HE
    Laboratory Animal and Comparative Medicine    2022, 42 (2): 141-145.   DOI: 10.12300/j.issn.1674-5817.2021.091
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    Objective Establishment and optimization of arachidonic acid-induced diffuse cerebral thrombosis model in rats.Methods Arachidonic acid was injected into the internal carotid artery to establish a diffuse cerebral thrombosis model in rats, while the sham operation group was set as the control. The model was evaluated by detecting the exudate content of Evans blue (EB) in brain tissue and the pathological damage degree of brain tissue by HE staining.Results Compared with the sham operation group, diffuse EB exudation was observed in the injured brain tissue of the model group (P < 0.01), and the exudation was relatively uniform. The HE staining of brain tissue on the side of the injury showed ischemic pathological damage with disorganized cell arrangement, wrinkled nuclei, enlarged cell gaps, increased vacuolated cells, and red striped tubular shape of each individual microvessel.Conclusion Arachidonic acid can successfully induce diffuse cerebral thrombosis model, and the optimized model has better stability and lower mortality.

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    Efficacy of DZ1462, a Novel Sodium-phosphate Transporter Inhibitor, on 5/6 Nephrectomy-induced Hyperphosphatemia Model Rats
    Xiao LU, Lin ZHANG, Hui JI, Shanxiang JIANG
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 187-193.   DOI: 10.12300/j.issn.1674-5817.2021.138
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    Objective To study the efficacy of DZ1462, a novel sodium-phosphate transporter inhibitor, on rat hyperphosphatemia models established by 5/6 nephrectomy.Methods Totally 156 rats were randomly selected into four groups. Rats fed a normal diet were control group, named as group Ⅰ (n=6); rats fed a normal diet after 5/6 nephrectomy were named as group Ⅱ (n=60); rats fed a high phosphate diet after 5/6 nephrectomy were named as group Ⅲ (n=60); rats fed a high phosphate diet after sham surgery were named as group Ⅳ (n=30). The molding cycle was 10 weeks. Serum Pi was detected and the number of animal deaths was recorded every two weeks. Hematoxylin-eosin (HE) staining was performed to observe the change in kidney pathology, and to screen animal models with high phosphorus blood syndrome. Totally 18 model rats that met the inclusion criteria (all of group Ⅲ) were selected and randomly assigned to three groups: the model control group recorded as the G2 group; the DZ1462 administration group (30 mg/kg, tid, 21 d) recorded as the G3 group; the Sevelamer administration group (250 mg/kg, tid, 21 d) recorded as the G4 group. In addition, the normal control group was set as the G1 group. Serum phosphate levels were measured using a kit.Results In the 8th and 10th weeks, compared to group Ⅰ, serum phosphorus in group Ⅲ showed a significant difference (P < 0.01). The kidneys in group Ⅲ had obvious glomerular sclerosis, renal tubular atrophy, degeneration, interstitial inflammation, fibrosis, and calcification. Similarly to chronic kidney disease accompanied by hyperphosphatemia, the animal model was established successfully. At each time point, the serum phosphorus inhibition rate of the G3 group was significantly higher than that of the G4 group (P < 0.05).Conclusion DZ1462, as a novel small-molecule inhibitor of intestinal sodium and phosphorus transporter, can effectively inhibit intestinal phosphorus ion absorption in rat hyperphosphatemia model, and is expected to become a potential drug for the clinical treatment of hyperphosphatemia.

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    Construction Methods and Influencing Factors on Animal Model of Sepsis
    Xiao LI, Haipeng YAN, Zhenghui XIAO
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 207-212.   DOI: 10.12300/j.issn.1674-5817.2021.121
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    Sepsis is a common acute and critical illness, and its pathogenic mechanism is complex, often involving multiple organs and systems in the body. Various factors such as inflammatory response, immune dysfunction, and coagulation dysfunction are connected into an interconnected and mutually influencing network system, aggravating the severity of the disease. At present, the case fatality rate of sepsis is about 25%, which is a serious threat to human health. Establishing a stable and reliable experimental animal model of sepsis is an important means to understand the mechanism of host defense regulation in the early stage of infection, the mechanism of host response disorder in the stage of disease progression and to study the therapeutic effect of new therapeutic drugs. At present, there are many methods to establish animal models of sepsis, and there are many influencing factors. Therefore, this paper reviewed the preparation methods and influencing factors of animal models of sepsis, in order to provide some references for researchers to select suitable animal models.

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    Characteristics and Application of Transgenic Mouse Models in Alzheimer's Disease
    Feng WEI, Weiwei CHENG, Yafu YIN
    Laboratory Animal and Comparative Medicine    2022, 42 (5): 432-439.   DOI: 10.12300/j.issn.1674-5817.2021.182
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    Alzheimer's disease is a common neurodegenerative disease characterized by progressive memory loss and overall cognitive decline. Two typical pathological features are senile plaques and neurofibrillary tangles detected in the brain, which consist of large amounts of precipitated amyloid peptide and hyperphosphorylated Tau protein, respectively. In addition, there are other pathological features such as neuroinflammatory response and extensive loss of neurons. In the past decades, a lot of research has been done on Alzheimer's disease, but its etiology and pathogenesis are still unclear, and there is no ideal treatment or radical cure. This review introduced the characteristics of various transgenic animal models and their current application in preclinical studies, in order to provide theoretical basis for future experimental studies.

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    Necessity of an Acclimatization Period in a Home Cage Experiment of Mice
    YIN Yuan, LU Lu, WANG Yun, YANG Jing, FU Heling
    Laboratory Animal and Comparative Medicine    2021, 41 (4): 358-362.   DOI: 10.12300/j.issn.1674-5817.2020.154
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    Objective To investigate whether an acclimatization period should be introduced into the home cage experiment for the detection of metabolic function in mice, and how to judge and set its length. Methods Data from 31 home cage experiments in 2016-2017 were collected, and each experiment was set up with a 3-day (72 hours) acclimatization period. Data such as water consumption, food intake, heat production, and body weight were recorded. The data were analyzed using 24-hour interval analysis to determine the acclimatization effect. Results Approximately 12% of the 356 mice drank less than 1 mL at the end of 96 hours. There were significant differences in water consumption, food intake, heat production rate, and body weight between 24-48 hours and 48-72 hours, but no significant differences were detected between 48-72 hours and 72-96 hours, except in food intake. Independent verification of the food intake of each experiment showed that there was a significant correlation between food intake adaptability and weight. Conclusion Approximately 12% of the mice were unable to learn or adapt to the new water bottle after the 72-hour acclimatization period, therefore, researchers should consider increasing the sample size of the experiment to eliminate invalid data. If food intake is not the focus of a study, the 48-hour acclimatization is sufficient to obtain reliable results.
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    Recent Advances of Animal Models of Renal Interstitial Fibrosis
    Can LAI, Lele LI, Tala HU, Yan MENG
    Laboratory Animal and Comparative Medicine    2023, 43 (2): 163-172.   DOI: 10.12300/j.issn.1674-5817.2022.171
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    Renal interstitial fibrosis is a common pathway in the progression of many renal diseases. Whether it is chronic kidney disease or acute kidney injury that cannot be fully recovered, the progression process mostly enters end-stage renal failure after renal interstitial fibrosis. The animal model of renal interstitial fibrosis is an important research tool for exploring the pathogenesis of renal interstitial fibrosis and new diagnostic and treatment methods. Different animal models have their own characteristics. Researchers can establish different models based on their own experience and experimental purposes, and carry out scientific research on this basis to provide more new methods for the prevention and treatment of kidney diseases. The authors focused on several common animal models of renal interstitial fibrosis to provide the reference for related researchers, including surgical models induced by unilateral ureteral obstruction, ischemia-reperfusion injury, 5/6 nephrectomy, and microembolization; chemical models induced by cyclosporine A, adriamycin, aristolochic acid, mercuric chloride(HgCl2), gentamicin, cisplatin, and adenine; transgenic hybridization and kidney injury molecule 1 (KIM-1) induced transgenic modification model; composite model induced by bilateral ischemia-reperfusion injury (BIRI) combined with gentamicin, unilateral nephrectomy combined with angiotensin II (Ang II), and unilateral ischemia-reperfusion injury (UIRI) combined with pLVX-shTNC plasmid.

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    Injurious Effect of Cisplatin on the Function of Hypothalamus-pituitary-adrenal/gonadal Axis in Mice and the Intervention Effect of Dehydroepiandrosterone
    Zhiqiang PAN, Zixin NONG, Haina XIE, Peike PENG
    Laboratory Animal and Comparative Medicine    2023, 43 (3): 229-242.   DOI: 10.12300/j.issn.1674-5817.2022.182
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    Objective To study the pathway of cis-dichlorodiamineplatinum (DDP) inhibiting the synthesis of steroid hormones in mice, and to observe the intervention effect of dehydroepiandrosterone (DHEA). Methods Sixty adult ICR mice were randomly divided into three groups: control group, DDP modeling group, and DHEA group, with 10 male and 10 female mice in each group. The DDP modeling group mice were intraperitoneally injected with DDP solution at a dose of 2.5 mg·kg-1·d-1, once every 3 days, a total of 7 times. On the same day of modeling, the control group mice were injected with an equal amount of physiological saline intraperitoneally. The DEHA treatment group mice were treated with DDP and given a dose of 8.3 mg·kg-1·d -1 of DHEA by gavage for 21 consecutive days. The changes of fatigue indexes of mice were observed by open field, grip and rod rotation tests. The morphology changes of adrenal gland, testicular and ovarian tissue were observed by pathological section and HE staining. The levels of serum steroid hormones were detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The mRNA and protein expression levels of the related genes of the hypothalamus, hypophysis, adrenal, testis and ovary were tested by real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting. Results Compared with control group, both male and female mice in DDP modeling group were significantly losing weight (P<0.05), their abilities in horizontal movement and vertical movement decreased (all P<0.05), and the stay time and grip also significantly decreased (all P<0.05) in female mice. Indexes of fatigue were improved after DHEA supplement (all P<0.05). In the DDP modeling group, the arrangement of spermatogenic cells at all levels in the testicular tissue was disordered and the testicular interstitial edema was observed, and a large number of primordial follicles in the ovarian tissue were activated, the number of atresia follicles increased, and the number of granulosa cells in the follicles decreased; while in the DHEA group, the damaged phenotype of testicles and ovaries was significantly improved. Compared with control group, the levels of serum testosterone and dihydrotestosterone in both male and female DDP modeling mice significantly decreased (P<0.01), the pregnenolone was down-regulated but corticosterone was up-regulated significantly (P<0.05) in male mice, the corticosterone was down-regulated significantly (P<0.05) in female mice. Compared with the DDP group, after DHEA supplement, the pregnenolone in male mice and the progesterone in female mice increased significantly (P<0.05), but the pregnenolone in female mice and the progesterone in male mice decreased significantly (P<0.05). Compared with control group, the expression levels of Cyp21a1 and Cyp11a1 genes in the adrenal gland and Gnrh gene in the hypothalamus of male and female mice in the DDP modeling group significantly decreased (all P<0.05); the expression levels of Hsd3b2 gene in the adrenal gland, Star, Cyp11a1, and Lhr genes in the ovaries, Crh, Pomc, and Lhb genes in the hypothalamus, pituitary, and pituitary of female mice significantly decreased (all P<0.05); the expression levels of Star gene and StAR protein in the testicles of male mice, as well as Fshb and Lhb genes in the pituitary gland, were significantly down-regulated (all P<0.05). After DHEA supplement, compared with the DDP modeling group, the mRNA expression levels of Cyp17a1 in the adrenal gland of male mice and Cyp17a1, Lhr and Fshr genes in testis were down-regulated significantly (P<0.05); the expression level of Cyp11a1 gene in the adrenal gland of female mice was also decreased (P<0.05); while the expression levels of Hsd3b2 gene in the adrenal gland, Star, Cyp11a1, Hsd3b2 and Lhr gene in the ovary, and Lhb gene in the pituitary gland were all up-regulated ( P<0.05). Conclusion The function of hypothalamus-pituitary-adrenal/gonadal axis was inhibited by DDP intermittent injection, especially in female. Supplementation of DHEA can help regulate the homeostasis of steroid hormone levels.

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    Perspective Review of Animal Models for Osteoporosis Research
    QIAO Wei-wei, ZHAO Xian-zhe
    Laboratory Animal and Comparative Medicine    2011, 31 (1): 73-78.   DOI: 10.3969/j.issn.1674-5817.2011.01.016
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    Osteoporosis is an important systemic disorder, impairing mainly the health and life quality of the elderly, with a diverse multifactorial etiology. The proper animal models of osteoporosis lay the foundation of sophisticated studies on this disease. Here, we review some typical animal models of osteoporosi and summarize the drawbacks from the previous using experiences and pose the corresponding improvement of these animal models in actual application. Then, we introduce some novel animal models of osteoporosis and take a perspective view of the requisite needs for large animal models of osteoporosis.
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    Helicobacter hepaticus Infection Promotes High Fat Diet-induced Non-alcoholic Fatty Liver Disease in Mice
    SHEN Chen, WU Zhihao, YIN Jun, ZHU Liqi, ZHANG Quan
    Laboratory Animal and Comparative Medicine    2021, 41 (2): 122-130.   DOI: 10.12300/j.issn.1674-5817.2020.181
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    Objective To investigate the effect of Helicobacter hepaticus (H.h) on non-alcoholic fatty liver disease induced by a high fat diet (HFD). Methods Twenty 6-week-old male BALB/c mice were randomly divided into four groups: control group, H.h group, HFD group and H.h+HFD group. The H.h+HFD group was fed a HFD after H.h infection. After 12 weeks of feeding, the levels of triglyceride (TG), alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured. Besides, the liver index was calculated, and oil red O staining, Sirius red staining, hematoxylin-eosin staining, real-time fluorescence quantitative PCR (RT-PCR) and immunohistochemistry were conducted to evaluate liver pathological changes in the liver samples. Results The serum levels of TG, ALT and AST in the H.h+HFD group were significantly higher than those in the control group, H.h group and HFD group (all P<0.05). The livers of mice in the H.h+HFD group showed multiple lesions, fat accumulation, ballooning degeneration and necrosis, collagen fiber deposition. The livers of mice in the H.h group exhibited inflammatory cell aggregation and a small amount of collagen fiber deposition, whereas the livers of mice in the HFD group showed lipid droplets accumulation, steatosis and a small amount of collagen fiber deposition. Moreover, the mRNA levels of interleukin (IL)-6, IL-1?, transforming growth factor-? (TGF-?) and tumor necrosis factor-〈 (TNF-〈) were significantly elevated in the livers of mice in the H.h+HFD group compared to the other three groups (all P<0.05). The expressions of alpha-smooth muscle actin (〈-SMA) and collagen typeⅠ(CollagenⅠ) were significantly increased in the H.h+HFD group. Conclusion H.h infection can promote non-alcoholic fatty liver disease induced by feeding HFD to mice.
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    Anesthetic Effects of Different Doses of Zoletil Combined with Serazine Hydrochloride on C57BL/6J Mice
    Chengji WANG, Qing CHAI, Hui GONG, Jue WANG, Yinghan WAN, Zhengye GU, Xu BAO, Ruling SHEN
    Laboratory Animal and Comparative Medicine    2022, 42 (1): 31-35.   DOI: 10.12300/j.issn.1674-5817.2021.064
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    Objective To observe the duration of anesthesia in C57BL/6J mice anesthetized using different doses of Zoletil combined with serazine hydrochloride to provide an effective reference for all types of mouse surgery and related experimental design. Methods One hundred C57BL/6J mice (half male and female) were randomly divided into five groups, with 20 mice (half male and female) in each group. The mice in the four groups were intraperitoneally injected with 55 mg/kg Zoletil and 13.75 mg/kg serazine hydrochloride, 65 mg/kg Zoletil and 16.25 mg/kg serazine hydrochloride, 75 mg/kg Zoletil and 18.75 mg/kg serazine hydrochloride, or 85 mg/kg Zoletil and 21.25 mg/kg serazine hydrochloride, respectively. After the righting reflex stopped, one drop (about 20 μL) was injected into each eye, and the mice were placed on a heat preservation pad. Mice in the control group were intraperitoneally injected with 200 μL normal saline. Differences in the anesthesia induction time, maintenance time, and awakening time were observed and compared. The mice were fed for one day after anesthesia; serum was collected, and liver and kidney function indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (CREA) were determined using Hitachi 7080 automatic biochemical analyzer. Results The success rate of anesthesia in C57BL/6J mice treated with Zoletil combined with serazine hydrochloride was 100%. When the anesthetic dose was 55-75 mg/kg, the anesthesia was induced quickly and safely, and the anesthetic effect was good. The duration of anesthesia was proportional to the injection dose of Zoletil (r2 = 0.827 in male mice, r2 =0.841 in female mice, both P < 0.01), and the induction time was inversely proportional to the injection dose (r2 =0.432 in male mice, r2=0.410 in female mice, both P < 0.05). However, there was no significant difference in liver and kidney function between the groups and the control group (P>0.05). Conclusion Anesthetizing C57BL/6J mice with Zoletil combined with serazine hydrochloride is a reliable and stable method, and the duration of anesthesia can be controlled by adjusting the dosage.

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    Introduction to the International Guide for Animal Research Reporting ARRIVE 2.0, and Its Implementation Plan in the Journal
    Junyan ZHANG, Xiaoyu LIU, Yao LI, Guoyuan CHEN, Xiao LU, Yu BAI, Xuancheng LU, Wanyong PANG, Baojin WU
    Laboratory Animal and Comparative Medicine    2023, 43 (1): 86-94.   DOI: 10.12300/j.issn.1674-5817.2023.014
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    Animal experiments play an important role in the process of biomedical research, and is a necessary way to transform basic medicine into clinical medicine. The standardization of animal experimental studies and reports determines the reliability and reproducibility of research results, and is also the key to transforming the results of animal experiments into clinical trials. In view of how to design and implement animal experiments, write animal experiment reports, and publish relevant academic papers in a more standardized way, LACM (Laboratory Animal and Comparative Medicine) has launched a new column of comparative medical research and reporting standards from 2023, focusing on the introduction and interpretation of international general norms related to laboratory animal and comparative medicine, such as ARRIVE 2.0 guidelines (Animal Research: Reporting of In Vivo Experiments). This article focuses on the development and application, basic content and priority of ARRIVE 2.0, as well as the scheme of implementing ARRIVE 2.0 guidelines in international biomedical journals, and explains the current situation and future plans of LACM following ARRIVE 2.0 guidelines. The research and report of animal experimental medicine following the ARRIVE 2.0 guidelines and other international norms is one of the important driving forces to promote the high-quality development of experimental animal science and biomedicine in China, and also a powerful means to implement the 3R principle and improve the welfare of laboratory animals. Through this article, we hope the majority of scientific researchers and editors will attach great importance and actively implement these international standards.

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    A Brief Interpretation of AVMA Guidelines on Euthanasia of Animals: 2020 Edition
    LU Jin, ZHANG Ying, PAN Xueying, WANG Jian, YAN Guofeng, ZHOU Jing, ZHU Lian, CHEN Xuejin, LI Yao, PANG Wanyong
    Laboratory Animal and Comparative Medicine    2021, 41 (3): 195-206.   DOI: 10.12300/j.issn.1674-5817.2021.086
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    Overdose of injectable barbiturates or barbituric acid derivatives is the most preferred euthanasia method for the majority of animal species. However, these controlled drugs have limited access, and in this case or in any other scientific concerns, veterinarians may choose alternative, conditional acceptable methods as recommended by American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals. In the newest 2020 Edition, existing euthanasia methods, techniques and agents of euthanasia are updated according to recently released articles. This article summarized the updated content of the new version of the AVMA Guidelines and on this basis, enumerated the most preferred methods of euthanasia, methods acceptable with conditions and unacceptable methods to euthanize different animal species. In addition, principles and precautions related to animal euthanasia were also briefly described.
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    Explanation and Elaboration for the ARRIVE Guidelines 2.0—Reporting Animal Research and In Vivo Experiments (Ⅰ)
    Jian WANG, Jin LU, Zhengwen MA, Guoyuan CHEN, Xiao LU, Yu BAI, Xiaoyu LIU, Xuancheng LU, Jing GAO, Yao LI, Wanyong Pang
    Laboratory Animal and Comparative Medicine    2023, 43 (2): 213-224.   DOI: 10.12300/j.issn.1674-5817.2023.043
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    Improving the reproducibility of biomedical research results is a major challenge. Researchers reporting their research process transparently and accurately can help readers evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as the reliability, repeatability, and clinical translatability of animal experimental results. The use of ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and integrity of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. this article is a Chinese translation based on the best practices of international journals following the ARRIVE 2.0 guidelines in international journals, specifically for the complete interpretation of the ARRIVE 2.0 guidelines published in the PLoS Biology journal in 2020 (original text can be found at https://arriveguidelines.org ). The first part of the article includes the preface and the "Key 10" section, which covers "study design" "sample size" and "inclusion and exclusion criteria". Its aim is to promote the full understanding and use of the ARRIVE 2.0 guidelines by domestic researchers, enhance the standardization of experimental animal research and reporting, and promote the high-quality development of experimental animal technology and comparative medicine research in China.

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    Overview of Studies in Animal Models of Schizophrenia
    Ling HU, Zhibin HU, Yunqing HU, Yuqiang DING
    Laboratory Animal and Comparative Medicine    2023, 43 (2): 145-155.   DOI: 10.12300/j.issn.1674-5817.2022.174
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    Schizophrenia (SCZ) is a highly destructive and complex psychiatric disorder illness, accompanied by a variety of positive and negative symptoms along with cognitive impairment, which brings a heavy social burden. Elucidation of the pathogenesis and therapeutic development is challenging because the complex interplay between genetic risk factors and environmental factors in essential neurodevelopmental processes. Therefore, preparing appropriate animal models can help people better understanding the neurobiological basis of SCZ and provide theoretical basis for finding new treatments. In order to provide reference for the application and improvement of SCZ animal models, this commentary reviewed several main modeling methods for animal models of SCZ, including neurodevelopmental models, drug-induced animal models, and genetic models, and the behavioral evaluation, histological analysis and possible molecular mechanisms of SCZ animal models were also outlined.

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    Anatomical Characteristics and Background Lesions in Laboratory British-shorthair Cats
    Yu WANG, Dan GAO, Nana PENG, Ai HANG, Bin SHEN, Jian HUANG, Liming TANG
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 229-236.   DOI: 10.12300/j.issn.1674-5817.2021.151
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    Objective To investigate anatomical characteristics and background lesions in laboratory British-shorthair cats (BSCs) through gross and histopathological examination, and provide effective basis for the research and application, standard establishment and market promotion of this experimental animal. Methods Gross system dissection and histopathological examination were performed on 14 adult BSCs (half male and half female), and the histological characteristics and background pathological data were collected and analyzed. Results The body weight and organ index of spleen of BSCs was higher in males than females (P < 0.05, P < 0.01), the organ coefficients of brain and thymus in BSCs were lower in males than females (P < 0.05). The anatomical structure of testicles, heart, thyroid gland and tentorium of BSCs is different from that of rodents and canine. Furthermore, histopathological examinations revealed that the structures of heart, pancreas, spleen in BSCs differed from two experimental animals mentioned above. In addition, there were multiple hepatic cell vacuolar degeneration in BSCs (9/14), and occasional renal, brain and lymphoid tissues were also found in some animals. Conclusion There were six differences in body weight, and organ-coefficient of spleen, thymus, and brain in BSCs, while the hepatocyte phospholipidosis of liver and background lesion in BSCs were found.

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    Preliminary Study on Raising and Maintaining Clean Mice with Micro-barrier Cages in Conventional Environmental Facilities
    Qi REN, Yandong LI, Qiang SUN
    Laboratory Animal and Comparative Medicine    2022, 42 (5): 440-447.   DOI: 10.12300/j.issn.1674-5817.2022.129
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    Objective To explore the feasibility of breeding cleaning degree mice with micro-barrier cages in conventional environmental facilities. Methods Clean-grade mice were housed and maintained in positive-pressure microbarrier cages in a general environment, during which third-party sampling of the microbial status of the animals in the microbarrier was performed on a quarterly frequency. Results From June 2020 to July 2022, no microorganisms that must be excluded by the national standard for cleaning degree mice have been detected in two consecutive years. Conclusion Micro-barrier cages can be used to raise and maintain cleaning grade mice in conventional environmental facilities.

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    Establishment and Comparison of Mouse Pancreatic Cancer Orthotopic Model for Minimally Invasive Ablation Therapy Study
    Lujing MAO, Nana ZHANG, Hao LIU, Aihua SHI, Ziyu ZHU, Yi LÜ
    Laboratory Animal and Comparative Medicine    2022, 42 (2): 127-134.   DOI: 10.12300/j.issn.1674-5817.2021.094
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    Objective To explore the advantages and disadvantages of orthotopic mouse model of pancreatic cancer established by orthotopic injection of tumor cells and transplantation of tumor tissue block, in order to provide technical reference for the establishment of orthotopic mouse model of pancreatic cancer with the purpose of precision ablation treatment.Methods A total of twenty healthy aged 6-8 weeks male C57BL/6 mice were divided into four groups, with five mice per group. Direct injection of mouse pancreatic cancer Panc02 cell was used in group A, direct injection of mouse pancreatic cancer Panc02 cell (containing matrigel) was used in group B, tumor tissue block transplantation of mouse pancreatic cancer was used in group C, the tumor tissue block hydrogel bonding method was used in group D. The tumor formation rate, tumor size, the degree of abdominal organ adhesion, tumor metastasis were observed after surgery in each group of mice. Tumor histomorphology and expressions of Ki67 and α-smooth muscle actin (α-SMA) protein were detected by HE staining and immunohistochemistry, repectively.Results The tumor formation rates in groups A, B, C, and D were 60%, 80%, 100%, and 100% respectively. After modeling for 16 d, the tumor volume of mice in group A was (47.80±42.99) mm3, with poor homogeneity. The tumor volume of mice in groups B, C and D [(68.43±16.77) mm3, (105.86±17.25) mm3, (128.98±13.41) mm3 , respectively] was significantly larger than that in group A (P < 0.01), with better homogeneity. The severe abdominal adhesion rate in group A mice was 100% and 80% in group B, and no severe abdominal adhesions occurred in groups C and D. The metastasis rate was 100% in group A and 60% in group B, and no tumor metastases were found in mice in groups C and D. There was no difference in the tumor formation of the four groups of mice, and no significant difference in the expression of Ki67 and α-SMA proteins in the tumor tissues (P > 0.05).Conclusion The establishment of orthotopic pancreatic cancer in mice by tumor tissue transplantation and hydrogel adhesion has the advantages of high tumor formation rate, less metastasis, mild adhesion of abdominal cavity, no change in the biological characteristics of tumor cells, easy operation and popularization, and better modeling effect.

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    Research Progress in Animal Model of Alzheimer's Disease
    Zhejin SHENG, Limei LI
    Laboratory Animal and Comparative Medicine    2022, 42 (4): 342-350.   DOI: 10.12300/j.issn.1674-5817.2021.122
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    Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, which seriously affects the health of the elderly people. The drugs currently approved for the treatment of AD can only reduce the symptoms severity of AD, but can't cure AD or prevent the deterioration of AD. Over the past 40 years, there have been numerous treatments for AD, including compounds that prevent amyloid deposition in the brain or remove existing amyloid plaques, but their clinical curative effects are not significant. Therefore, more basic and clinical studies are needed to improve our understanding of the biological mechanism of AD. Experimental animal models are very important not only for the study of the pathogenesis of AD, but also for the development of AD drugs. This paper reviewed the main histopathological characteristics, genetic factors, the current animal models and model evaluation of AD.

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    Explanation and Elaboration of the ARRIVE Guidelines 2.0—Reporting Animal Research and In Vivo Experiments (Ⅱ)
    Guoyuan CHEN, Xiao LU, Yu BAI, Lingzhi YU, Ying QIAO, Jian WANG, Jin LU, Xiaoyu LIU, Xuancheng LU, Jing GAO, Yao LI, Wanyong PANG
    Laboratory Animal and Comparative Medicine    2023, 43 (3): 323-331.   DOI: 10.12300/j.issn.1674-5817.2023.042
    Abstract327)   HTML30)    PDF (1187KB)(406)       Save

    Improving the reproducibility of biomedical research results remains a major challenge. Transparent and accurate reporting of progress can help readers evaluate the reliability of research results and further explore an experiment by repeating or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs), provide a checklist applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as the reliability, repeatability, and clinical translatability of animal experimental results. The use of the ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and integrity of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is the second part of the Chinese translation of the complete interpretation of the ARRIVE 2.0 guidelines published in PLoS Biology in 2020 (original text can be found at https://arriveguidelines.org ) and based on the best practices for following the ARRIVE 2.0 guidelines in international journals. This part includes Items 4-7 of "ARRIVE Essential 10" in the ARRIVE 2.0 guidelines: "Randomization", "Blinding", "Outcome Measurement", and "Statistical Methods". Our Chinese translated version aims to promote the full understanding and use of the ARRIVE 2.0 guidelines by domestic researchers, enhancing the standardization of experimental animal research and reporting, and promoting the high-quality development of experimental animal technology and comparative medicine research in China.

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    Research Progress on Biological Characteristics in Naked Mole Rat
    ZHAO Shan-min, CUI Shu-fang
    Laboratory Animal and Comparative Medicine    2013, 33 (5): 400-405.   DOI: 10.3969/j.issn.1674-5817.2013.05.016
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    As a rodent mammal, the naked mole rat inhabit the arid regions of Africa Kenya, Ethiopia, etc. Owing to its social behavior and ecophysiology, the naked mole rat may be commonly used in biomedical research. Compared with traditional animal models, it has unparalleled advantages in cancer and aging research, mechanistic studies of geriatrics and cardiovascular disease, research and development of pain killers. The naked mole rat, as a new experimental animals, have aroused great concern at home and abroad in recent years.
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