Abstract:Objective To obtain gene-targeted mouse embryos expressing Cas9 protein specifically in muscleusing CRISPR/ Cas9, to lay the foundation for the construction of animal model expressing Cas9 protein specifically inmuscle. Methods The sgRNA targeted Rosa26 locus was designed and synthesized according to the sequence of theRosa26 gene in mice. The editing efficiency was tested by in vitro cleavage assay. Rosa26 sgRNA and Cas9 protein weresubsequently co-injected into mouse pronuclear-stage embryos to examine the editing efficiency in vivo. A mouse Rosa26locus homologous targeting vector for the muscle-specific expression of Cas9 protein was designed and constructed. Finally,gene-targeting embryos were obtained through co-injecting the homologous targeting vector and Rosa26 sgRNA with Cas9protein into mouse embryos. Results The sgRNA designed and synthesized according to the sequence of mouse Rosa26gene was effective at gene editing in the in vitro digestion experiments. The homologous targeting vector for the musclespecific expression of Cas9 protein, Donor-SP-px459, was successfully constructed by PCR and homologous recombinationligation. Mouse embryos injected with Rosa26 sgRNA and Cas9 protein showed normal cleavage and supported blastocystdevelopment. PCR and sequencing result demonstrated that gene editing occurred in the obtained embryos, after which theembryo grew into a Rosa26 gene edited mouse. Mouse embryos for the muscle-specific expression of Cas9 protein weresuccessfully obtained after co-injection of a homologous targeting vector and Rosa26 sgRNA with Cas9 protein. Conclusions Rosa26 gene-edited embryos and mice are obtained using the CRISPR/ Cas9 system, and mouse embryos with musclespecificexpression of Cas9 protein are successfully obtained, laying the foundation for the construction of animal models expressing Cas9 protein specifically in muscle.

Abstract:Objective To study the photothermal killing effect on bacteria means of the strong photothermalproperties of gold nanoparticles system (GNPs system) after responsive aggregation. Methods Synthesized peptides A andB were modified at their surface by gold nanoparticles (GNPs) through the Au-S bond reaction, and then mixed at equal Acta Lab Anim Sci Sin,June 2019,Vol. 27, No. 3proportions to form the GNPs system. First, dynamic light scattering (DLS) and transmission electron microscopy (TEM)were used to assess the responsive aggregation under weakly acidic conditions. UV absorption changes under weakly acidicconditions were measured by a multifunction microplate reader. In order to understand the photothermal conversion of thenanoparticles in the bacterial suspension, their temperature curves in the solution under weakly acidic conditions and aftertreated with bacteria were measured, respectively. Finally, the antibacterial effect was tested in vitro. Results The particlesize of the synthesized GNPs system was increased from 16 nm to 900 nm as detected by DLS under weakly acidic conditions.Obvious aggregates were observed by TEM, and the UV absorption signal was significantly increased at 650~900 nm. Underthe weakly acidic conditions of simulated bacteria, the GNPs system achieved a rapid temperature rise of the solution withmixed bacterial under laser irradiation conditions. The highest temperature was 69. 8°C, significantly different from the controlgroup of GNPs-PEG2000. The result of antibacterial experiments in vitro showed that the GNP system had the strongest killingeffect against Staphylococcus aureus, which was 50% and 100% killing of the bacteria at concentration of 50 and 200 μg/ mL,respectively, showing a significant difference compared with the control group of GNPs-PEG2000. Conclusions This study provides a new approach for the design of GNPs and a new method to apply GNPs to photothermal therapy.

Abstract:Objective Magnetic resonance imaging (MRI) and pathological analysis were performed on Isca1myocardial conditional knockout rats to explore whether Isca1 myocardial conditional knockout elicits abnormal cardiacstructures in newborn rats. Methods Bred Isca1 myocardial conditional knockout rats and the genotyping and knockoutefficiency of Isca1 were verified by PCR. MRI was performed on the postnatal 0. 5 d and 2. 5 d Isca1 myocardial conditionalknockout rats. Pathological examination using H&E staining and transmission electron microscopy were performed on themyocardial tissues of postnatal 2. 5 d Isca1 myocardial conditional knockout rats. Results The knockout efficiency of Isca1myocardial conditional knockout rats was more than 78%. Compared with wild type rats, the 0. 5 d Isca1 myocardialconditional knockout rats showed no significant dilatation; however, the right ventricles of 2. 5 d Isca1 myocardialconditional knockout rats showed a tendency to dilate. Moreover, the myocardial fibers of 2. 5 d Isca1 myocardial conditionalknockout rats were irregularly arranged and disordered losing hierarchy or polarity. Part of the myocardial fibers showeddissolution and rupture. In addition, the sarcomere and Z-line were blurred, the sarcolemma was damaged, withmitochondrial swelling and rupture of cristae. Conclusion Isca1 myocardial conditional knockout results in abnorma lcardiac structures in newborn rats.

Abstract:Objective To establish a mouse model of endogenous infection induced by intestinal disseminationand provide a reliable experimental model for studies of the mechanism of intestinal microecology and endogenous infection.Methods Twenty-four female ICR mice were randomly divided into model group A, model group B, and control group C.The mice in group A were administered a broad spectrum antibiotic solution orally to disturb the balance of normal intestinalflora, and then 5-fluorouracil was injected into the tail vein for immunosuppression. The mice in group B were administeredwith Candida albicans by gavage after the same treatment as the group A. The control group C was administered with normalsaline by the same method. Changes of fecal flora in the mice were continuously observed during the experiment. Theamount of bacteria in mouse tissues was detected by the plate counting method. Pathological changes of the lung, liver,cecum, and large intestine were observed using HE staining. Quantitative changes of intestinal flora in the mice wereobserved by quantitative PCR. Results At the end of the experiment, bacterial infection occurred in the tissues and organsof the mice in group A, and mixed bacterial and fungal infections occurred in the group B. Lung and liver histology of themice in both infection groups showed typical inflammatory manifestations, while the cecum and large intestine showedmucosal inflammation and disrupted barrier integrity. Quantitation of intestinal flora showed disruption of the main intestinalflora structure in the two model groups, and the ratio of the intestinal colonization resistance index was less than 1.Conclusions Under the conditions of intestinal flora disturbance and immune suppression, intestinal pathogenic bacteriaor opportunistic pathogenic bacteria break through the intestinal mucosa barrier and cause tissue and organ infection inmice. This model can provide a reliable basis for the studies on prevention and control of endogenous infection from the perspective of intestinal microecology.

Abstract:Objective To explore the damaging effect of X-ray whole body irradiation on hematopoiesis andimmune functions in KKAy mice with type 2 diabetes mellitus. Methods KKAy mice were exposed to 4 Gy total bodyirradiation (TBI) ,and compared with C57BL/6J mice. All mice were euthanized for routine analysis of peripheral blood,hematopoietic progenitor cells (HPC), hematopoietic stem cells (HSC), and long-term hematopoietic stem cells (LTHSC)frequencies and the percentages of splenic lymphocytes and thymic lymphocytes. The function of HPCs was measuredby colony-forming unit-granulocyte and macrophage (CFU-GM) assay. Results The frequency of HSCs and LT-HSCs inKKAy mice was lower than that in C57 mice. After 4 Gy whole body irradiation, the percentages of WBCs, RBCs, PLTs,HG B and LYM% in peripheral blood of KKAy mice were decreased by 68. 42%, 12. 17%, 8. 78%, 30. 12%, and70. 84%, respectively. The percentages of HPCs, HSCs and LT-HSCs in bone marrow were decreased by 34. 02%,29. 49%, 35. 74%, respectively. The proportions of splenic B and T cells were decreased by 57. 85% and 58. 81%,respectively. The proportion of thymic CD4+ / CD8+ cells was decreased by 51. 7%. The HPC function (CFU-GM) was alsoimpaired. The decrease levels of bone marrow HSC, LT-HSC, peripheral blood RBC and HGB in KKAy mice weresignificantly lower than those in C57 mice.Conclusions Whole body irradiation by 4 Gy X-rays impairs the hematopoiesis and immune functions, and KKAy mice might show a greater tolerance to ionizing radiation than C57 mice.

Abstract:Objective To investigate the effects of icariin and its metabolite, baohuoside I, on the pathology andinflammation of lung tissue in tracheotomized rats. Methods Seventy-two SPF male Sprague-Dawley rats were randomlydivided into four groups: normal control group (A), model control group (B), and model treatment group (C and D) with18 rats in each group. A rat tracheotomy tube indwelling model was established. At 6 hours after successful modeling, thegroups C and D were administered icariin and baohuoside I, respectively. The groups A and B were administered an equalamount of 0. 9% normal saline. Lung tissue and alveolar lavage fluid were collected at 24, 72, and 168 h. Pathologicalexamination of the lung tissues was performed using HE staining. ELISA was used to detect the interleukin-6 (IL-6) andtumor necrosis factor alpha (TNF-α) in alveolar lavage fluid. Results After the tracheotomy, the degree of histologicalchanges in the lung tissues of the group B was gradually increased over time, significantly higher than that in the group A( P < 0. 05). The degree of lung injury in the groups C and D was significantly lower than that in the group B, and that inthe group D was significantly lower compared with the group C at 24 and 168 h after tracheotomy ( P < 0. 05). Thepathological score of group D was significantly lower at 168 h ( P < 0. 01 compared with 24 h). The contents of IL-6 andTNF-α in alveolar lavage fluid of the rats after tracheotomy were significantly higher than those in the group A ( P < 0. 05).After treatments with baohuoside I and icariin, the levels of IL-6 and TNF-α in the groups C and D were significantly lowerthan those in the group B at 72 and 168 h ( P <0. 05), and the IL-6 and TNF-α contents in the groups C and D at 72 h and168 h were significantly lower than that after 24 h ( P <0. 05). There was no significant difference in the IL-6 contents ofgroups C and D at 72 h and 168 h ( P > 0. 05). TNF-α contents in the group D at 72 and 168 h were significantly lowerthan that in the group C ( P < 0. 05). Conclusions Baohuoside I and icariin have certain therapeutic effects on the earlylung inflammation after tracheotomy. The mechanism is related to inhibiting the release of inflammatory factors IL-6 andTNF-α into alveolar lavage fluid and alleviating lung tissue damage. Moreover, the effect of icariin is better than that of baohuoside I.

Abstract:Objective To construct bone morphogenetic protein 9 (Bmp9)-knockout mice using CRISPR/ Cas9technology. Methods sgRNA were designed and synthesized according to the Bmp9 sequence in Genbank. After in vitrotranscription of Bmp9 sgRNA, a Cas9 and sgRNA mixture was microinjected into zygotes of C57BL/6 mice, which werethen transplanted into ICR mice. The offspring mice were identified with Sanger sequencing and mutant mice were matedwith wild-type mice to screen for mice harboring a homozygous mutation. Meanwhile, qPCR, western blot, andimmunohistochemistry were used to detect the expression of BMP9 in the heart, liver, spleen, lung, and kidney. Results A 20-bp sgRNA was synthesized and transcribed into RNA. After microinjection, transplantation, and mating, homozygousF2-generation mice were obtained. The results of sequencing revealed two genotypes: one with a 5-bp deletion and anotherwith a 13-bp deletion and 1-bp insertion. Compared with the wild-type C57BL/6 mice, results of qPCR, western blot, andimmunohistochemistry showed a marked decrease in BMP9 in the liver of Bmp9-knockout mice. Conclusions Bmp9-knockout mice are successfully generated using CRISPR/ Cas9 technology.

Abstract:Objective To observe the effects of micro-arc oxidation (MAO) and alkali (NaOH) treatment on theporous surface tantalum, and evaluate the biocompatibility and osteogenic ability of porous tantalum in vivo. Methods Porous tantalum was immersed in simulated body fluid (SBF) for 1 week after MAO and alkali treatment. Micropores,calcium, and phosphorus deposition on the surface were observed by scanning electron microscopy (SEM). The contact anglewas observed by X-ray photoelectron spectroscopy (XPS). For in vivo experiments, bone healing was evaluated at 4 and 12weeks after the porous tantalum implantation into a rabbit skull defect model. Results Compared with the control and MAOonlytreated specimens, NaOH-treated tantalum metal formed more apatite on its surface in SBF. Moreover, a sodium tantalatehydrogel layer and reduced contact angle were observed on the specimen surface by XPS ( P < 0. 05). In vivo, the woundshealed well and there was no swelling or suppuration in the rabbit implant model. Computerized tomography imaging revealedthat the porous bract and surrounding bone tissue were well coupled after 4 and 12 weeks. Calcein fluorescent labeling anddetection indicated that new bone had grown into the interior of the multi-porous material at 12 weeks. Moreover,neovascularization and new trabecular bone were observed by SEM. Conclusions MAO and alkali treatment can change the surface shape of porous tantalum material, exhibiting good biocompatibility and osteogenic ability in vivo.

Abstract:Objective To generate a Fancm gene knockout mouse model and to elucidate the biological functionof Fancm in mouse development. Methods Fancm ^{-/ -} mice were generated by the CRISPR/ Cas9 method. We analyzedtheir body weight, birth rate, gender ratio, and fertility. Blood samples were analyzed by a complete blood count (CBC).Testes from the Fancm ^{-/ -} and wildtype littermates were subjected to pathophysiological assessment. Results C57BL/6background Fancm knockout mice were generated by ATG region deletion using the CRISPR/ Cas9 method. Western blottingindicated the complete depletion of FANCM protein in the testis lysate from Fancm ^{-/ -} mice. The Fancm ^{-/ -} mice showed nosign of embryonic lethality. However, there were significantly less female Fancm ^{-/ -} mice compared with male Fancm ^{-/ -} mice.There was no significant difference in body weight between the Fancm ^{-/ -} mice and wild type littermates. The CBC indicateda slight, but significant, increase in the Hb level. The Fancm ^{-/ -} mice were infertile. The male Fancm ^{-/ -} mice had a reducedtesticular size and abnormal testicular architecture. The IHC and TUNEL assays indicated increases in cell cycle arrest andapoptosis in spermatogenic cells. Conclusions Fancm gene knockout causes defects of male reproductive organ development in mice.

Abstract:Objective To observe the various parameters related to metabolic syndrome and prediabetes in aLeptin receptor-knockout ( Lepr ^{-/ -} ) rat model established by CRISPR/ Cas9 technique. Methods Periodically, wemeasured the weights, daily food intake, random and fasting blood glucose, and serum biochemical indexes of the Lepr ^{-/ -}rats, and performed glucose and insulin tolerance tests. Pathological changes in the main organs of Lepr ^{-/ -} rats wereexamined at 14 and 18 weeks of age. We also observed the lipid deposition in the main organs of Lepr ^{-/ -} rats. Results Lepr ^{-/ -} rats exhibited obesity, high food intake, dysfunctional glucose tolerance and insulin resistance as well asdyslipidemia. Islet and myocardial hypertrophies, fatty liver, and obesity-related glomerulopathy were observed in the Lepr ^{-/ -} rats at 14 and 18 weeks of age. Lipid deposition was found in hepatocytes, renal tubular epithelial cells, and skeletalmuscle cells. Conclusions Lepr ^{-/ -} rats are an ideal animal model of metabolic diseases and may contribute to revealing the pathogenesis and new drug development for such metabolic disorders.

Abstract:Objective To explore the phenotypic differences and pathological mechanisms of insulin resistanceand atherosclerosis (IR-AS) in white hair black eye (WHBE) rabbits and Japanese white (JW) rabbits. Methods Twelve JW rabbits and 12 WHBE rabbits were randomly divided into the normal control group (NC) and high fat and sugardiet (HF) group with six rabbits in each group. The IR-AS model was induced by feeding a high fat and sugar diet for 12weeks. At the end of modeling, blood samples were collected to determine blood lipid, superoxide dismutase (SOD), andmalondialdehyde (MDA) levels. A glucose tolerance test was conducted, and the area under the curves of blood glucoseand insulin was calculated. mRNA expression of microsomal triglyceride transfer protein (MTTP), nuclear factor-like 2(Nrf2), and SOD1 genes in the liver was detected, pathological changes in fat tissues and aortic wall by HE staining, andCD68 expression in aortic tissues were observed. Results Compared with the NC group, HF rabbits showed significantobesity, hyperlipidemia, glucose intolerance, hyperinsulinemia, and increased HOMA-IR. Moreover, HF rabbits exhibiteddecreased SOD activity and increased MDA contents in their plasma and liver, increased mRNA expression of MTTP andNrf2 in the liver tissue, and decreased mRNA expression of SOD1. In addition, vascular lipid deposition, AS plaque size,and CD68 expression were increased significantly. Compared with the JWHF group, TG, LDL-C, HOMA-IR, U_GLU,MDA content, fat diameter, SOD1, AS lesion degree, and vascular CD68 expression in the WBHF group were significantlydifferent. Conclusions A high-fat and sugar diet induces the formation of IR-AS in rabbits, resultsing in an obvious lipidmetabolism impairment, inflammatory and AS lesions. However, the degree of pathological changes in WHBE rabbits issignificantly more serious than that in JW rabbits, which may be related to the differences in lipid metabolism and the oxidative stress response between the two rabbit strains.

Abstract:Objective To characterize the rat model of diabetic nephropathy (DN), to evaluate the diagnosticvalue of urinary laminin for early detection of DN, and to investigate the expression of perilipin in diabetic rat kidneys.Methods Fourteen male Sprague-Dawley rats were randomly divided into a control group (regular diet, six animals) anda diabetic nephropathy model group (high sugar and high fat diet, eight animals). After feeding for 4 weeks, the rats of thedisease model group were injected with a dose of 30 mg/ kg of 1% streptozotocin. Induction of diabetes was consideredsuccessful when blood sugar levels were ≥ 16. 7 mmol/ L. Upon induction of diabetes, animals were fed for an additional 6weeks. Induction of diabetic nephropathy was considered successful when the 24-hour urinary protein level was ≥ 30 mg/ kg.Coomassie brilliant blue (CBB) was used to determine the 24-hour urine protein levels, ELISA was used to measure urinelaminin, and hematoxylin and eosin (H&E) staining was performed to observe the pathological changes in kidney tissues.Perilipin (Plin) expression in kidney tissues was determined by real-time PCR and western blotting. Results Thedetection of 24-hour urinary protein levels ≥ 30 mg/ kg confirmed the successful induction of the rat model of diabeticnephropathy. The kidney-to-body weight ratio of the disease model group was increased significantly, when compared withthe control diet group ( P <0. 05). Urinary volume and laminin increased by the 5th week, while 24-hour urine proteinincreased by the 6th week. All the three indicators were increasing over time. Pathological examination of the renal tissuesrevealed glomerular hypertrophy, basal membrane hyperplasia, microhemangioma formation, tubular cavity deformation,epithelial shedding and vacuolization, inflammatory monocyte and lymphocyte infiltration, and interstitial collagendeposition. A significant increase in Plin expression at the mRNA and protein levels in the kidney tissues of diabeticnephropathy rats was also observed. Conclusions Urinary laminin is increased earlier than the 24-hour urine protein level,thus can be used as an early biomarker of diabetic nephropathy. Increased Plin expression may play a role in thepathogenesis of diabetic nephropathy, and this protein therefore warrants further investigation to acquire a better understanding the molecular mechanisms underlying this disease.

Abstract:Objective To study porcine circovirus 3 (PCV3) infection in BALB/ c mice. Methods FemaleBALB/ c mice were divided into two groups. Mice in the experimental group were infected with PCV3 derived from infectedpig tissues. The mice in the control group were injected with the same volume of PBS. The status of the mice was observeddaily after infection, and blood samples were analyzed by quantitative RT-PCR and ELISA at days 0, 3, 7, 11 and 14 postinfection. At the end of the experiment, all animals were euthanized, and samples of heart, liver, spleen, lung, kidney,brain and lymph nodes were taken for quantitative RT-PCR and pathological examination. The PCV3 CAP gene wassequenced in the PCR-positive tissues. Results Mice infected with PCV3 did not show obvious clinical symptoms orpathological changes, and the virus was detected in serum during early infection. The liver and spleen showed the highestviral copy numbers, and the nucleic acid sequence was not changed in the infected organs. Antibody titers were increasedduring the infection. Conclusions BALB/ c mice can be infected with PCV3. This study provides useful information to study the pathogenicity of PCV3 as well as prevention and control of the disease.

Abstract:Objective To investigate the effects of different exposure periods of intake of high- or low-dosefluoride combined with aluminum exposure on longitudinal bone growth and bone metabolism in rats. Methods Forty-eight2-month-old Sprague-Dawley rats were randomly divided into a vehicle control group and two groups exposed to fluoridecombined with aluminum (0. 1 mg/ kg) as follows: low-dose fluoride (5 mg/ kg) + aluminum, and high-dose fluoride (30mg/ kg) + aluminum. In these two groups, the durations of intervention were 45 and 90 days, respectively. At the end ofthe experiment, all proximal tibias were harvested and processed for bone histomorphometric analysis of both the epiphysealgrowth plate and epiphyseal trabeculae. Results Compared with the findings in the control group, increased growth platethickness accompanied by a neat arrangement and normal morphology of chondrocytes was observed at 45 days in bothtreatment groups. In addition, hypertrophy and retention of chondrocytes was observed at 90 days in the high-fluoride +aluminum group. Percent mineralized surface, bone formation rate, and osteoblast circumference were increased in the lowdosage fluoride + aluminum group at both 45 and 90 days, while bone resorption perimeter was increased in secondarytrabeculae at day 90 compared with the age-matched controls. Bone formation and bone resorption parameters mentionedabove were all elevated in the high-fluoride + aluminum group at day 45, but were reduced with bone volume loss in thesame group at day 90. Conclusions Short-term exposure to high-fluoride + aluminum stimulates the growth of platecartilage, while long-term exposure leads to cartilage osteogenesis. Short-term exposure to low-fluoride + aluminum onlyincreased secondary bone formation, whereas both long-term exposure to low-fluoride/ aluminum and short-term exposure tohigh-fluoride/ aluminum can stimulate bone formation along with bone resorption in secondary trabeculae; in contrast, longterm high-fluoride + aluminum exposure has an inhibitory effect on the longitudinal bone formation.

Abstract:Objective To analyze the structure and composition of intestinal flora in the common cotton-earedmarmoset using the Illumina MiSeq sequencing platform. Methods Feces of the common cotton-eared marmoset werecollected and investigated for microbial diversity using the Illumina MiSeq sequencing platform. Results In total, 315511sequences and 596 OTUs were obtained after sequencing. According to the Shannon-Wiener curve, the sequencing datawere reliable for all bacteria in the samples. The bacteria in the common cotton-eared marmoset included 9 phyla, 14classes, 26 orders, 50 families, 82 genera, and 64 species. Among them, Firmicutes and Bacteroidetes had the highestabundance (54. 52% and 25. 39%, respectively). The dominant classes were Bacteroidia and Negativicutes at 54. 5% and17%, respectively. The abundance of Lactobacillales and Bacteroidales was higher at 50. 01% and 20. 52%, respectively.Dominant families were Prevotellaceae and Bifidobacteriaceae at 43. 14% and 11. 33% respectively. Lactobacillus andStreptococcus were dominant at 20. 03% and 19. 62%, respectively. The abundance of beneficial bacteria, such asBifidobacterium, was high, which were found in samples. The top 10 species with the highest abundance were classified intoseven families and five classes. These 10 species accounted for 33. 16%, and the other 53 species only accounted for0. 74%. Other species were not identified, and the abundance was relatively high, which require further study. PICRUStfunctional prediction showed an abundance of functional genes such as those involved in amino acid transport andmetabolism as well as genetic information processing. Conclusions The composition of fecal microbiota in common cottonearedmarmoset has rich diversity. Many bacteria that are relatively abundant remain unidentified, and further study is warranted.

Abstract:Degeneration of intervertebral discs is a major cause of lower back pain that seriously affects quality oflife and productivity. Although the specific pathogenesis is still unclear, recent research of related animal models has madegreat progress. The modeling method include structural damage, stress changes, and gene knockout. In this review, wefocus on the advantages and disadvantages of these Methods and their applications to establish a theoretical foundation for subsequent research.

Abstract:The global incidence of autism spectrum disorders (ASDs) is increasing. However, the etiology andpathogenesis of ASDs are not known, and animal models are used to disclose them. Understanding of ASDs and their studyusing animal models are relatively new in China. The internationally commonly used animal models of ASD can be dividedbroadly into three categories: genetic animal models, idiomatic animal models, and animal models developed byenvironmental interventions. Among them, the genetic animal model has a high profile but a small scope of application. TheBTBR mouse model (which is an idiomatic animal model) and the animal models developed by environmental interventionsusing valproic acid can present typical clinical symptoms and some pathologic features of ASDs better than those elicited byother models. These two models should be selected before research is commenced. Nevertheless, research into ASDs lacks an “ideal” animal model that meets all the “three types of validity”: structural, surface, and predictive validities.

Abstract:Ca²⁺ / calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/ threonine proteinkinase in a large number of neurons and is widely involved in pain modulation. Neuropathic pain is chronic refractory paincaused by disease or damage to the somatosensory system. CaMKII plays an important role in the occurrence anddevelopment of various types of neuropathic pain such as central, peripheral, diabetic and drug-induced neuropathic pain.This review focuses on the regulation of CaMKII-mediated neuropathic pain and its upstream and downstream pathways to provide a reference for the future study of CaMKII in the field of neuropathic pain.

Abstract:Drug resistance is a major problem in the prevention and treatment of epilepsy. Animal models ofepilepsy are powerful tools to study the mechanism of epilepsy, screening antiepileptic drugs, and explore the mechanismsof drug actions. The 6 Hz corneal kindling seizure model is an excellent animal model of drug-resistant epilepsy, which isrecommended by the NIH as a screening tool to evaluate new drugs against drug-resistant epilepsy. However, there iscurrently no systematic report of this model. Here, we review the development history, production method, symptoms,pathogenesis, and application status of the model to provide a reference to explore the pathogenesis of drug-resistant epilepsy and screening drugs for the treatment of drug-resistant epilepsy.

Abstract:Low-back pain (LBP) is common and the cure rate is low. Its mechanism of action is incompletelyunderstood and may be related to degeneration of intervertebral disks, facet-joint injury, or inflammation of muscle fascia.Establishing an appropriate animal model can help to study and understand the pathogenesis of LBP, as well as explore itsprevention and treatment methods. This article summarizes the research progress of animal models which can be used to induce low-back pain.

Abstract:Canine hip dysplasia (CHD) is a common congenital hereditary disease characterized predominantly byhip joint relaxation. While both environmental and genetic factors are known to contribute to the disease, the underlyingmechanism of pathogenesis remains unknown. In recent years, significant progress has been achieved in the genomics ofCHD. For example, a quantitative trait locus (QTL) was identified for CHD that is associated with the Norberg angle of thehip joint, the dorsolateral subluxation score and the separation index. In addition, genes such as FBN2, LRR1, COL6A3and FN1 have been shown to be associated with CHD. In this review, we summarize current research in this field, withparticular focus on the chromosomal position of the identified QLT and the known functions of candidate disease-causing genes associated with CHD.

Abstract:Gastric emptying is important for measuring digestive tract function and plays an indispensable role inthe research on etiology, diagnosis and treatment of digestive diseases. In recent years, a series of detection methods hasbeen used to measure gastric emptying in humans: intubation, real-time ultrasound, radionuclide imaging and respiratorytesting. However, these method are relatively rarely used in laboratory animals. A method for evaluating the gastricemptyingability of laboratory animals correctly is very valuable for the study of the drug bioavailability and gastrointestinaldiseases. In this review, we discuss some of the methods commonly used for detection of gastric emptying in humans. We hope that we can provide some new ideas for detection of gastric emptying in animals.