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.

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.

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 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.

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.

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.

Experimental Studies on immune-Complex in Situ Type Glomerulonephritis in Rabbits Treated with Mai-Luo-Tong and Natural Indigo

By injection of C-BSA. immune-complex in situ type glomerulonephritis was duplicated in rabbits and treated with Mai-Luo-Tong and natural Indigo.The resuts showed that proteinuria in the treated groups M and Q was decreased.The difference between group M and control group is statistically significant (P<0.05). Under light and electron microscope.although glomerular basement membrane was irregularly thickened and subepithelial dense electron deposited in the treated group, but microthromhus. erythrocytes and platelets aggregation and leukocytes impaction were not seen within glomerular capillaries. Also in groups C,Q,M, mesenteric cell count was 99. 40±18.53,92.87±17. 89,66. 55±7.75 respectively,the M.Q groups are compared with group C, the result is of statistical significance(P<0.05)and there is no apparent glomerular fibrosis in the treated groups.

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.

Animal modeling in bone research—Should we follow the White Rabbit?

Animal models are live subjects applied to translational research.They provide insights into human diseases and enhance biomedical knowledge.Livestock development has favored the pace of human social development over millennia.Today's society is more aware of animal welfare than past generations.The general public has marked objections to animal research and many species are falling into disuse.The search for an ideal methodology to replace animal use is on,but animal modeling still holds great importance to human health.Bone research,in particular,has unmet requirements that in vitro technologies cannot fully address.Standardizing novel models remains necessary and rabbits are gaining in popularity as potential bone models.Our aim here is to provide a broad overview of animal modeling and its ethical implications,followed by a narrower focus on bone research and the role rabbits are playing in the current scenario.

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.

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.

Alteration of Nitric Oxide Synthase in Experimental Spinal Cord Injury in Rats

In order to detect the role of NO to the secondary damage following spinal cord injury (SCI). NOS in the injury site (T\-8) were studied using a rat SCI model induced by Allens weight drop method (10 g2.5 cm). The results suggested that activities of NOS significantly increased in 10 min\, 1\,2\,4\,8 h. The results indicated that NO was related to SCI. The rise of NO following SCI might lead to secondary spinal cord damage.\;

An Experimental Study on Somatostatin Receptors in the Brains of Hepatic Encephalopathy Rats

The present study was undertaken to evaluate the effect of somatostatin (SS) receptor,a brain-gut peptide receptor which is capable of inhibiting central neurons, on the pathogenesis of hepatic encephalopathy (HE).By means of radioligand binding assay, SS receptors in crude synaptosomal membrane of rat brains were investigated in a rat model of HE induced by partial hepatectomy following carbon tetrachloride intoxication and in controls. Binding to SS receptor was studied using125 I-SS as radiolgand Scatchard analysis of binding data was linear, yielding a dissociation constant (Kd) of 3.99 ±0.22 nmol/L and a maximal binding capacity (Bmax) of 238± 14.2 fmol/mg of protein in HE rats.Only increased Bmax values were observed (P< 0.005),while the Kd values were statistically unchanged (P>0.50),in HE rats as compared with those in controls.The results suggest that the changes of SS receptors in brains play a significant role in the pathogenesis of HE.The mechanism of HE induced by the alterations of SS receptors in the brains was discussed in this paper.

Complete Achilles Tenotomy:A New Improved Experimental Surgical Technique in Rats

Rupture of the Achilles tendon is one of the most frequent tendon injuries in humans. However, there is no standard surgical technique thus far to reproduce complete rupture of this tendon in rats. Surgical procedures were performed in Wistar rats under light microscopy, with posterior longitudinal incision and preservation of the plantaris tendon. The animals were sacrificed on 2nd and 8th postoperative week and we used hematoxilin and eosin, picrosirius-red and Weigert’s resorcin-fuchsin to observe general tendon healing. The mean operative time was one minute and 24 seconds. Histological studies showed cellular proliferation and fibrillogenesis at two weeks, with decreased amounts of cellularity and elastic fibers at the 8th week, besides changes in structural organization of collagen fibers. The complete Achilles tenotomy in rats, was improved under light microscopy and sparing the plantaris tendon. This surgical technique was simple and quick, showed signs of normal healing process, could be easily reproducible, and triggered translational researches in this area.

Experimental study of tibial transverse bone transfer on wound healing of diabetic rabbit leg ulcer

Objective To investigate the efficacy and mechanism of tibial transverse bone transfer in the treatment of lower limb ulcer wounds in diabetic rabbits.Methods Animal models of diabetic foot lower extremity ischemia were made,and grouped Animal models of diabetic foot lower extremity ischemia were made,and grouped control studies were designed to evaluate the time of wound healing and the expression level of vascular endothelial growth factor(VEGF),platelet derived growth factor(PDGF),and epidermal cell growth factor(EGF)in the wound during the same period of time.Results In animal experiments,transverse tibial bone transfer can shorten the healing time of diabetic ulcer and increase the expression of wound growth factor(VEGF,PDGF,EGF).Conclusion In animal experiments,diabetes can inhibit the expression of growth factors(VEGF,PDGF,EGF)in ulcer wounds,and tibial transverse bone transfer can promote wound healing.The mechanism may be related to the increased expression of VEGF,PDGF and EGF in the wound surface.

Advances in cytokine-mediated mechanisms for cardiac regeneration and repair post-myocardial infarction:a comprehensive review

Cardiovascular disease(CVD)has become the leading cause of death globally,imposing significant health and economic burdens.Among these,myocardial infarction(MI)is a predominant cause of mortality.Several animal studies have shown that cytokines participate in cardiac regeneration and repair by modulating cellular proliferation,differentiation,and apoptosis post-MI.Here,we explored the crucial role of cytokines in cardiac regeneration and repair processes in experimental animal models,detailing how cytokines modulate cellular mechanisms involved in repairing cardiac tissue post myocardial infarction(MI).Specifically,it highlights the activation of cardiac stem cells and progenitors,the regulation of inflammatory responses to prevent excessive damage,and the involvement in matrix remodeling to ensure functional integrity of the heart.This comprehensive examination underscores the therapeutic potential of enhancing cytokine secretion to mitigate adverse effects and promote recovery following MI,offering insights into possible interventions that could improve patient outcomes in clinical settings.

Polar residual network model for assisting evaluation on rat myocardial infarction segment in myocardial contrast echocardiography

Objective To investigate the value of polar residual network(PResNet)model for assisting evaluation on rat myocardial infarction(MI)segment in myocardial contrast echocardiography(MCE).Methods Twenty-five male SD rats were randomly divided into MI group(n=15)and sham operation group(n=10).MI models were established in MI group through ligation of the left anterior descending coronary artery using atraumatic suture,while no intervention was given to those in sham operation group after thoracotomy.MCE images of both basal and papillary muscle levels on the short axis section of left ventricles were acquired after 1 week,which were assessed independently by 2 junior and 2 senior ultrasound physicians.The evaluating efficacy of MI segment,the mean interpretation time and the consistency were compared whether under the assistance of PResNet model or not.Results No significant difference of efficacy of evaluation on MI segment was found for senior physicians with or without assistance of PResNet model(both P>0.05).Under the assistance of PResNet model,the efficacy of junior physicians for diagnosing MI segment was significantly improved compared with that without the assistance of PResNet model(both P<0.01),and was comparable to that of senior physicians.Under the assistance of PResNet model,the mean interpretation time of each physician was significantly shorter than that without assistance(all P<0.001),and the consistency between junior physicians and among junior and senior physicians were both moderate(Kappa=0.692,0.542),which became better under the assistance(Kappa=0.763,0.749).Conclusion PResNet could improve the efficacy of junior physicians for evaluation on rat MI segment in MCE images,shorten interpretation time with different aptitudes,also improve the consistency to some extent.

CT perfusion at early stage of hepatic diffuse disease

AIM: To determine the validity of the non-invasive method of CT perfusion (CTP) in rat model of hepatic diffuse disease. METHODS: Twenty-eight Wistar rats were divided into two groups. Liver diffuse lesions were induced by diethyln-itrosamine in 14 rats of test group. Rats in control group were bred with pure water. From the 1st to 12th wk after the test group was intervened, both groups were studied every week with CTP. CTP parameters of liver parenchyma in different periods and pathologic changes in two groups were compared and analyzed. RESULTS: The process of hepatic diffuse lesions in test groups was classified into three stages or periods according to the pathologic alterations, namely hepatitis, hepatic fibrosis, and cirrhosis. During this period, hepatic artery flow (HAF) of control group declined slightly, mean transit time (MTT), blood flow (BF) and volume (BV) increased, but there were no significant differences between different periods. In test group, HAF tended to increase gradually, MTT prolonged obviously, BV and BF decreased at the same time. The results of statistical analysis revealed that the difference in the HAF ratio of test group to control group was significant. The ratio of BV and BF in test group to control group in stage of hepatitis and hepatic cirrhosis, hepatic fibrosis and early stage of hepatic cirrhosis was significantly different, but there was no significant difference between hepatitis and hepatic fibrosis. The main pathological changes in stage of hepatitis were swelling of hepatic cells, while sinusoid capillarization and deposition of collagen aggravated gradually in the extravascular Disse's spaces in stage of fibrosis and early stage of cirrhosis. CONCLUSION: The technique could reflect some early changes of hepatic blood perfusion in rat with liver diffuse disease and is valuable for their early diagnosis.

High-dose dietary zinc promotes prostate intraepithelial neoplasia in a murine tumor induction mode

To evaluate the role of high-dose dietary zinc in the process of prostate malignancy,60 Sprague-Dawley rats were randomly divided into four groups：tumor induction with carcinogen and hormone （group 1）,oral zinc administration without tumor induction （group 2）,oral zinc administration with tumor induction （group 3） and a control without zinc administration or tumor induction （group 4）. Zinc was supplied orally in the form of zinc sulfate heptahydrate dissolved in drinking water to groups 2 and 3 for 20 weeks. Although the serum level of zinc measured at 20 weeks was maintained similarly in each group （P = 0.082）,intraprostatic zinc concentrations were statistically different. Group 1 prostates contained the least amount of zinc in both the dorsolateral and ventral lobes at levels of 36.3 and 4.8 μg g^-1,respectively. However,in group 3,zinc levels increased in both lobes to 59.3 and 12.1 μg g^-1,respectively,comparable with that of group 4 （54.5±14.6 and 14.1±2.4 μg g^-1）. In spite of these increases in zinc concentration,the prevalence of prostate intraepithelial neoplasm was rather increased in group 3 （53.3% and 46.7%） compared with group 1 （33.3% and 33.3%） in both dorsolateral and ventral prostate lobes. Although prostate intraepithelial neoplasm did not develop in any prostate in group 4,zinc administration did induce prostate intraepithelial neoplasm in group 2 （46.7% and 40.0%）. Thus,although high dietary zinc increased intraprostatic zinc concentrations,it promoted,instead of preventing,prostate intraepithelial neoplasm in a murine prostate malignancy induction model.