Abstract:Objective A cytokine storm occurs during infection by highly pathogenic viruses such as avian influenza virus. Higher levels of inflammatory responses are more commonly observed in the elderly, associated with worse clinical outcomes. In this study, we investigated the effect of inflammatory responses on the immune response against viral infection in the lung of aged mice. Methods Aged mice (18 -24 months old) were infected with influenza virus H9N2 to establish an infection model. Adult mice (6 - 8 weeks old) were used as the control. After infection, we quantitatively analyzed the expression of inflammatory cytokines in the lung and periphery blood. During the acute infection, murine lung tissues were collected and subjected to in situ analysis of the distribution of recruited immune cells by immunohistochemistry, and pulmonary T cells were counted among digested single cells of lung tissue. Results Compared with the adult mice infected with H9N2, aged mice showed significant weight loss and a low survival rate of 50%.Inflammatory cytokines were rarely detected in the infected adult mice, but were highly detected in the lungs of aged mice.Among them, IL-6 and chemokine MCP-1 were significantly high, which reached peaks of more than 4000 pg/ mL and were 100 - 1000 times higher than those in the adult control mice at day 2 post-infection. Additionally, the pulmonary macrophage response and migration of neutrophils were weaker. On day 7 post-infection, the number of CD8 + T cells decreased significantly in the aged lung, while the number and proportion of CD4 + T cells remained normal. Conclusions An inflammatory cytokine storm is found in the lung of aged mice infected with low pathogenic influenza virus H9N2.Compared with adult mice, the migration ability of immune cells is decreased, and the acquired cellular immunity intensity is reduced significantly.

Abstract:Objective The aim of this study was to explore the reparative effects of glucosamine hydrochloride(GAH) and its derivatives on skeletal damage in zebrafish, and compare the preventive effects of GAH and alendronate sodium (AL), a drug known to be effective against osteoporosis. Methods Zebrafish embryos were exposed to various agents (GAH, glucose, mannitol, galactose, and acetylglucosamine) at the same concentration (0. 1%, 1 mg/ mL), and the mortality and phenotype were analyzed. Furthermore, a zebrafish model of osteoporosis induced by ferric ammonium citrate (FAC) was treated with the above agents to assess their reparative effects on the damaged skeleton examined using alizarin red and alcian blue staining. We also compared the preventive effects of GAH and AL on osteoporosis zebrafish.Results After treatment with GAH and its derivatives, the trend of their effects on embryonic development was glucose Conclusions Compared with other agents, GAH has an excellent reparative effect on zebrafish bone damage and a good preventive effect on osteoporosis in zebrafish. This study provides the foundation and approaches for screening of natural anti-osteoporosis drugs and product development using the zebrafish model.

Abstract:Objective To observe the effects of curcumin pretreatment on myocardial oxidative stress and apoptosis in heatstroke rats in a dry heat environment and its possible mechanism. Methods Fifty male Sprague-Dawley rats were randomly divided into five groups (n =10): normal control group (NC), dry and control group (DHC), and 50 mg/ kg curcumin (L-cur), 100 mg/ kg curcumin (M-cur), and 200 mg/ kg curcumin (H-cur) pretreatment groups. NC and DHC groups were gavaged with saline, and curcumin pretreatment groups were gavaged with the various concentrations of curcumin once daily for 7 days. On day 8, except in the NC group, the rats were transferred to a climate cabin (Simulated Climate Cabin for Special Environment of Northwest of China) under the conditions of 40. 5 ± 0. 5°C and 10 ± 1% relative humidity for 150 min to establish the heatstroke model of a dry heat environment. Then, the rats were anaesthetized and sacrificed at 150 min, and blood and heart tissues were collected. Serum myocardial enzyme creatine kinase (CK) and lactate dehydrogenase (LDH) were detected by an automatic biochemical detector. Myocardial cell apoptosis was detected by TUNEL method, and the apoptosis index was calculated. Myocardial superoxide dismutase (SOD) and malonaldehyde (MAD) were detected with SOD and MDA kits, respectively. Results Serum CK, LDH,cardiomyocyte apoptosis index, and MDA were significantly higher in the DHC group than in the NC group ( P < 0. 01).CK, LDH, cardiomyocyte apoptosis index, and MDA of curcumin pretreatment groups were decreased with the increase in curcumin concentration, and there was a significant different among the curcumin pretreatment groups ( P < 0. 01).However, SOD showed an opposite trend to MDA. Correlation analysis indicated a positive correlation between the myocardial apoptosis index and serum CK and LDH in rats (r = 0. 302, r = 0. 304, P < 0. 05). There was a positive correlation between the myocardial apoptosis index and MDA (r = 0. 916, P < 0. 01). However, there was a negative correlation with SOD (r = - 0. 863, P < 0. 01). Conclusions Curcumin pretreatment has a protective effect on myocardial injury in heatstroke rats caused by a dry heat environment, which may be mediated through inhibition of oxidative stress and reducing apoptosis in cardiomyocytes.

Abstract:Objective To explore the feasibility of establishing a stable mouse model of thin endometrium by intrauterine injection of 95% ethanol, characterized by immunohistochemistry and fertility assessment, and provide an ideal animal model for the study of pathological features and repair mechanisms of thin endometrium. Methods Seventy-eight female unmated C57BL/6J mice with sexual maturity and regular estrus were used in this study. Thirty mice were randomly divided into three groups: the blank group, control group, and experimental group. A mouse model of thin endometrium was established by intrauterine infusion of 95% ethanol injured endometrium. The experimental mice were euthanized by cervical dislocation in the third estrus period after modeling, and uterine samples were collected. The regeneration of endometrial cells was evaluated by immunohistochemistry for cytokeratin, vimentin, vascular endothelial growth factor(VEGF) and estrogen receptor α(ERα). Another group of 48 mice were randomly divided into the blank group, control group, unilateral injury group, and the bilateral injury group. All surviving mice were simultaneously caged after modeling to analyze the effect of thin endometrium on the fertility of mice and to evaluate whether the mouse model of thin endometrium was successfully established. Results The results of the immunohistochemistry showed that the expressions of cytokeratin, vimentin, VEGF and ERα in the endometrial cells of the experimental group were significantly lower than those in the blank and control groups. Fertility assessment showed that mice in the blank and control groups were normally conceived after mating and that no mice in the bilateral injury group were conceived. In addition, no mice were conceived in the injured side of the uterus in the unilateral injury group, whereas mice in the uninjured side of the uterus were conceived normally. The mean pregnancy rate of the injured side of the uterus in the experimental group was significantly lower than that on the uninjured side ( P < 0. 05), indicating that intrauterine injection of 95% ethanol damaged the endometrium, resultsing in reduced fertility. Conclusions We have successfully established a mouse model of thin endometrium, which can be used to study the repair mechanisms of the thin endometrium.

Abstract:Objective To explore a three-dimensional visualized modeling method of miniature pig model of renal vasculature and the value of its application. Methods A pair of fresh normal miniature pig kidneys was selected,and to fill the abdominal aorta with epoxy resin-lead oxide (red) and the posterior cava vein (ligation of the right renal vein) with epoxy resin-titanium dioxide (yellow) for casting. Then 128 layer spiral CT thin layer scanning was applied to obtain a twodimensional image data set of the casted specimens to segment and reconstruct the three-dimensional visualization model of miniature pig renal vasculature using Mimics 19. 0 software. Results Using Mimics 19. 0 software, we reconstructed a three-dimensional visualization model of miniature pig renal vasculature. The distribution and walking tracks of the renal artery and vein in this model were in accordance with the casted specimens. The renal artery and vein were separately displayed by vascular threshold segmentation. The effect was ideal and the three-dimensional sense was strong.Conclusions A three-dimensional visualization model of miniature pig renal vasculature is reconstructed based on casted specimens and effective segmentation. It may provide a simulation platform and important guidance for research and virtual training in urology.

Abstract:Objective To investigate the effects of luteolin on the invasion and migration of papillary thyroid carcinoma TPC-1 cells and its possible mechanism. Methods Various concentrations of luteolin (0, 20, and 40 μmol/ L)were applied to human papillary thyroid carcinoma TPC-1 cells. The experiment included three groups: blank control group (with the same amount of dimethyl sulfoxide), 20 μmol/ L group and 40 μmol/ L group. The survival rate of cells was detected by MTT assays, and cell invasion and migration abilities were analyzed by Transwell assays. Western blotting and qRT-PCR were used to measure the expression levels of phosphorylated protein kinase B ( p-AKT), and matrix metalloproteinase (MMP)-2 and -9. Results Compared with the blank control group, luteolin at various concentrations had a significant inhibitory effect on the proliferation of TPC-1 cells (all P < 0. 05). Luteolin concentrations of 20 and 40 μmol/ L significantly inhibited the invasion and migration of TPC cells. Compared with the blank control group, the expression levels of p-AKT, MMP-2, and MMP-9 proteins and mRNAs were significantly decreased in TPC-1 cells after luteolin treatments (all P < 0. 05). Conclusions Luteolin inhibits the invasion and migration of papillary thyroid carcinoma TPC-1 cells through the PI3K/ AKT signaling pathway, which might play an important role in the treatment and prognosis of papillary thyroid carcinoma.

Abstract:Objective To study the similarities and differences in growth and reproduction of Tlr 4 knockout and KM mice. Methods Twenty Tlr 4 knockout mice and 20 KM mice (half male and half female) were selected to measure body weight, body length, and growth rate from 4 to 12 weeks. Twenty cages were randomly selected with one female and one male in each cage. Statistical analysis was performed for the number of second born pups. Results The body weight and growth rate of Tlr 4 knockout mice were significantly lower than those of KM mice ( P < 0. 05), but there was no significant difference between 4 and 5 weeks in body length and growth rate. The body length and growth rate of Tlr 4 knockout mice at other periods were obvious. Tlr 4 knockout mice had a significantly lower reproductive ability than KM mice. Conclusions Tlr 4 knockout affects the growth, development, and reproduction of mice.

Abstract:Objective To observe the effects of fluoxetine on the behavior in rats of ischemic post-stroke depression (PSD) and the influence on neurogenesis in the hippocampus. Methods Thirty-two adult male Sprague-Dawley rats were randomly divided into control, stroke, PSD, and fluoxetine groups (n = 8 each). Complete cerebral ischemic rat models were established by left middle cerebral artery occlusion. Chronic unpredictable mild stimulation(CMUS) and an isolation feed were used to establish the rat depression model. Changes in rat behavior were evaluated by a sucrose preference test, open field test, and weight changes on days 0, 7, 14, 21, 28, and 35 after the operation.A forced swim test was performed on day 35, and then all rats were sacrificed to detect neuron regeneration in the hippocampus by immunohistochemical staining. Results The rat body weight, sucrose preference test, and horizontal and vertical movement scores in the open field test on days 28 and 35 after CMUS were measured. The differences in the PSD group compared with stroke and fluoxetine prevention groups had statistical significance ( P <0. 05). Compared with the stroke group, in the forced swim test, the immobility time of rats was increased in the PSD group ( P < 0. 01), and the swimming and climbing times were decreased ( P < 0. 01). However, immobility and swimming times were improved after fluoxetine treatment ( P < 0. 01). Immunohistochemical staining showed that, compared with the stroke group, the number of new neurons in the hippocampal dentate gyrus of rats was significantly reduced in the PSD group ( P < 0. 01), but compared with the PSD group, it was increased in the fluoxetine-treated rats ( P < 0. 01). Conclusions Fluoxetine may effectively improve PSD rat depression behavior, and hippocampal neurogenesis plays an important role in this process.

Abstract:Objective To investigate the anti-tumor effect and immunological mechanism of lactobacillus casei in a rat model of gastric cancer. Methods Fifty male SD rats were randomly divided into five groups: control, model, and low, medium and high dose groups with 10 rats in each group. The model group and the three dose groups were treated with N-methyl-N-nitro-nitrosoguanidine (MNNG) to establish the gastric cancer model, and the control group was administered an aqueous alcohol solution. From week 28, the three dose groups were administered 4, 8, and 12 mL/ kg lactobacillus casei by gavage,respectively, and 10 mL/ kg sterile saline was administered to the model and control groups per day for 8 weeks. Indexes of the thymus and spleen were compared. Natural killer ( NK) cells ( TCRαβ⁺ CD161a⁺ ) and T lymphocyte subsets (CD4 ⁺ , CD8 ⁺ , and CD4 ⁺ / CD8 ⁺ ) in blood and tumor tissues were detected and compared. Relative protein expressions of Toll-like receptor-4 (TLR-4) and NF-κB p65 were compared. Results Pathological observations revealed that inflammatory cells infiltrated into the fore and gland stomach of the model group, keratinization of squamous epithelial cells occurred, and cancer cells were found under a light microscope. Inflammatory cells in the fore and gland stomach of the three dose groups were decreased, and the number of cancer cells was decreased with the most significant decrease in the middle dose group. Indexes of the thymus and spleen, TCRαβ⁺ CD161a⁺ , CD4 ⁺ , and CD4 ⁺ / CD8 ⁺ cells in peripheral blood, and TCRαβ⁺ CD161a⁺ and CD8 ⁺ cells in tumor tissues of the model group were significantly lower than those of the control group ( P < 0. 05). The above indicators of the three dose groups were significantly higher than those of the model group ( P <0. 05), and those of the middle dose group were significantly higher than those of low and high dose groups ( P <0. 05), but there were no significant differences between the low and high dose groups ( P >0. 05).CD4 ⁺ and CD4 ⁺ / CD8 ⁺ cells, relative protein expression of TLR-4 and NF-κB p65 in tumor tissues, and CD8 ⁺ cells in peripheral blood of the model group were significantly higher than those of the control group ( P < 0. 05). The above indicators of the three dose groups were significantly lower than those of the model group ( P < 0. 05), and those of the middle dose group were significantly lower than those of the low and high dose groups ( P < 0. 05), but there were no significant differences between the low and high dose groups ( P > 0. 05). Conclusions Lactobacillus casei modulate the activity of T lymphocytes and NK cells in tumor tissues and peripheral blood of gastric cancer model rats, and inhibit tumor growth and enhance immune regulation by downregulating protein expression of TLR-4 and NF-κB p65 and inhibiting the TLR-NF-κB signaling pathway. Among the groups, 8 mL/ kg Lactobacillus casei had the optimal effects.

Abstract:Objective To screen a panel of suitable microsatellite loci to analyze the genetic structure of experimental cat populations. Methods Seventy-four candidate microsatellite loci on 18 pairs of autosomes in cats were chosen from GenBank and related literature. Then, the PCR conditions were optimized by exploring the optimal annealing temperature. Based on the results of agarose gel electrophoresis and STR scanning, a set of microsatellites with clear and stable bands, abundant alleles, and even distribution on the 18 pairs of autosomes in cats were selected. Results Fiftyfive polymorphic and stably amplified STR loci were screened from 74 alternative microsatellite loci. Then, one to two higher polymorphic STR loci were selected in each autosome (other than A1 and B1 chromosomes) of the cat. Finally, 31loci with multiple alleles and even distribution on the 18 pairs of autosomes in cats were screened from 74 candidate microsatellite loci. Conclusions A set of microsatellite loci suitable for genetic structure analysis of cat populations is successfully screened.

Abstract:Objective To explore the effect and mechanism of low molecular weight heparin calcium (LMWHC)on mouse embryo implantation. Methods A mouse pregnancy model was established and LMWC was injected intraperitoneally. The effects of LMWHC on mouse embryo implantation were then observed. Mouse trophoblasts were isolated, cultured, and treated with various concentrations of LMWHC. Transwell chambers were used to examine cell invasiveness. ELISAs, western blotting, and RT-PCR was used to detect the expression levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2). Results After intraperitoneal injection of LMWHC into pregnant mice, the numbers of embryo implantations at days 6 and 9 of pregnancy were increased significantly ( P <0. 05).At 24 h after LMWHC injection at 1 × 10² , 1 × 10³ , and 1 × 10⁴ IU/ L, invading trophoblast numbers were (84. 83 ±14. 15), (162. 48 ± 25. 49), and (98. 73 ± 12. 77) respectively, significantly different from the cells without LMWHC treatment (65. 27 ± 13. 92) ( P <0. 05). The level of MMP-2 in the culture supernatant of trophoblasts was higher than that in the culture supernatant of cells without LMWHC treatment ( P < 0. 05), while the level of TIMP-2 was lower than that in cells without LMWHC treatment ( P <0. 05). Conclusions LMWHC promotes mouse embryo implantation, and its mechanism may be related to enhancement of the invasiveness of trophoblasts by affecting the expression of MMP-2 and TIMP-2.

Abstract:Objective Three human hepatoma cell lines were injected into liver tissue of four mice with different immune function defects to establish orthotopic xenograft models of human hepatoma for comparison. Methods Human HepG2, HUH-7, and QGY-7703 cell suspensions were injected into the livers of mice with different immune function defects [BALB/ c nude, non-obese diabetic (NOD) SCID, NOG (NOD. Cg-PrkdcscidII2rgtm1Sug / JicCrl), and NPG mice]. Survival time, mortality, liver weight, B-mode ultrasound, and histology were used to analyze and compare the characteristics of liver cancer models in the various immunodeficient mice. Results B-ultrasonography and gross anatomical observations indicated that all experimental animals showed tumor nodule formation in liver tissue. Moreover, all animals injected with a HepG2 cell suspension into the liver died at about 20 days. The survival time of NOG and NPG mice was significantly shorter than that of BALB/ c and NOD SCID mice ( P <0. 001). Experimental groups with injected HUH-7 and QGY-7703 cell suspensions into the liver were autopsied at day 92 and 104, respectively. The liver volumes of NOG and NPG model mice were increased significantly and formed large tumor masses, whereas BALB/ c nude and NOD SCID mice showed only small tumor nodules in liver tissues. The weights of NOG and NPG mouse livers were significantly higher than those of BALB/ c nude and NOD SCID mouse livers ( P < 0. 05). Histological examination showed that all groups of animals exhibited tumor cell growth with large areas of necrosis and some animal lung tissues had tumor metastasis. Conclusions Compared with BALB/ c nude and NOD SCID mice, hepatoma cells grow more rapidly in the liver tissues of NOG and NPG mice, and the survival time is short, the liver volume is large, and the weight is increased.The human hepatoma cell lines can complete malignant proliferation in NOG and NPG mice in a short time for time-efficient model study. Therefore, human-derived hepatocyte xenografts in NOG and NPG mice are an ideal model for the development of anti-hepatoma drugs.

Abstract:Objective To investigate the activities of major CYP enzymes in rat models of nonalcoholic fatty liver(NAFL) established by carbon tetrachloride (CCl₄ ) for various time periods and compare their activities with another NAFL model established by a high fat diet. Methods The experimental rats were divided into two different model groups with corresponding vehicle groups. The model groups either received a subcutaneous injection of 40% CCl₄ twice a week for 9 weeks (CCl₄ model) or continuous administration of a high fat diet for 9 weeks (high fat model). Histopathological observation, liver lipid content, and liver index (liver-to-brain ratio) were determined to confirm the rat NAFL modeling.Blood biochemical ALT and AST were measured, and the main CYP enzyme activities were measured. Results Histopathological findings of the two models were consistent with NAFL characteristics, and there was a significant increase in intrahepatic lipid content and the liver-to-brain ratio. The activities of the main CYP enzymes (except CYP2B6) in the NAFL model established by CCl₄ was significantly lower than those in the vehicle group ( P <0. 001), which was decreased over time. Both ALT and AST were increased significantly in the model group established by CCl₄ . There was no significant changes in the main CYP enzyme activities of the model established by high fat diet. The difference between the two models was significant ( P < 0. 001). Both ALT and AST were significantly elevated in the model group established by CCl₄ , but no increase was found in the model group established by high fat diet. Conclusions Activity of the main CYP enzymes in liver tissue can be used to verify the rat NAFL model established by CCl₄ or a high fat diet.

Abstract:Objective Echocardiographic techniques were used to study the changes in left ventricular (LV)function of cynomolgus monkeys with acute myocardial infarction (AMI), providing a reference for application of the cynomolgus monkey AMI model. Methods Cynomolgus monkeys were subjected to echocardiography before surgery, and the changes in LV morphology, LV hemodynamics, transmitral peak inflow velocity, and mitral annulus velocity were determined at 3 days and 1 month after modeling. Results Compared with that before modeling, the LVPWd of cynomolgus monkeys was increased significantly at 3 days after modeling ( P < 0. 05), and LVIDs were significantly increased at 1 month after modeling ( P < 0. 05). LVEF, SV, and LVFS indexes of the cynomolgus monkeys were significantly decreased at 3 days and 1 month after modeling ( P < 0. 05, P < 0. 01). CO was significantly decreased at 1 month after modeling ( P < 0. 05), whereas HR was significantly increased at 3 days after modeling ( P < 0. 05).Conclusions Echocardiographic techniques can be applied to LV cardiac function evaluation in the cynomolgus monkey AMI model. In particular, the indexes of LVEF, SV, and LVFS reflect the extent of AMI. The results of echocardiographic evaluation in the cynomolgus monkey AMI model are similar to those of human AMI.

Abstract:Objective To establish a hedth evaluation system and to evaluate the health status of captive rhesus macaques. Methods Combined with more than 10 years of breeding management experience with rhesus macaques, 500 rhesus macaques were evaluated in this study. The evaluation involved grading rhesus macaques by observing their mental status, feeding status, physical health status, short-term weight gain, age, and obesity. Then, a comprehensive score was obtained according to a certain weight ratio. Results Based on the comprehensive score, the current condition of the animals was divided into four levels: fine, good, normal, and bad. Conclusions This study provides the scientific basis for breeding management and disease prevention of rhesus macaques.

Abstract:Objective To find a simple staining method to determine the four phases of the estrous cycle, vaginal smear cells from female Sprague-Dawley (SD) rats. Methods Twenty female SD rats were randomly divided into two groups (10 each). The inclusion criteria were age 10 -13 weeks and weight 216 - 234 grams (mean: 225 ± 6 g). Rat vaginal smears were checked daily for 6 days. A wet cotton swab was inserted into the vaginal canal at 0. 5 -1. 0 cm deep,gently turned once or twice, and then placed on a clean glass slide with a saline solution. After air drying, the sample was stained. Rapid Gram and crystal violet staining was performed. The staining was detected under a microscope to determine the rat estrous cycle. Results The cell nuclei were stained deep purple, cytoplasm was lilac, and leukocytes were deep purple in crystal violet staining. The cell nuclei were stained amaranth, cytoplasm was rose red, and leukocytes were darkly red in rapid Gram staining. The estrous cycle in female rats averaged 4 -5 days. The estrous cycle is divided into different four phases: proestrus, estrus, metestrus, and diestrus. During proestrus, cells were large round, well-formed nucleated epithelial cells. During the estrus, cells were almost all large polygonal cornified squamous epithelial cells packed into clusters. During the metestrus, small and round leukocytes predominated, and nucleus-free keratinocytes were present.During the diestrus, there were three kinds of cells, mainly small leukocytes. Both crystal violet and rapid Gram staining could determine the four stages of the estrous cycle in female SD rats. The two staining method were simple, and the results were similar. However, the morphology of the crystal violet-stained cells was sometimes deformed slightly. The cell morphology of the rapid Gram staining method was complete, and the images were clear. Rapid Gram staining was timeefficient without fixing by absolute ethyl alcohol. Conclusions Vaginal smears with rapid Gram staining are a simple approach to easily and quickly determine the phases of the estrous cycle in female SD rats without changing their reproductive cycle. This method can be applied to large scale experiments.

Abstract:Objective To realize stable operation of an experimental animal barrier system, we investigated an automated control systems for specific pathogen-free barrier facilities. Methods Mobile communication and internet control technologies were used to develop the remote monitoring and alarm error correction system for laboratory animal barrier facilities, and to observe the operation of this animal center barrier system. Results The system achieved centralized management and automatic detection and repair of failure in the barrier facility instruments and equipment.Conclusions Timely warning and automatic repair can ensure that instruments and equipment operating safely and stably,realize intelligent management, reduce the operation cost, and improve management efficiency.

Abstract:Nasopharyngeal carcinoma is one of the most common malignancies of the head and neck in China. In particular, there is a high incidence in Guangdong and Guangxi, Hong Kong, and the southeast coast of China. Because of the inconspicuous location of nasopharyngeal cancer, it is mostly detected at mid- and late-stages. Early detection and treatment of this tumor are difficult for clinicians. Experimental animals provide a good model to study the pathogenesis and therapeutic measures of nasopharyngeal carcinoma. This article reviews the establishment of animal models of classical nasopharyngeal carcinoma and the recent research progress in animal models of nasopharyngeal carcinoma to provide a basis for research of human nasopharyngeal carcinoma and the translation of new research findings into clinical application.

Abstract:Drugs are among the most important therapeutics for kidney diseases, including glucocorticoids and antirejection agents. Zebrafish is widely used for chemical screening and analyses of gene mutagenesis and molecular mechanisms of the pathogenesis of kidney diseases. Recently, several models of kidney disease have been established in zebrafish, providing the potential to identify and verify novel renoprotective drugs. Here, we discuss the feasibility of zebrafish for small-molecular drug screening in nephrology and summarize kidney disease models in zebrafish as well as new drugs for kidney diseases.

Abstract:Hereditary tyrosinemia I (HT I) is an autosomal recessive disease characterized by progressive liver and kidney damage with a high risk of hepatocellular carcinoma. HT I is caused by mutations of the gene encoding fumarylacetoacetate hydrolase (FAH), the last enzyme in the tyrosine catabolic pathway. Several animal models of Fah deficiency have been established, including mouse, rats, rabbits, and pigs, using a recently developed gene-modifying technique. These animal models have become important for liver biology research and are widely used in liver stem cell and hepatic gene therapy studies. Furthermore, Fah mutants can be used as a bioreactor for the expansion of hepatocytes. These chimeric animals have become valuable models for basic research of infectious diseases, metabolism, and gene therapy.Here, we review the progress of animal models of HT I and their applications.

Abstract:Chemotherapy-induced diarrhea is a common toxic side reaction of chemotherapy; The pathogenesis of CID has not been fully elucidated; and research cannot be carried out directly in humans; Therefore; it is necessary to establish related animal models; In this study; we searched literature databases; summarized the existing methods of model construction; and reviewed the various models of CID; including tumor-bearing; non-tumor-bearing; and gene knockout models; to provide a reference for the research and prevention of CID.

Abstract:To compare the experimental methods, precautions, evaluation indicators, application characteristics,advantages, and disadvantages of five mazes to provide a reference for better use of maze experiments to evaluate the learning and memory abilities of rodents. We accessed the China National Knowledge Infrastructure, and PubMed, collected the relevant documents of the Morris water maze, Y-maze, eight-arm radial maze, T-maze, and Barnes maze, and compared their experimental methods, precautions, evaluation indicators, application characteristics, and mechanisms related to learning and memory examination of each maze. The Morris water maze test has more evaluation indicators, and more reliable results.Operation of the Y-maze test is simple, but it more affects the tested animals. The eight-arm radial maze test avoids water and electrical stimulation, and its operation is simple. A T-maze test without water and electrical stimulation relies on the animal’s nature to complete the task. The Barnes maze test stimulates animals to complete their tasks with light and sound,and has many limitations. To evaluate the spatial learning and memory abilities of rats and mice, all the five mazes are suitable, and the results of the Morris water maze test are more accurate. All the Morris water maze, Y-maze, T-maze, and eight-arm radial maze tests are suitable to evaluate working memory capabilities, but the Y-maze (autonomous alternation experiment) and T-maze test are less stressful to animals, and the results may be more reliable.