Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The field of genome modification in rabbits has progressed slowly.However,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

Advances in viral encephalitis:Viral transmission,host immunity,and experimental animal models

Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.

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

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

Exploration of the Characteristics of Animal Supply and Demand in University Experimental Teaching Pratice

The supply and demand of laboratory animals for teaching in colleges and universities has its own internal characteristics.To grasp the supply and demand characteristics of laboratory animals for teaching is of vital importance to the planning,supply and use of teaching animals,the realization of teaching objectives and the completion of teaching tasks.Based on the supply of teaching experimental animals and the work of animal experimental teaching in our university in recent years,this paper expounds the inherent characteristics and practice of supply and demand of teaching experimental animals.

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

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

Animal experimental studies using small intestine endoscope

AIM To assess the feasibility and safety of a novel enteroscope,negative-pressure suction endoscope in examining the small intestine of a porcine model.METHODS In vitro experiments in small intestinal loops from 20pigs and in vivo experiments in 20 living pigs were conducted.RESULTS In in vitro experiments,a negative pressure of>0.06MPa was necessary for optimal visualization of the intestine,and this pressure did not cause gross or histological damage to the mucosa.For satisfactory examination of the small intestine in vivo,higher negative pressure(>1.00 MPa)was required.Despite this higher pressure,the small intestine did not show any gross or microscopic damage in the suctioned areas.The average time of examination in the living animals was 60±7.67 min.The animals did not experience any apparent ill effects from the procedure.CONCLUSION Small intestine endoscope was safely performed within a reasonable time period and enabled complete visualization of the intestine in most cases.

Standardization of experimental animals temporal bone sections

Preparation of the temporal bone for light microscopy is an important step in histological studies of the inner ear. Due to the complexity of structures of the inner ear, it is difficult to measure or compare structures of interest without a commonly accepted standardized measure of temporal bone sections. Therefore, standardization of temporal bone sections is very important for histological assessment of sensory hair cells and peripheral ganglion neurons in the cochlear and vestibular systems. The standardized temporal bone sectioning is oriented to a plane parallel to the outer and internal auditory canals. Sections are collected from the epitympanum to the hypotympanum to reveal layers in the order of the crista ampullaris of the superior and lateral semicircular canals, macula utriculi and macula sacculi, superior vestibular ganglion neurons, macula of saccule and inferior vestibular ganglion neurons, cochlear modiolus, endolymphatic duct and endolymphatic sac, and finally the crista ampullaris of the posterior semicircular canal. Moreover, technical details of preparing for temporal bone sectioning including fixation, decalcification, whole temporal bone staining, embedding penetration, and embedding orientation are also discussed.

Preparation of Filling Porous Osteoconduction Materials and Its Animal Experiment Study

Titanium rods were processed into implant samples with cavity and groove in which was filled with HAP/β-TCP porous osteoconduction composite materials in order to increase the mechanical stability of the implant in vivo.The phase compositions of the composite was characterized by X-ray diffraction （XRD） and scanning electron microscopy（SEM）.Histological evaluation showed that the biogradable composite could enhanced the ability of new bone formation.The composite can conduct new bone tissue growing into the cavities gradually after implanted into animal,and then achieve mechanical fixation.The filling biogradable compound exhibited excellent biocompatibility,which combined with the new bone tissues tightly without inflammation and loosing.

Diversified Teaching Methods in Nursing:Using Animal Experimentation to Promote Core Professional Competencies in Basic Nursing Training

Objective： The aim of this project was to train highly professional and specialized nursing students from medical colleges to adapt to bedside clinical care by exploring and discussing various methods of injection and IV infusion in animal experimentation to hone the core professional nursing competencies. Methods： Two classes from the 2012 senior graduating nursing class were randomly selected by a computer to conduct the diversified practical teaching methods based on animal experimentation. A hospital environment was simulated by requiring students to perform different types of injections and practical IV infusion techniques. A comprehensive evaluation of the core professional competencies, as well as other integrated competencies, was conducted to determine the effectiveness of the teaching methods. Results： Two-sampled, pairwise u-tests were performed between the scores of the experimental （nursing class 2） and control （nursing class 1） groups. These findings showed that the overall test scores were significantly higher in the experimental group compared to the control group and that the average P-values for the competencies in various categories were 〈0.01, which indicated statistically significant results. Conclusions： Based on the data from this project, diversified teaching methods for basic nursing training founded on animal experimentation can help nursing students perfect their core professional competencies and improve their overall professional standing. The introduction of animal experimentation requires further verification, and an increased acknowledgement of its benefits through the widespread dissemination of this information.

Animal bone growth experiment of rapid-growing rats in different stress environment and its mathematical model

The aim of this study is to explore a way that quantify the qualitative equation of bone growth and remodeling which was based on the animal Experiment of rapid-growing Rats in Different Stress Environment. These results were proved to be of good stability and identification precision with the numerical method of inversion. It suggested that the growing coefficient and the threshold in function were variables changing with time and space. The idea and method used in the research of bone growth and remodeling adaptation in this paper also provided clue and reference to establish other models for living system.

Congratulations to the new journal: Animal Models andExperimental Medicine

I would like to extend my best congratulations to all concerned for the publication of the inaugural issue of Animal Models and Experimental Medicine (AMEM), an English journal published jointly by the Chinese Association for Laboratory Animal Sciences (CALAS) and the Institute of Laboratory Animal Sciences of Chinese Academy of Medical Sciences & Peking Union Medical College. Basic medical research has been at the forefront of science and technology development. Essential to that, laboratory animal science is of foundamental importance in biomedical research, providing key advantages in understanding mechanisms of health and disease without posting actual risks to human beings.

Experimental Studies on the Irradiation of Facial Bones in Animals:A Review

Introduction: Radiotherapy is often used to treat head and neck malignancies, with inevitable effects on the surrounding healthy tissues. We have reviewed the literature concerning the experimental irradiation of facial bones in animals. Materials and Methods: A PubMed search was performed to retrieve animal experiments on the irradiation of facial bones that were published between January 1992 and January 2012. The search terms were “irradiation facial bone” and “irradiation osteoradionecrosis”. Results: Thirty-six publications were included. The irradiation sources were Cobalt60, orthovoltage, 4 - 6 megavolt photons, and brachytherapy. The total dose varied between 8 - 60 Gy in single or multiple fractions. The literature presents a broad range of animal studies that differ in terms of the in vivo model, irradiation, observation period, and evaluation of results. Discussion: The different animal models used leave many questions unanswered. A detailed and standardized description of the methodology and results would facilitate the comparability of future studies.

Clinical application of full automatic animal experimental cabin of normobaric/hypobaric hypoxia and high carbon dioxide

To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobaric hypoxic and high carbon dioxide environment. Methods： Sixty SPF-class male DS rats were divided into 2 groups, 20 for normobaric, hypoxic conditions and the other 40 for hypobaric, hypoxic conditions. For each group, the pulmonary arterial pressure and carotid arterial pressure indicators of rats were examined by using the physiological multi-detector, and the pulmonary vascular changes in the structure were observed. Results： The normobaric/hypobaric hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxic with high carbon dioxide environment, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform for clinical research.

Announcing the launch of a new journal: Animal Models andExperimental Medicine

In the Chinese Year of the Dog,we are pleased to present to you the first issue of the new journal we have organized:Animal Models and Experimental Medicine(AMEM).Why do we need a new journal in this area?Laboratory animal sciences is an emerging interdisciplinary subject,which integrates theories and methods from many disciplines,including biology,medicine,pharmacy,veterinary,bioengineering,biomedical engineering,etc.In recent years,many outstanding papers based on laboratory animals have been published around the world,highlighting how laboratory animal sciences has,among other things,provided systematic biological materials and pertinent technologies for the development of related disciplines;integration into many frontier disciplines;development of new disciplines such as comparative medicine,experimental animal medicine,and comparative biology;and supported development in fields such as life sciences,medicine,food,environment and aerospace.However,there are very few specialized journals in this field,and their impact is very limited.Therefore,it is urgent to establish a professional English-language journal to meet the need of all researchers in this important field.

China's Space Animal Experiments Obtained Achievements

Entering into the 1990s, Chinese scientists have made mice, drosophila and silkworm eggs experiments in space with satellites and achieved remarkable results. These animals were put in space environment units with the ability of adjusting pressure, temperature and moisture control, air conditioning and purifying as well as foods and water supply. After 8-days’ flight, all performance parameters were normal and met the design requirements. The two mice kept alive for 5 days and 10 hours

Mesenchymal stem cells in the treatment of inflammatory and autoimmune diseases in experimental animal models

Multipotent mesenchymal stromal cells [also known as mesenchymal stem cells(MSCs)] are currently being studied as a cell-based treatment for inflammatory disorders. Experimental animal models of human immune-mediated diseases have been instrumental in establishing their immunosuppressive properties. In this review, we summarize recent studies examining the effectiveness of MSCs as immunotherapy in several widely-studied animal models, including type 1 diabetes, experimental autoimmune arthritis, experimental autoimmune encephalomyelitis, inflammatory bowel disease, graft-vs-host disease, and systemic lupus erythematosus. In addition, we discuss mechanisms identified by which MSCs mediate immune suppression in specific disease models, and potential sources of functional variability of MSCs between studies.

Clinical Application of the Full Automatic Animal Experimental Cabin of Normobaric/Hypobaric Hypoxia and High Carbon Dioxide

Objective： To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobarie hypoxic and high carbon dioxide environment. Methods： 60 SPF-class male SD rats were divided into two groups, 20 for normobaric, hypoxie conditions and the other 40 for hypobarie, hypoxic conditions. For each group, we examined the pulmonary arterial pressure and carotid arterial pressure indicators of rats by using the physiological muhi-detector measurement, and observed the pulmonary vascular changes in the structure. Results： The normobaric/hypobarie hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxie with high carbon dioxide enviromnent, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform tor clinical research.

THE ANIMAL EXPERIMENTAL OBSERVATION OF THE INFLUENCE OF THE DIFFERENT FONTAN PROCEDURES ON PULMONARY MICROCIRCULATION

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Animal experiments and clinical application of CT during percutaneous splenoportography

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Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.