Abstract:Objective To investigate the mechanism of memantine on ERK/ CREB signaling and synapticplasticity in a mouse model of cerebral ischemia-reperfusion. Methods Sixty mice were randomly divided into a shamoperation group (Sham), middle cerebral artery occlusion model group (MCAO), 20 mg/ kg memantine group (M20), 4mg/ kg memantine group (M4), and saline group (NS). With the exception of the Sham group, ischemia-reperfusion wasestablished in groups using a suture to achieve MCAO. Changes in body weight and degree of neurological deficits wereobserved in the mice. Brain atrophy volume was measured using cresyl violet staining, while sensorimotor function wasobserved by an adhesive removal test and cognitive function was detected by Morris water maze. Expression of ERK1/2,phosphorylated ERK1/2 (p-ERK1/2), CREB, p-CREB, postsynaptic density protein 95 (PSD-95) and synaptophysinwere detected by western blot assay. Results Compared with MCAO, M4, and NS groups, the M20 group exhibitedreduced weight loss, decreased neurological severity scores, decreased volume of brain atrophy, and improved sensorimotorfunction. In addition, the results of water maze testing showed that the degree of learning and memory impairment wasreduced in the M20 group. Expression of p-ERK1/2, p-CREB, PSD-95, and synaptophysin proteins were increased in theM20 group compared with other groups. Conclusions Continuous treatment with memantine (20 mg/ kg) after cerebralischemia in mice can improve the recovery of neurological function, ameliorate deficits in learning and memory, and improve synaptic plasticity of the brain.

Abstract:Objective The aim of this study was to screen enterovirus 71(EV71) pathogenicity-related genesusing genetic diversity mice to further understand the pathogenesis of the EV71, and lay the foundation for clinicaldiagnosis, treatment and prognosis. Methods Four-to-six week old genetic diversity mice were challenged with 10⁷copiesof enterovirus 71 by intraperitoneal injection. The blood and hind limb skeletal muscles were collected, and the viral loadwas determined by real-time quantitative PCR. Then, the GeneMine system genetic database was used to analyze theinfection data, and EV71 pathogenicity-related genes were screened. Results Fifty-three genes related to EV71 infectionwere screened using genetic diversity mouse infection data. Conclusions Genetic diversity mice have significantadvantages for simulating population genetic diversity and are a new resource to study complex trait diseases. Mostimportantly, they are an ideal and efficient resource for the screening of pathogenicity-related genes.

Abstract:Objective To provide experimental data for preclinical studies on the treatment of human diseases byautologous fat stem cell transplantation, including isolation and culture methods and the biological characteristics oflaboratory animals including C57 mice, SD rats, and cynomolgus monkey adipose-derived stem cells (ADSCs), which werecompared with those of humans. Methods hADSCs, mouse adipose derived mesenchymal stem cells (mADSCs), ratadipose derived mesenchymal stem cells (rADSCs) and cynomolgus monkey adipose derived mesenchymal stem cells(cADSCs) were identified via surface markers using flow cytometry, and adipogenic and osteogenic differentiation wasinduced. Results All the hADSCs, mADSCs, rADSCs and cADSCs showed fibroblast-like morphology. Flow cytometryshowed that mesenchymal stem cell surface markers CD90 and CD29 in ADSCs of each species were positive, while thevascular endothelial cell marker CD31 was negative. Oil red O and alizarin red staining showed that hADSCs, mADSCs,rADSCs and cADSCs differentiated into fat cells and bone cells. Conclusions Laboratory animal ADSCs and hADSCs canbe cultured using the same method and they all had similar surface marker expression, as well as adipogenic and osteogenic differentiation potential, indicating their usefulness for the pre-clinical study of autologous ADSC transplantation.

Abstract:Objective To establish a mouse-adapted influenza H3N2 virus-infected murine model and investigatethe molecular mechanism as well as the pathogenic changes of the mouse-adapted virus strain. Methods Mouse-adaptedstrain (MA-7) was obtained by continuous passage of the A/ Aichi/2/68(H3N2) virus in mouse lungs. BALB/ c mice wereinfected intranasally to establish the model. Clinical signs, body weight loss rate, virus load in tissues and histopathologywere observed and the DNA sequences of MA-1 and wild-type stains were analyzed. Results Mice infected with A/ Aichi/2/68(H3N2) showed no obvious changes in symptoms and no virus replication was detected. However, all mice infectedwith MA-7 died within 9 days post-infection and the weight loss rate was greater than 30%. Virus replication was detected inmultiple tissues, especially the lung tissues (10^{5. 5} TCID₅₀), which caused interstitial pneumonia. Genome sequencing andalignment indicated five mutations in the HA, NA, PA and NP genes. Conclusions A mouse-adapted seasonal H3N2virus-infected murine model is successfully established, and can be used to study its pathogenesis and to evaluate drugs and vaccines. Moreover, the increased virulence of the adaptive virus strain may be related to five mutations in the virus genes.

Abstract:Objective To construct miR-223 full-sequence-knockout mice with dual sgRNAs. Methods DualsgRNAs were designed and transcribed in vitro, then microinjected into zygotes of C57BL/6 mice with Cas9 mRNA. After themice were born, genomic DNA was subjected to PCR and sequenced to identify their genotypes. In addition, total RNA wasextracted from the livers of mice, and expression of miR-223 in the liver tissues was analyzed by real-time PCR. Results Dual miR-223 sgRNAs were designed and transcribed in vitro. After purification, mouse zygotes were microinjected to obtainmiR-223 mutant mice. Sequencing result revealed that the mutant mice had three genotypes: one with a 6-bp deletion that didnot affect the miR-223 sequence, and two with 162-bp and 168-bp deletions, respectively, resultsing in full-sequence-deletionof miR-223. Compared with wild-type mice, miR-223 expression was barely detected in liver tissues of the two full-deletion mice. Conclusions miR-223 full-sequence-knockout mice are successfully generated using dual sgRNAs.

Abstract:Objective To examine the effect of Astragalus (AS) injection on post-myocardial infarction-inducedcardiac remodeling in rats, and explore potential mechanisms underlying such effects. Methods A cardiac remodelingpost-myocardial infarction model was prepared in rats, which were divided into four groups: sham operation, myocardialinfarction (model group), low-dose AS (ASL, 1 mL/ kg), and high-dose AS (ASH, 3 mL/ kg). Survival rate of the ratsand activities of the alpha isoform of myosin heavy chain (α-MHC) and N-terminal pro b-type natriuretic peptide (NTproBNP)in rat serum were measured after 6-week treatment. Histopathological changes and myocardial fibrosis wereobserved by light microscopy using hematoxylin and eosin, and Masson trichome staining. Quantification of malondialdehyde(MDA), nitric oxide ( NO), and endothelial nitric oxide synthase ( eNOS) were carried out using enzyme-linkedimmunosorbent assays. Protein expression of phosphatidylinositol 3 kinase (PI3K), phosphorylated AKT (p-AKT), and peNOSwere analyzed by western blotting. Results Compared with the model group, the survival rate of the ASL and ASHgroup were increased, but not significantly ( P > 0. 05). Meanwhile, α-MHC and NT-proBNP contents in the ASH groupwere reduced ( P < 0. 05). In addition, inflammation, hyperemia, and interstitial fibrosis were reduced in the ASH group.Moreover, the ASH group exhibited increased protein expression of PI3K and p-AKT in the injured heart ( P < 0. 05). peNOSexpression in the ASH group was increased compared with the model group ( P < 0. 05). Conclusions AS elicits anobvious protective effect on cardiac remodeling after myocardial infarction in rats. Activation of the PI3K/ AKT pathway mayactivate p-eNOS, which is involved in the mechanism by which AS prevents oxidative stress during cardiac remodeling.

Abstract:Objective To investigate the effects of a Chinese medicine, Mai Qi Jiang Tang pill,on the bloodglucose level in ob/ ob mice. Methods Eight-week old male ob/ ob mice were randomly divided into Mai Qi Jiang Tang pillhigh (8 g/ kg), medium (4 g/ kg), and low (2 g/ kg) dose groups, as well as a metformin (250 m g/ kg) group, wereorally administered drugs once daily for 10 weeks. Age-matched C57BL/6 J control mice and ob/ ob mice were orallyadministered an equal volume of vehicle. Average food consumption per day and body weights of the mice were recorded,and fasting blood glucose and insulin levels were measured using a glycemic instrument and enzyme-linked immunosorbentassay, respectively. Pathological changes of the pancreas were observed using hematoxylin and eosin staining. Results Compared with the control ob/ ob mice, ob/ ob mice administered Mai Qi Jiang Tang pill exhibited significantly decreasedfasting blood glucose levels at 2, 6, 8, and 10 weeks after treatment ( P < 0. 05, P < 0. 01). Mai Qi Jiang Tang pill alsoattenuated the degree of pathological changes observed in islet cells and increased serum insulin levels ( P < 0. 05), butelicited no significant difference in body weight or average food consumption per day at 10 weeks after treatment.Conclusions Mai Qi Jiang Tang pill can decrease blood glucose levels of ob/ ob mice, which may be related to the amelioration of pancreatic pathology and promotion of insulin secretion.

Abstract:Objective To construct a nude mouse model of granulocytic leukemia with M1 cells. Methods Ninefemale BALB/ c nude mice, 5-6 weeks old, were randomly divided into three groups (n=3 per group): group A mice werethe blank control group, and groups B and C were inoculated via the tail vein with a logarithmic growth phase M1 cellsuspension (1×10⁶ and 5×10⁶, respectively). The general condition of the mice was observed. Blood samples, peripheralblood leukocyte differential count, and peripheral blood CD33CD117 positive cells were detected on days 0, 10, 20 and 30after modeling. On the day 30 or at the time of death, tissue sections were taken for pathological examination. Results Themice in the model group developed symptoms such as wilting and dorsiflexion on days 10-15 after inoculation. Comparedwith the blank group, the number of peripheral blood leukocytes in each mouse injected with 8 × 10⁶ M1 cells wassignificantly increased on the 30th day ( P <0. 05). On the 30th day, the proportion of peripheral blood leukemia cells inthe model group was significantly higher than that in the blank group ( P <0. 05), Compared with the blank group, theproportion of CD33+ CD117+ cells in the bone marrow of the other groups increased, and the high dose group was the mostsignificant. ( P <0. 05), and that on day 30, leukemia cells infiltrated into the spleen of model mice. Conclusions Theinjection of 8×10⁶ mouse leukemia M1 cells into the tail vein of BALB/ c nude mice can induce an acute myeloid leukemia model consistent with the biological characteristics of acute myeloid leukemia.

Abstract:Objective To explore the effects of a Chinese medicine, “Fujiu plaster” (developed by the AffiliatedHospital of Liaoning University of Traditional Chinese Medicine), on NGF/ TrKA and related inflammatory factors inasthmatic mice and its mechanism of action. Methods Fifty SPF adult BALB/ c mice were randomly divided into fivegroups: control, asthma model, dexamethasone, high-dose Fujiu plaster, and low-dose Fujiu plaster groups. To establishthe asthma model, the mice were sensitized through intraperitoneal injection of ovalbumin (OVA) and an asthmatic reactionwas provoked through ultrasonic aerosol inhalation. Expression of IL-4, total IgE, OVA-specific IgE, and IFN-γ in serumwas quantified by enzyme-linked immunosorbent assay. Pathological changes were examined using hematoxylin and eosin,and Masson trichrome staining. NGF and TrKA protein expression in the lung tissues was determined usingimmunohistochemistry. Results Compared with the control group, the model group exhibited significantly increasedexpression of NGF, TrkA, IL-4, total IgE, and OVA-specific IgE ( P < 0. 05), but decreased IFN-γ expression ( P <0. 05). Compared with the model group, the dexamethasone and high-dose Fujiu plaster groups exhibited significantlyreduced expression of NGF, TrkA, IL-4, total IgE, and OVA-specific IgE ( P < 0. 05), and increased IFN-γ expression( P < 0. 05). No significant changes to the aforementioned indicators were observed in the low-dose Fujiu plaster group ( P > 0. 05). Conclusions Fujiu plaster inhibites the secretion of IL-4 and IgE, and promotes the secretion of IFN-γ bydownregulating expression of NGF and TrkA proteins to regulate the imbalance of Th1/ Th2 lymphocytes, thus relieving the asthma attack.

Abstract:Objective To investigate the effect of sodium tanshinone II A sulfonate (STS) on cardiomyocyteapoptosis in rats with dilated cardiomyopathy (DCM), and its potential mechanism of action. Methods DCM rats wererandomly divided into DCM, STS-L, STS-M, STS-H, Carvedilol (CAR), and control groups,12 rats in each group. Leftventricular internal diameter at end-systole (LVIDs) and left ventricular internal dimension at end-diastole (LVIDd), andleft ventricular ejection fraction (LVEF) were measured by echocardiography. Pathological injury of myocardial tissues wasobserved using hematoxylin and eosin, and Masson trichrome staining. Tumor necrosis factor-α (TNF-α) and interleukin-6(IL-6) levels were quantified using enzyme-linked immunosorbent assays, while apoptosis in cardiomyocytes was detectedusingTUNEL staining. Expressions of phosphorylated phosphatidylinositol 3 kinase ( p-PI3K), phosphorylated proteinkinase B (p-Akt), Bax, caspase-3, and Bcl-2 were detected by immunoblotting and immunohistochemistry. Results Compared with the control group, the DCM group exhibited increased LVIDs and LVIDd, decreased LVEF, increasedmyocardial histopathologic scores and percentage of cardiac collagen fibers, increased serum levels of TNF-ɑ and IL-6, andincreased apoptosis index (AI) in cardiomyocytes ( P < 0. 05). Compared with the DCM group, the STS and CAR groupsexhibited decreased LVIDs and LVIDd, increased LVEF, decreased myocardial histopathologic scores and percentage ofcardiac collagen fibers, decreased serum levels of TNF-ɑ and IL-6, and decreased apoptosis index(AI) in cardiomyocytes( P < 0. 05). Compared with the control group, the expressions of p-PI3K, p-Akt, and Bcl-2 proteins were decreased inthe DCM group, while expressions of caspase-3 and Bax proteins were increased ( P < 0. 05). Compared with the DCMgroup, the expressions of p-PI3K, p-Akt, and Bcl-2 proteins in STS and CAR groups were increased, while expressions ofcaspase 3 and Bax proteins were decreased ( P < 0. 05). Conclusions STS may inhibit cardiomyocyte apoptosis in DCM rats by activating PI3K/ Akt signaling and exert protective effects.

Abstract:Objective To investigate the effect of vitamin E (VE) on myocardium in a rat model of renalischemia reperfusion (RIR). Methods Rats were divided into three groups: a control group, RIR model group, andexperimental (VE + RIR) group fed with VE for 4 weeks before the RIR model was prepared. Contents of malondialdehyde(MDA), myeloperoxidase (MPO), xanthine oxidase (XO), superoxide dismutase (SOD), and nitric oxide (NO) weremeasured in the myocardium. In addition, levels of creatine kinase (CK) and creatine kinase MB isoenzyme (CK-MB) inplasma were determined. Mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), maximal rise rate ofleft ventricular pressure ( dP/ dt_max ) and maximal fall rate of left ventricular pressure (-dP/ dt_max ) were monitored.Myocardial cell morphology and expression of endothelial nitric oxide synthase (eNOS) were observed by light microscopyand immunohistochemistry. Western blot analysis was conducted to quantify P47phox expression in cardiomyocytes. Results Compared with the control group, levels of MDA, MPO, XO, and NO were increased, and the level of SOD wasdecreased in the myocardium of RIR group rats; moreover, CK and CK-MB plasma levels were increased in this group.Compared with the control group, values of MAP, LVSP, dP/ dt_max, and -dP/ dt_max were obviously decreased in the RIRgroup. In addition, aggravation of myocardial damage, number of eNOS-positive cells, and P47phox protein expression wereincreased in the RIR group compared with the control group. Compared with RIR group, the VE + RIR group exhibiteddecreased levels of MDA, MPO, and XO, as well as increased levels of SOD increased in myocardium. In addition, plasmalevels of CK and CK-MB were decreased, NO content was increased, and values of MAP, LVSP, dP/ dt_max, and -dP/ dt_maxwere obviously increased in the VE + RIR group compared with the RIR group. Moreover, compared with the RIR group,microscopic cardiomyocyte injury was reduced, numbers of eNOS-positive cells were increased, and P47phox proteinexpression was decreased in the VE + RIR group. Conclusions VE potentially protects the myocardium from RIR by antiinflammatoryand anti-oxidative mechanisms, as well as by increasing NO content and decreasing P47phox protein expression.

Abstract:Objective To investigate the protective effect and mechanism of troxerutin ( TRX) on acutemyocardial toxicity induced by pirarubicin(THP) in rats. Methods THP was used to replicate acute myocardial toxicity inrats. Changes in cardiac weight, cardiac function, electrocardiogram, pathological morphology, and serum myocardialenzymes in the rats with acute myocardial toxicity induced by THP were observed. Western blot was used to determine theprotein levels of AKT, p-AKT, caspase-9, caspase-3, cleaved caspase-3, BCL-2 and BAX. Results TRX increased thecardiac coefficient of rats with acute myocardial toxicity induced by THP, improved their cardiac function, decreased thecontent of LDH, CK-MB, cTn-T and BNP, increased SOD and decreased the levels of MDA. TRX also activated AKT togenerate phosphoric acid. The levels of caspase-9, caspase-3 and BCL-2 were upregulated, and the levels of cleavedcaspase-3 and BAX were downregulated. Conclusions TRX attenuates acute myocardial toxicity induced by pirarubicin in rats by activating AKT and decreasing the expressions of related apoptotic proteins.

Abstract:Objective To investigate the effects of curcumin pretreatment on the numbers of neutrophils in bloodand tissues of heatstroke rats in a dry-heat desert environment. Methods One-hundred-sixty male Sprague-Dawley ratswere randomly divided into four groups (n=40 per group). All groups were given an isometric gavage for 7 days. On theeighth day, all groups were transferred to a Simulated Climate Cabin, which was set to mimic the special environment ofNorthwest China. At 0, 50, 100, and 150 min, ten rats per group were removed from the cabin and anesthetized to collectblood from the inferior vena cava to determine the neutrophil number. At 150 min, the ileum, liver, kidney, and lung ofthe rats were harvested for pathological observation to assess the number of neutrophils and tissue alterations. Results Numbers of neutrophils in the blood of all four groups were increased from 0 to 50 min, and then decreased from 50 to 150min. At 150 min, numbers of neutrophils infiltrating the ileum, liver, kidney, and lung tissues were decreased with theincreasing curcumin dose pretreatment. Moreover, significantly fewer neutrophils were observed in the medium- and highdosecurcumin pretreatment groups compared with the saline and low-dose curcumin pretreatment groups ( P < 0. 01). At150 min, the rats reached a severe heatstroke status. Pearson correlation analysis indicated that the number of neutrophils inblood was negatively and significantly correlated with numbers of neutrophils in the ileum, liver, kidney and lung tissues.Conclusions With continued exposure to the desert dry-heat environment, blood neutrophils in rats are first elevated andthen gradually decreased. In addition, numbers of infiltrating neutrophils in organ tissues are increased with the aggravationof heatstroke, and the decrease of blood neutrophils is intimately correlated to the increase of infiltrating neutrophils inorgan tissues. By inhibiting the decrease of blood neutrophils and accompanying increase of infiltrating neutrophils in organ tissues, curcumin may alleviate organ injury in heatstroke rats in a dry-heat desert environment.

Abstract:Objective To investigate the protective effect of wedelolactone ( Wed) against acetaminophen(APAP)-induced acute liver in mice. Methods A mouse model of APAP-induced liver injury was established. Thirty-twomale BALB/ c mice were randomly divided into normal, APAP, 10 mg/ kg Wed and 20 mg/ kg Wed groups (n = 8). Acolorimetric method was used to assay the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase(AST), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-PX) and superoxide dismutase(SOD) in mouse liver homogenates, and the serum levels of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6).Results In the model group,the serum levels of AST, ALT, IL-6 and TNF-α,and GSH and MDA in the liver homogenateswere significantly higher than those in the control group ( P < 0. 01). The levels of AST, ALT, SOD and GSH-PX in livertissue homogenates of the low- and high-dose Wed groups were significantly higher than those in the model group ( P <0. 01), and the levels of MDA and GSH in liver tissue homogenates and TNF-α and IL-6 in the serum of mice weresignificantly higher than those in the model group ( P < 0. 01). The levels of GSH-PX and SOD in the model group weresignificantly lower than those in the control group ( P < 0. 01). Histopathological examination using HE and TUNELstaining showed that Wed significantly reduced liver necrosis and apoptosis. Conclusions Wed has a protective effect on APAP-induced acute liver injury.

Abstract:Objective To establish a rapid genotyping method for detection of Pasteurella pneumotropica as astandard revision and effective control, in view of problems with classification of P. pneumotropica and its high infection ratein laboratory animals. Methods Genetic polymorphism and molecular epidemiological analyses of 314 isolates and twostandard strains of P. pneumotropica from laboratory animals were performed using an amplified fragment lengthpolymorphism ( AFLP) method. Results The AFLP method divided tested isolates into 11 gene clusters and 190genotypes; gene cluster AC7 was the main epidemic group. Polymorphic bands mainly occurred between 31~36, and theSimpson diversity index was 0. 992. Conclusions This study shows that P. pneumotropica genotypes are abundant inlaboratory animals in Beijing area, and different strains represented by the two standard strains have significantly differentpolymorphisms. Our results indicate the characteristics of cross contamination, abundant sources, and long-term contamination in some laboratory animals of different sources.

Abstract:Objective To study the effect of sodium fluoride on the pathological and morphological changes infemur, liver, kidney, and brain tissues of rats with fluorosis. Methods Ten healthy male and ten healthy female weanedSprague-Dawley rats were randomly divided into a control group and fluorosis group. Rats in the fluorosis group were fedwith tap water containing a fluorine ion concentration of 100 mg/ L for 12 weeks. Contents of fluoride ion in the femur,liver, kidney, and brain tissues of rats in each group were determined, as well the content of malondialdehyde (MDA) inserum, liver, kidney, and brain. Pathological and morphological changes in the femur, liver, kidney, and brain of ratswith fluorosis were observed using light microscopy and transmission electron microscopy (TEM). Results Body weight,body length, and tail length of rats in the fluorosis group were slightly lower than those in the control group, but theincidence of dental fluorosis in rats treated with fluoride was 100%. Fluoride levels in the femur, liver, kidney, and braintissues of fluorosis group rats were significantly increased compared with the control group ( P < 0. 01), and MDA contentin serum, liver, kidney, and brain of rats with fluorosis was higher than that of the control group ( P < 0. 01 or P < 0. 05).The results of pathological examination in rats with fluorosis revealed: 1) shortened bone trabecula, 2) wider trabecularspacing in bone tissue, 3) hepatocyte degeneration and vacuolization in liver tissue, 4) vacuolar degeneration of epithelialcells in the kidney proximal tubule, as well as mildly congestive and expanded interstitial tubules, and 5) sparselydistributed hippocampal cells exhibiting swelling and vacuolation. Under TEM, all the osteoblasts, hepatocytes, epithelialcells of the kidney proximal tubules, and neurons in rats treated with fluoride all exhibited shrinkage, chromatinmargination, and mitochondrial swelling. Conclusions Sodium fluoride can cause pathological damage in the femur, liver,kidney, and brain tissues in rats, and can induce cell apoptosis.

Abstract:Objective To explore the method of establishing a mouse model of levofloxacin resistance by infectionwith Pseudomonas aeruginosa (PA) in combination with a low-dose levofloxacin administration. Methods The model ofpneumonia was induced by infecting mice with a PA standard strain. Different concentrations of bacterial suspension, timesof infection and lerofloxacin administration method were analyzed. The therapeutic effect of levofloxacin was analyzed andthe feasibility of establishing the model was determined by measuring body weight changes and lung index of the mice.Results There were significant differences in lung indexes between the model groups 1 and 2 and normal group ( P <0. 01), and there was no significant difference between levofloxacin group 2 and model group 2 after single infection of PA(1×10⁹cfu/ mL) in mice treated with low-dose levofloxacin. In the experiment of single infection of PA (1×10¹⁰ cfu/ mL)plus low-dose levofloxacin,there were significant differences between the model groups 1 and 2 and the normal group ( P <0. 01), and there was no significant difference between levofloxacin group 3 and model group 2. Levofloxacin groups 1 and2 significantly reduced the lung index in model group. In the experiment of repeated infection of PA in mice,there weresignificant differences between model groups 1 and 2 and normal group ( P < 0. 01). There was no significant differencebetween the levofloxacin group 2 and model group 2. In each experiment, the body weight of mice in the experimentalgroups was lower than that of the normal group on the second day after infection, although this was not significantlydifferent. Conclusions Under the experimental conditions used in our study, this animal model can simulate thephenomenon of drug resistance to a certain extent generated by PA (1×10¹⁰ cfu/ ml) single infection and PA repetitive infection combined with administration of a low-dose levofloxacin.

Abstract:Objective To explore the effects of venlafaxine on anxiety and depression-like behavior in rats withchronic restraint stress. Methods Thirty-six SD rats were randomly divided into control, model, and venlafaxine groups,with 12 rats in each group. The model and venlafaxine groups were given chronic restraint stress for 21 days, and wererestrained for 6 hours at the same time every day. Venlafaxine was administered intragastrically (6. 75 mg/ kg), and thecontrol and model groups were given distilled water intragastrically. Rats were tested for anxiety using the elevated plus mazeand scene fear test. Depression behavior was tested using the open field and forced swimming tests. Hematoxylin and eosin(HE) staining was used for the pathological examination of the rat hippocampus. A high performance liquidchromatography-electrochemical method was used to measure the content of 5-HT, NE and DA in the hippocampus, andplasma HPA axis CRH, ACTH and CORT levels were detected by ELISA. Results Anxiety and depression-like behaviorsin the model group were significant ( P <0. 01). Pathological changes such as neuron loss, disordered arrangement, andvacuolization of some cells were observed in the hippocampus of model rats. The contents of 5-HT, NE and DA weresignificantly downregulated ( P <0. 05), and plasma CRH, ACTH, and CORT levels were significantly increased in themodel group ( P <0. 01). Compared with the model group, after treatment with venlafaxine, anxiety and depression weresignificantly relieved ( P < 0. 05), hippocampal neuron injury was alleviated, the contents of 5-HT, NE and DA wereincreased to different degrees ( P < 0. 05), and plasma CRH, ACTH, and CORT levels were decreased ( P < 0. 05).Conclusions Venlafaxine significantly improve anxiety and depression-like behaviors in rats with chronic restraint stress,and alleviate hippocampal neuronal damage, which might be related to the upregulation of monoamine neurotransmitters in the brain and inhibiting excessive HPA axis stimulation in vivo.

Abstract:Objective To investigate the anesthetics that do not interfere with electrocardiograms (ECG) bycomparing the effects of three anesthetics on ECG in C57BL/6 mice. Methods Mice were randomly divided into threegroups: intraperitoneal injection of 20% ethyl carbamate, 1% pentobarbital sodium, and 2. 5% chloral hydrate. Aftercomplete anesthesia, the mice were connected to an ECG scanner by a limb lead for 1 hour of electrocardiogram recording.Results Within the administration time between 0-40 min, 20% EC did not significantly affect the ECG parameters ofmice. However, mice in the 1% pentobarbital sodium group had a reduced heart rate, and prolonged PR interval and QRSduration. Mice in the 2. 5% chloral hydrate group had a reduced heart rate and prolonged PR interval. Conclusions Ourfindings indicates that 20% EC has the least effect on the ECG of C57BL/6 mice and that 2. 5% chloral hydrate is suitable for experimental studies 20 min after anesthesia is induced in mice.

Abstract:Pigs undergoing thoracotomy for the establishment of a model of myocardial infarction must first undergoanesthesia. Although management of anesthesia and analgesia in pigs is closely related to the success or failure of surgicalmodeling, the literature lacks detailed descriptions and analysis. To provide a reference for a standard of the establishmentof porcine myocardial infarction models, this article is combining with literature analysis, to summarize anesthesiamedication, anesthesia measures, anesthesia monitoring and evaluation, common anesthesia crises and pre- and postanesthesia management.

Abstract:Transient receptor potential (TRP) channels, which are important selective cation channels located inthe cell membrane, are widely expressed in the human respiratory tract, digestive tract, liver, and heart. Many studies havedemonstrated the involvement of TRP channels in the development and progression of malignant tumors. Herein, we reviewthe roles of TRP channels in the development, progression, and treatment of digestive tumors. We hope to provide furtherunderstanding of the mechanisms of pathogenesis and progression of digestive cancers, as well as an alternative direction for their treatment.

Abstract:Para-chlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor consumes 5-hydroxytryptaminein the brain that leads to insomnia. In recent years, the establishment of an insomnia animal model using PCPA has beenrecognized and widely used for animal experiments because of its simplicity and practicality. However, the low solubility ofPCPA in water and the difficulty of its injection has hindered the progress of experiments. In this paper, we review literatureregarding the use of PCPA, summarize the method for using PCPA in experiments, and discuss the best way to use PCPA.

Abstract:Hemophilia is a monogenic hereditary disease whose pathogenesis includes the reduction of coagulationfactors caused by mutations in genes encoding coagulation factors. The clinical manifestation of this disease is recurrentbleeding, which can be life-threatening in severe cases and cannot be cured. Currently, gene therapy might have thepotential to cure hemophilia. In gene therapy research, animal models are commonly used. The mouse hemophilia model isuseful because of its convenience for transportation and lower research costs when compared with other large animal models.It has become a hot spot for research using animal hemophilia models. After more than 20 years of development, technologyto generate a mouse hemophilia model has gradually matured. The aim of this paper is to summarize the research progress in generation of a mouse hemophilia model.