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    History, Current Status, Challenges and Opportunities of Laboratory Monkey Industry in China
    SUN Qiang
    Laboratory Animal and Comparative Medicine    2024, 44 (4): 343-356.   DOI: 10.12300/j.issn.1674-5817.2024.112
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    Laboratory animals play a crucial role in foundational scientific research and clinical medicine. Non-human primates (NHP), particularly Macaca mulatta and Macaca fascicularis, have long been highly valued due to their close resemblance to humans. After more than half a century of development, China's NHP laboratory animal industry has gradually transitioned from its early stage of rapid and unregulated growth to a mature stage of standardization and refinement. However, there has been a dramatic surge in global biopharmaceutical research in recent years, leading to a sharp increase in demand for NHP laboratory animals. This surge, coupled with the lack of long-term strategic planning among breeding enterprises, has resulted in severe aging of breeding populations and a significant decline in reproductive capabilities, further widening the supply gap. Under the dual pressures of rising demand and declining supply, the prices of NHP laboratory animals have surged. Although the cyclical downturn in the biopharmaceutical industry in recent years has lowered the demand for NHP laboratory animals to some extent, leading to significant price drops, the prices remain high. At the same time, against the backdrop of high prices, issues such as the accelerating aging of breeding populations, the lower standards for microbial quality control, insufficient genetic quality control, and blind investment in facility construction have emerged within the NHP laboratory animal industry. This report provides a comprehensive review of the history and current status of China's NHP laboratory animal industry, with a focus on laboratory monkeys. It explores the factors shaping the current industry landscape and identifies potential challenges and opportunities facing the industry. It aims to offer insights and references for the future development of China's NHP laboratory animal industry.

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    Establishment and Evaluation of a Rat Model of Non-Puerperal Mastitis
    YIN Yulian, MA Lina, TU Siyuan, CHEN Ling, YE Meina, CHEN Hongfeng
    Laboratory Animal and Comparative Medicine    2024, 44 (6): 587-596.   DOI: 10.12300/j.issn.1674-5817.2024.065
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    Objective This study aims to establish a non-puerperal mastitis (NPM) rat model by simulating hyperprolactinemia and immune-inflammatory states, and to evaluate its local inflammatory characteristics in the mammary gland, thereby laying the foundation for research on the diagnosis and treatment of this clinically challenging disease. Methods Twelve SPF-grade Wistar female rats were evenly divided into a control group and a model group. During the experiment, the control group received no experimental treatment or medication. The model group received daily subcutaneous injections of 100 mg/kg metoclopramide hydrochloride for 7 consecutive days. Serum prolactin (PRL) levels were measured using ELISA on the 10th, 20th, and 30th days after the first injection. After 7 days of injections, 200 μL of lactating SD rat milk was mixed with 200 μL of complete Freund's adjuvant to prepare an oil-in-water emulsion, which was administered by multiple subcutaneous injections into the back of the Wistar rats for the initial immunization. Seven days after the initial immunization, the emulsion was injected subcutaneously into the third, fourth, and fifth mammary glands for the final immunization. After the final immunization, the rats were observed for 28 days for changes in mammary gland appearance, and the size of mammary nodules was calculated. On the 3rd, 7th, 14th, and 28th days, hematoxylin-eosin (HE) staining was used to analyze mammary tissue morphology. Immunohistochemistry was employed to detect CD138 expression levels. ELISA was used to measure the levels of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) in mammary tissue to comprehensively assess the model. Results Rats in the model group exhibited mammary skin ulceration and foul odor at the ulcer sites. Palpation and ultrasound revealed the formation of mammary nodules. HE staining showed that on the 3rd day after the final immunization, normal ductal and lobular structures in the mammary glands disappeared, with significant infiltration of plasma cells. On the 7th day, ductal dilation, epithelial necrosis and detachment, and pronounced periductal plasma cell and lymphocyte (predominantly T-lymphocytes) infiltration were observed. On the 14th day, there was a proliferation of fibrofatty tissue, small blood vessels, and granulation tissue, with scattered plasma cells in the interstitium. By the 28th day, inflammatory cell infiltration and fibrous tissue proliferation were reduced, with granuloma formation. Serum PRL levels in the model group were significantly increased on the 10th day (P<0.05) and the 20th day (P<0.001). IL-6 and TNF-α levels in mammary tissue were higher in the model group compared to the control group on the 3rd, 7th, 14th, and 28th days (P<0.05). IL-1β levels were higher on the 3rd, 7th, and 14th days compared with the control group (P<0.01) but lower than the control group on the 28th day (P>0.05). iNOS levels were significantly higher on the 7th day after the final immunization (P<0.001). Conclusion A successful NPM model was established in rats, which exhibited typical pathological features such as local mammary masses, abscesses, ulcers, ductal dilation and plasma cell infiltration. This model can serve as a foundation for further research into the diagnosis and treatment of this clinically challenging disease.

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    Three Dimensions of Animal Experiment Ethics: Analysis Based on Value of Life, Animal Welfare, and Risk Prevention
    ZHAO Yong
    Laboratory Animal and Comparative Medicine    2024, 44 (4): 445-454.   DOI: 10.12300/j.issn.1674-5817.2024.108
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    Ethical review of animal experiments is based on factors such as the necessity of the experiment, its scientific validity, the professional competence of the experimenters, and research conditions, to determine the ethical permissibility of an animal experiment. Attitudes towards laboratory animals and animal experiments vary significantly due to differences in cultural traditions, religious beliefs, personality traits, and roles within the experimentation process. How animal experiment ethics can advance in tandem with the advancements of life sciences, while consistently providing forward-looking guidance and safeguarding fundamental ethics, is a subject that requires continuous exploration, practice, and research. Ensuring the welfare of laboratory animals has now become a widely accepted ethical consensus. However, attitudes and principles towards different types of animal experiments, and the methods to genuinely and effectively ensure the welfare quality of animals during live animal experiments, should be central to animal experiment ethics. Based on the deep integration of biotechnology in the field of laboratory animals, this paper considers the contribution of animal experimentation to the development of scientific ethical concepts. It systematically elucidates the special value of life in laboratory animals and their relationship with biosafety and ecological safety. It also outlines welfare quality assessment methods for different species of laboratory animals, demonstrating that the philosophical ideology of the value of life is the core of animal experiment ethics. The quality and significance of animal experiments determine the ethical level at which the value of life in laboratory animals is realized, and animal welfare technologies provide a robust ethical guarantee for animal experiments. The close integration of ethical theories with life sciences in laboratory animals is an objective requirement for animal experiment ethics. The value of life, animal welfare, and risk prevention collectively form the core elements of ethical review in animal experiments, serving as fundamental factors in improving the quality of ethical reviews and avoiding ethical deviations.

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    Establishment and Evaluation of a Moderate-to-Severe Knee Osteoarthritis Model in Rats Induced by Surgery
    SUN Xiaorong, SU Dan, GUI Wenjuan, CHEN Yue
    Laboratory Animal and Comparative Medicine    2024, 44 (6): 597-604.   DOI: 10.12300/j.issn.1674-5817.2024.066
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    Objective To establish a rat model of moderate-to-severe knee osteoarthritis, laying the foundation for studying the pathogenesis of moderate-to-severe knee osteoarthritis and its prevention and treatment methods. Methods Thirty male SD rats were randomly divided into three groups: a sham surgery group, an 8-week model group, and a 20-week model group, with 10 rats in each group. Rats in the 8-week and 20-week model groups underwent surgery to cut the anterior and posterior cruciate ligaments and medial collateral ligament of the right knee joint, and remove the medial and lateral menisci. After surgery, the rats were allowed to move freely. The rats in the sham surgery group had only skin incisions to expose the joint without any surgical treatment. At 8 and 20 weeks post-surgery, Micro-CT scans were performed to analyze the femoral osteoporosis in the rats. After euthanizing the rats, gross observations of the knee joints were made, and the cartilage of the joint surface was scored using the Pelletier scoring system. The knee joints were collected for hematoxylin and eosin (HE) staining and safranin O-fast green staining to observe changes in cartilage morphology. The modified Mankin's scoring system was used to assess the tissue pathology of the joint surface. Immunohistochemical staining was used to detect the expression of type II collagen and matrix metalloproteinase 13 (MMP13), reflecting the anabolic and catabolic metabolism of the knee joint cartilage. Results The knee joint cartilage in the 8-week and 20-week model groups was severely damaged, with Pelletier and modified Mankin's scores significantly higher than those in the sham surgery group (both P<0.01). The Pelletier and modified Mankin's scores in the 20-week model group were significantly higher than those in the 8-week model group (P<0.01). Micro-CT observations revealed irregular joint surfaces, osteophyte formation, and signs of osteoporosis in both the 8-week and 20-week model groups, with the 20-week model group showing more loose bodies around the knee joints. Immunohistochemical staining showed increased expression of MMP13 and decreased expression of type II collagen in the knee joint tissues of the model groups, indicating that the balance of anabolic and catabolic metabolism in the joint cartilage was disrupted. MMP13 increased while type II collagen decreased. Conclusion The surgical method of cutting the anterior and posterior cruciate ligaments and medial collateral ligament and removing the medial and lateral menisci successfully creates a moderate-to-severe knee osteoarthritis model in rats. Imaging examinations reveal osteophytes, osteoporosis, and loose bodies in the knee joints, while pathological observations show a reduction or even disappearance of joint cartilage, with a disruption in the balance of cartilage anabolic and catabolic metabolism.

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    Ginkgolide B Promotes Neural Function Recovery of Ischemic Stroke Mice by Regulating Characteristics of Brain T Cells and Their Interactions with Glial Cells
    Jia LIU, Yanrong YE, Yun SHEN, Qiying TANG, Meiqing CHEN, Kehui YI, Shaozhuang CHEN
    Laboratory Animal and Comparative Medicine    2024, 44 (2): 139-148.   DOI: 10.12300/j.issn.1674-5817.2023.121
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    Objective To investigate the regulatory effects of Ginkgolide B on the biological characteristics of brain T cells and their interactions with glial cells during the recovery phase of ischemic stroke in mice. Methods 36 adult C57BL/6 mice were randomly assigned to three groups: sham-operated group (Sham group), control group (PBS group), and Ginkgolide B treatment group (GB group). The Sham group underwent only sham surgeries, whereas the PBS and GB groups were subjected to a middle cerebral artery occlusion (MCAO) model using the filament method, followed by intranasal administration of an equivalent volume of either PBS or Ginkgolide B solution for 14 days post-injury. Neurological function changes were evaluated in all three groups using the rotarod test and a neurological scoring system. On day 15, single-cell sequencing was performed on fresh tissues from the brain injury areas, surrounding cortex, corpus callosum, and striatum of mice in the PBS and GB group to assess the biological characteristics of T cells and their subpopulations, and further explore the interactions and mechanisms among T cells, microglia, and oligodendrocytes. Results Compared with the Sham group, both PBS and GB group exhibited significant improvements in neurological scores and reduced pre-fall motor durations (P < 0.001). Compared with the PBS group, the GB group showed a downward trend in neurological scores and an upward trend in pre-fall motor durations on days 5, 10, and 15 post-ischemic brain injury, with a significant increase in pre-fall motor duration on day 15 (P < 0.05). Compared with the PBS group, the GB group exhibited a significant increase in T cell proliferative activity in the brain 15 days post brain injury (P < 0.05). The number of proliferative T cells and the levels of lipid metabolism were significantly elevated (P < 0.05), and there was a significant increase in extracellular matrix remodeling in all T cells (P < 0.05). Additionally, the interactions between T cells and both microglia and oligodendrocytes, as well as among the microglia themselves and between microglia and oligodendrocytes, were significantly enhanced in the GB group. This was primarily evident in the strengthened interactions between CD74 and macrophage migration inhibitory factor (MIF), as well as colony stimulating factor 1 receptor (CSF1R) and colony stimulating factor 1 (CSF1) (P < 0.05). However, the inflammatory levels of T cells showed no significant differences compared with the PBS group. Conclusion A mouse model of ischemic stroke can be successfully established by MCAO operation. Ginkgolide B may promote neurological recovery post-brain injury in mice by modulating the biological characteristics of T cells within the brain and their interactions with glial cells.

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    Advantages of Ciona intestinalis as a Model Organism and Its Applications
    Ruiqi LI, Han DUAN, Luo GAN, Yuan ZHENG, Wen YANG
    Laboratory Animal and Comparative Medicine    2024, 44 (2): 162-179.   DOI: 10.12300/j.issn.1674-5817.2023.159
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    With the continuous development of experimental biology, the limitations of commonly utilized model organisms are becoming increasingly apparent. Discrepancies between research conducted on laboratory animals and humans significantly impede the translational application of findings derived from animal experiments. This review introduces ascidian Ciona intestinalis as a novel model organism, an invertebrate that is evolutionarily closest to vertebrates and is a sister group to vertebrates. The review summarizes recent research progress on Ciona intestinalis in various fields to illustrate the significant advantages and promising application prospects of it as a model organism. The research progress outlined in the review mainly encompasses: (1) The whole-genome sequencing of Ciona intestinalis has been determined and numerous related databases have been established. Various embryonic gene editing technologies have been successfully applied, making it an animal model easy to manipulate genetically and study the functions and interactions of target genes visually. (2) In the field of neurobiology, Ciona intestinalis boasts a central nervous system structure similar to that of vertebrates and possesses numerous homologous neuropeptides and hormone molecules. These features grant it an edge in exploring the mechanisms and functional evolution of endocrine and neuroendocrine-related molecules. Additionally, the sensitivity and habituation of its larvae to light stimulation provide an avenue for exploring mechanisms related to behavioral plasticity. (3) In the field of immunology, Ciona intestinalis possesses a mature innate immune system and has evolved precursor genes to the adaptive immune system, with a relatively simple coding of immune-related genes. These features make it an exemplary model organism for immunological studies. (4) In the field of developmental biology, many studies have focused on the notochord development process in Ciona intestinalis and the regulatory mechanisms of gene expression within it, indicating common evolutionary developmental strategies among chordates. Additionally, insights into its heart development also significantly enhance our comprehension on the genetic network of human heart development. (5) In medical research, the ability of Ciona intestinalis to regenerate its neural complex and siphon, as well as the resilience of its heart to recover contractile function from substantial damage, renders it a valuable animal model for the study of regeneration and heart injury. It also has unique advantages as a research model for Alzheimer's disease and new drug development. Furthermore, its brief five-month lifespan facilitates the observation and recording of the entire aging process and the exploration of the effects of various factors on aging. In summary, this review aims to demonstrate that Ciona intestinalis stands out as a model organism with unique attributes and is expected to play a significant role in a wider range of scientific research areas.

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    Application of Allograft Endometriosis Rat Model in Pharmaco-dynamic Evaluation of GnRH Agonists
    Ruihua ZHONG, Guoting LI, Wenjie YANG, Xiangjie GUO, Jieyun ZHOU, Yingyi HU, Qicheng NI, Ye YANG, Min ZHANG, Yan ZHU
    Laboratory Animal and Comparative Medicine    2024, 44 (2): 127-138.   DOI: 10.12300/j.issn.1674-5817.2023.150
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    Objective To establish an allogeneic rat model of endometriosis and to evaluate the effects of gonadotropin-releasing hormone (GnRH) agonist GenSci006 on experimental rat endometriosis. Methods Endometrium from SPF grade donor female SD rats were transplanted onto the abdominal wall of recipient female rats to construct an allogeneic endometriosis model. The rats undergoing sham surgery were divided into the sham group. Three weeks later, the length, width and height of the ectopic endometrium were measured, and the volume of the endometrium (V1) was calculated before drug administration. The modeling rats were randomly divided into four groups: model group, triptorelin group (0.25 mg/kg), GenSci006-1 group (0.125 mg/kg) and GenSci006-2 group (0.25 mg/kg). Each group had 16 rats and received a single dose of the corresponding drug. The sham group and model group were administered an equal volume of solvent. Three weeks after administration, ectopic endometrium was measured to calculate the volume V2 and inhibition rate. The effect of GenSci006 on rat uterus and ovarian tissues was assessed by comparing organ coefficients and changes in pathological sections. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of serum estradiol (E2), progesterone (P4), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Real-time fluorescent quantitative PCR was used to detect the expression of GnRH receptor (GnRHR) mRNA in the hypothalamus and pituitary. Western blot was used to detect the expression of estradiol receptor alpha (ERα), beta (ERβ) and progesterone receptor (PR) in ectopic endometrium. Results Three weeks after administration, compared with the model group, the body weight of rats in the triptorelin and GenSci006-2 groups significantly increased (P < 0.05), while the volume of ectopic endometrium significantly decreased (P < 0.05). Compared with the sham group, the model group showed no significant changes in uterine and ovarian organ coefficients or endometrial thickness (P > 0.05). Compared with the model group, the uterine organ coefficients and endometrial thickness were significantly reduced in the triptorelin and GenSci006-2 groups (P < 0.05). Compared with the sham group, the serum levels of E2, P4, FSH and LH in the model group showed no significant changes (P > 0.05). Compared with the model group, the ovarian organ coefficient and serum P4 levels of rats in the Triptorelin, GenSci006-1, and GenSci006-2 groups were significantly reduced (P < 0.05), while the serum LH levels of rats in the GenSci006-1 group were significantly increased (P < 0.05). However, there were no significant changes in serum E2 and FSH levels in each group (P > 0.05). Compared with the model group, the expression levels of GnRHR mRNA in the pituitary tissue of rats in the triptorelin and GenSci006-2 groups were significantly downregulated (P < 0.05), with no significantly changes in the hypothalamus (P > 0.05). There were no significant changes in the expression level of GnRHR mRNA in the hypothalamus or the protein levels of ERα, ERβ and PR in the ectopic endometrial tissue in any group (P > 0.05). Conclusion The allogeneic endometriosis rat model is a suitable animal model for screening and evaluating drugs for treating endometriosis. The volume of ectopic endometrium, inhibition rate, uterine and ovarian organ coefficients, and serum E2 levels may serve as indicators for detecting drug efficacy.

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    Integrative Analysis of Omics Data in Animal Models of Coronavirus Infection
    WU Yue, LI Lu, ZHANG Yang, WANG Jue, FENG Tingting, LI Yitong, WANG Kai, KONG Qi
    Laboratory Animal and Comparative Medicine    2024, 44 (4): 357-373.   DOI: 10.12300/j.issn.1674-5817.2024.008
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    Objective This study analyzes the omics data resources in human-infecting coronavirus animal models collected from various public databases, focusing on data distribution, dataset quantity, data types, species, strains, and research content. It aims to enhance our understanding of biological characteristics and pathogenic mechanisms of coronaviruses, thereby providing a solid foundation for devising effective therapeutic strategies and preventive measures. Methods Query strategies, including specific virus names, time ranges, and inclusion and exclusion criteria, were defined to retrieve data from major public omics databases such as GEO and ArrayExpress. Secondary filtering was performed based on different field types to obtain a more accurate data list. An omics data text database was established for bibliometric analysis. Co-occurrence networks were constructed for the analysis of the correlation strengths between different research themes, technical methods, and involved species. The cell types, organs, and biological pathways involved in studies were examined to further elucidate the pathogenic interplay between pathogens and hosts. Results About twenty public databases containing coronavirus-related omics data were identified, with a primary focus on novel coronavirus infection. Commonly used species include humans, mice, hamsters, and monkeys, while the commonly used virus strains are Wuhan-Hu-1 and USA-WA1/2020. Lung tissues are primarily used in animal models such as mice, macaques, and ferrets, while airway epithelial cells and Calu-3 cells are predominantly employed in human-related studies. Expression profiling data indicate that gene pathways involved in inflammation, cytokine response, complement pathway, cell damage, proliferation, and differentiation are significantly upregulated after infection. Proteomics studies reveal significant changes in phosphoproteome, ubiquitinome, and total proteome of patient samples at different infection stages. Specific protein categories, including viral receptors and proteases, transcription factors, cytokines, proteins associated with coagulation system, angiogenesis-related proteins, and fibrosis markers, show alterations after coronavirus infection. In addition, metabolomics data suggest that phosphocholine, phosphoethanolamine, arachidonic acid, and oleic acid could serve as potential metabolic markers. Epigenomics research indicates m6A methylation plays a role in SARS-CoV-2 replication, infection, and transmission, affecting host cell-virus interactions. Among these, N, S, and non-structural proteins 2 and 3 exhibit the most significant ubiquitination. Trends in microbiomics research suggest that microbial communities in the gut and wastewater are emerging as new research focuses. Conclusion The data types of coronavirus omics are diverse, with a wide variety of models and cell types used. The selection of species and technical methods for modelling varies based on the characteristics of different viruses. Multi-omics data from animal models of coronavirus infection can reveal key interactions between hosts and pathogens, identifying biomarkers and potential therapeutic targets, and provide valuable information for a deeper understanding of biological characteristics and infection mechanisms of coronaviruses.

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    Research Progress on Animal Models of Sepsis-Related Organ Injury
    YANG Jiahao, DING Chunlei, QIAN Fenghua, SUN Qi, JIANG Xusheng, CHEN Wen, SHEN Mengwen
    Laboratory Animal and Comparative Medicine    2024, 44 (6): 636-644.   DOI: 10.12300/j.issn.1674-5817.2024.087
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    Sepsis is a multi-organ dysfunction syndrome caused by infection and immune dysfunction, with a high mortality rate. It affects multiple important organs such as the heart, lungs, kidneys, liver, and brain. Establishing corresponding animal models of organ dysfunction syndrome is an essential step in clarifying its pathogenesis, researching potential effective drugs, and evaluating the effectiveness and safety of treatment plans. This article first summarizes classic modeling methods for sepsis related organ injury, including the destruction of intestinal barrier tissue integrity and the implantation of pathogens or toxic drugs. The former mainly includes cecal ligation and puncture, ascending colon stent implantation, and cecal ligation incision. The latter is divided into intraperitoneal injection, intravenous injection, and intratracheal administration based on the clinical infection route being simulated. Cecal ligation and puncture and lipopolysaccharide intraperitoneal injection are the most commonly used methods. Secondly, this article summarizes the common modeling methods and evaluation methods for animal models of sepsis-induced cardiomyopathy, acute lung injury, acute kidney injury, acute liver injury, and brain dysfunction. It points out that almost all organ injuries use classic modeling methods, and different organ injury models have additional modifications according to their different pathogenesis. For example, in addition to the classic modeling methods, lipopolysaccharide instillation in the trachea is more effective in modeling acute lung injury as it better simulates lung barrier dysfunction. Cecal ligation and puncture followed by Pseudomonas instillation in the trachea in a secondary challenge model better represents sepsis-induced acute kidney injury. Intraperitoneal injection of galactosamine is a mature modeling method of sepsis-induced acute liver injury. Intracerebral injection of lipopolysaccharide is a feasible model of sepsis-associated encephalopathy. In addition to the different modeling methods, there are differences in the administration time, dosage and experimental time points according to the different experimental purposes. This article reviews the research progress of animal experimental models for sepsis-induced cardiomyopathy, acute lung injury, acute kidney injury, acute liver injury, and brain dysfunction, aiming to provide a reference for the selection of animal experimental models and optimization of experimental design.

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    Genetic Characteristics and Research Progress of Feline Coronavirus
    TAO Lingyun
    Laboratory Animal and Comparative Medicine    2024, 44 (6): 661-666.   DOI: 10.12300/j.issn.1674-5817.2024.069
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    Feline coronavirus (FCoV) is classified into two biotypes: feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV). FIPV and FECV might evolve and mutate via genetic recombination and mutation, leading to novel subtypes and variants. This study examined the genomic structure and biological subtyping of FCoV, analyzed the infection characteristics of FIPV and FECV, and investigated the mechanisms of FECV transforming into FIPV. The findings revealed that while their genome structures were fundamentally similar, differences in their ability to efficiently infect monocytes/macrophages significantly influenced their pathogenicity and transmission characteristics, with FIPV exhibiting higher virulence. Moreover, the analysis of the open reading frames (ORF)3/7 as well as the N/S sequences of FIPV indicated that its non-structural proteins were associated with modulation of the host immune system. These proteins enabled immune evasion, leading to more severe disease. The genomic variability of FCoV constitutes an important foundation for studying the pathogenicity and epidemiology of FIPV and FECV, and offers references for virus detection and drug development.

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    Application Analysis of Animal Models for Pelvic Inflammatory Disease Based on Data Mining
    ZHENG Yiqing, DENG Yasheng, FAN Yanping, LIANG Tianwei, HUANG Hui, LIU Yonghui, NI Zhaobing, LIN Jiang
    Laboratory Animal and Comparative Medicine    2024, 44 (4): 405-418.   DOI: 10.12300/j.issn.1674-5817.2024.012
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    Objective To investigate the key elements for model establishment and determine the evaluation indicators of animal models for pelvic inflammatory disease (PID), providing a reference for improving modelling methods and optimizing the application of PID animal models. Methods The search query "Pelvic Inflammatory Disease" AND "Animal Model" OR "Rat" OR "Mouse" OR" Guinea Pig" OR "Rabbit" OR "Dog" OR "Pig" was used to retrieve relevant literature on PID animal models published from 2013 to 2023 in China Knowledge Network Infrastructure (CNKI), Wanfang, and PubMed databases. The studies were analyzed and categorized based on experimental animal types, modelling methods, modelling cycles, detection indicators, positive control drugs, and administration duration. A database was established for statistical analysis. Results A total of 214 research articles on PID animal models meeting the inclusion criteria were identified. The most commonly used model animals are Sprague Dawley (SD) rats, followed by Wistar rats. The most frequently employed modelling method is a combination of mechanical injury and bacterial infection, followed by the phenol mucilage method. The most common modelling cycles for acute pelvic inflammatory disease (APID) and chronic pelvic inflammatory disease (CPID)/sequelae of pelvic inflammatory disease (SPID) are 8 to 14 days, while for PID models without specific staging, the cycles are 7 days. High-frequency detection methods and indicators include histopathological observation using hematoxylin-eosin staining, enzyme-linked immunosorbent assay (ELISA) for serum-related indicators, morphological changes of tissues observed with the naked eye, and immunohistochemical detection of related protein expression in uterine tissues, and pathological scoring. The most frequently used positive control drugs are Fuke Qianjin Tablets, followed by Jingangteng Capsules. The most common administration duration for APID is 7 days, and for CPID/SPID models, it ranges from 15 to 21 days. Conclusion Currently, SD rats and Wistar rats are commonly used as experimental animals for PID models. The dual modelling method of mechanical injury combined with mixed bacterial infection aligns closely with clinical pathogenesis and can be used to establish a PID model that simulates postoperative uterine cavity infection. Depending on the research objectives, different positive drugs and detection indicators should be selected for comprehensive evaluation. Most existing PID animal model studies are based on western medical diagnosis, with fewer studies focusing on Traditional Chinese Medicine (TCM) syndromes. There is a need to integrate TCM theories of etiology and pathogenesis to construct PID animal models that are more in line with TCM clinical symptoms.

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    Advances in Comparative Medical Research on Anatomy and Histological Structure of Intervertebral Discs in Humans and Other Animals
    Li ZHANG, Yu KUANG, Lingxia HAN
    Laboratory Animal and Comparative Medicine    2024, 44 (2): 192-201.   DOI: 10.12300/j.issn.1674-5817.2023.141
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    The 2023 China Health Report on Spine Degeneration noted a significant increase in lumbar surgery among patients under 35 years old in recent years, indicating a trend towards younger onset of cervical and lumbar diseases. Lumbar intervertebral disc herniation has become a major concern, making the study of disc degeneration pathogenesis and treatment methods clinically significant. At present, human intervertebral disc diseases are primarily diagnosed through imaging due to the challenges of obtaining tissue samples from the spine. Therefore, experimental animals have emerged as alternative research subjects because they are cost-effective, have short experimental cycles, and are easily accessible. Given the structural and physiological differences between human and other animal intervertebral discs, comparing their anatomy and histological characteristics forms the foundation of research into human disc degeneration. The purpose of this paper is to collect and review relevant studies on anatomical and histological structures of intervertebral discs in different animals and conduct a comparative analysis from four aspects, namely, intervertebral disc height, lumbar disc geometry, lumbar disc cartilaginous endplate characteristics, and extracellular matrix components. The results show that humans, kangaroos, sheep, pigs, and rats exhibit similar relative heights between the sixth and seventh cervical vertebrae. Mice possess lumbar disc geometries most akin to humans. Compared to other animals, humans have the thickest cartilaginous endplates and the lowest cell densities. The collagen within the fibrous annulus differs most notably in pigs compared to humans, while water content in the nucleus pulposus is consistent across pigs, sheep, rabbits, rats, and humans. Additionally, this paper describes the commonalities and discrepancies in disc degeneration manifestations between humans and animals, and summarizes modeling methods for disc degeneration in different experimental animals. Ultimately, the aims of this paper is to provide fundamental data for selecting suitable experimental animal models for the study of intervertebral disc degeneration.

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    Advances in Research on Pathological and Molecular Mechanism of Hyperuricemic Nephropathy Based on Animal Models
    Fangqi BAO, Haiye TU, Mingsun FANG, Qian ZHANG, Minli CHEN
    Laboratory Animal and Comparative Medicine    2024, 44 (2): 180-191.   DOI: 10.12300/j.issn.1674-5817.2023.123
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    Uric acid (UA), the final product of human purine metabolism, can cause hyperuricemia (HUA) when excessively accumulated. HUA is closely linked to chronic kidney diseases (CKD) and is considered an independent risk factor. Hyperuricemic nephropathy, a form of CKD induced by HUA, has seen significant advances in understanding through research into the pathogenic roles of uric acid and the development of HUA animal models. Although progress has been made in understanding the pathophysiological mechanisms by which UA induces CKD, much remains to be learned about its pathological molecular mechanisms. New approaches in animal modeling or the selection of model animals may potentially lead to significant breakthroughs in research on hyperuricemia as well as related CKD. This paper reviews the research progress on the molecular mechanisms of hyperuricemic nephropathy, focusing on oxidative stress, inflammation, autophagy, fibrosis, and gut microbiota. Oxidative stress is induced by uric acid intracellularly through xanthine oxidase, NADPH oxidases, and mitochondria, leading to cellular damage. In terms of inflammation, uric acid crystals can activate the NLRP3 inflammasome, triggering an inflammatory cascade. The role of free uric acid as a pro-inflammatory agent, however, remains controversial. Depending on the study conducted, autophagy has been found to either alleviate or exacerbate inflammation induced by uric acid. Fibrosis, particularly through epithelial-mesenchymal transition (EMT), is a major mechanism by which uric acid causes glomerulosclerosis and tubulointerstitial fibrosis. Extensive research has explored various signaling pathways involved in uric acid-induced EMT. Beneficial gut microbiota protect the kidneys by synthesizing short-chain fatty acids, reducing urea’s enterohepatic circulation, and decreasing uric acid production. This paper aims to enhance understanding of the complex relationships between HUA and CKD, serving as a reference for further research and new drug development.

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    Analysis of the Progress in Identification and Evaluation of Laboratory Animal Resources in China
    DU Xiaoyan, LIU Yunbo
    Laboratory Animal and Comparative Medicine    2024, 44 (5): 469-474.   DOI: 10.12300/j.issn.1674-5817.2024.050
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    Laboratory animals are not only a national strategic resource but also an important support for development of science and technology. The Committee of Identification and Evaluation for Laboratory Animal Resources, organized by Chinese Association for Laboratory Animal Sciences and established in May 2019, is currently the only specialized academic agency dedicated to the identification and evaluation of laboratory animal resources in China. This paper first discusses the significance of identifying and evaluating laboratory animal resources, summarizes three new approaches to developing these resources, including the domestication and standardization of laboratory animals (economic, ornamental, agricultural, and wild animals, etc.), the acquisition of new strains (species) through natural mutation and induced mutation, and the creation of new laboratory animal resources through gene editing technology. It then introduces the workflow for resource identification and evaluation, including preliminary review (format review), written review (expert review), joint review or on-site inspection, final review (voting and public announcement),and the issuance of certificates. The required materials to be submitted include application, summary report, research or identification reports, appendices and other necessary documents. The paper further discusses related requirements for resource identification and evaluation, including population, genetic classification, biological characteristics, genetic stability, and application value. Finally, the current status of newly identified laboratory animal strains (species) and issues in current work practices are analyzed, as well as solutions to these issues. This paper aims to provide a valuable reference for further research in this field.

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    Establishment of a New Hyperglycemic Obesity Cardiac Dysfunction Mouse Model with Triacsin C
    ZHAO Xiaona, WANG Peng, YE Maoqing, QU Xinkai
    Laboratory Animal and Comparative Medicine    2024, 44 (6): 605-612.   DOI: 10.12300/j.issn.1674-5817.2024.078
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    Objective This study aims to establish a novel hyperglycemic obesity mouse model by utilizing Triacsin C, an inhibitor of acyl-CoA synthetase long-chain family member 1 (ACSL1), combined with a high-fat diet, to simulate the changes in adipose tissue and cardiac function observed in patients with obesity-related type 2 diabetes. Methods Twenty adult SPF-grade male C57BL/6J mice were randomly divided into two groups: the Control group (injected intraperitoneally with citric acid-sodium citrate buffer, Con group) and the TC group (injected intraperitoneally with Triacsin C, TC group). After four consecutive weeks of intraperitoneal injections, both groups were fed high-fat diets. Body weight and glucose tolerance of the mice were assessed every eight weeks. The models were considered successful if fasting blood glucose exceeded 8 mmol/L or blood glucose was above 15 mmol/L two hours after glucose injection. Cardiac function, including ventricular end-diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), end-diastolic interventricular septal thickness (EDIVS), left ventricular ejection fraction (LVEF), and left ventricular short-axis fractional shortening (FS), was measured by echocardiography. HE staining was used to detect the changes in epididymal white adipose tissue (WAT) and brown adipose tissue (BAT). Immunofluorescence technology was used to analyze changes in CD31 and UCP1 in BAT. ACSL1 expression in myocardial tissue was tested by Western blotting. Results The fasting blood glucose levels were (8.14±1.43) mmol/L in the Con group and (8.18±0.85) mmol/L in the TC group (P>0.05) , and the 2-hour postprandial blood glucose levels were (19.8±4.01) mmol/L in the Con group and (22.60±3.97) mmol/L in the TC group (P<0.05). This indicated that both groups of diabetic mouse models were successfully established. Compared to the Con group, the TC group showed poor glucose tolerance; significant decreases in LVEDD, LVEF and FS (P<0.05); significant increases in WAT and BAT areas (P<0.05); significant decreases in CD31 and UCP1 expression (P<0.05); and a significant decrease in the expression of ACSL1 in myocardial tissues (P<0.05). Conclusion Compared with the high-fat diet-induced type 2 diabetes model, the new hyperglycemic obesity and cardiac dysfunction mouse model, created by the combination of Triacsin C and a high-fat diet, is feasible and allows for easier observation of brown adipose tissue whitening, insulin resistance and cardiac dysfunction.

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    Optimization and Evaluation of Conditions for Orthotopic Nude Mouse Models of Human Liver Tumor Cells
    MENG Yu, LIANG Dongli, ZHENG Linlin, ZHOU Yuanyuan, WANG Zhaoxia
    Laboratory Animal and Comparative Medicine    2024, 44 (5): 511-522.   DOI: 10.12300/j.issn.1674-5817.2024.048
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    Objective The study aims to optimize the conditions for constructing orthotopic nude mouse models of liver cancer by injecting human liver tumor cell lines and to explore appropriate timings for drug administration. Methods Human hepatocellular carcinoma Hep3B and hepatoblastoma HepG2 cell lines, which stably expressing the luciferase reporter gene (LUC), were selected. The linear correlation between the luciferase luminescence intensity and the number of liver tumor cells was analyzed using a Small Animal In Vivo Imaging system to verify the luminescent efficiency of the human liver tumor cells. Different concentrations (8×106, 2.4×107, 7.2×107 cells/mL) and resuspension media (PBS, Matrigel) of human liver tumor cell suspensions HepG2-LUC and Hep3B-LUC were orthotopically inoculated into the liver lobes of 5-week-old female BALB/c nude mice (12 groups, 7 mice each) to construct human liver tumor nude mouse orthotopic cancer models. Every 7 days, the weights of mice were recorded, and the growth of orthotopic tumors was monitored using the Small Animal In Vivo Imaging system. On day 35 post-cell inoculation, mouse livers were dissected, and pathological slices were prepared for HE staining to observe histopathological changes in liver tissues. Results The luminescence intensity of human liver tumor cell lines was positively correlated with the number of cells (R2=0.983 1, R2=0.970 5), indicating their suitability for orthotopic model construction. Successful modeling was achieved in the high-concentration groups of HepG2-LUC, the low-, medium-, and high-concentration groups of HepG2-LUC+Matrigel, the medium- and high-concentration groups of Hep3B-LUC, and the low-, medium-, and high-concentration groups of Hep3B-LUC+Matrigel. For both HepG2-LUC+Matrigel and Hep3B-LUC+Matrigel groups, mice in the high-concentration groups exhibited significantly reduced body weight compared to the low- and medium-concentration groups (both with P<0.05). The luminescence intensity of successfully modeled mice increased exponentially over time (R2>0.950 0), and reached a minimum of 1.0×107 p/(s·cm2·sr) by day 14 post-transplantation. Mice in the low- and medium-concentration groups of HepG2-LUC and the low-concentration group of Hep3B-LUC showed no significant pathological changes, while the other groups exhibited evident liver tumors and hepatocyte lesions. Conclusion For the HepG2-LUC cell line, the recommended injection volume is 50 μL with a cell density of 2.4×107 cells/mL, resuspended with Matrigel, followed by drug administration or prognostic measures on day 7 post-modeling. For the Hep3B-LUC cell line, the recommended injection volume is 50 μL with a cell density of 7.2×107 cells/mL, not resuspended with Matrigel, with administration or prognostic measures on day 14 post-modeling.

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    Screening of Hypoxia-Sensitive and Hypoxia-Tolerant Wistar Rats and Preliminary Exploration of Hypoxia Sensitivity in Their G 1 Generation
    XIAO Pan, WANG Hongyi, LU Lu, ZHANG Mei, CHEN Keming, SHEN Dongshuai, NIU Tingxian
    Laboratory Animal and Comparative Medicine    2024, 44 (4): 374-383.   DOI: 10.12300/j.issn.1674-5817.2024.017
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    Objective By screening and passaging G0 generation Wistar rats, we obtained hypoxia-sensitive and hypoxia-tolerant G1 generation rats, and then the differences in hypoxia sensitivity among these rats were preliminarily explored. Methods 200 Wistar rats (half male and half female) were selected as G0 generation and placed in a controlled oxygen concentration system. The hypoxia tolerance time, which refers to the time from placement to near death, was recorded for the G0 generation rats at an oxygen volume fraction of 3%. 30 rats (half male and half female) with the shortest hypoxia tolerance time were selected for mating and passage to obtain G1 generation hypoxia-sensitive rats. Similarly, 30 rats (half male and half female) with the longest hypoxia tolerance time were selected for mating and passage to obtain G1 generation hypoxia-tolerant rats. An additional 24 standard Wistar rats were randomly divided into two groups: a control group and a model group, with 12 rats in each group (half male and half female). The control group was kept in a normoxic environment, while the model group, along with the G1 generation hypoxia-sensitive rats (G1 sensitive group) and G1 generation hypoxia-tolerant rats (G1 tolerant group), were placed in a hypobaric hypoxia chamber (simulating an altitude of 5 000 m). After 12 hours, various indicators, including blood gas, complete blood count, blood biochemistry, pathological sections, and hypoxia-related genes were detected or observed to compare the differences in hypoxia sensitivity among the 4 groups. Results Compared with the G0 generation standard rats, the hypoxia tolerance time of G1 generation rats was significantly prolonged (P<0.01). Compared with the model group, the oxygen saturation (SatO2) in G1 tolerant group was significantly higher (P<0.05). In the G1 sensitive group, the levels of white blood cell (WBC) count, neutrophil (NEUT) count, hemoglobin (HGB) concentration, hematocrit (HCT), red blood cell distribution width (RDW), platelet (PLT), and creatinine (Cr) significantly increased (P<0.05 or P<0.01), while actual bicarbonate (AB) content significantly decreased (P<0.05), and the brain and lung coefficients were significantly elevated (P<0.05). In addition, pathological section results showed that the brain and lung tissues in the model group, G1 sensitive group, and G1 tolerant group all suffered from significant damage, with no evident differences in the gene expression levels of hypoxia-inducible factor-1 α (HIF-1α) and vascular endothelial growth factor A (VEGFA) in brain tissues among the three groups (P>0.05). Conclusion Compared with standard rats, G1 generation hypoxia-sensitive/tolerant rats exhibit good signs of hypoxia sensitivity/tolerance traits, but further screening and passage are still needed to purify them.

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    Discussion on the Construction and Operational Experience of Intelligent Control Systems for Laboratory Animal Facilities: Shenzhen Institute for Drug Control as an Example
    Long ZENG, Junpeng LI, Xiaowei WANG, Ning CHEN, Ping WANG, Meirong QIN
    Laboratory Animal and Comparative Medicine    2024, 44 (2): 220-226.   DOI: 10.12300/j.issn.1674-5817.2023.162
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    Intelligent control systems can effectively assist in the construction and management of laboratory animal facilities, improving operational efficiency, ensuring the reliability of animal experimental results, and significantly saving human resources. The intelligent control system for laboratory animal facilities at Shenzhen Institute for Drug Control was completed in April 2021. It includes an intelligent management platform and an information management system for animal laboratories. The intelligent management platform regulates room environment parameters such as temperature, humidity, and pressure through building equipment management system, controlling devices such as the Venturi valve, electric air valve, electric water valve, and steam humidification valve. At the same time, various environmental parameters are monitored online through the environmental monitoring system. The laboratory’s intelligence is further enhanced by systems such as automatic lighting control, full HD video monitoring, automatic access control and door system, independent ventilation and feeding, automatic cleaning, automatic exhaust gas treatment, centralized gas supply, and real-time instrument parameter monitoring. The information management system for animal laboratories integrates inspection, instrument and equipment, personnel, documents, standard substances, reagents, inspection standards, books, records, scientific research management, relevant applications, quality management, and query statistics. For animal experimentation, a management module has been developed to achieve a comprehensive digitization of animal management. Furthermore, real-time collection and recording of data such as balance calibration, sample quality, and animal weight are facilitated through electronic experimental recording. In summary, the Animal Laboratory of Shenzhen Institute for Drug Control has extensively utilized intelligent systems to achieve real-time online control and monitoring, improve efficiency, ensure high-quality facility operation, and meet standard requirements. Smooth execution of all inspection and research activities has been achieved over the past three years. This paper provides insights into the construction, management, and operation of laboratory animal facilities at Shenzhen Institute for Drug Control, offering guidance for the implementation of intelligent control in similar facilities across China.

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    Construction and Evaluation of Theranostic Near-infrared Fluorescent Probe for Targeting Inflammatory Brain Edema
    Jing QIN, Yong ZHAO, Caiqin ZHANG, Bing BAI, Changhong SHI
    Laboratory Animal and Comparative Medicine    2024, 44 (3): 243-250.   DOI: 10.12300/j.issn.1674-5817.2023.166
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    Objective A novel compound based on near-infrared fluorescence (NIRF) probe was prepared to achieve dynamic monitoring of an inflammatory brain edema model in mice and real-time evaluation of therapeutic effects through in vivo imaging. Methods The NIRF probe IR-783 was chemically linked with clinical brain edema therapeutic drug furosemide (FSM) to obtain the new compound, IR-783-FSM. The ultraviolet fluorescence properties of the compound were evaluated using an ultraviolet spectrophotometer. The uptake of the compound by mouse macrophage cells RAW 264.7 was detected with in vitro cellular experiments. Its cytotoxicity was evaluated through CCK8 assays. A brain edema model was established in BALB/c mice via intraperitoneal injection of lipopolysaccharide (LPS), confirmed by HE staining and dry-wet weight methods for brain tissues. The mice in the brain edema model were divided into control group, IR-783, and IR-783-FSM treatment groups, receiving intraperitoneal injections of PBS, IR-783, and IR-783-FSM, respectively. Real-time in vivo fluorescence imaging was then performed. The mice in each group were euthanized after 10 hours. Ex vivo brain imaging and dry-wet weight measurements were performed to observe the NIRF imaging characteristics and therapeutic effects of IR-783-FSM on brain edema model. Results The newly synthesized compound, IR-783-FSM, retained the excellent near-infrared fluorescence characteristics of IR-783. It could target mouse macrophages with an IC50 of 48.82 μmol/L. A brain edema model could be successfully constructed with intraperitoneal injection of LPS, with significantly higher brain tissue water content compared to the control group (P<0.01). In vivo imaging showed that IR-783-FSM had a significantly stronger fluorescence signal in the brain edema model than IR-783. Compared to the control group, the brain water content was significantly reduced in the 2, 5, and 8 mmol/L IR-783-FSM treatment groups (P<0.01). Conclusion The newly synthesized NIRF probe IR-783-FSM facilitates dynamic monitoring of brain edema and real-time evaluation of therapeutic effects.

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    Advances and Challenges in the Research of Integration Methods of Animal Experimental Evidence
    ZHENG Qingyong, LI Tengfei, XU Jianguo, ZHOU Yongjia, MA Zhichao, WANG Na, LI Molan, YANG Wenjing, WU Peirun, WANG Haidong, TIAN Jinhui
    Laboratory Animal and Comparative Medicine    2024, 44 (5): 567-576.   DOI: 10.12300/j.issn.1674-5817.2024.079
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    Integrating evidence from animal experiments is a critical component of biomedical research, providing essential prior information for in-depth investigations of disease mechanisms and new drug development. Animal models have played an irreplaceable role in simulating human diseases. However, the integration of evidence from animal experiments has faced numerous challenges, including insufficient emphasis, significant heterogeneity in study designs, high publication bias, and discrepancies with clinical research practices. This paper first identifies existing issues in the original research evidence from animal experiments, such as the selection and applicability of animal models, considerations in the design of experimental studies, and factors influencing the translation of animal experimental evidence. It then discusses various methods for integrating this evidence, including systematic review and meta-analysis, overview of systematic review/umbrella review, scoping review, and evidence mapping, while highlighting recent advancements in their application. Finally, the paper addresses the main challenges currently encountered in the integration of evidence from animal experiments and proposes targeted improvement strategies aimed at enhancing the efficiency of translating research outcomes into clinical practice and promoting the advancement of evidence-based medicine. By continuously optimizing original experimental research protocols and evidence integration practices, this work aims to establish a more efficient and scientific environment for the synthesis of evidence from animal experiments, ultimately contributing to clinical trials and human health.

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    Research Progress on Animal Models of Long Bone Fractures
    Guangyuan YAO, Ping DONG, Hao WU, Mei BAI, Ying DANG, Yue WANG, Kai HU
    Laboratory Animal and Comparative Medicine    2024, 44 (3): 289-296.   DOI: 10.12300/j.issn.1674-5817.2023.183
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    Traumatic fractures and stress fractures are common orthopedic diseases, and there is great potential in researching bone turnover, repair, and promotion of fracture healing. Basic medical experiments often use animal models of long bone fractures in limbs to study the mechanisms of various interventions on fracture healing. Fracture healing is a complex process influenced by multiple factors and involves multiple molecules and pathways. Therefore, to explore the mechanisms more deeply, accelerate the translation of results, and improve the clinical efficacy, it is particularly important to choose the appropriate animal fracture modeling methods in experimental research. Based on this, this paper conducts a literature review of animal species and modeling methods commonly used for long bone fracture models in experimental research. It summarizes five methods: bone defect method, physical impact method, mechanical bending method, open osteotomy method, and drilling method. A side-by-side comparison of their advantages, disadvantages, and scope of application is made, aiming to provide suitable fracture models for studying the mechanisms of fracture healing interventions.

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    Establishment and Evaluation of Mouse Model of Pregnancy Pain-depression Comorbidity Induced by Chronic Unpredictable Stress, Complete Freund's Adjuvant and Formalin
    Yisu ZHANG, Xinru LIU, Ruojie WU, Rui LIU, Hong OUYANG, Xiaohong LI
    Laboratory Animal and Comparative Medicine    2024, 44 (3): 259-269.   DOI: 10.12300/j.issn.1674-5817.2024.005
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    Objective To establish a mouse model of pregnancy pain-depression comorbidity induced by chronic unpredictable stress (CUS), complete Freund's adjuvant (CFA), and formalin, and to systematically evaluate the associated phenotypes and preliminarily explore the pathological basis of the comorbidity. Methods Eight-week-old C57BL/6J female mice were randomly strarified divided into a control group (no intervention before pregnancy) and a CUS model group (CUS intervention before pregnancy) based on sucrose preference test (SPT) data. After completing the CUS treatment, female and male mice were paired and mated. Pain was induced by injecting 50% CFA and 5% formalin in the right hind foot during pregnancy to create a model of pregnancy pain-depression comorbidity. The experiment was divided into 8 subgroups: control-blank group, CUS-blank group, control-CFA group, CUS-CFA group, control-formalin group, CUS-formalin group, control-CFA+formalin group, and CUS-CFA+formalin group, with 10 mice in each group. The mice in each group were subject to behavioral tests, including the SPT, forced swimming test, tail suspension test, and open field test before and after CUS intervention, during pregnancy, and after delivery. Pain sensitivity changes were measured using mechanical allodynia and thermal hyperalgesia tests. Mice were then euthanized. Levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in hippocampus, as well as cortisol and adrenocorticotropic hormone (ACTH) in serum, were detected by enzyme-linked immunosorbent assay (ELISA). Results Compared with the control-blank group, the CUS-blank group showed a significant depression-like behavior with reduced pain threshold (P<0.001). The control-CFA+formalin group showed a decrease in pain threshold after both CFA injection and formalin injection (P<0.01). Compared with the control-blank and control-formalin groups, the pain threshold was significantly lower in the CUS-formalin group (P<0.01), with a sequential decrease among the three. Compared with the control-blank and control-CFA groups, the pain threshold was significantly lower in the CUS-CFA group (P<0.001), with a sequential decrease among the three. Compared with the control-blank and control-CFA+formalin groups, the mechanical pain threshold of mice in the CUS-CFA+formalin group was significantly lower (P<0.001) and the thermal radiation tolerance time was shorter (P<0.01), both with sequential decreases among the three. Compared with the control-CFA+formalin and the CUS-blank groups, the CUS-CFA+formalin group had a significantly lower percentage of sucrose preference (P<0.001), longer immobility time during the forced swimming test (P<0.001) and tail suspension test (P<0.001), reduced central exploration time in the open field test (P<0.001), reduced total exploration distance (P<0.001), and reduced percentage of distance traveled for central exploration (P<0.001). Compared with the control-CFA+formalin and CUS-blank groups, the serum cortisol and ACTH levels of the CUS-CFA+formalin group were significantly higher (P<0.01), and the levels of IL-6 and TNF-α in the hippocampus were higher (P<0.05). Conclusion The combination of CUS+CFA+formalin injections is an ideal method for establishing a C57BL/6J mouse model of pregnancy pain-depression comorbidity. The behavioral changes in model mice may be attributed to the regulation of inflammatory response in hippocampus and hormone levels in the hypothalamic-pituitary-adrenal (HPA) axis.

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    Investigation on Current Biosafety Management Status in Laboratory Animal Institutions in Hunan Province
    Meitong LIU, Zhang CHEN, Zhaoqiang ZHANG, Di FAN, Zhan HU, Hailing MA
    Laboratory Animal and Comparative Medicine    2024, 44 (2): 202-208.   DOI: 10.12300/j.issn.1674-5817.2023.129
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    Objective This study aimed to investigate the current status of biosafety management in laboratory animal institutions in Hunan Province, identify management shortcomings, and provide targeted recommendations for improvement. Methods A questionnaire survey was conducted in July 2023 among 40 laboratory animal institutions in Hunan Province, covering topics such as the establishment of laboratory management system and its overall operation status, emergency management for incidents, medical waste disposal, animal transportation, personnel practitioner management, environmental disinfection, and equipment maintenance. The awareness of biosafety, animal bite incidents, and vaccination history was surveyed from at least one animal feeder or experimental operation practitioner from each institution, totaling 50 practitioners. Through literature review and comparative analysis, this paper analyzed the current status of biosafety management in production, transportation, and use of laboratory animals in Hunan Province from aspects such as biosafety management systems, personnel training, disinfection of environmental facilities and waste disposal, and provided recommendations. Results Among the 40 laboratory animal institutions in Hunan Province,39 institutions (97.5%) had established laboratory management systems, 37 (92.5%) had emergency response plans for incidents of to transport laboratory animals, 15 (37.5%) had complete records of emergency drills for laboratory animal biosafety, and 39 (97.5%) had established protocols for carcass and waste management. Moreover, 26 institutions (65.0%) had laboratory biosafety risk assessment reports. 4 out of 8 (50.0%) production units had emergency plans for animal transportation, with 7 (87.5%) using special vehicles to transport laboratory animals. 2 (4.0%) of the 50 practitioners were unaware of emergency response plans, 6 participants (12.0%) did not consistently wear personal protective equipment, and 38 participants (76.0%) had been bitten or scratched by laboratory animals. The results of the survey showed that emergency management, transportation management and personnel management of laboratory animal incidents still need improvement in Hunan Province. Relevant functional departments should strengthen supervision and management efforts, establish local regulations for the transportation management of laboratory animals, ensure strict compliance with relevant documents, conduct emergency drills in all units, and strengthen training for practitioners. Conclusion While daily management practices in the 40 laboratory animal institutions in Hunan Province are generally satisfactory, there remains a need for further improvement in emergency management, transportation management, personnel management, etc. Gradually enhancing the level of laboratory animal safety management is essential to collectively safeguard public health safety.

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    Comparison of Methods between Soiled Bedding Sentinels and Exhaust Air Dust PCR for Health Monitoring of Rodent Laboratory Animals
    Lingzhi YU, Xiaofeng WEI, Ming LI, Zhihao KONG
    Laboratory Animal and Comparative Medicine    2024, 44 (3): 321-327.   DOI: 10.12300/j.issn.1674-5817.2023.168
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    The microbiological quality of laboratory animals is crucial for the validity and reproducibility of scientific research data, as well as human health and animal welfare. Currently, individual ventilation cages (IVC) have become the mainstream feeding system for rodent laboratory animals. The most commonly used pathogen monitoring method for this feeding system is soiled bedding sentinels (SBS). This method monitors the microbial carrying status of mouse colony through indirect contact and delayed feedback. It can effectively monitor pathogens transmitted via the fecal-oral route, such as mouse hepatitis virus and reovirus. However, this method has difficulty detecting pathogens mainly transmitted through aerosols or direct contact, such as Sendai virus and Pasteurella pneumotropica. The exhaust air dust (EAD)-PCR monitoring method involves swab sampling in the IVC exhaust ducts to monitor the corresponding racks of the ducts; swab sampling before the prefiltration of the host to monitor the entire IVC rack; and EAD collection device sampling to monitor all racks connected to the same host. Different IVC manufacturers have developed corresponding EAD collection devices for their respective IVC systems, making operations convenient and standardization easy. Compared with the SBS method, the EAD-PCR method significantly improves detection rate and timeliness, with the fastest detection possible after one week of exposure. It can serve as a supplement or replacement for the SBS method. Currently, increasing evidence supports that EAD-PCR testing is a more reliable, sensitive, and cost-effective monitoring method, and is more beneficial to animal welfare. This article reviews the application progress of these two methods for monitoring pathogens, analyzes the existing limitations of the EAD-PCR method, and proposes solutions based on its implementation in our laboratory and examination units. The EAD-PCR method helps reduce the number of live sentinel animals used in pathogen monitoring, in order to better maintain the "3Rs" principle of laboratory animal welfare.

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    Glycyrrhizic Acid Showed Therapeutic Effects on Severe Pulmonary Damages in Mice Induced by Pneumonia Virus of Mice Infection
    Yun LIU, Tingting FENG, Wei TONG, Zhi GUO, Xia LI, Qi KONG, Zhiguang XIANG
    Laboratory Animal and Comparative Medicine    2024, 44 (3): 251-258.   DOI: 10.12300/j.issn.1674-5817.2024.014
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    Objective In this study, inbred BALB/c mice infected with the pneumonia virus of mice (PVM) were used to establish an animal model of viral pneumonia, and the changes in the pro-inflammatory alarmin molecule, high mobility group box 1 protein (HMGB1), during PVM infection were observed, as well as the in vivo intervention effects of the HMGB1 inhibitor, glycyrrhizic acid (GA), on PVM-induced lung injury. Methods Three-week-old female BALB/c mice were randomly divided into three groups, each consisting of 6 mice. One group, uninfected by PVM, served as the control group (Control). The other two groups were inoculated intranasally with PVM at a dose of 1×104 50% tissue culture infective dose (TCID50)/25 μL, and subsequently treated with GA saline solution (GA group) or plain saline solution (normal saline, NS group) via gavage for 15 consecutive days. During this period, changes in body weight and appearance were monitored in each group. At the end of the experiment, lung tissue samples were collected from all groups. The distribution of PVM and HMGB1 proteins in the lung tissues was analyzed using hematoxylin-eosin staining and immunohistochemistry. The expression levels of HMGB1 and its Toll-like receptor 4 (TLR-4), advanced glycosylation end-product-specific receptor (AGER), and inflammatory cytokines such as interleukin (IL)-1β, IL-2, and tumor necrosis factor-α (TNF-α) in lung tissues of mice were measured using real time fluorescence quantitative PCR. Results Compared with the Control group, the NS group showed a significant weight loss after 6 days (P<0.05). Histopathological tests revealed pronounced inflammatory lesions in their lungs. Immunohistochemistry results showed that HMGB1 was released from the nucleus to the cytoplasm, and real time fluorescence quantitative PCR results indicated that the expression levels of HMGB1, IL-1β, and IL-2 were significantly upregulated (P<0.05). In the GA group, there was no significant change in the clinical symptoms or body weight. However, compared with the NS group, the pathological damages of lung tissues in the GA group were significantly reduced, and the expression levels of HMGB1, IL-1β, IL-2, and interferon-γ (IFN-γ) in lung tissues were also significantly decreased (P<0.05), although the expression level of AGER was significantly increased (P<0.05). Conclusion PVM infection can cause significant inflammatory pathological lung damages in mice, and GA can effectively alleviate the damages. Its therapeutic effect may be related to the activation of HMGB1 signaling pathway.

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    Analysis of Institutional Characteristics and Implementation of Guangdong Province Laboratory Animals Ordinance in the Past Decade
    DENG Shaochang, LIN Danrong, LIANG Chujun, LEI Weiqiao, YANG Jinchun, ZHAO Weibo
    Laboratory Animal and Comparative Medicine    2024, 44 (4): 455-462.   DOI: 10.12300/j.issn.1674-5817.2024.030
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    The Guangdong Province Laboratory Animals Ordinance (the GPLAO), officially enacted and implemented in October 2010, marked a new phase of legal management in the administration of laboratory animals in Guangdong Province. The GPLAO clearly authorizes the laboratory animal monitoring institutes in Guangdong Province to conduct laboratory animal quality monitoring and assume corresponding legal responsibilities. It also specifies the standards for the production and use of laboratory animals, while bringing attention to laboratory animal welfare and ethics. Through the formulation of supporting documents, the active promotion of the standardization and regulation of administrative law enforcement, and the implementation of measures to delegate power, streamline administration, and optimize government services, significant improvements have been made in the standardized management of laboratory animals in Guangdong Province and in supporting the innovative development of biomedicine. Moreover, notable achievements have been made in areas such as the construction of experimental animal technology platforms, standardization work, the preservation and development of unique resources, and talent pool development. However, with the advancements in science and technology, social economy, and legislative work, some aspects in the GPLAO have been identified for improvement. These include the need for clearer provisions on laboratory animal welfare, more specific guidelines for the management of genetically engineered animals, improved regulations on the safety and welfare of practitioners, further refined implementation of the "one-vote veto system", continued promotion of laboratory animal standardization, and the exploration of effective mechanisms for resource sharing. This paper reviews and summarizes the institutional characteristics, post-legislation implementation, and effectiveness of the GPLAO, as well as the issues and countermeasures identified during the implementation. It concludes the laboratory animals management practices in Guangdong Province during the past 10 years, aiming to provide a reference for laboratory animal legislation.

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    Preliminary Study on Construction Method of Type 1 Diabetes Model in Banna Miniature Pig
    LIU Kai, HU Yuqi, GENG Yatian, CHENG Wenjie, WANG Jing, WEI Taiyun, ZHAO Hongfang, LI Jiayu, JIAO Deling, ZHAO Hongye, WEI Hongjiang
    Laboratory Animal and Comparative Medicine    2024, 44 (4): 384-392.   DOI: 10.12300/j.issn.1674-5817.2024.060
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    Objective To construct a Type 1 diabetes model in miniature pigs and explore postoperative care strategies for effectively prolonging the survival time of the model pigs. Methods Seven Banna miniature pigs were selected for pancreatectomy. Glucose, vitamins, and antibiotics were administered for 3-5 days after surgery to aid recovery. Blood glucose and urine glucose levels were measured twice a day in the morning and evening to adjust insulin supplementation accordingly. The model pigs were observed daily and records were kept, including orexis, psychosis, weakness, skin ulcer, and feces and urine. Body weight was measured weekly until the death of the model animals. Based on the model pigs' condition, glucose injection and Ringer's lactate solution were administered to supplement nutrition and correct electrolyte imbalances. Results All seven Banna miniature pigs showed typical symptoms of diabetes: random blood glucose levels higher than 11.1 mmol/L after pancreatectomy, far exceeding the average blood glucose level of 6.0 mmol/L in normal pigs; positive urine glucose; and progressive weight loss. These features indicated the successful construction of Type 1 diabetes model. Additionally, Type 1 diabetic pigs that survived more than 8 weeks showed progressive hair loss and skin ulceration. Euthanasia was performed on model pigs when they were unable to stand or even eat independently, and pathological examination and HE staining were conducted on tissues collected from affected organs such as the liver, kidneys, and skin. Pathological sections revealed liver congestion, massive glycogen accumulation, ballooning degeneration of hepatocytes, and progressive liver fibrosis, along with glomerular congestion, vacuolar degeneration in renal tubular epithelial cells, proteinuria, dermal congestion, thinning of vascular walls, and varying degrees of parakeratosis and dyskeratosis in the liver, kidneys, and skin tissues due to prolonged hyperglycemia. The average survival time of the constructed Banna miniature pig diabetes model was 44 d, with a maximum survival time of 121 d. Conclusion Type 1 diabetes model can be constructed successfully in Banna miniature pigs through pancreatectomy. With meticulous postoperative care, a long-term Type 1 diabetes model with significant complications can be achieved, providing a stable large-animal model for Type 1 diabetes treatment strategies.

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    Guideline Checklist for Publishing Research Papers on Animal Experimentation and Comparative Medicine in China (2024 Edition)
    Editorial Board of Laboratory Animal and Comparative Medicine
    Laboratory Animal and Comparative Medicine    2024, 44 (5): 577-582.   DOI: 10.12300/j.issn.1674-5817.2024.149
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    The standardization, transparency, and completeness of research papers in animal experimentation and comparative medicine research are crucial for ensuring the credibility, reproducibility, and clinical applicability of research findings. Internationally recognized guidelines, such as the ARRIVE guidelines, serve to standardize animal experimentation and reporting. In China, there is already a comprehensive framework of regulations and standards governing laboratory animal research. However, the practical guidance in these documents remains insufficient to effectively guide Chinese researchers in writing and publishing in vivo animal research papers. To address this gap, the Editorial Board of Laboratory Animals and Comparative Medicine has developed a checklist of publication standards tailored for Chinese scholars, informed by the ARRIVE 2.0 guidelines and Chinese regulations and standards. This checklist is applicable for authors to self-check during manuscript preparation and submission, for peer experts during the review process, for journal editors in pre-publication verification, and for readers to evaluate published works. It aims to effectively promote the standardization and high-quality development of laboratory animal and comparative medicine research in China.

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    Analysis of Major Vertically Transmissible Pathogens and Their Detection Standards in SPF Chickens
    Mengjie WANG, Wenjie MA, Yu PAN, Jianxing CHEN, He ZHANG, Changyou XIA, Yu'e WANG
    Laboratory Animal and Comparative Medicine    2024, 44 (3): 305-312.   DOI: 10.12300/j.issn.1674-5817.2023.181
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    Specific pathogen-free (SPF) chickens are widely used in the research of avian diseases and vaccines. Vertically transmissible diseases are transmitted to chickens through vertical transmission, seriously affecting their survival rate, increasing production costs, and causing significant economic losses to the poultry industry, while severely impacting the breeding and use of SPF chickens. Therefore, it is crucial for researchers and managers to enhance their understanding of vertically transmissible pathogens in chickens and to develop effective monitoring measures. Quality monitoring is an important part of ensuring the quality of SPF chickens, with pathogen detection being the primary step. Based on this, it is necessary to cultivate qualified SPF chickens through purification methods and biosecurity measures. This paper reviews the major vertically transmissible pathogens in chickens, including viral pathogens, bacterial pathogens and mycoplasmas, as well as their detection methods. This study compares the differences in microbiological testing items and methods for SPF chickens between the U.S. corporate standard and the Chinese national standard. Analysis of the results shows that in both standards, vertically transmissible pathogens such as Escherichia coli, Proteus mirabilis, Salmonella, and avian leukosis are not included in the microbiological testing items for SPF chickens. Instead, these pathogens are characterized by mixed infections, and outbreaks can seriously affect flock health. To produce higher-quality SPF chickens, it is necessary to include these pathogens in the mandatory testing items. The aim of this paper is to help readers understand the relevant standards for microbiological monitoring of SPF chickens, the hazards of vertically transmissible pathogens, and prevention and control strategies, so as to provide a reference for the detection and purification of pathogens in SPF chickens.

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    Advances in Development of PM 2.5-Exposed Animal Models and Their Application in Reproductive Toxicity Research
    TIAN Fang, PAN Bin, SHI Jiayi, XU Yanyi, LI Weihua
    Laboratory Animal and Comparative Medicine    2024, 44 (6): 626-635.   DOI: 10.12300/j.issn.1674-5817.2024.068
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    Atmospheric fine particulate matter (particulate matter 2.5,PM2.5) is a major component of haze, and its potential hazards to human reproductive health have garnered widespread attention. Establishing appropriate animal models is crucial for in-depth research into the reproductive toxicity of PM2.5 exposure and its underlying mechanisms. This paper, based on recent literature, summarizes current methods for establishing PM2.5-exposed animal models and the evaluation criteria for reproductive toxicity research. The primary modeling methods for PM2.5 exposure include whole-body inhalation exposure and intratracheal instillation exposure. While whole-body inhalation exposure effectively simulates real-life human inhalation environments, it requires sophisticated experimental equipment. Conversely, intratracheal instillation exposure is more cost-effective and easier to operate but faces challenges in accurately mimicking the distribution and deposition of PM2.5 during natural inhalation. Therefore, researchers must carefully weigh these exposure methods to enhance model rigor and achieve the most realistic simulation of human exposure conditions. When summarizing the application evaluation indicators of PM2.5-induced reproductive toxicity, this review finds that the main indicators of male reproductive toxicity include reduced sperm quality, testicular tissue damage, and hormonal imbalances. For female reproductive toxicity, the primary indicators are reduced ovarian reserve, endocrine dysfunction, endometrial damage, and adverse perinatal reactions. Additionally, this review highlights the need for detailed chemical composition analysis of PM2.5, exploring the reproductive toxic targets and mechanisms of particles containing different chemical components, such as heavy metals and polycyclic aromatic hydrocarbons. Long-term studies are also necessary to assess the effects of PM2.5 exposure on reproductive health and transgenerational effects, to predict potential long-term risks for humans. Additionally, interdisciplinary collaboration should be encouraged, involving cooperation between environmental science, toxicology, reproductive medicine, and other disciplines, to comprehensively assess the environmental health risks of PM2.5 and provide scientific support for the development of integrated prevention and control strategies. This review summarizes animal modeling methods, evaluation criteria, and their applications, providing valuable methodological references for future reproductive toxicity research on PM2.5.

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    Optimal Adaptation Period for Metabolic Cage Experiments in Mice at Different Developmental Stages
    TAN He, YANG Xiaohui, ZHANG Daxiu, WANG Guicheng
    Laboratory Animal and Comparative Medicine    2024, 44 (5): 502-510.   DOI: 10.12300/j.issn.1674-5817.2024.034
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    Objective To investigate the optimal adaptation period for mice at different developmental stages during metabolic cage experiments, aiming to provide a reference for conducting metabolic research using mice. Methods A total of 80 male C57BL/6J mice at three developmental stages (weaning period M1, adolescent M2, and adulthood M3) were subjected to a 7-day metabolic cage experiment. Data on food intake, water intake, energy expenditure, respiratory quotient, body weight, and activity levels were recorded every five minutes. The collected data were processed using time series decomposition and comprehensive cluster analysis. Statistical differences were compared using repeated measures ANOVA combined with t-test to determine the optimal adaptation period. Results Significant differences in metabolism were observed among mice in different developmental stages (P<0.01). Compared with adolescent (M2) and adult (M3) mice, weaned mice (M1) exhibited lower activity level (P<0.01) and less distinct circadian rhythm. M1 mice had higher oxygen consumption, carbon dioxide production, and energy expenditure, as well as a lower respiratory quotient (all P<0.001), indicating that they mainly relied on fat as an energy source. Analysis of food intake, water intake, and energy expenditure revealed significant differences between the first light cycle (0-12 h) and the second light cycle (24-36 h) across all developmental stages (all P<0.05) . However, there was no significant difference in daily food intake or water intake after 24 hours (both P>0.05). Comprehensive cluster analysis of multiple indicators showed that the overall indicators of mice during the first 24 hours in the metabolic cages did not cluster with those of the subsequent 6 days, demonstrating significant differences. Conclusion Metabolic cage experiment can be used to detect continuous physiological changes in mice. The results suggest that mice can adapt to new metabolic cages environment within 24 hours, providing a theoretical basis for the design of metabolic experiments using mice.

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    Effects of Puerarin on Bone Density in Rats and Mice: A Meta-analysis
    Jinhua HU, Jingjie HAN, Min JIN, Bin HU, Yuefen LOU
    Laboratory Animal and Comparative Medicine    2024, 44 (2): 149-161.   DOI: 10.12300/j.issn.1674-5817.2023.127
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    Objective To evaluate the effects of puerarin on bone density in rats and mice through a meta-analysis. Methods The databases, including CNKI, SinoMed, Wanfang data, VIP, PubMed, EMBase, Web of Science, the Cochrane Library, and Scopus from their inception to November 6, 2023, were searched for literature on the effects of puerarin treatment on bone density in rats and mice. Inclusion criteria for the literature were randomized controlled trials with a placebo or blank control group; the subject animals were rats or mice; the intervention was puerarin; and the results included bone density measurements. Exclusion criteria included combination therapy with puerarin; lack of original research data; unpublished studies; and using mandible as the measurement site for bone density. Risks of bias were assessed using SYRCLE's RoB tool. Data analysis was conducted with Stata 16.0 and Rev Man 5.3 software. Results After applying the inclusion and exclusion criteria, a total of 429 records were identified and 42 articles covering 41 studies were ultimately included. 925 animals were involved and the data analysis results indicated that puerarin improved bone density in rats and mice compared to the control group: femur [37 studies, n=824, standardized mean difference (SMD)=2.12, 95% confidence interval (CI)=1.69-2.54, P < 0.000 1], lumbar spine (13 studies, n=271, SMD=2.25, 95% CI=1.49-3.01, P < 0.000 1), tibia (4 studies, n=95, SMD=0.94, 95% CI=0.05-1.83, P=0.04), and the whole body (4 studies, n=94, SMD=1.89, 95% CI=0.50-3.29, P=0.008), with all inter-group differences in bone density being statistically significant. Conclusion Puerarin can improve bone density in rats and mice. This study provides a valuable reference for clinical studies on the prevention and treatment of osteoporosis with puerarin.

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    Effects of Different Pellet Feed Hardness on Growth and Reproduction, Feed Utilization Rate, and Environmental Dust in Laboratory Mice
    Dong WU, Rui SHI, Peishan LUO, Ling'en LI, Xijing SHENG, Mengyang WANG, Lu NI, Sujuan WANG, Huixin YANG, Jing ZHAO
    Laboratory Animal and Comparative Medicine    2024, 44 (3): 313-320.   DOI: 10.12300/j.issn.1674-5817.2023.138
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    Objective To study the effects of different pellet feed hardness on the growth and reproduction, feed utilization rate, and environmental dust in laboratory mice. Methods One hundred of fifty 50 3-week-old SPF-grade C57BL/6JGpt and 150 ICR laboratory mice were randomly divided into three groups, with an equal number of males and females. They were fed diets with different hardness of 18.62 kg, 23.15 kg, and 27.89 kg. Body weight, feed utilization rate, and dust levels in cages were recorded and calculated for mice aged 3-10 weeks. Forty-five 6-week-old male mice and ninety 4-week-old female mice from each strain were randomly divided into three groups and fed pellet feeds with three different hardness levels. After 2 weeks of adaptation to the same hardness feed, the mice were paired at a 1∶2 male-to-female ratio and monitored for reproductive data for 3 months. Results At the age of 4 weeks, the body weight of male C57BL/6JGpt mice in 23.15 kg group was significantly higher than that in the 18.62 kg and 27.89 kg groups (P<0.01), and the body weight of females in the 18.62 kg group was significantly higher than that in the 27.89 kg group (P<0.05). There was no significant difference in body weight among ICR mice aged 3-10 weeks across different feed hardness groups (P>0.05). For both strains, feed utilization rate for males was higher than that for females across different feed hardness groups at all weeks of age (P<0.01). Compared to the 27.89 kg group, both the 18.62 kg and 23.15 kg groups showed a significant increase in the 50-mesh dust levels in cages for both strains aged 4-8 weeks (except for 7-week-old C57BL/6JGpt mice) (P<0.05). For both C57BL/6JGpt and ICR mice, there was no significant difference in basic reproductive performance such as interval between the first litter and the monthly production index among the three feed hardness groups during the experimental period (P>0.05). However, the monthly production index of C57BL/6JGpt mice first increased and then decreased with the increase of feed hardness, while that of ICR mice increased with increasing feed hardness, though these differences were not statistically significant (P>0.05). Conclusion Different strains and genders had different tolerance to feed hardness. C57BL/6JGpt mice are more adapted to lower hardness feeds, while ICR mice are better suited to slightly higher hardness feeds.

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    Discussion on Management Experience of Public Cell Culture Platform in Laboratory Animal Center of Shanghai Jiao Tong University
    Lina PENG, Man ZHANG, Min AI, Wangjie XU
    Laboratory Animal and Comparative Medicine    2024, 44 (2): 227-233.   DOI: 10.12300/j.issn.1674-5817.2023.101
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    Public cell culture platform is an important facility in laboratory animal facilities, providing essential support for scientific research such as the development of animal tumor disease models and transgenic animals. By establishing a public cell culture experimental platform, laboratory animal centers can effectively integrate experimental animals and cell culture resources, optimizing the allocation of scientific research resources to facilitate better research outcomes. The majority of cells cultured in these platforms are used for animal experiments. Contamination or quality issues in these cells not only affect experimental results but also jeopardize the health of experimental animals, potentially leading to microbial infections and contamination of entire animal facilities. Therefore, public cell culture laboratories within experimental animal facilities impose stricter quality control measures than conventional cell culture rooms. This study takes the public cell culture platform at the Laboratory Animal Center of Shanghai Jiao Tong University as a case study to discuss management experiences, focusing on facility maintenance and management, personnel management and quality control of cell biological risk. The aim is to provide useful reference for the management of public cell culture laboratories in experimental animal facilities and other institutions.

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    Research on Management Policies of Laboratory Animals in Sichuan Province
    Bing CHEN, Yixing ZOU, Lingyun YAO, Jingdong WANG
    Laboratory Animal and Comparative Medicine    2024, 44 (2): 209-213.   DOI: 10.12300/j.issn.1674-5817.2023.110
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    Improving laboratory animal management system is one of the effective ways to promote the legalization and standardization of laboratory animal management. This article systematically reviews the relevant content and requirements of the latest laws, regulations, normative documents, and standards formulated and promulgated by the state since 2019 regarding the management of experimental animals. It also analyzes the current institutional framework in managing experimental animals in Sichuan Province from four aspects: administrative management, quality assurance, biosafety, and local standards. Furthermore, this article summarizes the existing problems and proposes corresponding policy recommendations in a targeted manner, aiming to provide a reference for the formulation of robust experimental animal management policies in Sichuan Province.

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    Analysis of Breeding and Application Data for Laboratory Cats
    WU Xiansheng, HUANG Wei, LIANG Yongfen, DENG Hui, ZHAI Yonghuan, YANG Jiajun, HUANG Ganquan, WANG Gang
    Laboratory Animal and Comparative Medicine    2024, 44 (4): 428-435.   DOI: 10.12300/j.issn.1674-5817.2024.033
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    Objective To cultivate and breed laboratory cats in conventional laboratory animal facilities, collect background data on laboratory cats, and compare them with purchased domestic cats to assess the feasibility of breeding laboratory cats. Methods Indigenous cat breeds were introduced for reproduction and population expansion under conventional laboratory environment, with recording of kitten survival rates and growth curves. Indicators of 20 laboratory cats of F1 generation (half male and half female), including complete blood count, blood biochemistry, organ mass, organ coefficient, heart rate, and blood pressure, were detected and comparisons between sexes were made. Blood pressure values and sensitivity to histamine of these cats were measured using depressor substance detection method in the Pharmacopoeia of the People's Republic of China-Four Parts: 2020, and were compared with the data from 173 concurrently purchased domestic cats. Results Laboratory cats adapted well to the environment of conventional laboratory facilities, with a survival rate of 77.08% of kittens at 8 weeks of age. Red blood cell count, hemoglobin content, mean corpuscular hemoglobin concentration, and hematocrit in male laboratory cats were significantly higher than those in females (P<0.01), while the mean corpuscular volume in males was significantly lower than that in females (P<0.01). The levels of serum alanine aminotransferase, total bilirubin, creatinine, triacylglycerol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in male laboratory cats were significantly higher than those in females (P<0.05 or P<0.01), while cholesterol, globulin, total protein, and the albumin-globulin ratio were significantly lower in males (P<0.01). The liver coefficient in male laboratory cats was significantly lower than that in female cats (P<0.05), while the kidney coefficient was significantly higher (P<0.05). The spleen-brain and kidney-brain ratios were significantly higher in males compared to females(P<0.05 or P<0.01). No significant differences were found in heart rate, systolic pressure, diastolic pressure, mean blood pressure, or sensitivity to histamine between male and female laboratory cats (P>0.05). Compared to laboratory cats, purchased domestic cats had significantly higher heart rate, systolic pressure, and mean blood pressure (P<0.01), and the magnitude of blood pressure changes induced by medium and high doses of histamine was significantly reduced (P<0.05 or P<0.01). Conclusion It is feasible to breed laboratory cats in conventional laboratory animal facilities. The accuracy of experimental results can be improved by using laboratory cats with clear and standardized background data.

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    Perioperative Animal Care for Xenotransplantation from Genetically Edited Pigs to Monkeys
    ZHU Chan, ZHANG Dongliang, ZHAO Deli, SHI Xueqin, QIAN Lei, ZHANG Xuan, JIN Yan, DUAN Wei, QI Ruocheng, LIU Chaohua, YANG Xuekang, HAN Juntao, PAN Dengke
    Laboratory Animal and Comparative Medicine    2024, 44 (5): 495-501.   DOI: 10.12300/j.issn.1674-5817.2024.043
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    Objective To discuss the perioperative care and wound protection of xenotransplantation from genetically edited pigs to monkeys, with the goal of improving the success rate of such experimental procedures. Methods From October 2022 to October 2023, perioperative care and wound protection were performed on 7 recipient rhesus monkeys undergoing xenotransplantation of genetically edited pig tissues and organs. Customized wound protective garments were designed based on monkeys' size and surgical area to protect the wounds, alongside meticulous perioperative care. This included preoperative preparation and medication, intraoperative monitoring of physiological indicators and anesthesia management, and postoperative care comprising wound protection, observation and monitoring, and nutritional support. Results All seven monkeys successfully underwent xenotransplantation. With the aid of protective garments and detailed care, all surgical wounds healed by first intention, and postoperative recovery was satisfactory. Conclusion Proper care and wound protection during xenotransplantation from genetically edited pigs to monkeys not only promote wound healing, but also alleviate pain and harm to animals. This has significant implications for advancing experimental research in pig-monkey xenotransplantation and enhancing animal welfare.

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