Abstract: Objective To establish an orthotopic neuroblastoma xenograft model and evaluate it by comparison with the ectopic xenografted model. Methods SCID-Beige mice were used in the study. Neuroblastoma cells were implanted into the fat pad that surrounds the left adrenal gland to establish the orthotopic xenografted model or into the subcutaneous tissue of the right flank for the ectopic xenografted model. After the implantations, the tumor formation rate and size were evaluated at 7, 14, and 21 days, and histopathological analysis was performed. Results After implantation of the same number of neuroblastoma cells, tumors formed in all orthotopic xenografted mice at the three time points, whereas 33%, 67%, and 78% of ectopic xenografted mice had tumors, respectively. The orthotopic xenografted model showed a higher tumor formation rate than the ectopic xenografted model at the three time points. In the orthotopic xenografted model, the tumor volumes were ( 116. 21 ± 78. 82), ( 245. 32 ± 97. 31), and ( 3091. 21 ± 2042. 39) mm³ , whereas the tumor volumes were (7. 26±6. 04), (41. 67±38. 52), and (292. 14±167. 12) mm³ in the ectopic xenografted model at 14, 21, and 28 days, respectively. Orthotopic xenografted tumors were larger than ectopic xenografted tumors at each time point. HE staining showed that the density of orthotopic xenografted tumor was higher than that of ectopic xenografted tumors. Conclusions The orthotopic xenografted model is applicable. Compared with the ectopic subcutaneous xenograft model, the orthotopic xenografted model had the advantages of higher tumor formation and growth rates. These data indicate that the orthotopic xenografted model is a better model for neuroblastoma research.

Abstract: Objective To investigate the effect of silencing heme oxygenase-1 ( HO-1) on the progression of leukemia in xenografted mouse models of acute monocytic leukemia (M5). Methods U937 cells were infected with a lentivirus to silence expression of HO-1. Then, modified U937 cells were subcutaneously injected into the armpits of NOD/ SCID mice to establish M5 xenografted mouse models that were divided into blank and experimental groups ( U937, vehicle, and siHO-1 groups). Subsequently, the tumor formation time, tumor volume, tumor infiltration into surrounding tissues, peripheral white blood cell and platelet counts, hemoglobin content, and survival time of the mice were assessed. Results Fluorescence microscopy and Western blot confirmed successful infection. After formation of an axillary mass, an increased white blood cell count and leukemic cells in peripheral blood and expression of CD13, CD14, and CD64 in bone marrow indicated successful establishment of the xenografted mouse models. Compared with the U937 and vehicle groups, there was a significant increase in disease latency in the siHO-1 group (P<0.05). Xenografted mouse models with HO-1 downregulation developed tumors more slowly (P< 0.05), and the peripheral white blood cell count was increased and platelets were decreased more slowly(P<0.05). Mice in the HO-1 downregulated group survived significantly longer than those in the other two groups (P<0.05). Conclusions Silencing expression of HO-1 may slow the progression of leukemia in M5 xenograft mouse models.

Abstract: Objective To manufacture a simple device for securing the hind limbs of mice for acupuncture and moxibustion treatment, and provide a convenient economical, efficient, and practical tool for acupuncture and moxibustion experiments. Methods A holding device for mouse hind limbs was made according to design drawings. Four investigators secured mice with specialized cloth ( clothing method ) or the mouse hind limb device, and then needled mice at the Zusanli point. To compare the effects of these two holding method in acupuncture, the holding time, number of hind limbs retracted, number of needles shed and the body weight of mice were recorded, and the influence on the stress response of mice observed. In addition, the effects of different holding method on pain threshold, cognition and emotion were observed by the thermal radiation pain threshold, open field and elevated cross maze tests. Results Compared with the clothing method , there was no significant difference in the body weight of mice with the holding device during acupuncture. The mouse hind limb holding device was easy to make, more efficient, and had less frequent hind limb retraction and needle shedding compared with the clothing method. There were no significant differences in the thermal radiation pain threshold, open field and elevated cross maze tests between the two holding method. Conclusions The hind limb holding device was convenient, which helped to improve the efficiency of the experiment, and had no significant impact on pain threshold, cognition and emotion compared with the clothing method. The holding device can be used for specific experimental needs.

Abstract: Objective To explore a rat model for disease pathogenesis and drug discovery research of microvascular dysfunction by comparing two modeling method : sodium laurate injury of endothelium and microsphere embolization. Methods Thirty male SD rats were randomly divided into sham operation, sodium laurate, and microsphere embolization groups with 10 rats in each group. After anesthetizing the rats, their chest was opened. Then, 0. 2 mL sodium laurate (1 g / L) or embolization microspheres ( 40 ~ 120 μm, 1 × 103 ) were injected into the left ventricle. The sham operation group was injected with an equal volume of normal saline. Rats were anesthetized to determine relevant indicators and then sacrificed to obtain materials at 24 hours after surgery. Results In the sodium laurate group, coronary microvessel thrombosis and myocardial cell injury were observed, but there were no differences in cardiac functions, hemodynamics, or myocardial enzyme indexes compared with sham operation. However, in the microsphere embolization group, coronary microvessel embolization and myocardial injury were observed. Moreover, left ventricular ejection fraction, left ventricular shortening rate, and the maximum rate of left ventricular pressure were decreased significantly and the activities of creatine kinase MB isoenzyme and lactate dehydrogenase were increased significantly. Conclusions Both modeling method induced coronary microcirculation dysfunction and damaged cardiac functions. The animal model established by microsphere embolization was more reliable than the other method. This method might be widely used to study pathogenesis and drug treatment of coronary microcirculation dysfunction.

Abstract: Objective To explore the effects of dehydrocostus lactone (DHCL) on autophagy, apoptosis, and oxidative stress of gastric cancer cell line SGC-7901. Methods SGC-7901 cells cultured in vitro were divided into 0, 10, 20, and 40 μmol / L DHCL groups. Cell proliferation was analyzed by CCK-8 assays. Autophagic activity was assessed by immunofluorescence. Apoptosis was detected by flow cytometry. The levels of superoxide dismutase ( SOD ), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in culture supernatants were detected by ELISA. The level of intracellular reactive oxygen species (ROS) was detected by the DCFH-DA probe. Expression of LC3-I, LC3-II, Beclin-1, autophagy-associated protein 7 (ATG7), p62, B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), BH3 interaction domain death agonist ( Bid), truncated Bid, Caspase-8, Caspase-9, Caspase-3, cleaved Caspase-8, cleaved Caspase-9, and cleaved Caspase-3 were detected by Western blot. A 0. 2 mL suspension of SGC-7901 cells (1× 10⁷ / mL) was implanted subcutaneously. After intraperitoneal injection of 20 mg / (kg·d) DHCL for 2 weeks, tumor tissues were weighed. Results Cell survival rates in 40 and 20 μmol / L DHCL groups were lower than that in the 0 μmol / L DHCL group (P<0.05). In comparison with the 0 μmol / L DHCL group, autophagy and the apoptosis rate were higher in the 40 μmol / L and 20 μmol / L DHCL group (P<0.05). SOD and GSH-Px levels were lower than in the 0 μmol / L DHCL group (P<0.05). MDA and ROS levels were higher than in the 0 μmol / L DHCL group (P<0.05). Expression of p62 protein was lower in the 0 μmol / L DHCL group. Expression of Beclin-1, LC3II/ LC3I, ATG7, Bax / Bcl-2, tBid / Bid, cleaved Caspase-8/ Caspase-8, cleaved Caspase-9/ Caspase-9, and cleaved Caspase-3/ Caspase-3 was higher in the 0 μmol / L DHCL group (P<0.05). The nude mouse tumorigenicity assay showed that the weight of transplanted tumors in the DHCL group was lower than that in the control group (P<0.05). Conclusions DHCL promotes production of ROS in SGC-7901 cells and induces autophagic death and apoptosis.

Abstract: Objective To investigate the neuroprotective effect of 2,4-diamino-6-hydroxypyrimidine (DAHP) on rats with brain injuries and its possible mechanism. Methods SD rat models of brain trauma were prepared by the Feeney method. The rats were randomly divided into model, DAHP, NOS activator [ tetrahydrobiopterin (BH4)], and DAHP + BH4 groups with 12 rats in each group. Another 12 rats were used for the sham operation group that only underwent bone window opening without percussion. Two hours after modeling, the DAHP group was injected with 0. 5 g / kg DAHP through the caudal vein, the BH4 group was injected with 0. 3 mg / kg BH4 through the caudal vein, the DAHP+BH4 group was injected with 0. 5 g / kg DAHP and 0. 3 mg / kg BH4 through the caudal vein, and sham operation and model groups were injected with the same volume of normal saline at an injection volume of 10 mL/ kg once a day for 1 week. After the last treatment, rat behavior was assessed by positioning navigation and space exploration experiments. Hematoxylin-eosin staining was used to observe histomorphology of the rat brain. TUNEL staining was used to observe apoptosis of brain cells. The Griess method was used to measure the level of nitric oxide (NO) in brain tissue, and expression of neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase ( iNOS), nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), Caspase-3, and B-lymphoma-2 (Bcl-2) in brain tissue was detected by Western blot. Results In the sham operation group, the morphology of nerve cells in brain tissue was normal and nuclei were stained evenly. In the model group, nerve cells had swelled, deformed, and underwent nuclear pyknosis, which were accompanied by inflammatory cell infiltration. Compared with the model group, the morphology of nerve cells in the DAHP group was improved to some extent and the degree of inflammatory cell infiltration was reduced. The number of necrotic nerve cells was increased and the degree of injury was aggravated in the BH4 group. Morphological changes of nerve cells in the DAHP+BH4 group were not significant. Compared with the sham operation group, escape latency was prolonged; the proportion of space exploration time and Bcl-2 protein in brain tissue were decreased; and the apoptosis rate, NO level, and nNOS, iNOS, NF-κB, TNF-α, COX-2, and Caspase-3 protein expression were increased in brain tissue of the model group (P< 0.05). Compared with the model group, escape latency was shortened; the proportion of space exploration time and Bcl-2 protein in brain tissue were increased; and the apoptosis rate, NO level, and nNOS, iNOS, NF-κB, TNF-α, COX- 2, and Caspase-3 protein expression in brain tissue were decreased in the DAHP group (P< 0.05). Compared with the model group, escape latency was prolonged; the proportion of space exploration time and Bcl-2 protein in brain tissue were decreased; and the apoptosis rate, NO level, and nNOS, iNOS, NF-κB, TNF-α, COX-2, and Caspase-3 protein expression in brain tissue were increased in the BH4 group (P< 0.05). The escape latency; apoptosis rate in brain tissue; NO level; and nNOS, iNOS, NF-κB, TNF-α, COX-2, and Caspase-3 protein expression in the DAHP+BH4 group was lower than those in the BH4 group and the proportion of space exploration time and Bcl-2 protein expression in brain tissue were higher than those in the BH4 group (P< 0.05). Conclusions DAHP alleviates neurological impairment and reduces neuronal apoptosis in rats with brain injuries and its mechanism may be related to inhibition of the iNOS signaling pathway.

Abstract: Objective To study the detailed process and mechanism of glycogen storage disease (GSD) type 0 using a zebrafish disease model established by CRISPR/ Cas9 gene editing technology. Methods Target sites were determined for gys1 and gys2. After gene editing, homozygous mutants were screened. The expression levels of gys1 and gys2 were quantified with qPCR at early developmental and adult stages. Glycogen accumulation was assessed by periodic acid-Schiff staining. Results Homozygous F₂ gys1 and gys2 genes with two effective mutation types were successfully obtained. Homozygous gys1^{- / -} F₃ had a delay in early embryonic development and died within 48 hpf, whereas homozygous gys2^{- / -} developed normally. Gene expression analyses of gys1 and gys2 in wildtype zebrafish showed that their expression levels decreased first and then increased during early developmental stages (0~ 125 hpf) with the highest expression at the fertilized egg stage. At the adult stage, gys1 was highly expressed in heart and muscle tissues, while gys2 was highly expressed in the liver. Glycogen staining showed no significant glycogen accumulation in the heart or muscle of gys1^{- / -} or in the liver of gys2^{- / -} compared with the corresponding wildtype tissues. Conclusions The phenotypes of gys1 and gys2 knockout zebrafish models were similar to those of mouse models, but there were some differences. In the Gys1 knockout mouse model, most F₂ homozygotes die. Among gys1 knockout zebrafish, gys1^{- / -} homozygous F₂ developed normally, whereas F₃ generated by self-crossing did not survive. The model of gys1 and gys2 knockout in zebrafish provides materials for further study on the pathogenesis of human GSD type 0.

Abstract: Objective To investigate the effects of astragaloside II on the interleukin (IL)-21 / signal transducer and activator of transcription 3 (STAT3) pathway and airway inflammation in young asthmatic rats. Methods Young rats were randomly divided into control, model, astragaloside II low-dose, astragaloside II medium-dose, astragaloside II high- dose, and dexamethasone groups with 12 rats in each group. Except for the control group, the groups were challenged with ovalbumin to prepare asthma models and the rats in each group were treated with corresponding drugs. Airway reactivity (Penh value) was measured and the levels of IL-6, IL-21, and transforming growth factoR-β1 (TGF-β1) in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assays. HE staining was used to observe pathological changes in lung tissues. Western blot was used to detect protein expression of IL-21, phosphorylated STAT3 (p-STAT3), and STAT3 in lung tissues of the rats. Results Compared with the control group, the structure of bronchial epithelial tissue was disordered, pulmonary epithelial cells were edematous and exfoliated, and inflammatory cells had infiltrated in the model group. After stimulation with acetylcholine (Ach) at various concentrations, the Penh value, total number of leukocytes, numbers of eosinophils, neutrophils, lymphocytes, and macrophages in BALF, the contents of IL-6, IL-21, and TGF-β1 in BALF and serum, the lung tissue inflammation score, and protein expression of IL-21 and p- STAT3 in lung tissues were increased significantly (P< 0.05). Compared with the model group, the lung tissue structure of young rats in astragaloside II treatment groups and dexamethasone group was gradually complete, after stimulation with Ach at various concentrations, the Penh value, total number of leukocytes, numbers of eosinophils, neutrophils, lymphocytes, and macrophages in BALF, contents of IL-6, IL-21, and TGF-β1 in BALF and serum, the lung tissue inflammation score, and protein expression of IL-21 and p-STAT3 in lung tissues were decreased significantly (P< 0.05), which were dependent on the dose. Conclusions Astragaloside II alleviates airway inflammation in young asthmatic rats, repairs lung tissue and the bronchial structure, and improves asthmatic symptoms by inhibiting the IL-21 / STAT3 pathway.

Abstract: Objective To establish a rat model of acute-on-chronic liver failure (ACLF). Methods On the basis of immune liver fibrosis induced by bovine serum albumin (BSA), the rat model was established by intraperitoneal injection of D-galactosamine and lipopolysaccharide. Histopathology of the liver and intestinal mucosa as well as the ultrastructure of intestinal mucosa were used to judge whether the rat model of ACLF was established successfully. Results Eighty-eight percent of the rats produced BSA antibodies after subcutaneous injection of a BSA emulsion within 34 days. After further injections of the BSA emulsion via the tail vein for 6 weeks, liver histopathology revealed obvious liver fibrosis. The rat model was established by intraperitoneal injection of 100 μg / kg lipopolysaccharide ( LPS) and 200 mg / kg D- galactosamine. The liver and intestinal mucosa were examined by hematoxylin-eosin staining and ultrastructural analysis by transmission electron microscopy. The result were consistent with the pathological characteristics of ACLF. Conclusions One intraperitoneal injection of D-galactosamine combined with LPS successfully establishes a rat model of ACLF with a high modeling rate and low mortality, which can be used for further study.

Abstract: Objective Current hemorrhagic animal models often have a wide range of blood pressure fluctuation and limited brain tissue damage. We aimed to develop a prolonged severe hemorrhagic shock model without significant blood pressure fluctuation in rats. Methods A 10 mL syringe was fixed on a wall at 47. 58 cm above a surgical operating board to serve as a blood reservoir. A hemorrhagic shock model was induced by automatically withdrawing blood into the 10 mL syringe. Mean arterial blood pressure (MAP) was controlled by adjusting the blood level inside the syringe. Twenty-eight rats were randomly divided into four groups in accordance with different resuscitations. The hemorrhagic shock episode lasted for 3 h. The physiological conditions and hemodynamic indexes of rats in each group were monitored in real-time and arterial blood gas was analyzed before and after the shock. Brain hippocampal neuronal damage was assessed by HE staining. Results MAP was accurately maintained at 31~ 35 mm Hg by keeping the blood level inside the syringe at 47. 58 cm above the surgical operating board throughout the 3 h hemorrhagic shock episode. The rats in all groups had survived at the end of the 3 h shock. Rats in the non-resuscitation group had died within 2 h after the end of the shock and those in resuscitation (RB and RR) groups had survived within 3 h after resuscitation. There was a significant decrease in blood pH and increase in blood lactate. Maximum blood loss had occurred at 20 ~ 30 min after hemorrhagic shock and the maximum blood loss was very close to the final blood loss. Pathology revealed marked hippocampal neuronal damage in all rats. Conclusions The syringe blood reservoir is useful to establish lengthy severe hemorrhagic shock with accurate control of MAP. This highly reproducible hemorrhagic shock model induces reliable brain damage to investigate pathophysiological changes and therapeutic effects of hemorrhagic shock.

Abstract: Objective To explore the therapeutic effect and mechanism of downregulating AQP-4 in cerebral ischemia-reperfusion injury model rats. Methods A total of 10 healthy male SD rats were used as the normal group and 30 rats were divided into model, downregulated AQP-4, and upregulated AQP-4 groups. AQP-4, BMP4, and P-Smad expression was examined by Western blot, TNF-α was detected by resonance light-scattering turbidimetry, and IL-1β levels were measured. Learning and memory abilities as well as neurological functions were evaluated in each group of rats. Water content was measured in brain tissue. Results Compared with the normal group, rats in the other three groups had a longer escape latency and lower number of crossings of the platform at each time point (P< 0.05). Compared with model and upregulated AQP-4 groups, the downregulated AQP-4 group had a shorter escape latency and higher number of platform crossings at each time point (P< 0.05). Compared with the normal group, neurological scores of model, upregulated AQP-4, and downregulated AQP-4 groups were increased, while water content in brain tissue was increased (P< 0. 05). Compared with model and upregulated AQP-4 groups, the downregulated AQP-4 group showed decreases in neurological scores and brain water content (P< 0. 05). Compared with the normal group, the other three groups of rats had increased TNF-α and IL-1β levels (P< 0. 05) Compared with model and upregulated AQP-4 groups, TNF-α and IL-1β levels were decreased in the downregulated AQP-4 group (P < 0.05). Compared with the normal group, the other three groups showed an increase in expression of AQP-4 and decreased expression of BMP4 and P-Smad (P< 0.05). Compared with model and upregulated AQP-4 groups, the downregulated AQP-4 group showed a decrease in expression of AQP-4 and increased expression of BMP4 and P-Smad (P< 0.05). Compared with the normal group, Na⁺ and P-dp were increased in the other three groups (P< 0.05). Compared with model and upregulated AQP-4 groups, the contents of Na⁺ and P-dp were decreased in the downregulated AQP-4 group (P< 0.05). Conclusions Downregulation of AQP-4 rescues the blood- brain barrier, improves learning and memory abilities, and reducea the inflammatory response in cerebral ischemia- reperfusion injury model rats through the BMP4 / Smad pathway.

Abstract: Objective To study the effect of apigenin ( AGN) on autophagy and oxidative stress, and its neuroprotection in MPP⁺ -induced Parkinson’ s model cells. Methods CCK-8 assays were used to screen the effective concentration of AGN. SH-SY5Y cells were divided into six groups: ① Control group; ② MPP⁺ group; ③ group A: 10 μmol / L AGN; ④ group B: 20 μmol / L AGN; ⑤ group C: 40 μmol / L AGN; ⑥ group D: 100 μmol / L AGN. After determining the effective concentration of AGN, the cells were divided into three groups: Control, MPP⁺ , and AGN+MPP⁺ groups. Apoptosis, protein expression of Caspase 3, Bcl-2, Bax, LC3-II, LC3-I, Beclin-1, and ULK-1, and propylene glycol, superoxide dismutase, and glutathione peroxidase levels were examined. Analyze each group of GFP-LC3 spots. Results AGN at 40 μmol / L significantly reduced the cytotoxic damage induced by MPP⁺ . Therefore, 40 μmol / L AGN was chosen as the optimal protective concentration for subsequent experiments. The apoptosis rate of the AGN+MPP⁺ group was lower than that of the MPP⁺ group ( P< 0.05). Compared with the MPP⁺ group, expression of Caspase 3 was decreased and the the Bcl-2/ Bax ratio was increased in the AGN+MPP⁺ group (all P< 0.01). Compared with the MPP⁺ group, expression of MDA was inhibited (P < 0. 05) and the activities of GPX and SOD were restored in the AGN+MPP⁺ group (P< 0.05). Intracellular GFP-LC3 spots in the AGN+MPP⁺ group were significantly reduced compared with those in the MPP⁺ group (P< 0.05). Compared with the MPP⁺ group, the LC3-II/ LC3-I ratio and expression of Beclin-1 and ULK1 were significantly reduced in the AGN+MPP⁺ group (all P< 0.05). Conclusions AGN alleviates apoptosis of SH- SY5Y cells induced by MPP⁺ and enhances their antioxidant capacity. Its cytoprotective effect may be related to reduction of autophagy.

Abstract: Objective To explore the therapeutic effects of aqueous extract of Mosla chinensis Maxim cv. Jiangxiangru (MCM) on a high -fat diet rat model, and to provide modern pharmacological evidence for the traditional effects (known as warming the stomach and strengthening the spleen from dampness) of MCM. Methods The high-fat model was established by providing a high-fat diet to rats, which were divided into a model group ( distilled water), low- dose (0.2 mg / kg) MCM group and high-dose (1 mg / kg) MCM group. The MCM was administered for 8 weeks, and a normal control group (distilled water) received a normal diet. Body weights, blood routine biochemical and physiological indicators, energy metabolism, gastrointestinal function, the immune inflammatory response, and small intestinal propulsion of each group were compared by statistical analysis. Data from each group was compared to evaluate the effects of the aqueous extract of MCM on the high-fat model and the effect of MCM on stomach warming and spleen dampness. Results The experimental results showed that the aqueous extract of MCM had a significant effect on reducing the body weight and lipid levels of hyperlipidemic rats. Compared with the control group, the small intestine propulsion speed, intestinal moisture content, and gastrin (GAS) and motilin (MTL) levels were reduced in the model group. Compared with the model group, the intestinal propulsion rate, intestinal water content, and serum GAS and MTL levels showed a dose- dependent increase in MCM-treated rats, with a significant difference in small intestine propulsion (P< 0.05). Compared with the control group, serum sodium potassium pump and amylase (AMS) vitalities were reduced, and aquaporin 2 (AQP2) concentration increased, in the model group, but only AMS activity was significantly different ( P< 0.05). Compared with the model group, serum Na⁺ -K⁺-ATPase and AMS activity increased with an increasing dose of MCM, and the content of AQP2 increased but decreased with the increase of dose. The change in AMS activity was significantly different (P< 0.05). Conclusions The aqueous extract of MCM can significantly promote small intestine propulsion in hyperlipidemic rats, regulate gastrointestinal function, and significantly improve the activity of AMS. Additionally, MCM can improve some symptoms, including MTL, GAS and related biochemical and immune functions, of hyperlipidemia in rats.

Abstract:The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is involved in the pathogenesis of arthritis. Knee osteoarthritis (KOA) is considered to be an inflammatory disease. Increasing attention has been paid to the correlation between the NLRP3 inflammasome and KOA. The assembly and activation of the NLRP3 inflammasome produces a large number of pro-inflammatory factors and degradative enzymes, leading to cartilage destruction, synovial inflammation and pain onset. This review will summarize the evidence related to the involvement of the NLRP3 inflammasome pathway in KOA and its role in the pathology of osteoarthritis, with the aim of enhancing the management of KOA and providing new directions for the diagnosis and prevention of KOA.

Abstract:In recent years, the incidence of premature ovarian failure (POF) has been increasing. Because of its complex etiology and difficult treatment, POF has attracted wide attention from scholars at home and overseas. To study the occurrence and development of POF, and to find better treatment options, it is essential to construct a reliable animal model of POF. This review will discuss and analyze the method used to construct POF mouse models by domestic and foreign investigators in the past five years. Furthermore, we will compare the advantages, disadvantages and clinical relevance of various modeling method , which aim to provide new insights into the basic scientific understanding and clinical diagnosis and treatment of POF.

Abstract:Local allergic rhinitis (LAR) is a local allergic disease of nasal mucosa that is different from allergic rhinitis (allergic rhinitis, AR). Although the prevalence of LAR is high, research and understanding of LAR is still in its infancy. Animal models are a necessary means to deepen understanding of the pathogenesis, pathophysiology and immunology of LAR. Animal models of AR are relatively well established. Because there are some similarities between AR and LAR, despite each disease having their own characteristics, this study has reviewed the selection of animal models for LAR research, including allergen selection, the modeling process and animal model evaluation, in comparison with the AR animal model.

Abstract:Traumatic optic neuropathy greatly impairs the eyesight of patients and there is no effective treatment. A large number of studies on traumatic optic neuropathy have been carried out and animal models are widely used in these studies. With the need for further research, new animal models are constantly emerging. This article summarizes the recent animal models of traumatic optic neuropathy.

Abstract:Osteosarcoma is the most common bone tumor, which mainly occurs in children and adolescents. It usually occurs at the metaphysis of long bones with the characteristics of late discovery, rapid progression, early invasion and metastasis, and high mortality. Clinically, the treatment of osteosarcoma is mainly surgery, but the curative effect is unsatisfactory. Thus, it has become an urgent clinical issue to improve the survival rate and quality of life of osteosarcoma patients. Melatonin is an indole hormone, and melatonin levels are related to bone formation; deficiency of melatonin may be directly related to osteosarcoma. This article summarizes the recent research progress of melatonin in osteosarcoma treatment to provide new ideas and future directions for the clinical application of melatonin in osteosarcoma treatment.

Abstract:Inflammatory bowel disease ( IBD) is an autoimmune chronic inflammatory disease of unknown etiology. An abnormality in the intestinal mucosal immune system is a major factor in the development of IBD. Mesenchymal stem cells (MSC) have a self-renewal capacity and multipotent differentiation potential, which makes them important for the treatment of various diseases. Increasingly more researchers believe that the immunomodulatory function of MSCs is essential for the treatment of IBD. Upon tissue injury, MSCs improve the inflammatory microenvironment by regulating the immune response, which plays an important role in the process of tissue repair. This article mainly summarizes the research progress of MSCs in the treatment of IBD through immunomodulatory mechanisms.

Abstract:This study investigated the background of the modernization movement of Japanese laboratory animals in terms of time, examines the establishment of the main laws, regulations and guidelines of Japanese laboratory animals, and introduces the administrative framework and education and training system of Japanese laboratory animals. Throughout the developmental history of laboratory animal management in Japan, we can see: (1) Modernization movement of laboratory animals in Japan started in an early stage. (2) Through continuous improvement and revision, Japan finally formed a set of rigorous and standardized laws and regulations for laboratory animal feeding and animal experimental management. (3) In the management of laboratory animals, the administrative agencies of the government have strong power and responsibility to guide researchers actively. Various scientific research institutions and universities participate in industry management to form a characteristic independent management model. ( 4) Other laboratory animal-related groups actively cooperate with each other to formulate a series of industry guidance and standards. The Japanese Laboratory Animal Society and other groups actively carry out education and training of laboratory animal practitioners. To examine the history of laboratory animal management in Japan and analyze the laws, regulations, and management system to provide a reference for legislation of laboratory animals and improve the management system of experimental animals in China. Drawing lessons from the experience of Japan and other developed countries can promote the management of laboratory animals in China.